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ACUTE CONTAGIOUS DISEASES.
BY
WILLIAM M. WELCH, M.D.,
DIAtiNOS'ilCIAN TO THli BUREAU OIC HEALTH AND CONSULTING PHYSICIAN TO THE PHILADKLPHIA
MUNICIPAL HOSPITAL FOR CONTAGIOUS AND INFECTIOUS DISEASES; FOR THIKTY-THREK
YEARS PHYSICIAN-IN-CHARGE OF THE MUNICIPAL HOSPITAL; FELLOW OF
THE COLLEGE OF PHYSICIANS OF PHILADELPHIA;
AND
JAY F. SOHAMBERG, A.B., M.D.,
PROFESSOR OF DERMATOLOGY AND OF INFECTIOUS ERUPTIVE DISEASES, PHILADELPHIA POLY-
CLINIC AND COLLEGE FOR GRADUATES IN MEDICINE; ASSISTANT DIAGNOSTICIAN TO
THE BUREAU OP HEALTH AND CONSULTING PHYSICIAN TO THE MUNICIPAL
^ HOSPITAL FOR CONTAGIOUS AND INFECTIOUS DISEASES; FELLOW
OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA;
MEMBER OF THE AMERICAN DERMATOLOGICAL
ASSOCIATION.
ILLUSTRATED WITH 109 ENGRAVINGS AND 61 FULL-PAGE PLATES.
LEA BROTHERS & CO.,
PHILADELPHIA AND NEW YORK.
1905.
Entered according to the Act of Congress, in the 3'ear 1905, by
LEA BROTHERS & CO.,
In the Office of the Librarian of Congress. All rights reserved.
DOEN.'VN, PRINTER.
PREFACE.
In this work on Acute Contagious Diseases the writers have endeav-
ored to present a practical treatise for the guidance of students and
practitioners of medicine.
Perhaps some explanation may be sought for the adoption of the
title. We have somewhat arbitrarily included in this work but a
small group of diseases, particularly those with which we have had
experience in the Municipal Hospital of Philadelphia. The use of the
term "infectious diseases" would have necessitated the inclusion of a
great number of maladies upon which we do not feel specially qualified
to write. Furthermore, the group of contagious diseases is distin-
guished by great transmissibility, being communicated by the merest
contact or even by proximity, and therefore the term in its strict
etymological sense appears to us to be justified. Vaccinia is, of course,
not contagious, but its relation to the prophylaxis of smallpox makes
the consideration of the two inseparable.
The comparative infrequency of epidemics of smallpox renders it
quite possible for accomplished and otherwise experienced physicians
to be somewhat unfamiliar with this disease. We have, therefore,
devoted to this affection, and particularly to its diagnosis, an amount
of space not usually accorded to it in text-books of medicine.
We have furthermore endeavored to elucidate the subject-matter
with numerous photographs of patients under our care. The text is
based upon a personal study of over 9000 cases of smallpox, 9000
cases of scarlet fever, and 10,000 cases of diphtheria, in addition to
a considerable number of cases of the other diseases discussed, all of
which have been treated in the Municipal Hospital of Philadelphia
during the past thirty-five years.
vi PREFACE
We desire to acknowledge our indebtedness to Dr. E. L. Graf,
formerly Resident Physician in the Municipal Hospital, for assist-
ance in securing some of the photographs; to Dr. Burton K. Chance,
for the contribution of the chapters on Eye Complications and Treat-
ment in Variola; and to the publishers^ Lea Brothers & Co., for the
uniform courtesy extended to us.
W. M. W.
Philadelphia, Mat, 1905. t xri o
J. r. o.
CONTENTS.
CllAVlTAi I.
PAGE
Vaccinia 17
CHAPTER II.
The Relationship oi- Cowpox or Vaccinia to Smallpox 87
CHAPTER III.
The Variolous Diseases of Lower Animals 135
CHAPTER IV.
Smallpox 144
CHAPTER V.
Complications and Sequels of Smallpox 229
CHAPTER VI.
Chickenpox 316
CHAPTER VII.
Scarlet Fever 341
CHAPTER VIII.
The Diagnosis of Scarlet Fever 447
CHAPTER IX.
Measles 476
,•;; CONTENTS
VUl
CHAPTER X.
PAGE
547
Rubella
CHAPTER XI.
Typhus Fever
CHAPTER Xn.
.... 598
Diphtheria
CHAPTER Xni.
The Treatment of Diphtheria
CHAPTER XIV.
The Serum Treatment of Diphtheria 730
CHAPTER XV.
Disinfection
(MIAPTER r.
VACCINIA.
Synonyms. ^ — Latin, vaccinia, or variola vaccina; fJenner); P^nglish,
cowpox or Jcinepox; French, la vaccine; German, Kuhpocken,
ImpfpocJcen, Schutzbldttern; Italian, vaccinia; Spanish, vacuna.
Definition. — Vaccinia is a disease commiinical^le only by inocula-
tion, and is characterized by one or more skin lesions, accordinf( to the
number of insertions of the specific virus, running through the stages
of papulation, vesiculation and pustulation, ending in desiccation and
falling of the crusts at the end of the third week. The process is attended *
by slight febrile disturbance, and when completed confers immunity
against smallpox.
History.— When Edward Jenner was pursuing his professional studies
with his master at Sodbury, a young country woman, on hearing small-
pox mentioned, immediately observed, "I cannot take that disease,
for I have had the cowpox." This incident created a deep impression
in the mind of the young medical student, and may be said to have been
the awakening impulse, which, after years of patient study and experi-
ment, culminated in a discovery which has conferred the greatest bene-
fits upon the human race.
To properly appreciate the life-saving value of Jenner's discovery
it is necessary to know something of the fearful mortality of smallpox
in the prevaccination days. It was the most dreadful of all scourges,
not excluding the plague, for that disease came but rarely, while small-
pox was always present. Admiral Berkeley, chairman of the committee
of the House of Commons (in 1S02) to investigate the petition of Jenner
for a Parliamentary grant, in an elociuent speech said:^ "The discovery
of Dr. Jenner is unquestionably the greatest discovery ever made for
the preservation of the human species. It is proved that in these united
kingdoms alone 45,000 persons die annually of the smallpox; but through-
out the world what is it? Not a second is struck by the hand of time
but a victim is sacrificed at the altar of that most horrible of all dis-
orders, the smallpox."
King Frederick William III. of Prussia stated in 1803 that 40,000
people succumbed annually to smallpox in his kingdom. The French
Minister of the Interior, in reporting on vaccination in 1811, estimated
that 150,000 persons died annually in France from smallpox. In
' Quoted by Baron. Baron's Life of Jenner.
2
18 VACCINIA
Russia smallpox is reported to have destroyed 2,000,000 lives in a
single year.^
The mathematician, BernouilK, calculated that not less than 15,000,000
human beings died of smallpox every twenty-five years, which would
give a yearly average of 600,000. Dr. Lettsom estimated that Europe
alone claimed 210,000 victims each year. When to this number are
added the deaths produced by devastating epidemics in Asia, Africa,
and America, the aggregate estimate mentioned is seen to be conser-
vative. The early records of the London Asylum for the indigent blind
showed that three-quarters of the inmates had lost their sight through
smallpox.^ De la Condamine says that this disease destroyed, maimed,
or disfigured the fourth part of mankind.
Traditions Concerning Cowpox Protection. — The fact that cowpox con-
ferred protection against smallpox appears to have been noticed by
dairymen in England as far back as the middle of the eighteenth cen-
tury. It was observed by these people that when smallpox prevailed,
those who had been accidentally infected by the matter exuding from
certain sores, known as cowpox, which often appeared on the teats
• and udders of cows, resisted the infection of smallpox.
It is said that Benjamin Jesty, a Yetminster farmer, was the first
person in England to employ cowpox virus for the purpose of protecting
against smallpox. In 1774 he vaccinated his wife and children with
matter taken from the teats of cows that had the cowpox. In about a
week the arms became inflamed and considerable constitutional dis-
turbance was present. The children were later inoculated with small-
pox matter without result.
In Germany the protective influence of cowpox was known and prac-
tised prior to this date. Jobst Bose, a government official, called atten-
tion (General Conversations of Gottingen, part 39, May 24, 1769) to the
fact that the protection conferred by cowpox against smallpox was
recognized by reputable persons. He says: "I am reminded of the
not unknown attacks of cowpox which were prevalent in this country,
and to which to this day milkmaids are subject. In passing I wish to
remark that, in this country, those who have had the cowpox flatter
themselves to be entirely free from all danger of getting smallpox, and
assert, as I myself, to have heard this same statement made by entirely
reliable persons."^
In 1791 a school teacher by the name of Piatt, who lived in Starken-
dorf, near Kiel, vaccinated several children of his landlord to protect
them against a prevailing epidemic of smallpox. Several years later
they escaped smallpox, although intimately exposed to the disease. He
was prompted to perform this procedure by the popular belief concern-
ing cowpox protection that prevailed in Saxony and in Holstein. A
1 Woodville on Smallpox. Quoted by Baron.
2 According to Sir William Aitken 90 per cent, of the cases of blindness met with in the bazaars in
India are due to same disease.
3 Quoted by Kubler, History of Smallpox and Vaccination, Berlin, 1901. Kubler states that the
writer of the above commentaries was a man with practical experience in farming.
DISaOV/'^RV OF VAC'CTNATfON 19
Holstein fanner, JeiiscMi by iiuine, is also said to have etii{)lrjyed prophy-
lactic cowpox inoculation.
The same tradition, according to Humboldt, existed in certain parts
of Mexico for many years, and similar statements are made concerning
this belief in Baluchistan.
But it remained for Jenner to crystallize this half -forgotten tradition
into a scientific theory, and then, by painstiiking study and experiment,
to establish its truth and prove it to the world.
Referring to the vaccinations performed prior to -Tenner's time, Dr.
Baron says: "They did not advance the knowledge or the practice of
vaccination beyond what casual observation and popular rumor had
rendered common in many districts; if indeed they ever took place
(which I think more than doubtful) they were quite unknown to Dr.
Jenner, and had it not been for his publication they never would have
been drawn forth from their obscurity."
Early Practice in England. — Edward Jenner was born in the vicarage
at Berkeley, in Gloucestershire, in 1749. He was the third son of Stephen
Jenner, rector of Rockhampton and vicar of Berkeley. He exhibited
an early taste for natural history, and as a boy interested himself in
zoology and geology. After his scholastic education was finished he
removed to Sodbury, where he became apprenticed to Mr. Ludlow, an
eminent surgeon there, to be instructed in surgery and pharmacy.
In 1770 he went to London to study medicine under the direction of
the celebrated John Hunter, with whom he lived for two years.
In 1778 Jenner won the fellowship of the Royal Society, chiefly
through his admirable essay On the Natural History of the Cuckoo.
Despite his studies in natural history, the tradition concerning cowpox
gave him much food for thought and was frequently mentioned by
him in conversation with his friends.
After completing his course in medicine and locating in Berkeley,
England, where dairy farming was common, Jenner gave close atten-
tion to this tradition, and it was not long until he was convinced of its
reality. In medical coteries and societies he frequently expressed his
belief in the protective power of cowpox, but his views on this subject
were always regarded by his confreres as idle fancies of an overcredii-
lous mind. On one or more occasions, in a certain medical society to
which Jenner was a liberal contributor, the proposition was made, half
earnestly and half jokingly, to expel him if he did not cease boring
them with his absurd notions about the prophylactic power of cowpox.
But the evidence he had already collected from various sources was too
convincing to be set aside by such idle threats.
At length, after having devoted much time and thought to the sub-
ject, Jenner determined to inoculate into a human being the vaccine
disease, and to test its efficacy by actual experimentation. James
Phipps, a lad of eight years, has had his name made historical by ha%ing
been the first subject to undergo the experiment. The wus used was
taken from a vesicle on the hand of a milkmaid named Sarah Xelms,
who had been accidentally infected while milking a cow. This vaccina-
20 VACCINIA
tion was performed May 14, 1796, and was the beginning of Jenner's
work which has made his name immortal. On the second day of July
following Jenner proceeded to test the efficacy of this vaccination by
inoculating the lad with smallpox matter taken from a patient suffering
from that disease, but no result followed. At various intervals after-
ward, until this lad grew to be a man, he was inoculated with smallpox
matter, in all as often as twenty times, and each time was found to be
immune to that disease. It is no wonder, then, that Jenner arrived at
the conclusion in his treatise on vaccinia that a single vaccination con-
fers permanent immunity from smallpox.
The course of the vaccine disease in this case was very carefully
noted by Jenner each day fram the time the virus was introduced until
the crust came off spontaneously, and, finding the affection was benign
and wholly unattended by unpleasant results, he proceeded to subject
others to the "new inoculation," as vaccination was called in those days.
All his early cases were subjected to the same crucial test that was
applied in the case of James Phipps, to prove the protective power of
cowpox. It will thus be seen that the investigations of Jenner were
conducted so carefully and thoroughly as to demonstrate most con-
clusively the value of his discovery before he ventured to publish his
observations to the world. Quoting his own words: "I placed it on a
rock, where I knew it would be immovable, before I invited the public
to look at it."
It was not, therefore, until Jenner felt perfectly secure of his position
that he ventured to detail his experiments and formulate his conclusions
in a paper. This paper was prepared in 1797. It was Jenner's inten-
tion that this should first appear in the Transactions of the Royal Society,
but this design was abandoned and the work subsequently appeared
as an independent publication. In 1798 he published it as a modest
brochure, entitled An Inquiry into the Causes and Effects of the Varioloe
VaccincB, a Disease Discovered in Some of the Westerji Counties of
England, Particularly Gloucestershire, and Known by the Name of Cow-
pox.
This publication at once attracted great attention from the medi-
cal profession in London and throughout England. Like all innova-
tions, the "new inoculation" was viewed favorably by some, with
distrust and skepticism by others, while a few resolved to test it for
themselves.
Among the first in London to make use of the new discovery were
Dr. George Pearson, physician to St. George's Hospital, and Dr. William
Woodville, physician to the Smallpox and Inoculation Hospital. But
the early work of these gentlemen tended to impair confidence in vac-
cination. They reported that vaccinia was attended with a generalized
eruption more or less copious, resembling that of variola. When Jen-
ner's attention was called to the matter he denied that such a result
followed true vaccinia, and, on investigating the cases presenting this
eruption, he found that Woodville had carelessly permitted the virus
which he and Pearson were using to become contaminated with the
KAIUA' IIISTOnV OF V/\ CCINA T/0 \' 21
infection of sinallpox. A coiisi(lorji})l(; ((uuntify of lliis virus was sent
by these gentlemen to viirioiis j),'irts of Eii/^land aixl tfic C>)ntinent, and
in many instances its use was followed by disastrous results. Foreseeing
that vaccination was likely to be (Jiseredittive
of vaccinia, and recpiested that they he ^iveri to sf>nie careful and dis-
cerning practitioner — to his own family physician, if he preferred. He
also sent a lengthy letter full of instruction as to the use f)f the virus,
and courteously reim"nded the ('resident that amidst the pelting storms
of his adversaries Jenner had the countenance of his sovereign; that
the Duke of York v\^as a patron of the London Vaccine Institution; that
Bonaparte took a lively interest in the dissemination of vaccination in
France, and so did the German nobility at the Court of Vienna. He
e.xpressed the hope that the President of the United States would lend
his influence to extend the blessings of the new discovery to the Middle
and Southern States, believing, as he said, if it came from the hands
of the Chief Executive of the nation it would make a greater and more
favorable impression on the minds of the public.
The President's reply convinced Waterhouse that he had made Jio
mistake in the course he decided upon. The virus which had been sent
him was entrusted to a judicious and successful physician, but it failed
to communicate the vaccine disease. So also did the second and even
the third lot sent to the President by Waterhouse. A number of com-
munications passed between these gentlemen, when at last Jefferson
suggested that as the weather was warm the virus be placed in a small
vial hermetically sealed, and that this vial be immersed in water in a
larger one, which must also be hermeticallly sealed. The virus thus
conveyed was used on some members of the President's family by Dr.
Wardlaw, of Monticello, and proved successful. This occurred August
6, 1801. From his own family the President supplied Dr. Gantt, of
Washington, with a small quantity of vaccine matter, and thus was the
seed of vaccination planted at the capital of the United States.
All apphcations made to the President for virus received his careful
attention. To him belongs the honor of sowing the seed of vaccination
not only in the District of Columbia, but in Pennsylvania, Maryland,
Virginia, and the States farther South. He studied the process of
vaccinia so carefully that he was able to advise others as to the proper
time for taking the virus. This period he fixed at eight times twenty-
four hours from the date of vaccination. His advice in this matter,
we regret to say, was frequently disregarded by physicians, who be-
lieved themselves wiser than he, but never Avithout detriment to vaccin-
ation.
Waterhouse had the satisfaction of knowing that the virus which
first proved effective in New York City came from him. To speak more
definitely, it was taken from the arm of Governor Sargent's domestic,
who had been vaccinated in Boston by Waterhouse, and thence was
inoculated into several persons in New York City, on ]May 22, 1801, by
Dr. Valentine Seaman. Vaccine virus first reached Philadelphia in an
eft'ective state November 9, 1801. It was forwarded by Jefferson, through
Mr. John Vaughan, to Dr. John Redman Coxe, and was accompanied
by a personal letter from the President, full of valuable instruction as
30 VACCINIA
to its proper use. The first person who is said to have been successfully
vaccinated in Philadelphia was Dr. Coxe himself.
Soon after Jenner's brochure was published there appeared in almost
every civilized country in the world one or more supporters of the new
discovery who adhered more faithfully than others to the teachings of
the master, and consequently achieved distinction in this new field of
beneficent work.
Waterhouse, of Boston; Sacco, of Milan; and De Carro, of Vienna,
were the most faithful followers of Jenner. Of his many disciples,
Waterhouse was probably the ablest and worthiest. It is, perhaps, not
too much to say he was so regarded by the great benefactor himself.
The published letters of Jenner clearly indicate his high esteem of this
disciple. He well deserved the confidence of the master; for, single
handed and alone, in his own city, he faithfully and earnestly defended
and vindicated vaccination against the ridicule of the profession and
the prejudice of the public for seven years, or until conviction became
too strong for argument, and theoretical objections were forced to give
way to stubborn facts. So earnestly, constantly, and successfully did
Waterhouse devote his time and talent to the dissemination of vaccina-
tion in this country, and always so precisely in accordance with the
teachings of Jenner, that he received the complimentary title of the
"Jenner of America;" not, as might be supposed, by favor of the medi-
cal profession of his own country, but by the unanimous voice of the
London Medical Society.
THE HYGIENE OF VACCINATION.
In order that a vaccination may pursue a perfect course and remain
free of subsequent complications it is important that certain precautions
be observed. These may be classified as follows: Care as to (1) purity
of the vaccine virus; (2) condition of the vaccinee; (3) asepsis dur-
ing insertion of the virus; (4) subsequent protection of the vaccine
lesion.
Purity of Vaccine Virus. — Vaccine virus may be of human or bovine
origin. Within recent years the use of calf-lymph has become generally
and, indeed, almost universally adopted. The German government^ in
1884 passed a law that vaccinations and revaccinations in the Empire
of Germany be performed exclusively with animal vaccine.^
Humanized Virus.— In cases where it is necessary to employ human-
ized lymph, it is best taken from a vaccine pock from the fifth to the
eighth day. Virus should only be used from a perfect, primary, vaccine
vesicle containing clear or opalescent fluid. Where there is excessive
inflammation or any other irregularity present, the vaccinifer should be
rejected. The employment of the contents of lesions which have become
1 Resolution of the Imperial Vaccine Commission of 1884 ; approval of the resolution by the
Bundesrath, 1885.
- In Mexico humanized lymph is still extensively employed, and is preferred by the physicians of
that country to bovine virus.
Till': II Yd I EN K OF VACCINATION 31
purulent is strongly to he condemned. Jcniicr's dicfinii \v;i.s flujl lympli
should never he taken from a lesion after the fornuition of th(r areola;
this he regarded as the "golden rule of vaccination." 'I'he vaccine
crust is inferior to direct arm-to-arm vaccination with fhiiri lymph.
When a crust is employed at the present day it should be moistened
v^ith boiled water and rubbed up upon a sterile piece of glass.
The condition of health of the vaccinifer is of the greatest importance.
When humanized virus is employed careful incjuiry as to the health of
the parental antecedents should be made. The subject from whom
the vaccine is obtained should be in thoroughly good health. The
greatest care should be taken to determine that the vaccinifer is free of
hereditary syphilis. While the transmission of this disease by vaccina-
tion is extremely rare, its possibility is sufficiently well established to
warrant every precaution being taken.
It is the custom to obtain vaccine virus only from young subjects;
these are, of course, less apt to be suffering from certain transmissible
diseases. It is well, however, that the infant vaccinifer should have
reached the age of six months or thereabouts, so as to have passed the
period at which evidences of hereditary syphilis usually make their
appearance.
To obtain human vaccine lymph the vesicle, after having been pre-
viously cleansed with soap and boiled water, should be punctured in
several places with a lancet and the droplets of lymph allowed to flow
out. These are then transferred upon a clean lancet to the individual
about to be vaccinated; or if the lymph is to be used later or employed
upon some one at a distance, it may be collected in a sterile capillary
tube. After the vesicle is punctured the tube is thrust through the
opening, the lymph filling the tube by capillary attraction. When it is
about two-thirds full the tube is withdrawn and the ends sealed by
heating them in a Bunsen flame. The tubes should be kept in a cool
place until used. To expel the lymph from the tube the ends should be
broken off and the fluid blown out with a small rubber bulb.
At the present day we are chiefly concerned with hovine lymph . This
material is employed in two different forms — as a lymph and as a vesicle
pulp. Lymph, which is the clear fluid contents of well-developed vac-
cine vesicles, has been in use a long time. Pulp, which is a combination
of the lymph and the interior epithelial structure of the pock, has more
recently come into favor, and is at the present time regarded as possessing
greater vaccinal activity than the clear fluid. Vaccine lymph is used
either in the dry form upon strips of ivory or celluloid (so-called "dry
points") or in sealed capillary tubes in the form of a glycerin emulsion.
There is a growing sentiment among the best observers in favor of
the use of glycerinated lymph. This form of lymph has the sanction
and endorsement of the British Royal Vaccination Commission. The
method of preparation of dry and glycerinated lymph is elsewhere
considered.
Condition of the Vaccinee. — There is nothing in the condition of a
child that constitutes a sufficient contraindication to the performance
32 VACCINIA
of vaccination, if there be liability of exposure to the infection of small-
pox. We have vaccinated scores of children suffering from scarlet fever
and diphtheria in the Municipal Hospital during the presence on the
grounds of smallpox cases. We have never seen any untoward results
from vaccinating these patients, but the vesicles have not always been
as perfect as we would have liked to see them.
When smallpox is not prevalent it is proper for physicians to exercise
discretion in choosing the time for the vaccination of an infant. There
being no urgency, the medical adviser may wait until the child has reached
a favorable age and is in good condition for the reception of the vaccine
disease.
Age of Child. — In order that the proper protection against smallpox
may be granted to infants it is advisable that they should be vaccinated
during the first year of life. The vaccination laws of Germany require
that every child be subjected to this measure before the expiration of
the first year of life, unless it is contraindicated by reason of poor health.
The age which is generally considered most appropriate is between Jour
and six months, for at this period the child has not yet begun to be dis-
turbed by the process of dentition. If there be danger of smallpox
there is no reason to delay because of the tender age of the child. We
have on a number of occasions vaccinated infants immediately upon
their appearance into the world, and we do not recall any bad effects
that have resulted from such early vaccinations. Indeed, we have
been impressed with the very slight degree of constitutional disturbance
that has attended such vaccinations. Where, however, no haste is
necessary, we deem it well to wait for several months until the child
becomes stronger and more accustomed to its mundane environment.
Health of the Child .^ — It is best to delay the performance of vaccina-
tion (provided smallpox be not prevalent) if the child is poorly nour-
ished, or suffering from diarrhoea or vomiting, scrofulous glands, eczema,
etc., or if the infant has been recently weaned or placed upon some new
food. Vaccination of such children is prohibited by the regulations of
the English Local Government Board. In general terms it may be
said that when smallpox is not prevalent the physician may select
such time for the vaccination of an infant as may find it in the best
physical condition.
TECHNIQUE OF VACCINATION.
Vaccination being in a sense a surgical procedure, its performance
must be guarded by those precautions of asepsis which at the present
time apply to all chirurgical manipulations. Laboratory studies and
practical experience have both shown that even in the most trivial of
all surgical procedures — the introduction of a hypodermic needle into
the skin — certain precautions as to bacterial cleanliness are necessary.
Many years ago, before the days of bacteriology, this truth was not
known and consequently proper care was not, as a rule, observed either
in surgery or in the practice of vaccination.
TECIINIQIJI': OF VACfUNATION \\\\
Asepsis.- It is, of course, dcsirahlc that the vaccine lynipli he free
of foreign bacteria. In oi'der that all wcjurui infections niay be avcjifled
it is advisable that the arm of tlu; vaccinae, the instrutiKint to be em-
ployed, and the hands of the vaccinator 1)6 perfectly clean. Further-
more, the vaccine vesicle must l)e so y)r()te(-ted as to prevent subsecjuent
infection at the site of vaccination.
Disinfection of the Skin. Some difference of ojjinion exists as to
the thor()U(>;hness with which disinfection of the j)roj)()sed vaccination
area should be carried out. Some writers urj^e such a preparation of
the skin as is practised prior to an ordinary surgical operation. Others
believe that the use of strong antiseptics is to be avoifled, inasmuch as
they may destroy the activity of the vaccine material when placed upon
the skin.
We would counsel the following techni(jue: It is advisable for the
patient to take a tub bath on or before the day on which the vaccination
is to be performed, and to put on clean undergarments. fUnfoitunately,
it is difficult to have these measures carried out in the very people who
most need them.)
The vaccination area, usually the arm, is to be thoroughly washed
with potash soap and hot water, some friction being used so as to dis-
tend the cutaneous capillaries. Personally, we prefer to follow this
cleansing with the application of alcohol, although in cleanly persons
this is perhaps not necessary. The arm is then to be dried with sterile
absorbent cotton, or, when this is not available, a perfectly clean towel.
The operator may employ an ordinary lancet or a needle to produce
the necessary abrasion. If the former is used it should be previously
disinfected by boiling, immersion in an antiseptic solution, or thorough
cleansing with soap and water or alcohol. It is perhaps better to employ
a needle for the purpose, inasmuch as a new and clean one can be used
for each vaccination.
The insertion of the deltoid muscle is the site usually selected for the
introduction of the virus. The skin is made tense through the grasping
of the inner side of the arm with the left hand. The epidermis is then
abraded over an area of a third or a half inch; this is done either by
vertical or cross scarification with a needle or simple scraping with a
lancet or scalpel.
It is important that the ahrasion he not too deep. The drawing of
blood is to be avoided, inasmuch as it may float away the lymph and
prevent absorption; it is further claimed that the deep scarification is
more likely to be followed by an excessive degree of inflammation. It
is not desirable to abrade deeper than is necessary to see the little red-
dish points which represent the loops of the papillary bloodvessels.
It is a matter of some importance to rub the virus well into the abraded
surface. The hasty smearing of the hiiiph upon the arm with no further
manipulation is probably responsible for a certain percentage of failures.
Some writers have advocated vaccination by hypodermic or, rather,
intradermic puncture. This is accomplished by expelling the iMnph upon
the previously cleansed vaccination site, and then passing a thoroughly
34 VACCINIA
sterile hypodermic needle obliquely through the skin over this area.
Several punctures should be made v^ithin an area of 1 cm. square, but
they should not be deep enough to draw blood. The puncture carries
the lymph into the skin. The alleged advantage that little or no scar
results from this method appears to us to be in reality a disadvantage —
for the presence of a scar and its character constitute, as a rule, visible
evidence of the amount of protection against smallpox which the
individual enjoys. We therefore see no special advantage of this over
other methods of vaccination.
It is best to allow the lymph to dry upon the arm by exposure to the
air; this will ordinarily take from ten to thirty minutes. Where it is
inconvenient to keep the arm bared for this time, there is no objection
to protecting the abraded surface for a few hours with a loosely fitting
shield made of pressed linen. It is important that no shield should be
applied which congests the parts by peripheral pressure or which exerts
any suction.
The vaccine vesicle when formed should be sedulously guarded
against mechanical violence or injury. Nature provides an excellent
protective covering for the vaccine wound — a hard, concrete, firmly
attached crust. This crust is formed by desiccation of the vaccine
pock. When the vesicle is ruptured by traumatism, some of the con-
tents escape and form an irregular, friable crust which is easily detached,
leaving an open wound which is liable to infection with pathogenic
organisms.
Shields. — Various forms of shields have been devised to protect the
vaccine lesion from injury and infection. Many of these have failed
utterly of their purpose, and some have done actual injury by increasing
the inflammation, and by rubbing off the scabs and thus producing
open sores. Some writers condemn all shields; we have seen a few
made of a light metal like aluminum which appeared to protect the
vaccine lesions from the adhesion of the sleeve and from accidental
injury without exerting any injurious compression. The use of such a
shield, which can be easily sterilized, may be recommended. The
application of a sterile gauze compress over the vaccine vesicle is also
advocated; there is no objection to this save where the vesicle becomes
ruptured, when the crust will adhere to the gauze and be torn off with
its removal.
Patients should be advised not to allow the sleeve of the shirt or
undershirt to rub against the vaccine vesicle. It is often a good plan
to have a thoroughly clean piece of linen sewed into that portion of the
sleeve which comes in contact with the vesicle. Caution should be
given patients against rubbing, scratching, or otherwise fingering the
vaccination scab; manipulation of this character is a fertile source of
ulceration and late wound infection.
Number of Insertions. — It is the custom abroad to insert the lymph
at several sites. When this is done the scarifications should not be too
close, for fear of interfering with the vitality of the intervening skin,
thus leading to sloughing. It is best to allow three-quarters of an inch
8YMPT0MH AND ractice (jf a col-
leajijue — thirteen attempts at vaccination to he made Ix-fore a snccessfnl
result was obtained.
Insusceptibility to vaccinia, or rather failure of result after repeated
attempts to vaccinate, does not of necessity indicate an insusceptibility
to smallpox. We recall to mind a youn^ ])hysician who had been
repeatedly vaccinated in childhood aiul youth without successful result,
who on brief exposure to a mild case of variola contracted a severe
attack of confluent smallpox. We have also in mind a young woman
wlio fell ill with hemorrhan;ic smallpox, although she liad had seven
unavailing trials at vaccination made upon her, three of which were
performed within a year preceding the attack of smallpox.
The late Mr. Spurgin, of Northampton, forwarded some years ago
to the Epidemiological Society the particulars of a case in which in
1825, a boy fourteen years old, whose family was greatly opposed to
vaccination, was inoculated with variola six or seven times without any
result, that disease being then prevalent. The father then allowed
vaccination to be tried, and the boy was vaccinated six or seven times,
but equally without effect. About a year after, when at a distance from
home, he contracted natural smallpox of the discrete kind, and went
through the disease favorably (Seaton).
REVACCINATION.
Experience has demonstrated the fact that in a certain number of
persons the protection from vaccinia in infancy is permanent, while in
others it gradually diminishes, and after the lapse of a number of years
may become entirely extinguished. The extinction of immunity is evi-
denced by the large number of persons in adolescent and adult life who
are susceptible of revaccination; also by the observation that in all epi-
demics of smallpox a large proportion of the cases occur among persons
who were vaccinated in infantile life. The statistics of smallpox hospitals
in this country and in England show that from 41 to 78 per cent, of the
admissions are postvaccinal cases. It is very difficult to determine the
proportion of persons vaccinated in infancy that fail of permanent pro-
tection, but it is beheved to be not far from 75 per cent. Some yeais
ago a very careful observation in a certain American city showed
that of 2362 persons revaccinated with reliable virus (no child under
twelve years old with a good scar being included in this nimiber) 77.1
per cent, were susceptible to some form of vaccinia.
We have no means of ascertaining the age or period of life at which
the protection from vaccinia in infancy is liable to diminish or cease
entirely, save by applying the test of revaccination or by noting at what
age after primary vaccination any considerable number of persons
suffer from smallpox. Data tending to demonstrate the latter may be
found in the followino- table:
46
VACCINIA
Cases.
Deaths
Percentage
of deaths.
Under one year j
Unvaccinated
Vaccinated
Unvaccinated
Vaccinated in infancy, good scars
" " " fair
" " " poor "
Total number vaccinated
Unvaccinated
Vaccinated in infancy, good scars
" " " fair "
" poor "
Total number vaccinated
Unvaccinated
Vaccinated in infancy, good sears
" " " fair
" " " poor
Total number vaccinated
134
2
g6
64.18
0.0
676
280
41.42
One to seven years ....
11
11
16
1
1
0.0
9.09
6.25
.
38
2
5.26
320
61
24
64
87
2
2
9
27.19
Seven to fourteen years . .
3.28
8.33
14.06
L
149
13
8.72
r
1742
868
49.83
Fourteen years and upward
1864
894
1240
138
114
313
7.4
12.75
25.24
3998
565
14.13
Among over 9000 cases of smallpox admitted to the Municipal Hos-
pital of Philadelphia during the past thirty-four years we have admitted
only two vaccinated patients under one year old. One of these was a
child eleven months old who had been vaccinated two months pre-
viously and showed a good scar. The eruption consisted of only six
small vesicles, and the child's health was scarcely at all disturbed. The
other patient had the diseass so indistinctly marked that it was almost
impossible to feel certain of the diagnosis of varioloid. An exceedingly
modified form of smallpox was occasionally seen among well-vaccinated
children between the ages of one and seven years, but no deaths occurred
except where there was a serious complication. The child that died,
whose case is classified under the head of "fair scars," was a foundhng
about a year old, badly nourished and very feeble, with a disordered
digestion. The eruption consisted of only a very few small vesicles.
Death really resulted from inanition. Very little need be said of the
cases classified in this age period under the head of "poor scars," as
the vaccination in them had been in good part either imperfect or
spurious.
The query is often asked, What constitutes a successful revaccina-
tion ? This is a question about which there is considerable diversity of
opinion. Many believe that, unless the vesicle and areola observe the
course of true vaccinia, the effect is merely local and devoid of prophy-
lactic power. But it is evident on a little reflection that there is no more
reason why we should expect the vaccine disease produced by revac-
cination to be typical than we should expect smallpox after vaccination
to run the typical course of variola vera. If there be modified smallpox
or varioloid after vaccination, so should there be modified vaccinia or
UKVAddlNATION
47
vaccinoid. l^'rom tlicsc; premises the coiicliision m;iy Ix' (Iciliiccrl thai
}is varioloid conlors iitiiniiiiity a(i;a,iii,sl a rcciirrcncc oF smallpox, so also
(Iocs tlic inodificd form ol" vaccinia, I'csiilliii^ IVoiri rcvaccinalioii rciriove
froni the individiiaJ whatever siisccplihilily U> the disease riiay he present.
It is frecjucntly a matter of ^reut didiculty in revaccinations to dis-
tinfi;uish between irritative local reactions and lesions which rcsnit from
the S])ecific action of the vaccine princij)le.
Course of Revaccination. The S(;a h's 5X
RETROVACCINATION OR VACCINATION FROM TKE HUMAN
SUBJECT BACK TO THE BOVINE SPECIES.
The inoculation of lyin[)li from a Imiiian vaccination into tin; cow
produces quite constantly a ty})i('al vaccine lesion. 'J'his expedient
was at one time resorted to with the viev^^ of restoring j)otency to the""
attenuated lymph of lonf^" humanization. ]\Iost careful investij^ators
concluded, however, that lonr^ humanized virus so transplanted gained
neither in strength nor in purity, and, indeed, became more difficult to
retransfer back to the human subject, although this (Jifficulty was
overcome in the second human remove. Retrovaccination is seldom
employed at the present day.
VACCINAL SCARS.
Physicians are often in doubt as to what constitutes a typical vaccine
cicatrix. We deem the subject of sufficient importance to warrant a
brief study of the objective features of vaccination scars.
When an individual has undergone a vaccinia which has been per-
fect in every respect, there is left after the fall of the crust a cicatrix
which is characteristically distinctive in its features. Such a scar is
indicative of the fact that the bearer thereof has passed through the
vaccine disease in its most perfect form. The typical cicatrix is round
or oval, distinctly excavated, with well-defined margins, reticulated or
foveolated, and altogether presenting the appearance of having been
stamped into the skin with a sharply cut die. Not all true vaccinations
are followed by scars presenting these characteristics, but the more
closely the cicatrix approaches to this standard the greater is the assur-
ance that the vaccine disease has been genuine in every respect, and is
calculated to give the greatest degree of immunity against smallpox.
However, the appearance of the scar may vary within certain limita-
tions and still be regarded as the sequential imprint of a genuine vac-
cinia.
The variety of vaccine scars is very great; the most frequent ^•aria-
tions from the type above depicted are the result of the employment
of lymph which has become more or less enfeebled by long human
transmission. Modifications of the resulting scar may also be due to
abnormalities or complications of the vaccine process, and to mechanical
injury or interference with the normal development of the vesicle.
In 1851, Decanteleu, of Paris, published an excellent monograph
on the subject of vaccine scars, in which the classification is given after
the system of Lamarck.^ The author distinguishes fifteen species of
vaccine scars and depicts these and many sub^•arieties in .well-executed
drawings, some of which are here reproduced. These drawings represent
the type of each species. Fig. 10 represents examples of perfect scars
resulting from vaccinations with vigorous bovine l^inph or of an early
1 Monographic des cicatrices de la vaccine, par J. E. B. Deuarp-Decanteleu. Paris, 1S51. Quoted
by Dr. H. A. Martin.
62 VACCINIA
human remove therefrom. The centre of the cicatrix is rounded,
smooth, and convex, and surrounded by a deep, depressed, circular
furrow or sulcus, which is traversed by short ridges radiating from the
centre to the periphery. Most of these scars are round, but occasionally
those of oval shape are encountered. Decanteleu found this type of
scar in 24 per cent, of over five thousand scars examined.
Fig. 10
J a ■■ 'I ! (I
Ih
Various forms of good vaccinal scars, showing a central, elevated disk surrounded by a furrow
with radiating bands ; the scars look as if they had been' punched out with a die. (Alter Denarp-
Decanteleu.)
Fig. 11
Smooth scars on a level with the surrounding skin, showing slight pitting; such scars may result
from genuine vaccination with long humanized virus. (After Denarp-Decanteleu.)
It is but natural that vaccine scars should present variations. A
cutaneous scar, no matter from what cause, is the result of the destruc-
tion of dermal tissue. When merely epidermis is lost no scar results,
for the cells of the rete mucosum proliferate and restore the complete
integrity of the cuticle. When, however, a portion of the cutis proper
is destroyed, repair takes place through the formation of fibrous con-
nective tissue, which is scar tissue.
The appearance of a cicatrix will depend upon the character, extent,
and depth of the tissue loss, and sometimes upon certain personal pre-
dispositions.
The minute joveolations or 'pits which are commonly seen in vaccine
VA (JCJ/NA L S(!A ILS 53
scars, and which are ref^arded by some as essci)ti;il (o tlif [x-rfcrt cifjdrix,
represent the (h'latcd orifices of hair folhclcs and schaccous ^hirids. It
is readily seen that if tlie vaccine [process (h-stroys tlic si,aymen and even
physicians are too prone under such circumstances to apply the prin-
ciple of post hoc ergo propter hoc. Vaccination immunizes only against
smallpox; it will not protect one from tuberculosis, syphilis, skin dis-
eases, etc. Therefore, as these are common diseases, it will of necessity
happen that they will from time to time attack persons who have been
recently vaccinated. We do not desire to convey the impression that
vaccination never does any harm, but we are convinced that many mor-
bid conditions are attributed to vaccination which bear no relation to it
save a chronological one.
1 Quoted by Holt, Diseases of Children. - History of Smallpox and Vacciiiation, 1901.
60
VACCINIA
Vaccination and Cutaneous Disease. — The following classification
of skin diseases associated with vaccination is a modification of that
formnlated by Malcolm Morris and later revised by Frank:
Local .
{
Eruptions attributable to ,
the vaccine virus pure j
and simple.
t Constitutional
II. Eruptions attributable to
mixed infection at time
of vaccination or later.
Local .
Constitutional
Normal vaccinia.
Erythematous dermatitis (areola).
Generalized vaccinia.
Diffuse vaccine erythema.
Vaccinal roseola .
Vaccinal lichen.
Vaccinal miliaria.
Purpura.
Erythema multiforme.
Urticaria.
{Erysipelas.
Impetigo contagiosa.
Furunculosis.
Vaccinal ulcer.
Localized gangrene.
L Cellulitis.
f Disseminated gangrene.
Syphilis.
Leprosy (?).
Tuberculosis (?).
III. Eruptions sometimes fol-
lowing vaccination.
f Eczema.
I Bullous eruptions (acute pemphigus, dermatitis bullosa,
j dermatitis herpetiformis).
1 Psoriasis.
I Furunculosis.
i Urticaria.
The above classification is doubtless faulty in many respects and
open to criticism, but will perhaps serve the purpose of indicating in a
general way the etiological factors in the production of the various der-
matoses that may complicate vaccinia.
Generalized Vaccinia. — This is perhaps the only eruption among those
enumerated (with the exception, of course, of the normal vaccine dis-
ease) which may with positiveness be attributed to the pure vaccine
virus. There are two varieties of generalized vaccinia — 1. Spontaneous
generalized vaccinia (vaccinal eruptive fever, vaccinola). 2. General-
ized vaccinia from autoinoculation.
Spontaneous generalized vaccinia is an extremely rare condition;
many cases formerly regarded as instances of spontaneous diffusion
of the eruption are in all likelihood cases of autoinoculated vaccinia.
The eruption appears usually from the fourth to the tenth day after
vaccination and most often from the sixth to the ninth day.
The lesions appear in successive crops and pass through the stages
of papule, vesicle, and pustule. The eruptive lesions, being of different
age, may be seen in varying stages of development. Complete subsi-
dence of the efflorescence usually occurs before the twenty-first day.
The lesions may be few or numerous and may appear upon any portion
of the body surface. Fever is absent in some cases and present in others,
being usually proportionate to the extent of the eruption and the asso-
ciated complications, particularly glandular enlargement.
The causes of generalized vaccinia are but poorly understood. An ab-
normal susceptibility to the vaccine virus has been invoked as a cause.
The administration of the vaccine material through the digestive, cir-
culatory, or respiratory system is regarded by Acland as capable of
VACCINA 1. COMPIJdArrONS AND fNJfl/if/'JS fj]
iiuluciiij^ ii j^ciKTiiliziitioii of llic cnipdc))!. This wrilcr niciilion-, ;iii
observation of Etieiine tfiut a ^(Micralized vaccinal crii})tion had been
|)ro(liice(l in children who had sucked their vaccination pocks; general-
ized vaccinia has also been produced by the intentional feedinj^ of pow-
dered vaccine crusts to subjects |)reviously rej^arded as insusceptible
to vaccinia.
Chauveau was able to produce a generalized eruption in horses by
subcutaneous injection of vaccine lymph and also by administration
through the res])irat()ry and digestive tracts.
Generalized vaccinia may present a considerable resemblanr-e to
variola. It may usually be distinguished by the absence of an initial
stage, its occurrence after vaccination, the appearance of the eruption
in crops, and the irregular distribution of the lesions. Its differentiation
from inoculated variola is rather more difficult.
Generalized Vaccinia from Autoinoculation. — This foim of generaliza-
tion of the vaccine lesions is by no means rare. Many writers at the
present day are inclined to regard the vast majority of cases of general-
ized vaccinia as due to external inoculation. French writers have
reported a number of instances of diffusion of the vaccinal eruption
over an extensive cutaneous area the seat of a moist eczema. Unless
there is danger of exposure to smallpox, it is, indeed, advisable to post-
pone vaccination if the subject is suffering from a dermatosis in which
there is denudation of the skin. The number of lesions may be but two
or three or there may be a profuse eruption. The development of a
few supermnnerary lesions in the neighborhood of the original vaccine
insertion is by no means uncommon; this may occur even when there
is no demonstrable abrasion of the skin. The virus may be transferred
by the patient himself through scratching, or it may be conveyed by a
second person. Fig. 12 represents six vaccine lesions upon the face of
a woman which were produced by the finger-nails of an infant in arms;
both the mother and child had been vaccinated upon the arm. We
recall the case of an infant born of a variolous mother at seven and a
half months. The child was immediately vaccinated, the insertions
"taking:" well. From eleven to fourteen davs after the vaccina-
tion, lesions indistinguishable from vaccine vesicles appeared upon
the left side of the thigh, the left loin, the middle of the back, the
hip, the splenic region, and the scrotum. These varied in diam-
eter from five-eighths of an inch to three-quarters of an inch, were
depressed in the centre, the depression later acquiring brownish crusts.
Sixteen days after the vaccination a half-doxen firm variolous papules
developed upon the face, neck, scalp, and foot. The infant was feeble
and died a few^ days later. In this case it w^as difficult to determine
whether the multiplicity of vaccine lesions was due to circulatory diffu-
sion or autoinoculation. Accidental vaccine lesions may appear upon
any portion of the cutaneous or mucous surfaces. They may even occur
upon the conjunctiva or upon the eyeball. In the latter case there may
be loss of vision. One of the writers recently saw in the practice of a
medical friend, an ophthalmologist, a case in which a vaccine lesion
62
VACCINIA
had been accidentally produced upon the bulbar conjunctiva. The
family physician while vaccinating several children was requested by
the mother to remove a foreign body from her eye. The physician,
without cleansing his hands, everted the eyelids to determine the pres-
ence of the offending substance. In the due course of time a vaccine
vesicle appeared, accompanied by tremendous chemosis; the eye was
saved only after prolonged skilful treatment.
The lesions in vaccinia generalized by autoinoculation appear at
intervals after the original vesicle is well advanced; they seldom con-
tinue to make their appearance after the third week.
Fig. 12
Accidental, multiple vaccinations produced by the scratching of an infant's hand
contaminated from a vaccine lesion on its own arm.
Sore Arm. — Under this caption we shall discuss a condition which
only in its severer phases is to be regarded as a complication. A certain
amount of inflammatory reaction (areola) about the fully developed
vesicle is to be viewed as a not undesirable and probably an essential
part of the normal evolution of the vaccine lesion. It not infrequently
happens that instead of a moderate erythema and oedema of the skin,
these phenomena are present to an excessive degree. Now and then
the inflammation about a vaccination reaches a violent degree of inten-
sity and spreads over a considerable portion or the whole of the affected
arm. In such cases the cellular tissue may become implicated, giving
VA(/('fNy\fj COMI'lJdATIONH AND / N.KU!/ i:S
C/.i
rise to a difl'iise cdluliiis. Tlie Jirin uruJer such coixliiicjiis is i'(;fl, swfjllcn,
hot, and painful, and there is apt to be some associated systemic dis-
turbance.
In other cases the inflammation is more circumscribed and its force
is spent upon the vaccine lesion and the skin in its imni(;diatc ncifrhbor-
hood. In such cases a necrosis of the cutaneous and suljcutaneous
tissues may occur, with the formation of a slouch. Wlien this is thrown
off an ulcer is left at the site of vaccination. In other cases the vaccinia
may pursue a normal course to the development and decline of the
areola, but instead of the formation of a typical scab an excavated
ulcer appears, covered by a soft, thin crust, which fre(|uently falls off
and is renewed, the idcer persisting in this manner for a lont^ time. Mar-
Fro, i:'.
Sloughing at the vacciuation site accompanying au unusually inflammatory vaccination.
tin, of Boston, repeatedly observed this irregular course upon arms
which had been vaccinated with long humanized virus, whereas upon
the opposite arm on which bovine virus had been simultaneously em-
ployed a perfect result was obtained.
This observation, as well as the scientific investigations of later-day
observers, suggests that the excessively "sore arm" is due to the intro-
duction of something in addition to the pure vaccine \urus, and, further-
more, that this additional something is of the nature of extraneous
micro-organisms. The Lancet Special Commission on Glycerinated
liymph^ says that "the presence of a large number of organisms in an
1 London Lancet, 1902
64 VACCINIA
active vaccine lymph renders the local lesion more severe," and that
"many of the bad results obtained in vaccination are due to imperfect
sterilization of the skin and want of protection against the invasion of
the weakened and abraded tissues by extraneous organisms." It is
also stated that "one of the most certain methods of producing severe
oedema is for the patient to use his arm freely and to bring about per-
spiration just before and after the vesicles have begun to form."
Tt is not uncommon for the arm to become very "sore" as the result
of thoughtless or accidental traumatism on the part of the vaccinee.
The vesicle is frequently ruptured by a blow, friction of clothing, scratch-
ing, and other like causes. Where the vesicle is unprotected the shirt-
sleeve often becomes glued to the vaccination lesion, and attempts at
separation cause a detachment of the crust. All of these forms of trau-
matism doubtless act in the same manner; they prevent the formation
of a firm, compact crust which is nature's protective covering of the
vaccine wound. By opening up the wound they permit of infection
with extraneous germs which may produce merely excessive inflamma-
tion or may lead to ulceration or other more severe vaccinal complications.
Inasmuch as we can obtain a lymph which is rendered free of extra-
neous germs by the process of glycerinization, by proper care of the arm
before, during, and after vaccination, we should be able, in the vast
majority of instances, to prevent the development of "sore arms."
Vaccinia Hemorrhagica. — From time to time cases of vaccinia are
seen in which the areola about the vesicle at the acme of its development
becomes hemorrhagic, assuming the appearance of a diffuse ecchyraosis.
In some instances the skin beyond the areola may present a bluish
appearance. In rare cases there may occur scattered petechise and
ecchymosis and hemorrhages from some of the mucous membranes.
The cause of this complication is obscure; it is doubtless not so much
due to any peculiarity of the lymph as to some underlying systemic
condition favoring hemorrhagic extravasation, such as scorbutus.
Vaccinal Ulceration. — Ulceration at the site of insertion of the lymph
is by no means an uncommon complication of vaccinia. Acland' says
that nearly 4 per cent, of the vaccinal injuries inquired into by the
English Local Government Board (1888-91) were due either to ulcera-
tion or glandular abscess. There is in all probability one of two factors
which may give rise to vaccinal ulceration — either the introduction into
the skin of extraneous micro-organisms (at the time of vaccination or
later) capable of producing a tissue necrosis, or an abnormal or vitiated
state of health which permits of an excessive and unusual local reaction.
Both of these factors appeared to play an important role in the produc-
tion of "bad arms" among the soldiers during the United States Civil
War. In the admirable report of the Board of Health of Louisiana of
1884, compiled by Dr. Joseph Jones, we read the following: "In scor-
butic patients all injuries tended to form ulcers of an unhealthy charac-
ter, and the vaccine vesicles, even when they appeared at the proper time
and manifested many of the usual symptoms of the vaccine disease,
1 Article on Vaccinia, Allbutt's System of Medicine, p. 59G.
VA(J(JINAIj (JOMriJdATIONS and INJlfltll'lS 65
were nevertheless larger and more slow in licalin^r, und tlic srahs [jrc-
sented an enlarged, scaly, dark, unhealthy aj)j)caranc-e. In many cases
a large ulcer, covered with a thick, laminated crust, from f)M(;-f|uarter to
one inch in diameter, followed the introduction of the vaccine matter
into scorbutic patients." In the same report Dr. Paul F. Eve describes
certain abnormal manifestations of the vaccine disease due to the use
of an improper scab. "The scab used in Atlanta which did so much
mischief was soft, porous, and spongy, resembling concrete inspissated
pus In every instance in which vaccination was attempted
with it, premature effects were developed. No proper period of incuba-
tion nor papular nor vesicular eruption was observed, but in a few days,
even as early as the second, inflammation had set up, and by the fourth
or fifth day sores were produced, covered by a thick, dirty crust, with
an ichorous discharge. Soon an ill-constituted ulcer, with perpendicular
edges, ensued, extending through the dermoid to the cellular and mus-
cular tissues, and involving the neighboring lymphatics." These cita-
tions indicate that either a weakened resistance on the one hand, or
an extraneous infection on the other, may be responsible for vaccinal
ulcerations.
We have seen a few cases of ulceration at the vaccination sites follow-
ing the use of bovine lymph. Fig. 13 shows such an ulceration occur-
ring about the fifteenth day after vaccination.
Septicaemia and Pyaemia Following Vaccination. — Blood poisoning
is a rare condition after vaccination at the present day, and with care in
the propagation and preservation of lymph, an aseptic technique, and
proper protection of the vaccinated arm, this unfortunate complication
will doubtless become rarer still. Several appalling epidemics of sep-
tictemia after vaccination are on record; one occurred in the United
States, one in Germany, and one in France. In all three the disastrous
results followed the use of humanized virus; in two instances there was
the grossest negligence in the preservation and preparation of the crusts,
and in the third a lymph was used which was producing in progressive
transmissions increasingly abnormal reactions.
These epidemics are of much importance, and a brief account of theui
is herewith presented:
In 1860, during the prevalence of smallpox in Westford, Massachu-
setts, a physician vaccinated a number of people with crusts which had
been shaken up in a bottle with snow-water in order to provide a suffi-
cient quantity of vaccine material. For ten or eleven days patients were
vaccinated with a lancet which was from time to time dipped into the
bottle. None of these people showed any results; but on the eleventh
or twelfth day, by which time the bottle of liquid emitted a horrible
stench, he "vaccinated" twenty-five more people. There at once
ensued in half the cases diffuse abscesses. Three of the oldest vaccinees
died in a short time, and a dozen or more of the remainder were only
saved by the most prompt and energetic treatment.^ As Dr. Martin,
who was foreman of the coroner's jury on this occasion, stated, "the
1 Mentioned by Dr. Henry A. Martin. Reprint from a letter in the Erie Observer.
5
QQ VACCINIA
fearful results were clearly to be ascribed to the development of a septic
poison of intense and virulent malignanty at a certain stage of the de-
composition of animal matter."
In 1878, at Grabnick, a similar but more extensive epidemic of
septicaemia occurred among children infected with some old virus which
had been exposed to the air for a long time. Fifty-three children were
inoculated with the decomposed vaccine material, and of this number
fifteen died. Some of the children had morbilliform and scarla-
tiniform eruptions, and others abscesses and erysipelatous symptoms.
According to Pincus the vaccine material contained septic bacteria.
Autopsies were made upon two children and the deaths ascribed to
septicaemia,
BrouardeP reports a series of cases of blood poisoning following
vaccination at Asprieres, France, in 1885. Brouardel, Pasteur, and
Proust were commissioned to determine the responsibility of the attend-
ing physician. The commission says: "In our investigations we were
enabled to trace the vaccine back through five generations and to deter-
mine that it was by employing a virus originally good, but which gave
rise successively to accidents, at first of slight gravity, then more and
more serious, that the preparation was made for the final disaster."
Forty-two children were vaccinated from the arm of a little girl who
herself had developed fever the first night after her vaccination, and
whose vaccination "took" on the following day. Of this number four
died within twenty hours and two others later. Almost all of those
vaccinated were more or less ill. The symptoms were fever, vomiting,
diarrhoea, and in the fatal cases convulsions. The fever appeared at
the latest eighteen hours after vaccination; in those who recovered it
lasted from two to four days. All the children developed on the first
day an inflamed area about 1 cm. in diameter surrounding the point
of inoculation. A serous or seropurulent discharge occurred from the
first to the third day. In all of the children a local and generalized
impetiginous eruption followed the inoculation.
These cases represent examples of acute intense septicaemia analo-
gous to that resulting from bad dissection wounds. The septic micro-
organisms were doubtless increased in virulency by successive trans-
missions from one subject to another.
A case of pyoemia^ after vaccination is recorded in the Lancet, 1884,
vol. i. p. 857. A child, aged six months, vaccinated with two other
children from the same source, showed on the ninth day appearances
of successful vaccination with no unusual symptoms, but on the six-
teenth day the sores were ulcerated and freely discharging pus. The
child was also suffering from bronchitis. Death took place on the
twenty-fifth day after vaccination. The autopsy revealed the presence
of pus in the left ankle, right sternoclavicular joint, both temporomaxil-
lary articulations, and in the bursa over the right olecranon. The lungs
presented a number of hemorrhagic infarcts.
1 Twentieth Century Practice of Medicine. Article on Vaccinia, p. 534.
2 Mentioned by Poole, Vaccination Eruptions, Edinburgh, 1893, p. 118.
VyiC('fNAIj (lOMI'lJdATIONS AND IN.iriilKS 07
There was in the .same house a man vnfh an ah.srrs.s of llie /oo/, unci
occasionally \\w. mother had washed some linen in the water which Ijufl
been used for cleansinn; his foot. This fact, with the early normal devel-
opment of the vaccine lesion, and the exeinj)tif)n of th(; other two chil-
dren vaccinated, constitute strong presumptive evidence that the septic
infection occurred subsefjuent to vaccination, probably through neglect
on the part of the child's carelakers.
Glandular and Subcutaneous Abscess. — In most normal vaccinations
enlargement and tenderness of the neighboring lymj)hatic glands are
observed. Where there is an unusual degree of inflammation about the
vaccine lesion or actual ulceration, the swollen glands not infre(juently
undergo suppuration. As has been already stated, glandular abscess
and vaccinal ulceration comprised nearly 4 per cent, of vaccination
injuries reported to the English Local Government ]}oard from 1888 to
1S91. Sinigar' reports four cases of abscess among 1160 vaccinations.
One appeared on the twentieth day in the lower half of the posterior
triangle of the neck, one between the pocks on the arm on the twenty-
fourth day, one on the arm on the twenty-ninth day, and one in the
axilla on the thirty-second day. These abscesses are seldom of serious
portent, usually healing rapidly after incision and evacuation.
Localized Vaccinal Gangrene. — In extremely rare instances death
of the tissues eii masse at the site of vaccination may occur, producing
a locahzed gangrene. It would seem that in these cases the gangrene
is due to low vitahty of the tissues rather than to any impurity of the
lymph. In cases observed by Balzer, Wheaton, and Acland, the chil-
dren were of syphilitic parentage. Hutchinson, however, saw three
cases of vaccinal gangrene in children in wdiom no such cause could be
invoked. The view that the condition of the tissues is the most important
etiological factor in the production of this complication is corroborated
by the experience of surgeons in the Confederate army during the
United States Civil War. Dr. Joseph Jones' writes: "After careful
inquiry w^e were led to the conclusion that these accidents were, in the
case of Federal prisoners, referable wdiolly to the scorbutic condition of
their blood and the crowded condition of the stockade and hospital.
The smallest accidental injuries and abrasions of the surface, as from
splinters or bites of insects, were in a number of instances followed by
such extensive gangrene as to necessitate amputation. The gangrene
following vaccination appeared to be due essentially to the same cause,
and in the condition of blood of these patients would most probably
have attacked any puncture made by a lancet, without any vaccine
matter or any other extraneous material."
Vaccinia Gangraenosa. — As has been pointed out by Crocker and
others, the term vaccinia gangrrenosa is a misnomer, inasmuch as the
affection recorded under this title occurs after varicella (varicella gan-
gnenosa) and other discrete pustular eruptions. Disseminated necrosis
of the skin which in rare instances follows vaccinia, varicella, and
1 Lftiicot, 1902. = Report of Louisiana Board of HeaUh, ]&<^S4.
68 VACCINIA
pustular dermatoses may occur independently of these diseases in
apparently healthy infants; a better designation, therefore, for this con-
dition is dermatitis gangroenosa infantum. The gangrenous changes in
the skin may occur early or late. Stokes/ of Dublin, reports a case of
so-called vaccinia gangrgenosa developing forty-eight hours after vac-
cination. The vaccinal or varicellous pustules may be directly con-
verted into blackish sloughs, which are thrown off and leave deep, ex-
cavated ulcers; or the gangrene may not set in until a week or two has
elapsed, beginning as papulopustules which crust over, become sur-
rounded by an areola, and then break down and ulcerate. High fever
is often present. The cause of this rare condition is obscure; it usually
supervenes in the course of some pustular febrile disease,^ particularly
in tuberculous, syphilitic, or rachitic children. It is quite possible that
the gangrene is due to infection with some virulent micro-organism.
Vaccinal Roseola (roseola vaccinosa, vaccinal rash, or erythema). —
Under the above designations has been described a rosy, macular rash,
which occasionally appears in vaccinated persons about the time of
maturation of the vesicle. While this eruption is ordinarily seen about
the tenth day after vaccination, it has been observed as early as the third
day and as late as the eighteenth. It usually appears first upon the
vaccinated arm, rapidly spreading to the trunk and other portions of
the body. The macules are large, irregular, blotchy in appearance, of
a rosy tint, and not elevated above the level of the skin. In rare instances
the macules may coalesce, giving rise to a diffuse erythema. The erup-
tion is of brief duration, lasting from a few hours to a day or two. It
may be accompanied by moderate elevation of temperature.
The rash is not unlike that of measles, with which, indeed, it has not
infrequently been confounded. The eruption of measles is more elevated,
being maculopapular in character and more persistent, and is accom-
panied by higher fever and the characteristic catarrhal symptoms of this
disease.
During epidemics of smallpox, vaccinal roseola has been mistaken
for the beginning eruption of confluent smallpox. Roseola vaccinosa
has a complete analogue in the roseola variolosa, an exanthem pre-
senting almost identical features, which is not infrequently observed
just before the appearance of the eruption of modified smallpox.
Vaccinal Lichen. — Crocker states that in his experience vaccine
lichen has been the most common of the true vaccinal exanthema. He
has made notes of twenty cases of this eruption. He states that it may
be either papular, papulovesicular or pustular. It appears from the
fourth to the eighteenth day, most commonly on the eighth; in about
one-half the cases it is seen first on the arms, appearing in the remainder
on the trunk, neck, or face; the eruption then extends in successive
crops over large portions or the entire cutaneous surface (Fig. 14).
1 Dublin Journal of Medical Science, June, 1880. Quoted by Crocker.
2 The writers recall the case of a young girl suffering from smallpox, who developed at the end of
the third week numerous punched-out areas of cutaneous gangrene. Tlie patient succumbed to this
complication, which was doubtless a condition analogous to the so-called vaccinia gangreenosa.
PLATE III.
Roseola Vaccinosa Appearing upon the Tenth Day
after Vaccination.
VA(J(!/NAIj aOMI'LKIATIONS AND IN.IUIUI'IS
69
The j);i,j)nl(',s urc rcuhJisli, (-(Hiic^al, piiilicad .siz(;(J, .siinoiiiidcd hy a
reddisli halo, and often surmounted by minute vesicles or pustules.
In the experience of the writers vaccine lichen has l)een excessively
rare.
KiG. H
VacciuiUion upon the tenth da}', showing an unusually inteiife areola. A papular vaccinal
eruption is also seen upon the face.
Vaccinal Miliaria. — In rare cases instead of a papular eruption a
vesicular outbreak may take place, usually from the eighth to the eleventh
day. Danchez^ writes: "We give the name vaccinal miliaria to a satel-
lite eruption of the vaccinal fever, appearing from the eighth to the twelfth
day (very rarely later) after vaccination. It is constituted by small vesi-
cles of the size of a grain of millet, accumulated in great numbers over
large surfaces, containing a transparent liquid at first, then opaque, fol-
lowed by slight furfuration, and never leaving cicatrices after it."
1 Vaccinides, "^hHe de Paris, 1SS3.
70 VACCINIA
A miliary vesicular eruption is occasionally seen in or around the
vaccination areola. These vesicles are not true vaccine lesions, for
Martin has shown that the contents inoculated upon another individual
fails to produce the vaccine disease.
Erythema Multiforme and Urticaria after Vaccination. — The erup-
tion of multiform erythema is occasionally seen in vaccinated individuals
between the first and the tenth day after the insertion of the virus. In
some cases the eruption is delayed considerably beyond this period.
The lesions may be erythematous, papular, tuberculous, vesiculobullous
or mixed.
At times the eruption is annular. Crocker saw a well-marked case
which began on the ninth day after vaccination, and was characterized
by shilling-sized annulopapular patches. Napier observed a case on
the eleventh day which began as rings.
Not infrequently urticarial lesions are present, the eruption being
a type of combined erythema multiforme and urticaria. Allen and
Sobel regard urticaria as one of the most common of the generalized
vaccinal eruptions.
Norman Walker^ has observed five cases of erythema multiforme after
vaccinations with glycerinated lymph. In all, the early course of the
vaccination was uneventful. The eruption was invariably seen on the
hands and face, but on other parts as well.
In a review of the vaccinal complications in 1160 vaccinations, Sinigar^
states that there were 23 cases of erythema, including simple erythema-
tous blushes, finely punctate erythemata, erythema of papular or urti-
carial type, and erythema multiforme. Concerning the date of appear-
ance, 1 rash appeared on the third day, 5 on the eighth, 2 on the ninth,
5 on the tenth, 4 on the eleventh, 1 on the twelfth, 4 on the thirteenth,
and 1 on the sixteenth day. No age was exempted ; in 4 cases the patient
was over seventy years of age. The average duration of the rash was
forty-eight hours, but in 1 severe case it lasted six days.
Impetigo Contagiosa. — This contagious disease of the skin is ex-
tremely common, independent of vaccination, among dirty and poorly
nourished children. Any abrasion of the skin increases the liability
to its development. Its occasional occurrence after vaccination, par-
ticularly among children in poor hygienic circumstances, is therefore
scarcely to be marvelled at. The introduction of the infection of impetigo
with the insertion of the vaccine virus must be an occurrence of the
greatest rarity; inasmuch as impetigo sores develop rapidly (from one to
two days) after the skin is infected, we would expect, if the disease were
invaceinated, to discover the impetigo lesions twenty-four to forty-
eight hours after the vaccination.
As a matter of experience, however, impetigo usually develops at a
considerably later period; it may make its appearance at any period
up to the complete healing of the vaccinal wound. It is not infrequently
observed at the end of the second or third week after vaccination. The
1 British Medical Journal, 1901, p. 1201. 2 Lancet, 1902.
VyiCC/Nyil. aoMI'LldATIONH AND I S.I IJ III HS
71
first lesions are usually seen about the site* of iusertirtn (jf the vaeciiK-
lyriipli. This area may heeoine quitc^ irifiain(!(l, the surrounding epi-
dermis raised up by a seropurulent fluid, and the process extend upon
the periphery, with the production of voluminous ochre-colored crusts.
From this as a focus other ])ortions of the skin become infected by
aut()ino(nilation through scratchinn; or other means. At times impetigo
may assume a bullous form, simulating ])emphigus; most oF the pem-
Secondary impetigo engrafted upon a late vaccination and subsequently upon other regions.
phigoid eruptions after vaccination would appear, however, to belong
to the group of bullous dermatitis presently to be described.^
In 1885 an outbreak of a cutaneous disease, said to have presented
the clinical features of impetigo, occurred in villages on the Island of
Rtigen, in the Baltic Sea, after the vaccination of seventy-nine children.
' Engman and Grindon have each described (Journal of Cutaneous and Genito-urinary Diseases,
1901, pp. 180 and 188) extensive cases of bullous impetigo, not, however, related to vaccination.
They state that this form of the disease is quite common in St. Louis, and that epidemics occasionally
occur in foundling asylums, attacking particularly weak and undernourished infants. Some of the
cases reported terminated fatally. [The differential diagnosis between bullous impetigo, acute
pemphigus, and dermatitis herpetiformis is sometimes fraught with difficulty.]
72 VACCINIA
Impetigo contagiosa is caused by invasion of the skin with the germs
of contagious pus, independently of its source. There are probably two
chief varieties due respectively to the streptococcus and the staphylococ-
cus pyogenes.
Vaccinal Erysipelas. — Erysipelas is an acute infectious disease
resulting from invasion of the body with the streptococcus of Fehleisen.
In the vast majority of cases of this malady the infection gains its
entrance to the system through a wound of the cutaneous or mucous
surfaces; the disease therefore is essentially a wound infection.
Inasmuch as vaccinia is attended with the production of a wound of
the skin, it is not surprising, particularly in view of the frequent neglect
of vaccination wounds, that erysipelas should occasionally occur after
this procedure. The erysipelatous infection is usually conveyed to the
vaccination wound at some period subsequent to the insertion of the
vaccine virus; in rare cases, however, the specific germs of erysipelas
may be present in the lymph, in which event this complication develops
on the second or third day after vaccination.
Erysipelas may develop in an infant after vaccination and still be
independent thereof. Erysipelas is a common disease among infants;
according to Dr. Ogle's testimony before the British Royal Vaccination
Commission, two thousand per million infants under three months of
age perish from it. It has been known to develop after very trivial
injuries, such as the scratch of a pin, abrasion from the friction of
clothing, etc.
Both vaccinal erysipelas and erysipelas from other causes are attended
with a rather high mortality rate in infants. Of the deaths attributed
to vaccination in England between 1886 and 1891 almost one-half
resulted from erysipelas.
Erysipelas may result from the employment of lymph containing
streptococci, from infected instruments, unclean hands, contact of
soiled linen, or from previous contamination of the skin at the vaccina-
tion site. When the disease develops late it is often favored by injury
or rupture of the vesicle, or forcible and premature detachment of the
crust. Bad hygienic surroundings and uncleanliness of the body or
garments increase the liability to infection. Humanized lymph derived
from a vaccinifer with an inflamed arm may give rise to erysipelas.
The improper preservation of crusts has likewise given rise to some
cases. One of the writers saw some years ago a series of cases of ery-
sipelas follow vaccination with a humanized crust which had been
rubbed up with water and kept in the pocket between two glass slides
for several days, during which time decomposition had taken place.
As a vaccinal complication, erysipelas appears to be distinctly on the
decrease. In 1877 Lotz was able to collect in Germany but two cases
of death from this cause in 1,252,554 vaccinations.
The increased attention to asepsis in vaccination, the careful protec-
tion of the vesicle when formed, and the employment of bovine lymph
will doubtless continue to lessen the frequency of this complication.
It is claimed that animal virus, on account of the comparative insus-
VACOfNAL (!()M/'/J(!AT/()NS AND IN.HHill-lS 70
ceptibility of the bovine species to erysipelas, gives a greater security
affainst this disease than humanized virus. In 1877 II. A. Martin
emphasized this advantage of animal lymph in the most positive terms.
He Mfrote: "During the sixteen years in which I snpj)li(;d humanized
virus the presence of this pest (erysipelas) in my prac-tice and in that
of my correspondents w^as the one great and serious drawback, the one
formidable source of anxiety and blame. Since I have issued bovine
virus to a far greater extent (from eight to nine thousand corre-
spondents),! have never received a single complaint of the (n-crurrence
of erysipelas. It is said to attack particularly cases of revaccination,
but in 1872-73 I revaccinated about twelve thousand patients with my
own hand, and there was not one case of erysipelas among them all,
nor have I ever known a case following the use of the bovine virus at
any other time." Martin abandoned the collection and propagation
of humanized virus in 1873 because in one week he had five cases of
erysipelas. These children were vaccinated on one arm with the hum an-
ized lymph and on the other with the bovine product, and in each in-
stance erysipelas appeared on the arm on which humanized virus had
been employed.
True vaccinal erysipelas should be trenchantly distinguished from
the dermatocellulitis which is not infrequently observed about the vac-
cine lesion, and which occasionally involves the entire upper arm and
even the forearm; this is nothing more than an exaggeration of the
inflammatory areola.^ The arm is swollen and intensely reddened,
but there is no tendency for the process to spread to other parts of the
body, the inflammatory phenomena subsiding after the height of the
vaccinia has been reached.
Tetanus Following Vaccination. — The development of lockjaw
after vaccination was until a few years ago an occurrence of the greatest
rarity. The minority contingent of the British Royal Vaccination Com-
mission in 1896, after extended investigation, was able to mention but
a single instance of this complication.
Tetanus after vaccination is said to be unknown in France, Germany,
and other continental countries of Europe. Within the past five years
(and particularly in 1901) a rather alarming number of cases has been
reported in the United States. Dr. R. N. Willson and Dr. Joseph
McFarland^ have independently presented analytical studies of all of
the cases recorded and of other cases personally communicated to them.
Willson reports 52 cases and McFarland 95, 28 of which, however, are
shrouded in considerable doubt.
Willson, from a painstaking study of the records of the cases reported,
came to the conclusion that while the tetanus infection gained entrance at
the site of vaccination, it was not introduced with the vaccine ^-irus, but
at some period subsequent to this.
1 Some of the older writers, including Jenner, referred to this condition under the rather mislead-
ing designation of "erysipelatous inflammation ;" but, as Jenner himself explains, it was not regarded
as true erysipelas, but as merely bearing a resemblance to it.
2 Proceedings of the Philadelphia County ^Medical Society, September, 1902.
74 VACCINIA
McFarland, on the other hand, beHeves that tetanus organisms may
be present in the virus, being derived from manure and hay; he further
states that the future avoidance of the comphcation is to be sought for
in greater care, in the preparation of the virus.
In October, November, and December, of 1901, there v^^as a small
epidemic of tetanus after vaccination in Camden, Philadelphia, and
to a certain extent in some nearby towns. Camden had 11 cases, and
Philadelphia even more than this number. These groups of cases
have been adduced as evidence in favor of the view that the tetanus
infection is in the virus. Willson, however, shows that there occurred
in Philadelphia during the above period 12 cases of tetanus inde-
pendent of vaccination. In Baltimore during the month of August
there were 6 cases of tetanus independent of vaccination, in September
6 cases, and in October (the month in which the Camden outbreak
occurred) 8 cases.
In 1899, in New York City, there were 63 deaths from tetanus
unrelated to vaccination; in Philadelphia, in 1901, there were 29
deaths from similar cases, and in Cook County, Illinois, from June
25 to July 14, 1900, 27 deaths from tetanus from causes other than
vaccination. In 1903 there occurred throughout the United States 406
deaths from tetanus as a result of wounds received on the Fourth of
July from toy pistols and blank cartridges (special article in Journal of
the American Medical Association). These figures indicate that such
epidemics of tetanus as occurred after vaccination in Philadelphia and
Camden might readily have developed from other causes.
Improper care of the vaccine wound and the development of exces-
sive inflammation and ulceration appear to be important factors in
predisposing to tetanus infection. Willson says: "In every instance
in the series of cases included in this paper, in which any information
could be obtained whatsoever, there has been found some gross breach
in the care of the wound, and usually the presence of some active influ-
ence that would offer more than a likely means of entrance for tetanus
or any other infection." " Nearly every case showed for days a large
open ulcer, burrowing deep into the tissues. Two cases were those of
soldiers, sleeping anywhere and everywhere, and looking on a bath as
a luxury. Several children lived^over^ and next to and played continually
in stables, the hotbed of the tetanus bacillus. One slept in bed every
night with her father, who had charge of horses. Two at least are known
to have forcibly maltreated the vaccine wound. Many removed the
scab for inspection. Two threw or dropped the scab on the ground
and replaced it in the wound, one wearing it for hours. One threw his
bandage on the ground and replaced it on the arm at a later time.
Several wore a shield over the wound without cleansing or removing
it until it was full of pus and dirt and foul to smell; one of these reached
the eighteenth day and the writer's case the twenty-eighth with the
shield still in place. One, when tetanus developed, exhibited a merino
shirt-sleeve, that had never been washed, matted in the vaccine
wound."
VAddlNAIj (JOMI'IjICATIONS AND IS'.HIIHI-IS 75
Rosenau/ in a study of the bacterial impurities of vaeoirif; virus, was
uiiahle to find tetaruis or(>;anistns in any of a consirtc(l
by Marcolini (IS]4 in IJdinej, Cerioli (1SI2 in Crenioiia;, 'Jassani
(1841 in (innnello), Wetreler (1840 in Coblentzj, Oherfianken i\^',2
in Freienfels), Marone (18r>() in Liipaiaj, J'accliiotti fhSf)) in liivaltaj,
Depaul (18GG in Morbihan, France), Kocevar (1870 in Schleinitz and
St. Veix), Jonathan Hutchinson (1871 in London, two series of cases),
and I>ayet (1880 in Algiers and 1885 in Turin).
A brief account of the Rivalta and Lupara epidemics, which are
fairly typical of all the rest, is herewith subjoined:
In 1801 Pacchiotti^ reported an extensive epidemic of vaccinal sy}>hilis
occurring in Rivalta, Italy: 46 children were vaccinated from the origi-
nal vaccinifer; of these 40 contracted syphilis. From 1 of these subjects
7 other children became infected through vaccination. In a(lditif)n 20
mothers or nurses contracted syphilis through contact with these children.
But 17 out of G3 vaccinees escaped infection.
About the same time Marone^ published an account of a similar
epidemic that occurred at Lupara in 1856. A large number of infants
were vaccinated with humanized lymph received in tid)es from Campo-
basso, and 23 were infected with syphilis. From 1 of these children 1 1
other infants were inoculated with the disease. As in the Rivalta tragedy,
a number of mothers and nurses subsequently developed chancres of the
nipple.
It will be seen that more than half of the cases of vaccinal syphilis
that have been recorded have occurred in Italy. The remainder have
been found in France, Germany, and England. Fortunately, such
infections in the United States have been extremely rare. It has been
estimated that the aggregate number of cases of vaccinal syphilis that
have occurred is about seven hundred. When we think of the millions
of lives that have been saved by vaccination during the past century,
we recognize the fact that the sacrifices, however deplorable, have been
relatively small. Many blessings are leavened with misfortune.
Pacchiotti, in 1861, laid down the following rules to be observed in
vaccinating: 1. Enquire into the state of the patient's health. 2. Take
the lymph in preference from those children who have passed the fourth
or fifth month, as hereditary syphilis appears, in general, before that time.
3. Do not use lymph taken from a vesicle which has passed its eighth
day, because on the ninth and tenth days the lymph becomes mixed
with pus, which later may be of an infectious character. 4. In taking
the lymph, avoid hemorrhage, as there is less danger with hiiiph free
from blood. 5. Do not vaccinate too many children with the same
lymph.
The observance of these precautions would obviate much of the risk
of transmitting syphilis, but would not confer absolute security against
such infection. The British Royal Commission on Vaccination says:
"Absolute freedom from risks of syphilis can be had only when calf-
1 Sifilide Transmissa per Mezzo Delia Vaceiiiazione in Rivalta Presso Acqui. Gazetta Delia Asso
ciazlone Meri., October 20, l^Bl.
s Impraziale de Florence, November 5, 1862.
78 VACCINIA
lymph is used, though where the antecedents of the vaccinifer are fully
ascertained, and due care is used, the risk may for practical purposes
be regarded as absent."
Inasmuch as bovine virus is at the present time generally and, indeed,
almost universally employed, the subject of syphilis may be dismissed
in a discussion of the complications of vaccination.
The employment of calf-lymph and the complete elimination of the
risk of transferring syphilis to the vaccinee have robbed the opponents
of vaccination of one of their most potent arguments against the enforce-
ment of vaccination.
The Relation of Vaccination to Tuberculosis. — Whether or not it
is possible to transmit tuberculosis in vaccine lymph is an undeter-
mined question. Toussaint^ claims to have successfully inoculated
rabbits and a pig w^ith tuberculosis with lymph taken from a vaccine
vesicle induced upon the vulva of a tuberculous cow. On the other
hand, Josserand^ injected lymph taken from vaccine vesicles in tuber-
culous individuals into the peritoneal cavity, under the skin, and into
the anterior chamber of the eye in 47 animals. Post-mortem exami-
nations gave absolutely negative results in 43 of these, and in no
animal was there conclusive evidence of tuberculosis.
The danger of conveying tuberculosis in bovine lymph is almost
inappreciable. The virus is obtained from calves, and it is pretty well
established that calves are but rarely the subjects of tuberculosis. It
is stated by Fiirst, on the authority of Pfeiffer, that but one case of
tuberculosis was found among 34,400 calves under four months of age.^
The statistics of the abattoirs of Augsburg and Munich corroborate
the above figures; only one tuberculous calf was discovered at Augs-
burg among 22,230 slaughtered, and a smaller percentage at Munich.''
Furthermore, in well-regulated vaccine establishments calves are
subjected to the tuberculin test before vaccination, and are autopsied
before the lymph is distributed for use. Even though it were possible,
despite these precautions, for tubercle bacilli to get into the lymph, they
would perish if the lymph were glycerinated. Copeman,^ speaking of
glycerinated lymph, says : " The tubercle bacillus is effectually destroyed
even when large quantities of virulent cultures have been purposely
added to the lymph."
Bollinger, Heron, and Acland all seriously doubt whether tubercu-
losis has ever been transmitted by vaccination.
Postvaccinal Lupus Vulgaris. — Cases of lupus occurring in and
around vaccination scars have been reported by I^enander, Besnier,"
Perry,'' Little,^ Colcott Fox, x^cland,^ Stelwagon,^" and others. Most of
1 French Academy of Sciences, August 8, 1881, quoted by Acland, Allbutt's System of Medicine,
p. 619.
2 Contribution a Tetude des contamination vaccinales, Lyons, 1884, p. 30, quoted by Aclaud.
3 Fiirst. DiePathologiederSchutz-Pocljen-Impfung, Berlin, 1896, par. 431, p. 112, quoted by Acland.
* Strauss. Gaz. hebdom. de mod. et de chirurg., 1885, p. 143, quoted by Acland.
s Vaccination, its Natural History and Pathology, London, 1899, p. 181.
8 Annales de dermat. et de syph. 1889, p. 576. ? British Journal of Dermatology, 1898, )>. r.m,
8 Ibid., 1900, p. 60. « Loc. cit.
'" Journal of the American Medical A.ssociation, November 22, 1902,
VAddlNA L aOMPLKIATlONS AND INJUIUES 7(j
these observers saw the lupus years after the vaccination had been per-
formed. Fox saw a case of hjpus begin in a vaccination scar shortly
after tlie sore had licalcd. Tl)(M"hild subsccjucntly d(;v.(?Iopcd a di.sserni-
nated hi])ns, subperiosteal tuberculous nodules, and jjulnionary phthisis.
It is higlily probable that this child was already tuberculous, as another
child in the family had previously died of this disease. Stelwagon saw
a palm-sized patch of lupus on the arm in a girl ten or twelve years after
a vaccination which was said to have been immediately followed by
the development of the lupus, the history being given by a physician,
the brother of the patient. All that can be stated as regards the rela-
tionship of vaccination to lupus is that vaccination may in rare cases
in tuberculous individuals give rise to a lupus at the site of vaccination.
That lupus should occasionally choose a vaccination scar for its seat is
no proof that it was caused by vaccination.
Vaccination and Leprosy.^ — Since the general adoption of bovine
lymph for vaccination, the question of the invaccination of leprosy has
resolved itself into one of academic and retrospective interest. It is
well, however, for physicians in leprous countries, if required by unusual
circumstances to employ humanized lymph, to remember that leprosy
has probably in isolated instances been conveyed by vaccination. Gaird-
ner,"^ Daubler,^ and Hillis have each recorded instances of vaccinal
leprosy, although some doubt attaches to all of these cases.
Beavan Rake and Buckmaster, who have given this matter much
study, believe "that the alleged cases of transmission of leprosy by
vaccination are open to serious doubt." Hansen,^ of Bergen, in 1890,
made extensive inquiry by circular to all of the physicians of Norway
as to the occurrence of vaccination leprosy. In not a single case was
there any ground to suspect such an origin. This statement is of espe-
cial importance inasmuch as there is much leprosy in Norway, and
vaccination is practised extensively in that country.
From experimental evidence we Would scarcely expect leprosy to be
transmissible by vaccination. Inoculation of man and lower animals
has been I'epeatedly attempted by Daniellson, Profeta, Hansen, and
others, who inserted fragments of leprous tissue and injected blood
from lepers beneath the skin, but with entirely negative results. There
is indeed no conclusive case on record of the successful experimental
transmission of leprosy.
It is true that lepra bacilli have occasionally been found in vaccine
lymph in vesicles raised upon leprous skin, but, as Beavan Rake properly
states, no responsible person would think of vaccinating a leper in an
affected part and using such l^aiiph for further vaccinations.
Eczema Following Vaccination. — Vaccination may now and then
induce the appearance of an eczema in a child predisposed to the dis-
ease, just as an attack of measles, scarlet fever, or simple teething may
act as an exciting cause. Eczema is an extremely common disease
' A Remarkable Experience Concerning Leprosy, Briiisb Nfedical Journal, 1SS7, vol. i. p. 12C9.
- Monatsheft. f. prakt. Derm., 1SS9, p. VIZ.
■■' Mentioned by Acland, Allbutt's System of Medicine, p. 6Jo.
80 VACCINIA
among infants and young children, and is particularly referable to
faulty feeding and digestive disturbances. Of 600 cases of eczema
under the care of Dr. T. Colcott Fox, 249, or 41.5 per cent., were seen
before the end of the first year; in 40 of these eczema was known to have
appeared before vaccination. Doubtless if these had appeared after
vaccination, the latter would have been viewed as a probable etiological
factor.
Crocker^ says: "In no case can vaccination be held responsible where
the vaccinia pustule has completely healed before eczema appears."
Eczematous children, if in good health otherwise, may usually be
vaccinated without any aggravation of the existing cutaneous disease.
Van Harlingen^ has carefully studied the influence of vaccination on
previously existing skin diseases. He writes: "During the smallpox
epidemic of 1872 I observed all cases of skin disease coming under my
notice in which vaccination had been practised. In a few some aggrava-
tion of the symptoms followed ; in others an apparent improvement took
place. But in the great majority of cases vaccination did not appear to
exercise any influence whatever on the course of the more common
diseases of the skin coming under my observation." We have from
time to time vaccinated persons with eczema and other cutaneous dis-
eases without any injury whatsoever. On the other hand, vaccination
has on a number of occasions been followed by improvement and even
cure of eczemas. Stelwagon^ says: "I have noted in several instances
that amelioration followed vaccination, and in one instance, in a chronic
case, a disappearance of the eczema." Duhring, Tait, and others have
testified to the occasional curative influence of vaccination on eczema.
While we would not elect to perform vaccination upon a child suffer-
ing from eczema, we should not consider the latter condition a sufficient
contraindication if smallpox were prevalent.
Bullous Eruptions (dermatitis bullosa; dermatitis herpetiforTnis ;
acute pemphigus). — In relatively rare instances vesicobullous eruptions
variously designated as pemphigus, bullous dermatitis, and dermatitis
herpetiformis (Duhring's disease) have followed vaccination. While
we have no proof positive of a causative relationship between vaccinia
and these eruptions, they have now been reported by careful observers
in a sufficient number of instances to warrant the assumption that the
antecedent vaccination has been of some etiological moment.
Pusey* reported a case of this character under the title of dermatitis
herpetiformis, in which the lesions were vesicobullous and erythema-
tous, followed by pigmentation.
Dyer^ reported two similar cases under the same title after vaccina-
tion. One case occurred three weeks after vaccination and one several
(?) weeks thereafter.
1 Diseases of the Skin, p. 324.
2 Remarks on Vaccination, in Relation to Skin Diseases and Eruptions Following Vaccination,
Philadelphia Medical Journal, 1902, p. 184.
3 Vaccinal Eruptions, Journal of the American Medical Association, November 22, 1902.
■* Journal of Cutaneous and Genito-urinary Diseases, 1897.
5 St. Louis Medical Gazette, 1898.
VACCINA [j (lOMI'LldATIONS AND IS.HHilHS 81
Bowen* has placed on record a series of six casfs f)f l)iil!f>ii,s dci-rnatitis
resemblinfij dermatitis herpetiformis following vaffination. In three of
the cases the eruption is stat(;d to iiav(; made its appearance within two
weeks after vaccination, in one within a week, while in two it did not
show itself until after the lapse of a month. Corlett exhibits two photo-
graphs of postvaccinal bullous dermatitis in his work on tlie acute
infectious exanthemata. Stelwagon^ saw within one year three cases
of bullous eruption after vaccination, two of which he regarded as acute
peni'phigus, and the third as a persistent bullous erythema multiforme
or dermatitis herpetiformis. In these cases the vaccination was what
is usually described as a "good take," but was somewhat slow in heal-
ing, the crust remaining adherent a long time. The eruption appeared
from two to four weeks after vaccination, and had persisted at
the time they were reported three, four, and eight months, respect-
ively.
Sequeira^ showed to the Dermatological Society of T.ondon in 1902
a case of 'pemphigus in a man aged thirty-nine years, the eruption
appearing three weeks after a revaccination. Three vaccine insertions
were made, and the first bleb is alleged to have developed at the site of
one of these. This was followed in several weeks by bullre on the arms,
and later on the thighs. Cultures from the early blebs were sterile, and
inoculations of this fluid into animals were negative.
In all of the above cases save the last, the patients were children
under twelve years of age. The eruption usually appeared from two
to three weeks after vaccination, and in no case after six weeks. In
most cases the eruption was extensive and of long duration, with marked
tendency to relapse. Some of the cases were cured at the end of three
or six months, but some persisted much longer. Pusey's case continued
to have relapses for four and a half years.
Rowen says : " The chief features that these cases present in common,
and that lead to a conviction that they have a common etiology, are
their occurrence in children after vaccination; their course, varying
from ssveral months to several years or perhaps longer; their urfiformly
vesicular and bullous character, with only occasional evidences of mul-
tiformity; the almost complete exemption of the trunk; the character-
istic grouping about the mouth, nose, ears, wrists, ankles, and feet, and
the very slight prominence of itching or other subjective symptoms."
While most of these cases run a relatively benign course, one of the
writers* saw a fatal termination in a case of bullous eruption of the acute
pemphigus type. This occurred in a girl of five years, the eruption
beginning two weeks after vaccination. The writers have also seen
four other cases of generalized bullous eruption of the t}^e described
above, occurring shortly after vaccination.
A remarkable series of bullous eruptions occurring after vaccination
1 Journal of Cutaneous and Genito-uriuary Diseases, September, 1901, p. 401.
- Journal of the American Medical Association, November 22, 1902.
3 British Dermatological Journal, May, 1902, p. 174.
* Schamberg and Keech. A Case of Acute Fatal Pemphigus, Annals of Gynecology and Pediatries
February, 1901, p. 321.
6
82 VACCINIA
is reported by' Howe/ of Boston. Ten cases are referred to, all but one
occurring in persons who had been recently vaccinated. The skin
lesions began on an average of five weeks after vaccination; the longest
time elapsing between vaccination and the appearance of the eruption
was sixteen Weeks, and the shortest period three weeks.
All of the patients were adults, the ages varying from twenty-one to
fifty-two years. Six of the ten cases proved fatal; the average duration
until recovery or death occurred was six weeks.
It will be seen that these cases present points of variation from the
cases described by Bowen. The interval between vaccination and the
appearance of the eruption in Bowen's cases was about two and a half
weeks; in Howe's cases it was double this period. Bowen's cases occurred
in children; none of them were fatal, and the trunk was, as a rule, free
of eruption, which was not true in the cases described by Howe.
Howe was inclined to attribute the eruptions to infectious material
introduced at the time of or after vaccination. The cases occurred at
a time when smallpox was prevalent in epidemic form, and when thou-
sands of vaccinations were being performed.
While these eruptions, when compared with the number of vaccina-
tions performed, are extremely rare, no effort should be spared to deter-
mine their cause with a view to their future avoidance. It is possible
that they are manifestations of an extraneous infection through the
vaccine wound. In this connection the investigations of Fernet and
Bulloch^ into the causation of acute pemphigus are of interest. These
writers report and analyze eight cases of acute pemphigus in butchers;
six of the cases proved fatal in from twenty-four hours to eighteen days.
Three patients gave histories of wounds which continued to suppurate
up to the time of the pemphigus outbreak. The period of incubation
would appear to be very long if the disease arose from an infection, as
is suggested. In the three cases referred to the wound antedated the
eruption three months, two months, and five weeks, respectively. Special
interest attaches to one case, in which the patient is alleged to have
inoculated himself by contact with a bullous eruption on the udders
of a coAV.
Psoriasis. — Psoriasis is known to have made its first appearance
at the point of vaccination, and also as a generalized outbreak after
vaccinia. No one, however, who is at all familiar with this disease
would look upon vaccination as a cause of psoriasis. It may simply
determine the time of outbreak in an individual predisposed to this
common skin affection; it is quite possible that those persons who
developed psoriasis after vaccination would not have been attacked
with this disease until a later period. The occurrence of postvaccinal
outbreaks of psoriasis has been noted by Klamann,^ 1 case; Camp-
bell,* 1 case; Roh€,* 2 acute general cases of psoriasis after vacci-
1 Cases of Bullous Dermatitis Following Vaccination, Journal of Cutaneous Diseases, 1903, p. 254.
2 British Journal of Dermatology, 1896, pp. 157 and 205.
3 Jahrbuch f. Kinderheilk., 1879, Bd. iv. p. 371. ^ Arch. f. Derm., 1877, p. 311.
5 Journal of Ciitaueous and Genito-urinary Diseases, 1882-83, p. 11.
UlSTOLOd Y Of TIIK Vy\(!(!INK LESION 8'}
nation; Piffard/ 1 case; Wood,^ 2 case."?' Hyde,'' 1 ease; Gaskoin/ 5
cases; Chain})ard,''' 1 case; and Kiohlanc," 1 case.
Furunculosis. — (Jropsof fxjils have occasionally been observed dur-
ing the course of and following vaccination. The complication is
usually a trivial one, the furuncles disappearing in a short time. Sinigar^
met v^ith 21 cases of furuncles among IKK) vaecinations in a large
institution, l^he boils develojx'd, as a rule, late in the course of the
vaccinia. One case appeared on the tenth day, 1 on the sixteenth, 4
on the twenty-second, 1 on the twenty-fifth, 2 on the twenty-seventh,
2 on the twenty-eighth, 4 on the twenty-ninth, 3 on the thirtieth, and
3 on the thirty-fifth day after vaccination. As bearing on the cau.se
of this complication, it is interesting to note that 13 of these cases
developed among epileptics, who, as Sinigar remarks, include some of
the dirtiest and most troublesome patients in the asylum.
HISTOLOGY OF THE VACCINE LESION.
But little literature is available upon the subject of the histological
changes in the vaccine pock. The following description is condensed
from Copeman's'^ presentation of the subject:
The vaccine lesion passes through three more or less defined stages
— namely, papule, vesicle, and pustule — just as does the characteristic
lesion of smallpox. In both diseases the papule results from inflam-
matory changes which are most pronounced in the epithelial cells of
the mucous layer of the epidermis. Through certain degenerative
processes, the most conspicuous of which are cell liquefaction and
intercellular oedema, the papule becomes converted into a vesicle.
The vesicle is made up of numerous loculi or compartments which
are formed by the spinning out of elongated epithelial cells. The more
pronounced swelling and vacuolation of the cells upon the advancing
edge of the vesicle leads to greater bulging upon the periphery, giving
rise to the umhilication. The process is identical in vaccine and vario-
lous vesicles.
Kent^ examined a series of vaccine vesicles removed by Copeman
at various stages of development from the calf. At a quite early stage
an outpouring of leukocytes occurs toward the site of injury. In the
course of time each bloodvessel is surrounded by a mass of leukocytes
which rapidly increase and convert the originally transparent fluid of
the vesicle into a purulent fluid, thus giving rise to the pustule.
The rupture of the epithelial trabecule or partitions converts the
multilocular pock into a unilocular one. The fluid now gradually
becomes inspissated and with the necrosed remains of epithelial cells
dries into a crust. Cicatrization and healing go on beneath the crust;
1 Journal of Cutaneous and Geuito-urinary Diseases, 1882-S3, p. 119.
2 Ibid., p. 161. 3 itid., p. 14.
* On Psoriasis or Lepra, 1875, p. 49.
5 Annales de derm., 1895, p. 498. « Ibid., p. 880.
^ Vaccinal Complications, Lancet, 1902. s Loc. cit., p. 73.
9 Britisb Medical Journal, 1894, vol. ii. p. 633. Quoted by Copeman.
84 VACCINIA
the depth of the resulting scar depends upon the extent of destruction
of the true skin.
The minute histological changes in the vaccine lesion have been
studied by Gustav Mann,^ for whom Copeman excised lesions at differ-
ent stages of development from the calf.
In a specimen removed within an hour after vaccination the wound
is blocked by a clot which externally is of a coarse, granular nature, and
between the edges of the epidermis finely granular. The bloodvessels
close to the injury are dilated and many completely thrombosed with
leukocytes. Red corpuscles may be seen adhering to the lumen of
the capillaries and arteries.
The nuclei of both the epidermal and dermal cells are swollen and
the basophile chromatin contained in them is doubly increased. In the
dermis an infiltration of leukocytes into the loose connective tissue is
visible.
At the end of twenty-four hours the epithelium close to the injury has
increased twofold or threefold in thickness and a characteristic phenom-
enon is already noticed, namely, the formation of Guarnieri's supposed
parasites. The nuclear and nucleolar chromatin is increased and a
considerable portion of the latter leaves the nucleus and is found lying
free in the cytoplasm. The granules may fuse and give rise to more
or less solid spheres lying alongside of the nucleus or even indenting it.
From the twenty-fourth to the forty-eighth hour the dermis shows
a gradually increasing oedema, associated with an emigration of leuko-
cytes. As a result of the oedematous condition the lymph is prevented
from escaping downward by the dense elastic layer of the dermis and
the thick fibrous bundles of the hypoderm. Toward the periphery
the lymph channels are blocked by leukocytes, and there is left but
one path for the lymph, namely, through the basal membrane and
then through the spaces between the epithelial cells. These lymph
spaces are distended by the fluid, which becomes limited by the dense
and resistant horny layer.
At the end of three days three zones may be distinguished. Farther
away from the line of inoculation the only noticeable change is a dilata-
tion of the interepithelial lymph channels. All of the cells immediately
within this region, save the horny cells, are swollen and contain granules
like those in the granular layer, thus indicating a premature aging of
the cells.
The dermis beneath fonns large bullae, the walls of which are made
up of compressed connective-tissue cells and leukocytes. No wander-
ing cells are seen in the blebs, but fairly numerous bacilli singly and
in pairs.
Still nearer the point of inoculation the epithelial cells show enlarged
nuclei, which undergo fragmentation into six or twelve smaller nuclei.
Concurrently with the formation of these multinucleated giant cells
there are seen greatly distended lymph vesicles in the epithehum, the
1 Quoted by Copeman, loc. cit.
lIlSTOLOdY OF Till': VA(J(;[NI<: LESION 85
walls of which are made up of stretched and degenerated ej;iUirli;il
cells. The vesicles contain a fibrin reticuluin and vaiions rnifMo-organ-
isms.
Internal to the zone just described the giant cells are re[>iaced by
cells but a fifth to a quarter of their size, and containing but one or two
nuclei, which appear to be derived from the multinucleated giant cells.
The centre of the vaccinated area shows no living epithelial fells, but
merely the remains of the horny layer and a dense, dri(;d blood chjt.
The above changes hold good for the fifth day, the only diH'erence
being an increase in size of the central necrosed area and a lateral
spreading of the zone of infection.
The increased infiltration of leukocytes causes the central area to
necrose more and more, the connective-tissue elements succu]id)ing to
the pressure exerted by the wandering cells.
The hypoderm shows, especially about the fifth day, a considerable
swelling of the thick, white, fibrous bundles called forth by the great
activity of the fixed connective- tissue cells.
Copeman considers the most characteristic feature of vaccination to
be the appearance, immediately outside the necrosed area in the super-
ficial, loose dermal tissue, of a number of globular masses, varying in size
and arranged singly or in pairs, and which are colored by a special
staining process. At the spreading edge, very short bacilli are seen.
It is suggested that the large globules represent either a capsulated,
sporulated, or involuted stage of the bacillus which Copeman elsewhere
intimates may be the specific microbe of the disease.
Much that pertains to the bacteriology of vaccinia will be found in
the chapter on the pathology of variola.
Tyzzer^ made a careful experimental study of vaccination and vario-
lation lesions in animals, particularly with reference to the presence of
Guarnieri's bodies. He successfully inoculated the corneas of twenty-
five rabbits with vaccine lymph, and the corneas of twenty rabbits with
variolous lymph. In addition a number of calves were vaccinated,
some upon the cornea and others upon different parts of the cutaneous
and mucous surfaces.
He interprets the cycle of development of the c}i;orrhyctes variola; in
vaccinia as follows:
Injection: Epithelial cells are invaded by small forms in which it
is difficult to distinguish structure. These small forms are found between
cells and in various parts of the cytoplasm, but after their entrance into
the cell they take a position near the nucleus. Groivth : After becoming
located near the nucleus they become larger, and with tliis growth the
character of their structure becomes apparent. They then consist of a
reticular protoplasm in which is a clear spot containing a mass of basic
staining material. Although it is impossible to distinguish a nuclear
membrane bounding this clear spot, it seems probable that this clear
spot with the granule in it is the chromatin of the organism. The
1 The Etiology and Pathology of Vaccinia, Journal of Medical Research. February, 1904.
86 VACCINIA
organism is situated n a space in the cell, generally many times its
own volume. This space is usually continuous with or is a part of the
perinuclear space. Division of the Nuclear Material: Certain forms,
in which the chromatin mass is irregular, precede those in which the
chromatin is divided. In the latter the chromatin granules may be few
or numerous. The chromatin granules later take a peripheral position,
where they then form the centres of minute masses which bulge from the
surface. Multiplication : These small masses, becoming free, are found
in the space occupied by the segmenting form and in the cytoplasm of
the same cell. They constitute the small forms described as the first
of the series. They now scatter and penetrate neighboring cells. The
invasion of the surrounding normal cells by the small forms resulting
from this multiplicative process constitutes autoinfection, and by it
the process extends. The immediate effect of the parasite is to cause
an increase in size of the epithelial cells. This increase in cell volume
is accompanied in the corneal lesion by proliferation. The' exudation
which usually accompanies the lesions is secondary to the degeneration
of the epithelium. Tyzzer states that he is "fully convinced that the
vaccine body is an organism and represents the etiological agent in this
disease."
THE BLOOD IN VACCINIA.
There is a constant leukocytosis during vaccination, the leukocytosis
appearing in two waves, according to Sobotka.^ The primary one
(varying from 12,000 to 23,000) is observed from the third to the seventh
day, and a secondary wave (10,000 to 17,500) from the tenth to the
twelfth day.
Billings^ states that, no changes are exerted upon the haemoglobin
or red cells by vaccination, but a definite leukocytosis is produced.
The counts average about 15,000 leukocytes per cubic millimetre.
The maximum of the leukocytosis is reached during the height of pus-
tulation of the vaccine lesion, after which a gradual diminution in the
white cells takes place.
1 Zeitschr. f. Heilk., 1893, Bd. xiv. p. 349.
2 Medical News, lh98, vol. Ixxiii. p. 301.
CHAPTER 11.
THE RELATIONSHIP OF COWPOX OR VACCINIA TO SMALLPOX.
It has taken almost a century of experiiiKsntution to prove the truth
of the statements, made by Jenner in his first publication, that smallpox
and cowpox were modifications of the same disease. What a tribute
to the intuitive discernment of this great man!
The experiments which have led to the general (although not univer-
sal) acceptance of this view have been in the direction of the conversion
of smallpox into vaccine by variolation of the cow. It is impossible to
produce in the cow a generalized eruption similar to the smallpox erup-
tion in man; it is, moreover, impossible to intensify the virulence of,
cowpox and convert it into smallpox, but it is possible to convert the
virus of human smallpox into vaccine virus by passage through the
bovine species.
The English Royal Commission on Vaccination presents in its official
report (1898) a valuable review of this subject, from which we freely
abstract.
Most of the endeavors to transfer smallpox from man to the bovine
species have been unattended with success, and have usually been with-
out any definite result. This has been true not only in attempts to
produce the disease by infection through the respiratory and digestive
tract, but also in many instances by direct inoculation. Most of the
inoculation experiments may be grouped in three categories.
The first class includes experiments in which inoculation of smallpox
matter into the cow produced a vesicle identical with or closely resem-
bling the vesicle produced by vaccine inoculation. If a typical vesicle
was not produced at the first inoculation, the transference of the mate-
rial from the first vesicle would in a second or third remove in the cow
give a typical vesicle capable of producing in man results indistinguish-
able from ordinary vaccination. Such experiments were carried out
by Thiele (1838),'Ceeley (1840), Badcock (between 1840 and 1860),
Voigt (1881), Haccius and Eternod (1890), King (1891), Simpson (1892),
and Hime (1892).
In the second category belong the experiments performed by Klein
and Copeman. Klein, who in 1879 had apparently failed in thirty-one
attempts, subsequently found, in 1892, that the result of the first inocu-
lation in the cow of smallpox matter was not a distinct vesicle, but
merely a thickening and redness of the wound. Lymph pressed from
the thickened wound produced, when inoculated into a second animal,
a similar but more pronounced result. In the third and fourth cow
the reddening and thickening were still greater. L^^Bph squeezed
88 RELATIONSHIP OF COWPOX OB VACCINIA TO SMALLPOX
from the wounds of the fourth cow produced typical vaccinia in a child,
and the crust from the child when reinoculated into the cow produced
similar vaccine vesicles. Copeman obtained results of a similar char-
acter, and succeeded in the third remove in the cow in producing a
reaction which showed commencing vesiculation.
In the third class may be placed the results obtained in an elaborate
investigation conducted by a commission of the Society of Medical
Sciences of Lyons, under the direction of Chauveau (1865). Their
results may be briefly summarized as follows:
Inoculation of the cow with smallpox matter in any one of the thirty
animals experimented upon did not give rise to a vaccine vesicle. Never-
theless a definite result was obtained in the form, not of a vesicle, but
of a thickening and inflammation of the wound; when a puncture was
made this became a papule. Lymph squeezed from such a papule and
inserted into a second animal gave rise to a like papule; and this, again,
might be used for a third animal, but often failed; and the effect could
in no case be carried through more than three or four removes. When
the inoculation was repeated on an animal in which a previous inocula-
tion had produced such a papule, no distinct papule was formed, and,
moreover, lymph squeezed from the seat of inoculation produced no
effect at all when used for subsequent inoculation of another animal.
Thus Chauveau and his commission found that smallpox implanted
in the cow gave rise to a specific effect which was not cowpox, but was
of the nature of smallpox, though its manifestations in the cow were
different from those of smallpox in man. Lymph from the lesions in
the first cow was capable of producing smallpox in the human subject.
It is evident from the above experiments that the results obtained
from attempted variolation of the cow have exhibited marked varia-
bility. The vast majority of the inoculations have been of a negative
character. These, however, do not invalidate the positive results
which have now attained a very considerable number, and which have
been reported by careful and trustworthy investigators at different
times and in different countries.
When reaction does result from the insertion of variolous material
into the cow, the local effects vary somewhat. There may be directly
produced a typical vaccine vesicle, or, as occurs in most instances, a
papule or inflammatory induration which on further inoculation yields
a vaccine vesicle. We are thus forced to the conclusion that smallpox
_^s converted into cowpox by passage through the tissues of the bovine
species. The transformation is at times sudden and complet&. _at other^
__times^gradual and incomplete, and sometimes fails altogether^__ The
circumstances wliichTavor such' a are but little unHer stood,
although it would appear that the youth of the inoculated animal is a
factor. The best results have been obtained with calves not ove rjjiree
or four months old. " ~~ — ^
It is claimed that it is possible for cows to develop cowpox through
inhalation of the contagium of variola. In this connection it is inter-
esting to refer to an occurrence noted by Ceely in 1840. This writer
BELATIONSmr OF f/OWPOX on VAC'C'/NFA TO SMALLPOX HU
states that he observed cowpox develoj) in five; out of eight milch cows
twelve to fourteen days after they were seen li<.'king some floek from a
mattress upon which a jjatiejit died of eonfliuMit smallj)OX, and which
had been spread upon the ground to be aired. (Jareful investigation
revealed the fact that the animals, which had been on the farm for
considerable time, were in good health before their admission to the
pasture where the exposed bedding lay. There had not been any cow-
pox in the neighborhood. That the cowpox may have resultcfl hom a
volatile contagium derived from the smallpox-infected bedding is not
improbable, in view of the simultaneous sickening of the cows after a
period of incubation of about two weeks. The possibility of infection
through the digestive tract, which Chauveau and others have shown
may take place, must not be entirely ehminated in seeking the explana-
tion of the manner in which the disease was received.
That the transformation of the smallpox into the vaccine virus is
frequently a gradual process which is not completed in the first bovine
inoculation has been on more than one occasion unfortunately proven
by the transference of true smallpox to persons who were vaccinated
with material taken from the first cow.
In 1836 J. C. Martin, of Attleborough, Massachusetts, inserted into
the udder of a cow lymph taken from a smallpox lesion upon the body
of a man who died of variola. Subsequently matter derived from the
cow was inserted into the arm of about fifty persons. Nearly all of
these individuals developed smallpox in the due course of time, and
three of the number died. The disaster so preyed upon the mind of
the unfortunate physician that he became insane.
A similar occurrence has been reported by Dr. Thomas F. Wood.^
We quote his own words: "I had occasion just after the war (1865-
66), while in charge of the Wilmington Smallpox Hospital during an
epidemic of the disease, to go over the same ground of attempting the
production of artificial cowpox. It happened, during the progress of
the experiment that an army medical inspector, whose name I have
forgotten, was making a tour of the hospitals; hearing of my experi-
ments, he visited my hospital and after examination pronounced the
small vesicles genuine cowpox, and confirmed his faith in his opinion
by making some inoculations on the arms of two children in an Irish
family near by. The inoculations resulted in a genuine smallpox,
which went through the family in various grades of intensity."
Other instances of a similar character have been recorded. That
such infections are not the result of inoculation with the unchanged
variolous material originally introduced into the cow is evidenced by
the fact that smallpox has been conveyed to the human subject from
a papule of the second remove. (Lyons Commission.)
These deplorable accidents have directed attention to the unwisdom
of using material of the first or second bovine generation, and empha-
size the importance of passing the variolous virus through four or five
or more animals before employing it upon man.
1 Chicago liledical Journal and'Examiner, October, ISSl.
90 RELATIONSHIP OF GOWPOX ORIVACCINIA TO SMALLPOX
The demonstration of the fact that vaccine virus may be produced
from a variolous source is of great importance. It is readily seen that
an epidemic of smallpox occurring in some inaccessible country, w^here
active vaccine lymph could not be obtained, could be made to supply
the material for its own suppression.
The proof of the common ancestry of vaccinia and variola refutes
the theoretical arguments advanced by Crookshank and others against
the protective influence of vaccination. These writers have attempted
to fortify their belief in the inefiicacy of vaccination by assuming the
duality of these two affections, the opinion being maintained that an
attack of disease could only afford protection against the same disease.
The premise being false, the entire inference falls to the ground.
Modern bacteriological research strongly supports the empiric dis-
covery of Jenner. Pasteur and others have shown that it is quite possi-
ble, by the use of an attenuated virus, to produce a mild attack of an
infectious disease and thus protect against a more severe type of the
same infection.
That vaccinia and variola are in essence the same disease is scarcely
to be doubted. The passage of smallpox matter through the compara-
tively insusceptible tissues of the bovine species attenuates the virus
to such an extent that it is permanently robbed of the virulence which
it once possessed. Instead of producing a dangerous and contagious
disease, it gives rise to an innocent affection capable of transmission
only by inoculation, and having the beneficent property of protecting
against the original disease which gave it birth. Shakespeare might
well have had vaccination in mind when he wrote:
" Take thou some new infection to thine eye,
And the rank poison of the old will die."
Jenner was strongly impressed with the fact that smallpox and cow-
pox were one and the same disease. Baron quotes the following notes
which were left by Jenner in one of his journals:
"The origin of the smallpox is the same as that of the cowpox; and
as the latter was probably coeval with the brute creation, the former
was only a variety springing from it." Cowpox and smallpox are "not
hona fide dissimilar in their nature ; but, on the contrary, identical. On
this ground I gave my first book the title of * An Inquiry into the Causes
and Effects of the Variolm Vaccinae' — a circumstance which has been
since regarded by many as the happy foresight of a connection which
was destined by further evidence to become more warranted."
From the above it will also be seen that Jenner regarded cowpox
as the progenitor of human smallpox. This belief he reiterated on a
number of occasions. It will be remembered that in the beginning of
the "Inquiry" he says: "This fluid (from the grease) seems capable of
generating a disease in the human body (after it has undergone the
modification I shall presently speak of — viz., transmission through the
cow) which bears so strong a resemblance to smallpox that I think it
highly probable that it may be the source of that disease." Again, in a
NAT!/ HAL SOUnaiCH OF LYMPH 91
letter to l)e Carro in IS()3 he remarks: "1 am happy to find an ojjinif^n
taken up by in(! <\,m\ nicntionc^l in my first [)ubli('jition hu.s so able a
supporter as yours(!lf. I thought it highly probal^lc tliat tlic smallpox
might be a mahgnant variety of the cowpox, but this idc-a was scouted
by my countrymen, particularly P. (Pearson) and W. (VVoodville)."
' Whether smallpox is a cowpox of exalted virulence or cowpox an
attenuated smallpox remains apparently unsolvable. Copeman is
inclined to support the view championed by Jenner. He says:^ "The
artificially inoculated form of cowpox which we term vaccinia is noth-
ing more nor less than variola modified by transmission through the
bovine animal. Perhaps the most reasonable inter[)retation of such
results may be that smallpox and vaccinia are both of them descended
from a common stock — from an ancestor, for instance, which res(;m-
bled vaccinia far more than it resembled smallpox. It is conceivable,
indeed, that the seeming vaccinia, obtained in the calf by inoculation
of smallpox matter into that animal, may after all be but a reversion
to an antecedent type."
The Various Natural Sources of Lymph. — During the investigation
of the casual cowpox, Jenner conceived the idea of propagating the dis-
ease by inoculation after the manner of the smallpox, first from the
cow, and finally from one human being to another. The first vaccina-
tion was performed in 1796 upon a lad by the name of James Phipps,
the virus being taken from the hand of Sarah Nelmes, a dairymaid
who had been accidentally infected with the cowpox. Notwithstanding
the resemblance of the vesicle produced to that obtained by variolous
inoculation, Jenner could scarcely believe that the patient was secure
from the smallpox. He was, however, inoculated with smallpox virus
some months afterward and on numerous occasions subsequently, but
each time without result.
In 1798 Jenner again came into possession of virus from the cow
and made arrangements for a series of inoculations. "A number of
children," he says, "were inoculated in succession, one from the other;
and after several months had elapsed they were exposed to the infection
of smallpox, some by inoculation, others by variolous effiuvia, and
some in both ways, but they all resisted it."
This strain of lymph was suffered to die out and none was found
until Woodville, in 1799, discovered a case of natural cowpox in Gray's
Inn Lane. With this lymph he vaccinated seven persons, and likewise
certain others from the hand of a dairj^maid who had contracted cow-
pox from one of the cows at this place. This virus was successively
passed through hundreds of persons and became known as "Wood-
ville's lymph."
Dr. Pearson also discovered a case of cowpox in a dairy at ]Maryle-
bone Road, although some of the lymph which he sent out was probably
obtained from Woodville's cases. Woodville and Pearson both dis-
tributed the lymph widely, and supplied it to many of the continental
1 Vaccination, Loudon, 1899, p. 64.
92 RELATIONSHIP OF COWPOX OB VACCINIA TO SMALLPOX
cities. Although Jenner himself used some of Woodville's lymph, he
later found another source of supply in the dairy of Mr. Clark, in Kentish
Town.
Dr. Waterhouse, of Boston, secured some of Jenner's lymph through
Dr. Haygarth, of Bath, who obtained it from Mr. Greaser. De Carro
of Vienna, Stromeyer of Hanover, and others also obtained some of
the Jennerian stock.
At this time other instances of natural cowpox became known. Sacco,
a faithful disciple of Jenner, discovered a case of cowpox on the plains
of Lombardy in 1800. A strain of lymph was developed from this,
some of which was sent to De Carro, at Vienna. This enthusiastic
vaccinator forwarded a supply to Constantinople, and subsequently
other lymph of Italian origin to India; the latter virus was of equine
ancestry, having been developed by Sacco from a case of accidental
horsepox in a coachman.
Natural cowpox is said to have been found in Naples in 1812, and
in Piedmont in 1830. Macerdoni discovered it in cows of Swiss breed
in Rome in 1832 and 1834, and in the latter year a lymph stock was
established. Cowpox occurred in Wiirtemberg in 1802, and in 1812
Bremer observed it in Berlin. Fischer saw a case near Luneberg, and
Mende noted one in Greifswalde. Giesker, Luders, Ritter, Riss, and
Albers encountered cases in various portions of Germany. Numann
says that in Holland cowpox was seen in 1805, 1811, and 1824.
An epizootic of this disease among cows is said to have occurred in
Russia in 1838, in a small village near St. Petersburg.
In France cowpox was first observed in 1810 in the department of
La Meurthe; in 1822 it was found in Clairvieux. In the next half-cen-
tury it was discovered some score or more times in different parts of
the country.
A famous strain of lymph was derived by Bousquet in 1836 from a
case of cowpox at Passy, in the environs of Paris. The disease occurred
upon the hand of a dairymaid, from whom Bousquet vaccinated a number
of children. In the second and subsequent removes, the virus proved
itself much superior to the lymph which had then been long in use.
Bousquet in a painstaking memoir accurately compared the course of
the old and the new lymph. These results were confirmed by Bruchir,
of Versailles, and by Steinbrenner, who worked with Mrs. Pass's lymph
in 1840, and compared it with virus obtained from other sources in
1841 and 1845. Similar results were obtained by Estlin, of Bristol, in
1838 with lymph derived from a Gloucestershire farm.
Don F. Xavier Balmes, director of the Spanish Vaccine Expedition,
discovered cases of natural cowpox in the Peruvian Andes and in other
regions of South America.
Ceely, in 1841, stated that he had experimented with lymph from more
than fifteen sources, six of which represented cases of natural cowpox.
In 1866 a milch cow with cowpox was discovered at Beaugency,
France. A valuable strain of lymph was developed from this case by
Professor Depaid. It was from this source that Martin, of Boston,
ANIMAL VA(H!INATr()N 93
obtained lymph with which he inaugurated animal vaccination in
America in 1870. It may be worth while to state the great probability
that in America only has th(^ "stock" of the Beaugency virus been
perpetuated.
The strain of lymph now used by the English Government Animal
Vaccine Establishment was derived in 1881 from a case of cowpox at
Tvaforet, near Bordeaux.
In 1881 Martin, of Boston, observed a case of spontaneous cowpox
at Cohasset, a small town in Massachusetts. The Cohasset and
the Beaugency stocks were for a while propagated separately in this
country, but subsequently became mixed.
Fischer and Voigt in Germany, Haccius in Switzerland, King in
India, and others have of late years propagated cowpox virus by vario-
lating heifers, producing thus what has been called variola-vaccine
lymph.
We are conscious of a reassuring sense of security in the knowledge
that reliable vaccine lymph can be produced by the inoculation of vario-
lous material into a succession of bovine animals, for if existing strains
of lymph are lost or become too much attenuated, we have at hand a
means of replenishing the prophylactic virus.
Animal Vaccination.— By the term animal vaccination is meant the
propagation of lymph through successive series of calves or heifers,
the original virus being derived ah initio from a case of spontaneous
cowpox. Martin^ says the term can and has been applied to: 1. Vac-
cination casually or intentionally from the original spontaneously occur-
ring disease in the milch cow. 2. Retrovaccination with virus obtained
from the vaccine disease in the human subject. 3. From vesicles, said
to be vaccine vesicles, obtained by variolation of kine, or the inocula-
tion of bovine animals with the virus of smallpox. 4. The method of
true animal vaccination, or the inoculation of a bovine animal with the
virus of original spontaneous cowpox; from this another, and so on in
continuous and endless series as a source of vaccine virus.
In 1810 a Neapolitan physician, Galbiati by name, published an
article advocating animal vaccination. He had employed this method
for some seven years, believing that it ensured greater vigor and purity
of the lymph. Galbiati seems to have espoused this procedure because
of the occasional transmission of syphilis by arm-to-arm vaccination.
The method was at first extremely unpopular, and its author, abused
and ridiculed, is said to have become insane and to have ended his life
by suicide. His disciple and successor, Negri (to whom Ballard gives
credit for the origin and introduction of animal vaccination), continued
the propagation of lymph from animal to animal, and successfully
brought the practice into general favor. The l}Tiiph wliich he employed
at first (in 1842) appears to have been of human origin, but subsequently
he obtained material from a case of natural co'u^ox in Calabria. Palas-
ciano, a townsman of Negri and a strong'advocate of animal vaccina-
1 Report on Animal Vaccination, read before the American Medical Association, 1S77. We are
indebted for much of the information conveyed in this chapter to this admirable report.
94 RELATIONSHIP OF COWPOX OB VACCINIA TO SMALLPOX
tion, disseminated knowledge on this subject throughout Europe, by
an address before the Medical Congress of Lyons. A young French
physician, Lanoix, one of those present, became greatly interested in
the subject and subsequently went to Naples to study animal vaccina-
tion under Negri. In 1864 he returned to Paris with a heifer which
had been vaccinated at Naples. Chauveau and Diday were permitted
to take some lymph from this animal at the Lyons railway station.
Lanoix proceeded to Paris and in company with Chambon established
a private institution for the propagation of animal lymph. The new
practice excited considerable interest, and the Academy of Medicine,
encouraged by a government appropriation, appointed a commission
with Professor Depaul at its head to investigate the subject. The report
was favorable to animal vaccination, although some dissentient opinions
were expressed. About this time natural cowpox was discovered at
Beaugency, and Depaul had an opportunity of employing lymph from
this source. It is said that this lymph stock was lost during the siege of
Paris in the Franco-Prussian War, and that the only extant derivative
from this source is that sent to America.
From Paris the practice of animal vaccination spread to Belgium
through the efforts of Warlomont, who obtained some Neopolitan
lymph from Lanoix. He later, in 1868, discovered a case of spontaneous
cowpox at Esneux (Liege).
Through private enterprise animal vaccine establishments were
organized in the various European capitals. The commercial spirit
rendered a real service to humanitarian science.
Pissin opened up such an animal vaccine institution in Berlin, and
Vienna soon had a similarly equipped establishment. Haccius in
1882 founded the "Institute Vaccinale Suisse," which received a cer-
tain recognition at the hands of the Swiss government. Paris now has
an "Institut de Vaccine Animale," which under the direction of Cham-
bon and St. Yves Menard, supplies the municipality with all the lymph
required for public vaccinations.
In Germany all or nearly all of the vaccine establishments are under
governmental control and supervision.
England in 1881 authorized the founding of the Government Animal
Vaccine Establishment in Lamb's Conduit Street, and the use of animal
lymph has now practically superseded arm-to-arm vaccination.
To Dr. H. A. Martin, of Boston, belongs the credit of introducing
animal vaccination into the United States. In 1870 he sent a special
agent to France, who returned with an abundant supply of Beaugency
lymph. Having secured a herd of young, healthy animals, he at once
began the propagation of animal lymph. He and his son subsequently
discovered a case of spontaneous cowpox in Cohasset, Massachusetts.
Advantages of Animal Vaccination. — The use of calf-transmitted
lymph has certain advantages over long humanized virus; these maybe
stated as follows:
1. Animal vaccination produces a vaccinia which approaches more
nearly the Jennerian prototype, and reaches therefore a greater degree
ADVANTAfJICS OF AN/AfAL VA(!N 95
of perfection than that produced by long liunianizcd virus. The cow-
pox casually produced on the hands of dairymaids was believed by
Jenner to confer full and cotn])lete protection against smallpox. The
bovine species ap[)ears to be; the natural soil of the j)roj)hylacti(; pock,
and the view is maintained by numy that l)ovine lymph, or that fJerived
from an early human remove, creates a more complete and more lasting
immunity. The inferiority of humanized virus is doubtless due to a
weakening or degeneration of the lymph product as a result of the long-
continued transmission through the human subject. Jenner really
anticipated such a deterioration in the quality of vaccine lymph from
this cause. Copeman says that "in the present state of our knowledge,
however, such enfeeblement of the specific virus can hardly be regarded
as probable, except. under conditions that may be obviated by reasona-
ble skill and care on the part of the operator. Jenner early discovered
that vaccine lymph only exhibited its full degree of activity when taken
at the stage of maturation of the vesicle, and before its contents became
at all purulent. If this precaution be observed, together with strict
cleanliness in the removal and insertion of the lymph, experience has
shown that no appreciable degeneration can be demonstrated."
2. The use of animal lymph precludes the possibility of transmitting
by vaccination diseases peculiar to the human species. One of the most
weighty reasons that led to the adoption of animal vaccination and to its
preference over arm-to-arm transmission was the recognition of the
possibility of inducing syphilis by vaccine inoculation. No matter
how rare such an accident might be, the remotest liability of such an
occurrence constitutes a serious argument against the use of humanized
lymph. The bovine species being totally insusceptible to syphilis, l^-mph
derived from this source is incapable of transmitting such infection.
Erysipelas appears to be a much rarer complication of vaccinia
since the general employment of animal l}Tnph. It is probable that
many cases of vaccinal erysipelas in the past were due to secondary
infection of the vesicle at the time that it was punctured to withdraw
lymph for further inoculations. The almost universal use of animal
lymph removes the necessity of tapping the vaccine vesicle, thus ren-
dering erysipelas from this cause practically non-existent. Again, many
cases of erysipelas were doubtless the result of the emplo}aiient of
crusts which had not been wisely selected or properly preserved. "\Miat-
ever the cause or causes may have been, actual experience shows an
enormous reduction in the relative and aggregate incidence of this com-
plication since vaccination w^ith humanized lymph has fallen into
desuetude.
There is little or no danger of transmitting tuberculosis in bovine
lymph, inasmuch as, in addition to the diagnostic use of tuberculin, all
calves are killed and carefully examined in well-regulated establish-
ments before the virus is sent out; furthermore, it has been sho-um that
the admixture of glycerin to the l>Tnph is capable of destropng the
life of any tubercle bacilli that may be present.
3. Animal vaccination offers an almost inexhaustible supply of vac-
96 RELATIONSHIP OF COWPOX OR VACCINIA TO SMALLPOX
cine lymph, for the number of calves yielding the same can be multi-
plied at will. During extensive epidemics of smallpox, v^hen human
vaccine was employed, the community was often placed in an embarrass-
ing and dangerous predicament owing to an insufficient supply of
vaccine material. During the great pandemic of smallpox from 1870
to 1873, a veritable vaccine famine existed in many countries. All
sorts of vaccinifers were drawn upon, and much worthless lymph derived
from spurious and irregular cases was employed, of course, with entirely
unsatisfactory results.
4. Animal lymph appears to give a much larger percentage of suc-
cessful revaccinations than long humanized virus. Martin says: "The
number of those who, in revaccination with the old, long humanized
virus (not that of early human removes) experience vaccinal effect may be
stated at the outside at 35 per cent. The number of those revaccinated
with equal care and repetition with animal virus and virus of very
early human removes, I affirm to be a fraction over 80 per cent. — a differ-
ence of 45 per cent. ; and this 45 per cent. I firmly believe to approxi-
mately represent the number of those insensible to the enfeebled influ-
ence of long humanized virus, but sensible to the intense contagium
of variola just in the same degree as sensible to the intense power of
bovine virus and that of the early human removes from it."
Comparison of the Course of Vaccinia Produced by Original Cow-
pox Virus, Long Humanized Virus, and Calf-transmitted Virus, Re-
spectively. Original Cowpox Virus. — ^The vaccine disease produced by
virus from a case of original cowpox or from early human removes
therefrom lasts from twenty-one to thirty-two days, counting from the
insertion of the lymph to the falling of the crust. At the end of the
third or beginning of the fourth day papulation occurs; vesiculation
takes place at the end of the fifth day, but the vesicle continues to grow
until the decline of the areola or even a few days after this. The vesicle
has a pearly or slightly bluish tint; it really resembles, as Jenner re-
marked, "a section of a pearl on a rose-leaf." The areola appears first
about the end of the ninth or beginning of the tenth day and persists
until the twelfth, thirteenth, or fourteenth day. Desiccation and forma-
tion of the crust are not complete before the sixteenth or seventeenth
day; the crust is never spontaneously detached before the twenty-first
day and usually not before the twenty-fifth to the twenty-eighth day.
Occasionally it will remain upon the vaccine site until the thirtieth or
thirty-second day. The crust is round, thick, umbilicated, and of a
rich brown or mahogany tint.
A very decided febrile reaction attends the rise, development, and
decline of the areola. This febrile disturbance was considered to be of
great importance by the early vaccinators, especially Jenner, who
regarded it as a sine qua non of vaccinal impression upon the system,
and an indelible characteristic cicatrix remains after the termination
of the disease. In the early days it was not at all rare for the vesicle
to break down and ulcerate, leading to a spreading and troublesome
loss of tissue and occasionally to erysipelatous infection.
COURSE OF VA(J(JJNIA WITH D/FFFJU'JNT LVM/'J/S f)7
Long Humanized Virus. — ^The most distirif^uisliirif^ characteristic of
the vaccinia produced l)y lonf^ huinanizcd virus is the f)revitv of the
course of the disease. The duration varies very much with different
lymph stocks. With a virus used by Martin and obtained from Ceely,
the course of the disease from the time of insertion of the lymph to the
spontaneous detachment of the crust was l)ut eleven days; whereas
with a lymph of French origin employed by Martin, th(! crust came off
from the twenty-first to the twenty-sixth day. Lymph from the National
Vaccine Institution of Great Britain ran a course of fourteen days to
the falling of the crust. These various "stocks," although propagated
for years, preserved their distinctive durations. It was even found,
when two different lymphs were inserted — one on one arm and the
second on the other — that each strain retained its special features.
In brief, it may be stated that long humanized lymph produces a
vaccinia of shorter duration and milder intensity than original and
early virus. With the lymph which induced a vaccinia of eleven days'
duration, the areola was formed on the seventh day and sometimes on
the sixth. The Jennerian "stock" of the British Vaccine Institution
induced a vaccina of fourteen days' duration, the areola developing on
the seventh or eighth day.
The crust derived from vaccination with long humanized lymph
is very small, thin, and often devoid of umbilication. The febrile reac-
tion accompanying such a vaccinia is slight or absent, even when many
insertions are made.
Calf-transmitted Virus. — As would be expected the vaccinia resulting
from the employment of calf-transmitted lymph closely resembles the
disease induced by early human removes from original cowpox, such
as were observed by Jenner. With the animal-transmitted virus, how-
ever, the reaction is not so violently inflammatory as that which occurred
with original cowpox lymph. Ceely, in 1840, stated his belief that the
tendency to undesirable intensity in the original cowpox is tempered
by successive transmissions through young animals. He inoculated a
series of eleven calves and found that the objectionable qualities of the
lymph, as determined by human vaccinations, w-ere gradually but pro-
gressively eliminated. The animal virus now used usually runs its
course from twenty-one to thirty days.
Glycerinated Lymph. — To S. Monckton Copeman^ belongs the
credit of advocating the addition of glycerin as a vaccine purifier, and
of establishing the employment of glycerinated l}'mph upon a scientific
basis. Glycerin had previously been used for the purpose of increasing
the volume of the lymph and also as a Ivmph preservative.
As far back as March, 1850, Mr. R. Cheyne- advocated (in a letter
appearing in the Medical Times) the use of fluid hmph to which some
glycerin had been added as superior to the dry points. In 1853 he
1 We desire to acknowledge our indebtedness for much of the material presented in this chapter
to the admirable book of S. Monckton Copeman (Vaccination, its Natural History and Pathology,
London, 1899), which we have freely consulted.
* Copeman appears to have been unaware of Cheyne's work until a few years ago.
7
98 RELATIONSHIP OF COWPOX OB VACCINIA TO SMALLPOX
demonstrated to the presidents of the Royal Colleges of Physicians
and Surgeons a child whom he had successfully vaccinated with glycer-
inated lymph prepared six months previously. Cheyne admitted that
he was indebted for knowledge of this procedure to the previous publi-
cations of Mr. J. Startin on the therapeutic uses of glycerin.
Miiller, of Berlin, further demonstrated the fact that vaccine lymph
could be considerably increased in quantity by the admixture of glyc-
erin without interfering with its specific activity. He proved that the
lymph might be diluted with three times its bulk of glycerin without
in any way lessening its potency. It is evident that Miiller's chief
object was to increase the quantity of available l}Tiiph, a matter of
much importance during smallpox epidemics, particularly when there
was danger of a vaccine famine.
With the same object in view Dr. Stephen Mackenzie, of the London
Hospital, during the great smallpox epidemic in 1870-71, added glyc-
erin to lymph in order to increase the amount just before conducting a
large series of vaccinations.
Dr. Warlomont, of Brussels, in 1882 placed upon the market, under
English patent, a method of admixture of glycerin with vaccine lymph,
but no mention was made of the contained glycerin until some years
later.
Copeman, in a paper presented to the International Congress of
Hygiene, held in London in 1891, advocated the addition of glycerin
to vaccine lymph for the purpose of purifying and preserving it. The
method consisted in the "intimate admixture of a given amount of
lymph, or rather vesicle pulp, with a sterilized 50 per cent, solution
of chemically pure glycerin in distilled water, and in subsequent storage
of the resultant emulsion in sealed capillary tubes for several weeks."
Copeman had previously endeavored by diverse means to inhibit
the growth in vaccine material of the various extraneous organisms,
and if possible destroy them without weakening the specific activity
of the lymph. These measures failing, he resorted to the addition of
glycerin.
Previous to Copeman's experiments there had been no appreciation
of the influence of the glycerin as a bacteriological purifier of lymph
when the mixture is stored for some time and protected from the access
of light and air.
When a glycerin emulsion of vaccine is prepared in the manner
indicated by Copeman, an inhibition and later destruction of the foreign
aerobic bacteria is brought about. The purification is a gradual one,
as can be determined by making plate cultures of the lymph from time
to time, and estimating the number of colonies of organisms present.
Since the publication of Copeman's paper in 1891, other careful
observers have fully substantiated the claims of this investigator.
Chambon and Menard, in 1892, were not only able to purify and pre-
serve lymph by glycerin admixture, but they claim to have produced
an improvement in the activity of lymph which in its fresh state had
given only mediocre results. Such a lymph produced after fifteen days'
(iLYCERINATKI) LYMI'll 99
admixture with glycerin a |)assal)le vesiele, aiul ;ifl,(;i- forty, fifty, or
sixty days a typical one. The improvcnnent in pot(!ncy was attrihuted
by them to the gradual destruction of foreign bacteria in the fluid.
Professor Straus, who made plate cultures of this lymph, achieved
results identical with those obtained by Copeman, although the work
was done prior to the publication of ("of)ernan's article. Fresh glyceiin-
ated lymph gave rise to numerous colonies of various organisms, espe-
cially the staphylococcus pyogenes aureus and staphylococcus albus,
but when stored for fifty to sixty days plate cultures proved to be
absolutely sterile as regards these extraneous bacteria. These experi-
ments were repeated many times, but always with the same result.
Leoni, in a paper read before the International Medical Congress,
held in Rome in 1894, concludes that (1) recently collected vaccine
is a contaminated vaccine, containing numerous foreign germs, some
of which are capable of exerting pathogenic properties when inoculated
into the system; (2) the contaminating organisms become extinguished
in vaccine preserved for a certain period in glycerin; (3) vaccine pre-
served in glycerin from one to four months after it is collected is the
type of fure vaccine, with an exclusively specific virulence; (4) this is
the quality of vaccine with which the hygienist of to-day should con-
cern himself in the prophylaxis of variola.
Klein has added the weight of his testimony as to the purifying influ-
ence of glycerin on vaccine lymph. In stating his belief that the specific
organism of variola is probably a spore-bearing bacillus, he incidentally
remarks: " .... it is established that the active principle of
vaccine is preserved in glycerin, although, as is also known, glycerin
is a germicide for cocci and sporeless bacilli."
In 1896 the German government appointed a commission presided
over by Schmidtmann, and including Koch, Pfeiffer, and Frosch,
together with the Directors of the Vaccine Institutes of Berlin, Cologne,
and Stettin, to investigate into the best methods for the collection,
preservation, storage, distribution, and use of vaccine lymph. The
report stated that fresh lymph contained numerous bacteria which
diminish progressively under the influence of the glycerin admixture.
Streptococci and diphtheria organisms added to the hinph were killed
in eleven days and twenty days, respectively. These experimenters,
as well as Kitasato, in Japan, determined that glycerin w^ith distilled
water could be added to the extent of from fifteen to twenty times the
weight of vesicle pulp without destroying the vaccine principle.
Copeman and Blaxall have shown that not only are the ordinary
foreign bacteria of fresh lymph destroyed by glycerinization, but that
pathogenic organisms such as those of tuberculosis and erysipelas, when
added in large number for experimental purposes, also perish.
The fact that the tubercle bacillus thrives particularly well upon agar
containing 6 per cent, of glycerin does not invalidate the claim that
this agent in a strength of 40 to 50 per cent, is a valuable microbicide.
Indeed, Copeman and Blaxall and likewise Klein have proven that
tubercle bacilli cannot be recovered after exposure for a month to the
100 RELATIONSHIP OF COWPOX OB VACCINIA TO SMALLPOX
action of glycerin, present to the extent of about 40 per cent., either
in a culture in sterile bouillon or in fresh vaccine material. These
investigators have furthermore shown that an emulsion of glycerinated
lymph inoculated with active tubercle bacilli, and allowed to stand for
a month, was incapable of producing tuberculosis in guinea-pigs, whereas
the contaminated vaccine lymph without the glycerin added invariably
produced this disease.
Rosenau^ (1903), in a study of the germicidal action of glycerin,
concluded that it has distinct but very feeble germicidal and antiseptic
properties.
Small quantities of glycerin, less than 10 per cent., added to nutrient
media, have well-known powers of favoring the growth and multiplica-
tion of many forms of bacteria.
The presence of 50 per cent, of glycerin will restrain all bacterial
growth. No growth or multiplication of bacteria takes place in nutrient
media containing 32 per cent, of glycerin, but moulds grow in stronger
percentages, viz., 40 to 49 per cent.
In order to prevent the growth and development of pus cocci, at least
33 per cent, of glycerin must be present.
The germicidal action of glycerin is probably due to its affinity for
water, causing a dehydration of the bacteria.
Glycerin ordinarily destroys the micrococci of suppuration, whether
the^e be in pure culture or in the pus itself, within two weeks. This
action varies according to the temperature. Pus cocci may live in
glycerin for months in the ice-chest, whereas at the body temperature
they die in a week.
Glycerin has a selective influence upon the diphtheria bacillus, which
succumbs much more quickly than most other organisms.
The bacteria of the typhoid and colon group often show a marked
resistance to the effects of glycerin in strong proportions.
Glycerin in all strengths has practically no effect upon endogenous
spores. Anthrax spores were kept alive and virulent two hundred days
in the strongest percentages of glycerin, and at warm temperatures.
Tetanus spores in pure culture, freed of all organic matter and washed
free of toxin, may lose their virulence in glycerin in thirty days at the
body temperature, but they live for months (one hundred and eighty
days) at room temperature or in the ice-chest. Glycerin, therefore,
cannot be depended upon to purify vaccine or other organic matter
containing this contamination. The virulence of the spores is lost
long before they actually die, for they still retain the power of growing
and multiplying if placed under favorable conditions.
Under these circumstances, therefore, they also regain their original
pathogenoid properties. Glycerin has practically no effect on diph-
theria toxin.
At a meeting of the British Medical Association in 1896, Copeman
and Blaxall presented a paper on " The Influence of Glycerin upon the
1 Director of the Hygienic Laboratory, United States Public Health and Marine Hospital Service,
Bulletin 16, 1903.
GLYCERIN ATI: I) LYAff'lf 101
Growth of liacteria." The bacteria employed in the experimentations
comprised staphylococcus pyogenes aureus, staphylococcus pyogenes
albus, streptococcus pyogenes, baf;illus pyocyuneus, hafillus subtilis,
bacillus coli communis, bacillus diphtherite, and bacillus tuberculosis.
Smallpox and vaccine material in the form of "crusts" and lymph
were also employed.
"Results: 1. No visible development of the micro-organisms em-
ployed took place in the presence of more than 30 per cent, of glycerin.
"2. None of the micro-organisms experimented with could be recov-
ered after exposure for a month to the action of from 30 to 40 per cent,
glycerin, with the exception of bacillus coli communis and bacillus
subtilis when kept in the cold.
"3. Bacillus coli communis, unlike bacillus typhosus, resists the
action of 50 per cent, glycerin in the cold for a considerable period — a
fact likely to prove of value as an addition to our present methods of
differentiating these microbes one from another.
"4. The samples of smallpox and vaccine material, whether as
'crusts' or lymph, were sterihzed completely, so far as extraneous
microbes were concerned, in a week, by the presence of glycerin to
the extent of about 40 per cent, in the broth tubes. This short period
of resistance is, doubtless, in part to be explained by the fact that the
smallpox crusts used in these experiments had been obtained several
months beforehand. Presumably, therefore, the number of microbes
which had been able to survive for so long a period the process of dry-
ing would be much less than might be expected to be present in * crusts'
recently obtained."
Copeman sets forth the advantages of glycerinated lymph in the
following terms:
"1. By employing the method of glycerination of lymph pulp, great
increase in quantity can be obtained without any consequent deteriora-
tion in quality, the percentage of insertion success following on its use
being equal to that obtained with perfectly active fresh lymph.
"2. Glycerinated lymph does not dry up rapidly as does unglycerin-
ated lymph, thus simplifying the process of vaccination.
"3. Glycerinated lymph does not coagulate; so that it never becomes
necessary to discard a tube on this account.
"4. Glycerinated lymph can be produced absolutely free from the
various streptococci and staphylococci which are usually to be found in
untreated calf lymph, and which are, under certain circumstances,
liable to occasion suppuration.
"5. In like manner the streptococcus of erysipelas, in the event of
its having been originally present in the IjTnph material, is rapidly
killed out by the germicidal action of the glycerin.
"6. The tubercle bacillus is effectually destroyed even when large
quantities of virulent cultures have been purposely added to the Ijinph.
"7. The possibility of inoculation of sj^hilis is eliminated, as the
calf is not subject to this disease.
" 8. The necessity for collecting children together, with the attendant
102 BELATIONSRIP OF COWPOX OB VACCINIA TO SMALLPOX
risk of spread of infectious diseases, or of transporting a calf from place
to place, is obviated, while the danger of 'late' erysipelas in the child
is diminished by reason of there being no necessity to open the mature
vesicles for the purpose of obtaining lymph.
"9. The bacteriological purity and clinical activity of large quantities
of the lymph can be readily tested prior to distribution.
" 10. By reason of the possibility of keeping large stocks of glycer-
inated lymph on hand for considerable periods of time v^^ithout appre-
ciable deterioration, any sudden demand, such as is likely to arise on
the outbreak of epidemic smallpox, can be promptly met.
"11. The expense of producing glycerinated lymph is proportionately
small, since the amount obtainable from each calf is enormously in-
creased."
Rosenau^ made a study of the bacteriological impurities of vaccine
virus as it occurs in commercial preparations upon the market in the
United States. The virus of ten different vaccine propagators was
examined during a period of more than a year. Of 190 dry points
examined, an average of 4354 bacteria per point was found. A number
of the points contained over 15,000 and one as high as 44,000 organisms.
Of 244 tubes of glycerinated virus examined, an average of 1742
bacteria per tube was found. A number of the capillary tubes con-
tained over 10,000 bacteria, and one as high as 30,000. This evidenced
lack of care in the preparation of the lymph.
Pus cocci, pathogenic for laboratory animals, were found both in
dry points and the glycerinated virus. Much of the virus above referred
to was "green" — i. e., it had not been glycerinated for a sufficient
period.
During the winter of 1901-02 the glycerinated virus contained an
average of 4698 bacteria per tube. In the spring of 1902 the average
fell to 1058 bacteria per tube. In the winter of 1 902, 89 tubes examined
gave an average of 29 bacteria per tube; the maximum was 239.
Glycerinated virus when properly prepared is freer from impurities
than dry points made with fresh lymph.
There is practically no difference between the glycerinated virus
dried upon ivory points and that hermetically sealed in capillary tubes,
so far as bacteriological impurities are concerned.
Tetanus spores may live a long time in vaccine virus; they remained
alive and virulent on dry points after two hundred and ninety-five days,
and in glycerinated virus sealed in capillary tubes three hundred and
fifty days.
Rosenau was unable to find tetanus germs or spores in any of the
considerable number of glycerinated points and tubes examined with
this object in view. He states that tetanus organisms cannot grow or
produce their toxin either in glycerinated virus or on the dry points.
"It would take gross carelessness to contaminate the vaccine with a
sufficient number of tetanus spores to carry the disease to those vac-
cinated."
i Loc cit., Bulletin 12, 1903.
QLYGEBINATED LYMPH 103
The writer concludes that the excessive irDpuriti(;s found in some of
the glycerinated virus upon the market is largely due to the overcon-
fidence in the germicidal value of glycerin.
Vaccine propagators become careless, ti-usting to the glycerin to
purify the product. Glycerin is too feehh; a germicide to purify vaccine
matter which has a great initial contamination.
The virus is also at times put upon the market with undue haste
when an unusual demand exists.
Howard' found actinomyces in virus from five vaccine establishments
twenty-four times in a total of ninety-five cultures. Nine difi'erent
species of actinomyces were found, of which six appeared to be pre-
viously undescribed. The organisms are supposed to reach the virus
from the air, water, soil, hay, straw, and hide.
The writer thinks it is not improbable that some of the postvaccinal
suppuration infections are caused by these organisms and are cases of
atypical actinomycosis.
Sabrazis, and Jolly and FoUi, also found actinomyces in vaccine virus.
The Preparation of Glycerinated Calf Lymph (Copeman). — "The method
best adapted for the production of glycerinated calf lymph which shall
be free from all extraneous organisms, of perfect efficacy, and yet afford-
ing material for the vaccination of many more children than the original
unglycerinated calf lymph, is briefly as follows:
"The Preparation of the Calf. — A female calf of suitable age,
about from three to six months, should be kept under observation for
a week, after which, if found to be quite healthy, it may be removed to
the vaccination station. It is there placed on a tilting table, and the
lower part of the abdomen, reaching as far forward as the umbilicus,
is shaved and thoroughly washed with a solution of carbolic acid and
then rinsed with sterile water and dried with soft, sterilized towels.
" Inoculation of the Calf. — With a sterilized, sharp scalpel incisions
about four inches long and half an inch apart, parallel to the long axis
of the body, are made on this clean-shaven area. The depth of the
incision should be such as to pass through the epidermis and to open
the rete Malpighii, if possible without drawing blood. As these incisions
are made, glycerinated calf lymph, which by examination has been
proved to be free from extraneous organisms, is run into them by means
of a sterilized blunt instrument, and the point of the scalpel is from
time to time dipped into the vaccine emulsion.
"Collection from the Calf. — After five days (one hundred and
twenty hours) the vaccinated surface of the calf is first thoroughly washed
with warm water and soap, rubbed over it by the clean hand of the
operator, and finally the whole area is carefully cleansed with sterile water.
The remaining moisture is then removed by sterilized sheets of blotting
paper. The vaccinated incisions will now appear as lines of continuous
vesicles raised above the surface, each line separated from its neigh-
bor by about a quarter of an inch of clear skin. Aiiy crusts wliich appear
1 A Study of Actinomyces Cultivated from Commercial Vaccine Virus, Journal of Medical Researchj
January, 1904.
104 BELATIONSHIP OF COWPOX OR VACCINIA TO SMALLPOX
in the vesicular lines are picked off with a blunt, sterilized instrument.
The vesicles and their contents are then removed by means of a steril-
ized Volkmann spoon, and transferred to a sterilized bottle of known
weight. By going over the lines only once with the spoon, it is quite
easy to remove the whole of the pulp without any admixture of blood.
The abraded surface is carefully washed, and may be dusted over with
fine oatmeal or starch and boracic powder. Subsequently, the calf is
transferred to the slaughter house and the carcass is examined by the
veterinary surgeon, who forwards a certificate of its condition. Should
this not be satisfactory, the vaccine pulp obtained from the animal is
destroyed.
Fig. 16
Belly of heifer, showing one of the approved modern methods of propagating vaccine virus ; lesions
photographed at the end of five days. (Courtesy of Dr. Wm. F. Elgin.)
"Preparation and Glycerination of the Lymph Pulp. — ^The
bottle containing the vaccine pulp is taken to the laboratory and the exact
weight of the material ascertained. A calf vaccinated in this way will
yield from 18 to 24 grams, or even more, of lymph pulp. This
material is then thoroughly rubbed up in a sterilized mortar or in a
mechanical triturating machine. When it has been brought to a fine
state of division, it is mixed with six times its weight of a sterilized
solution of 50 per cent, chemically pure glycerin in distilled water.
The resulting emulsion is then transferred to small test-tubes, which
are then aseptically sealed and should be stored in a cool place protected
from light. When required for distribution it is drawn up into sterilized
capillary tubes, which are subsequently sealed in the flame of a spirit
lamp.
STATISTTCJAL EVIDENCE OF EFFfdAdY OF VA CO f NATION lOo
'Bacteriological Examination of the Lymph Emulsion. — As
soon as the vesicular pulp is thoroughly emulsified with the glycerin solu-
tion, agar-agar plates are established from it, and, after suitable incubation
for seven days, the colonies that have developed on the plates are counted
and examined. Week by week this process is repeated, and invariably
the number of colonies diminishes with the age of the emulsion, until
at the end of the fourth week after the collection and glycerination of
the lymph material the agar-agar plates inoculated at that time show
no development of colonies. The lymph is then subjected to further
culture experiments, and if these results of freedom from extraneous
organisms are confirmed the emulsion is ready for distribution. The
elimination of the extraneous organisms in our experiments has occurred
with marked regularity at the end of the fourth week. The only excep-
tion to this rule arises when the lymph originally contained a consider-
able number of spores or bacilli of the hay bacillus or bacillus mesen-
tericus. These organisms are very resistant to the action of glycerin,
but if the precautions detailed are carried out in the treatment of the
calf their presence may generally be excluded.
"Duration of Activity of Glycerinated Calf Lymph. — This
varies in all probability with atmospheric conditions, with the fineness of
division of the vesicle pulp, and, above all, with the condition of the calf
itself. Some calves yield an excellent lymph, others a poor lymph,
and the problem is to determine the value of the lymph yielded by any
given calf. A lymph which was collected and glycerinated on July 13,
1897, has since been used at intervals of from twenty-four weeks to
thirty-two weeks after glycerination for the vaccination of children.
During this period sixty-one children have been vaccinated with this
lymph in five places each, with a mean insertion success of 98 per cent.
Thus, by the methods described, glycerinated calf lymph can be pre-
pared which becomes freed from extraneous organisms, is available
for a large number of vaccinations, at least 5000 from an average calf,
and retains full activity for eight months, and will, under favorable
circumstances continue to do so in all probability for still longer periods,
if necessary."
STATISTICAL EVIDENCE OF THE EFFICACY OF VACCINATION.
Although smallpox dates back many centuries, we have no trust-
worthy record of the extent of its prevalence before the fifteenth century.
About this time it began to be common in Western Europe, increasing
during the sixteenth and particularly the seventeenth century, and
prevailing still more extensively in the eighteenth.
The begimiing of the nineteenth century was characterized by a sudden
and striking decrease in the morbidity and mortality of smallpox.
Inasmuch as the announcement of the protective influence of vac-
cination (1798) and the diffusion of this practice immediately preceded
this decline, there is the strongest reason to regard Jenner's epoch-
making discovery as the causative influence.
106 RELATIONSHIP OF COWPOX OB VACCINIA TO SMALLPOX
As has been previously shown, smallpox was a great scourge before
the days of vaccination. But a small percentage of the population
escaped its ravages. It is claimed that in the eighteenth century, accord-
ing to contemporaneous writers, 95 per cent, of the inhabitants of
European countries suffered at one time or other from the smallpox.
In other words, but five persons out of every hundred went through life
without being attacked by this dread malady. This is rendered credible
when we appreciate the fact that smallpox is among the most contagious
of all diseases, and that nearly every human being is highly susceptible
to it. Haygarth, who lived in the eighteenth century, stated that the
proportion of mankind incapable of infection by smallpox "was observed
to amount to one in twenty;" this would account for the exemption of
the 5 per cent, referred to.
Fig. 17
annual deaths per million of population.
7000
6000
5000 -
4000
3000
2000
1000
500
BEFORE VACCINATION
AFTER VACCINATION
SMALLPOX WITH
MEASLES
SMALLPOX
SMALLPOX
© © ©
lO ^ t-
© © e
(M » e
!^ '" 2
© © © © ©
■-< e^ M •=Si IS
\ cx) or> ao
1
1
-
1
\
1
1
-
-
-
1
li
1
III
-
-
-
-
1
1
HI—
1
Hli
r
1
ij
H
m
ill
■IL
j|
iM
1
1
■
■
■
I
■
■
■
1
■
m
■
111
u.
Li
\m
JJ
6000
5000
4000
3000
2000
1000
500
Smallpox death rates for Sweden from 1749 to 1855. (Calculated by Mr. Haile Ijom returns com-
municated by the Swedish government. Published in papers communicated to the Houses of
Parliament, London, 1857.)
This author reports an epidemic of smallpox in Chester^in 1774, at
which time, out of a population of 14,713, 1202 persons took the disease
and 202 died. At the termination of the epidemic there were but 1060
persons, or 7 per cent., of the population who had never had smallpox.
In an epidemic of smallpox at Warrington in 1773, in a population
of 8000, 211 persons succumbed to the disease. The total deaths during
the year from all causes were 473.
In 1722 an epidemic raged in the small English town of Ware, which
had a population of 2515. Of this number there were only 914 persons
susceptible to smallpox, as 1601 had already had the disease. During
the epidemic 612 persons were attacked, leaving but 302 individuals
in the entire town who had never had smallpox.
STATfSTKJylL EVI I) l<:Nl<' l':FFI(!y\(JY OF VA(!(JINATI()N 107
Rapid Decline in Smallpox Mortality After the Introduction of
Vaccination. — iiiHsniuch as accurutc rcf-ocds of siiKillpox iMorlulity
wiM'c kept ill vjxrioiis coiiiitrics, it is possible to prove by (loeiiiiientary
evidence that a strikirif); fall in the niiiiihcr of deaths from this disease
oceurred shortly after the introduction of vaccination.
Sweden. — Vaccination was introduced into this country in Oetoher,
1801. According to the official fi<^ures of the Medical College, there
were performed 2^), ()()() vaccinations hy the year ISOo, 2."<,()()() in 1S05,
and about 19,000 in 1800. Vaccination was made compulsory in 1810.
The average death rates per million of j)opulation for the decades from
1774 to 1821 show a decided and progressive decrease in the mortality
of smallpox. (See Fig. 17.)
Average Yearly Death Rates from Smai.ltox per Million of
PorULATION FOR DeCADES FROM 1774 TO 1821. SWEIiEN.
(Bight years), 1774 to 1781 (before vaccination) 1999
Decade, 1782 " 1791 " " 2219
" 1792 " 1801 " " 1914
" 1802 " 1811 (after vaccination) 623
1812 " 1821 " " 133
The influence of vaccination in lessening smallpox mortality in
Sweden is so clearly shown in the above table as to require no fuither
discussion.
The contrast in smallpox mortality may be expressed in another
manner. In the twenty-eight years before vaccination in Sweden, there
died each year from smallpox, out of each million of population, 2050
persons; during the forty years folloiving vaccination, out of each million
of population the smallpox deaths annually averaged 158.
The official figures of the Medical Faculty of the University of Prague
(published in papers on vaccination issued by the London Board of
Health, 1857) are no less conclusive:
Population, Total Deaths, and Deaths by Smallpox During Seven
Years Before the General Introduction of Vaccination. Prague.
Population.
Deaths.
Year.
Total number.
From smallpox.
Remarks.
1796
1797
1798
1799
1800
1801
1802
3,003,482
2,991,346
3,045,926
3,041,608
3,047,740
8,036,481
3,111,472
92,242
86,855
84,743
99,079
110,730
105,576
85,460
6,6S6
1,988
3,105
17,587
17,077
3,169
4,029
(The proportion of the deaths generally
\ to population = 1 : 32.
/Deaths from smallpox to populations
1 = 1 : 396P:,.
/Deaths from smallpox to the total
t number of deaths = 1 : 12J^.
Total
21.278,055
664,685
53,641
Average
3.039,722Vt
94,955
7,663
108 BELATIONSHIP OF GOWPOX OR VACCINIA TO SMALLPOX
During Twenty-four Years Subsequent to Introduction op
Vaccination. Prague.
Population.
Deaths.
Year.
Remarks.
Total number.
From smallpox.
1832 1
1833 i
3,888,828
1
139,061
121,679
807
533
1834 ■)
i
122,171
285
The proportion of the total number
1835 Y
3,945,875
122,952
337
of deaths to popuJation = 1 : Z2%.
1836 j
(
124,015
291
1837 )
(■
141,982
104
1838 Y
4,027,581
\
108,419
62
1839 J
1
121,400
128
1840 ")
118,471
699
Deaths from smallpox to population
1841 Y
4,145,715
)
116,575
697
= 1 : 14,7413^.
1842 )
j
124,019
339
1843 )
(
142,876
332
1844 Y
4,285,730
J
118,184
150
1845 )
1
178,826
62
1846 ■)
j"
132,379
59
Deaths from smallpox to total number
1847 Y
4,480,661
J
134,490
9
of deaths = 1 :457^.
1848 j
j
141,409
115
1849 '
1850
131,493
383
176,211
478
1851 r
4,613,080
\
133,245
508
1852
134,921
343
1853
1
124,617
42
1854 \
1855 1
4,593,770
{
124,746
124,764
68
64
Total
33,985,240
3,153,905
6895
Average
4,248,155
131,412' 7/24
287 '/24
Tables Comparing Smallpox Mortality in Various Localities Before
AND After the Introduction of Vaccination.
Terms of years respecting
which particulars are
given.
Before After
vaccination, vaccination.
1777-1806 and 1807-1850
1777-1806
" 1807-1850
1777-1806
' 1807-1850
1777-1806
' 1807-1850
1777-1806
' 1807-1850
1777-1803
' 1807-1850
1777-1806
' 1807-1850
1777-1806
' 1807-1850
1777-1806
' 1807-1850
1777-1806
' 1807-1850
1787-1806
' 1807-1850
1817-1850
1817-1850
1817-1850
1831-1850
1776-1780
' 1810-1850
1780
' 1810-1850
1780
' 1816-1850
1776-1780
' 1810-1850
1776-1780
' 1816-1850
1776-1780
' 1816-1850
1781-1805
' 1810-1850
1776-1780
' 1816-1850
1780
' 1810-1850
1810-1850
1774-1801 '
' 1810-1850
1751-1800 '
' 1801-1850
Territory.
Austria, Lower .
Austria, Upper, and Salzburg
Styria
Illyria ,
Trieste
Tyrol and Voralberg
Bohemia
Moravia
Silesia (Austrian)
Gallicia
Bukowina .
Dalmatia .
Lombardy .
Venice
Military Frontier
Prussia (East Province)
Prussia (West Province)
Posen .
Brandenburgh .
Westphaha
Rhenish Provinces
Berlin .
Saxony (Prussian)
Ponierania .
Silesia (Prussian)
Sweden
Copenhagen
Approximate average.
Annual death rate by smallpox
per million of living population.
Before intro-
duction of
vaccination.
2,484
1,421
1,052
518
14,046
911
2,174
5,402
5,812
1,194
3,527
3,321
2,272
1,911
2,181
2,643
908
3,422
719
1,774
After intro-
duction of
vaccination.
2,050
3,128
340
501
446
244
182
170
215
255
198
676
516
86
87
70
288
556
356
743
181
114
90
176
170
130
310
158
286
STATIHTIdAf. l<:Vn)ICN(!l<: Oh' KFFKIAdY Oh' VAdCfNATfOy l()f)
It will be seen from the above tables tliat whereas in the seven years
preceding the introduction of vaccination smallpox in Prague caused
one-twelfth of the total numher of deaths, this disease during twenty
years of the vaccination period caused but -2^^-^ of the total numher of
deaths.
In Westphalia the annual deaths from smallpox from 177G to 1780
were 2G43 per million of population; during the tliirty-five years from
1816 to 1850 the death rate was only 114 per million.
In Copenhagen, for the half-century 1751 to 1800, the smallpox death
rate was 3128, whereas for the next fifty years it was only 286.
In Berlin for twenty-four years preceding vaccination the death rate
from smallpox was 3422, and for the first forty years of the vaccination
era it was 176.
By the middle of the nineteenth century the fatality of smallpox had
been reduced in Copenhagen to one-eleventh of the pre vaccination
death rate; in Sweden to a little over a thirteenth; in Berlin, and in a
large part of Austria, a twentieth; and in Westphalia, a twenty-fifth.
In the last-named place but four persons died about the middle of the
century compared to 100 in the prevaccination days.
Smallpox Deaths Each Year, from the " Bills of Mortality,"
London, 1801 to 1830.
Before vaccination era. After vaccination era.
Decade.
Smallpox deaths.
Decade.
Smallpox deaths
1761-1770
. 20,434
1801-
-1810
12,534
1771-1780
. 20,923
1811-
-1820
7,858
1781-1790
. 17,867
1821-
-1830
6,990
1791-1800
. 18,477
1801-1810
1811-1820
1821
-1830
1831-
-1837
1801 . .
1,461
1811. . . 751
1821.
. . 508
1831.
. 563
1802. .
1,597
1812 . . . 1287
1822 .
. . 604
1832.
. 771
1803 . .
1,202
1813 ... 898
1823.
. . 774
1833.
. 574
1804. . .
622
1814 . , . 638
1824.
. . 725
1834.
. 334
1805. . .
1,685
1815. . . 725
1825.
. . 1299
1835 .
. 863
1806 . . .
1,158
1816 ... 653
1826.
. . 503
1836.
. 536
1807 . . .
1,279
1817 . . . 1051
1827.
. . 616
1837.
. 217
1808 . .
1,169
1818. . . 421
1828.
. . 598
1809 . . .
1,163
1819. . . 712
1829.
. . 736
1810. . .
1,198
1820 ... 722
1830.
. . 627
Smallpox,
12,534
78D6
6990
3858
The above figures show a decided contrast in smallpox mortality
between the decades immediately preceding and following the intro-
duction of vaccination. In the twenty-seven years elapsing from 1811
to 1837 the smallpox deaths exceeded 1000 but three times.
Berlin. — Below are compared the deaths from smallpox per 100,000
inhabitants \\\ the prevaccination and postvaccination periods:
1758-1762
. . 407
persons.
1790-1794
. 310 persons
1763-1767
. 364
"
1795-1799
. 239
1768-1772
. 294
"
1S00-1S04
. 261
1773-1784
. ?
"
1805-1809
. 308
1785-1789
. 360
"
110 RELATIONSHIP OF COWPOX OB VACCINIA TO SMALLPOX
(In the first decade of the nineteenth century vaccination was not
actively practised in BerHn; it became generally employed in the year
1810.)
1810-1814 ^ .
31 persons.
1840-1844
13 person
1815-1819
. 40
1845-1849
2
1820-1824
4
1850-1854
5
1825-1829
. 13
1855-1859
. 18
1830-1834
. 19
1860-1864
. 30
1835-1839
. 18
1865-1869
. 26
In the quinquennium 1870-1874 occurred the great pandemic of
smallpox which swept the entire civilized world. There died in Berlin
during this period, per 100,000 population, a yearly average of 160;
this number considerably exceeds all the previous years of this period,
but still falls far below the average of the prevaccination years.
From 1795 to 1799, before the days of vaccination, smallpox caused
6.5 per cent, of all deaths in Berlin. In the five years following the
introduction of vaccination the figures were: 7.5 per cent., 6.4 per cent.,
0.7 per cent., 1.3 per cent., and 0.2 per cent.^
Copenhagen. — Between 1794-1798 (prevaccination period) smallpox
caused on an average 373 deaths each year.
1799 (before vaccination) .
. 54
1800
. 35
1801
. 486
1802
. 73
1803 (after vaccination) .
. 5
1804
. 13
805 (after vaccination)
806
809
810
From 1811 to 1823 not a death occurred from smallpox. (A period of
thirteen years. )^
It is thus seen from the statistics above quoted that after the discovery
of vaccination the deaths from smallpox markedly decreased in every
country in which this practice was introduced.
1 Denkschrift, li. k. Gesundheitsamt, Berlin.
- Beitrage aus der Gesundheitsamte. Quoted by Edvvardes, Smallpox and Vaccination in Europe,
London, 1902.
STATISTICAL KV I I)I<:Nriod of thirty-one years. During this time the
total deaths were .'iSfJO, and the deaths from smallj)ox 022. 'I'here were
nine epidemics of smallpox reenrrini;e of nine person.s
was not known.
In ChcMcr, in the epidemic of 1774, all of the smallpox deaths, nuiidxT-
inn^ 202, occurred in children under ten years of age, and onc-(|ii;irter
of them under one year.
In Kilmarnock, of 622 deaths from smallpox l)etween 172S and 1763,
only seven were of those above ten years.
In 1773, Warrington^ sustained an epidemic of smallpox which
resulted in 211 deaths (population SOOO). In 1S03 another epiflemic
occurred which resulted in 62 deaths (population 54,084, of whom 53,645
were vaccinated). The ages of the patients fatally attacked are tabulated
as follows:
Smallpox Deaths.
Age.
Under
1
year
1 to
2
years
2 "
3
3 "
4
4 "
5
5 "
6
6 "
7
7 "
8
8 "
9
9 "
15
15 "
20
20 "
30
30 "
60
Over
60
773.
Vaccinated.
Not vaccinated.
49
8 (under 1 month)
84
1
33
18
1
15
1
4
2
2
4
1
1
1
1
1
2
10
4
24
5
1
211
24
In 1773 all of the deaths were under ten years, and nine-tenths were
under five years of age.
In 1893 among the vaccinated not a death occurred under eight years
of age; indeed, not one vaccinated child under eight years of age
contracted smallpox.
The statement may be considered as proven that vaccination has
changed the age incidence of smallpox. It is a rarity for a successfully
vaccinated child under five years of age to die of smallpox. It is even
uncommon for a successfully vaccinated child under ten years to
succumb to the disease, as will be seen from the following table compiled
by the British Royal Vaccination Commission:
Quoted by Edwardes, loc. cit.
S
114 RELATIONSHIP OF COWPOX OB VACCINIA TO SMALLPOX
Smallpox in Children of the Age of 1 to 10 Years.
Vaccinated. Not vaccinated.
Attacks 570 Attacks 1235
Deathsi 16 Deaths 375
Fatality . . . .2.8 per ct. Fatality .... 30.3 per ct.
The saving of infant life by vaccination should have reduced the
general infant mortality in the postvaccination period; the following
table shows that such a reduction in infant mortality did take place.
It will be seen that the diminution in the general death rate of children
under ten, and more particularly under five years of age, is far more
pronounced than during adult life.
Annual Mortality to 1000 Persons Living. Sweden,
Before vaccination.
After vaccination.
Ages.
21 years
20 years
20 years
10 years
(1755-1775).
(1776-1795).
(1821-1840).
(1841-1850).
Under 5 years ......
90.1
85.0
64.3
56.9
5 to 10 "
14.2
13.6
7.6
7.8
10 " 15 "
6.6
6.2
4.7
4.4
15 " 20 "
7.6
7.0
4.9
4.8
20 " 30 "
9.2
8.9
7.8
6.8
30 " 40 "
12.2
11.6
11.8
9.8
40 " 50 "
17.4
16.1
16.7
14.5
iSO " 60 "
26.4
23.9
26.0
23.6
60 " 70 "
48.1
49.3
49.4
46.3
70 " 80 "
102.3
104.1
112.9
102.8
80 " 90 "
207.8
197.4
243.7
228.5
90 " and upward
394.1
351.3
396.4
375.8
All age
s
28.9
26.8
23.3
20.5
The opponents of vaccination urge that the decline of mortality from
smallpox at the beginning of the nineteenth century was not due to
vaccination, but to the discontinuance of inoculation.
It is probable that inoculation did tend to increase the prevalence of
smallpox, but there is no evidence to prove that it increased the mortality.
As the Royal Commission remarks: "It must be borne in mind that
inoculated smallpox was on the whole much less fatal than that naturally
acquired. The class of inoculated persons may thus have contributed
less to the fatal cases of smallpox than if they had been left to the chances
of natural contagion."
While inoculation was introduced into England in 1721, it found but
Httle favor until 1740. The Suttons popularized the practice in 1763,
and between 1770 and 1780 it was widely employed. Inoculation was
therefore only practised on a large scale in England in the second half
of the eighteenth century, and particularly in the last twenty-five years
of this period. The antivaccinationists claim that the increase of small-
pox mortality in the eighteenth century over the seventeenth was due
to the practice of inoculation. If this were true, the mortality should
have shown its increase particularly during the second half of the
I Six of tiiese deaths occurred in children in whom the success of the vaccination was doubtful.
STATISTIC A Ij KV f DICNd K Oh' KI^'lCAdY Oh' VAddlNATIOS 1|5
century. But the mortality wus as n;rca(, fil" woi ^n-c;i(d (,li;it inocnhition did not cntir-cly cease
in England upon the introduction of vaccination, but continued to be
practised for a number of years, until it was declared illegal by act of
Parliament in 1(S40.
It is evident from these considerations that the disc/'JN(,'JX
12'A
Carinthia, 1834-1835 .
1,626
14^
Yt.
Adriatic, 1835
1,002
15'/5
H
Lower Austria, 1835
2,287
25ry.
This was passed A|)ril S, IS74, and went into cH'cct on April I, JSyr;.
Its essential provisions an; as follows: Every eliild nnist be vaeeinated
before the expiration of the first year of its life, unless it has had small-
pox or unless some physical disability exists; in the latter event the
va(;einati()n is undertaken within one year of the removal of the existing
disability. Every ])U])il of a ])iiblie or private educational institution
must be vaccinated between the age of thirteen and fourteen years,
unless there is medical proof that he has had an attack of smallpox
within five years or has been successfully vaccinated within that time.
Parents, caretakers, guardians, or heads of schools who fail to comply
with the law are subject to fine or imprisonment. Vaccination must
be performed only by physicians, and anyone vaccinating illegally is
punished by a fine not exceeding 150 marks or imprisonment not
exceeding fourteen days.
Fig. 18
PRUSSIA, 1847-1897. ^
SMALL-POX DEATHS PER MILLION OF POPULATION.
AUSTRIA, 1847-1.897.
SMALL-POX DEATHS PER MILLION OF POPULATION.
Tables showing the decline of smallpox in Germany after the enaction of compulsory vaccination
in 1874; smallpox mortality is compared with that of Austria.
The Results of the German Compulsory Vaccination Law. — If
there was in existence no other statistical evidence of the efficacy of vacci-
nation and revaccination, the history of smallpox in Germany since
1875 would be all sufficient testimony.
From 1816 to 1870 the annual mortality from smallpox in Prussia
varied from 7.32 to 62.0 per 100,000 of population. This death rate
was small compared with the prevaccination periods.
During the disastrous pandemic of 1871-72 the rate was 243.2 and
262.67, respectively. After the law of 1875 went into effect the annual
124 RELATIONSHIP OF COWPOX OB VACCINIA TO SMALLPOX
mortality in Prussia fell so that between 1875 and 1886 the average
yearly mortahty per 100,000 of population was 1.91, the maximum
reaching 3.6 (in 1877).
On the other hand, in Austria, where the lax vaccination and revacci-
nation requirements remained unchanged, the mortality rate from small-
pox during about the same period (1875 to 1884) increased, varying
between 39.28 (1876) and 94.79 in 1882. (See Fig. 18.)
The results of the German vaccination law in the principal states of
the Empire are given in the following table:
The Results of the Geemak VAcciNATioisr Law, 1874.
(Smallpox deaths per million living. )
Year.
Prussia.
Bavaria.
Wtirtemberg.
German
Empire.
Contrast
Austria.
1866
620
120
133
...1
368
1867
432
250
63
484
1868
188
190
19
370
1869
194
101
74
374
1870
175
75
293
293
1871
2432
1045
1130
383
1872
2624
611
637
1866
1873
356
176
30
3094
1874
95
47
3
1725
2. Since 1874.
1875
36
17
3
576
1876
31
13
1
406
1877
3.4
17
2
555
1878
7.1
13
631
1879
12.6
5
534
1880
26
12
5.6
674
1881
36.2
15
3.6
807
1882
36.4
12
6.6
947
1883
19.6
6
35.2
596
1884
14.4
1
11.6
530
1885
14
3
600
1886
4.9
1
1
4.2
400
1887
5
1.8
3.5
417
1888
2.9
3.8
0.5
2.3
615
1889
5.4
5.2
4.1
537
1890
1.2
1.5
1.2
249
1891
1.2
1.2
1.0
287
1892
3
0.5
2.1
256
1893
4.4
0.7
1
3.1
244
1894
2.5
0.3
1.7
105
1895
0.8
0.2
0.5
49
1896
0.2
0.2
0.2
36
1897
0.2
0.1
61
1898
0.4
0.3
0.3
1899
0.5
The remarkable results of compulsory vaccination and revaccination
in Germany are perhaps the more striking when the mortality rate of
smallpox in Gerrnan cities is compared with cities of other countries.
After compulsory revaccination in 1875 the average annual death rate
from variola from 1875 to 1886 in the followins" cities was as follows:
1 No statistics.
VA C(,'JNA TION STA TISTICS 125
Death Ratk i^'kom SMAiii.i'ox i-ioii 100,000 ov I'oimjla'iion.
Uennai) (.'ities. Oilier CilioK.
Berlin .... I.IO iicrsons. Pariw .... 2C>.'i\ \>trtv>iin.
Hamburg . . . 0.74 " .St. I'cterwburfj . . 3.'). 82 "
Breslau .... 1.11 " Vioiina .... M.'M "
Dresden .... 1.03 " fragile .... 147.90 "
There is hut one e.xphuiation for the inarvcloiisly low dc'itli nitf iti
the German cities as compared with other coiiliiiciilnl (•(■ii(i«v^; ilmt
explanation is carrjvl and universal vaccination and rcracriiKilion.
A comparison of total .smallpox aUaclcs in the (jcrman, Frciicli, aiul
Austrian armies aft(M- 1X75 is e((ua,lly instructive:
German army (1875-1887) 148 men.
French army (1875-1881) 5,605 "
Austrian army (1875-1886) 10,238 "
In the German army, despite greater numbers and a longer period
of time, the smallpox attacks were enormously less than in the French
and Austrian armies.
Since the law of 1875 went into effect in Germany, there have been no
epidemics of smallpox in that country. The smallpox is frequently
introduced by foreigners, particularly on the frontiers, but the disea.se
can find no foothold. In 1899 there occurred in the German Empire,
among 54,000,000 people, 28 deaths from smallpox; these occurred
in twenty-one different districts, the largest number in any one district
being 3. Not a case occurred in a large town.
Kiibler^ in speaking of the importation of smallpox into Germany,
says: "Among the fatal cases there were many who had come from
foreign countries; in the interior of the Empire aliens, chiefly Russian-
Polish laborers, constituted a large percentage of those who contracted
the disease. The annual recurrence of the pestilence among these
people has recently necessitated a regulation that workmen before being
admitted to employment within the realms must produce proof of
successful vaccination or recovery from an attack of smallpox, and in
case they were unable to do so they must submit to vaccination."
The following figures indicate the prevalence of smallpox on the
German frontier as compared with the interior.
The mortality from smallpox in Germany from 1886 to 1889 was:
At the Frontier. In the Interior.
1886 UO cases. 45 cases.
1887 119 " 49 '•
1888 94 " 16 "
1889 188 " 12 "
In 1897 there were but five deaths from smallpox in the entire German
Empire (54,000,000 population).
Furthermore, for a period of th irtcen years in a population comprising
two-fifths of the total inhabitants of Germany, there were only five
instances of death from smallpox in successfully rcvaccinated persons.
1 Geschichte der Impfung und Blattern, 1901.
126 RELATIONSHIP OF COWPOX OR VACCINIA TO SMALLPOX
Germany has taught the world how to utihze Jenner's great discovery
SO as to exterminate smallpox.
The German Vaccination Commission of 1884, referring to the influ-
ence of the compulsory vaccination law, says:
"Previously to 1871 smallpox mortality in Austria behaved much
like that of Prussia, though higher on the whole. The great epidemic
of 1872-74 was more fatal and lasted longer than in Prussia. During
the next two years the mortality fell, as usual after epidemics. Here
the influence of the epidemic in lowering the mortality ceases, and the
latter rises at once to its old figures, viz., as before the epidemic, and
even higher, and this rise was not merely temporary.
"The remarkable and persistent decline in Prussia since 1875 can
only be due to the vaccination law of 1874, because all other conditions
remain the same in the two countries. The only difference is that in
Prussia the revaccination of all school-children at the age of twelve
years was made compulsory in 1874."
The Board of Health of Berlin has prepared tables comparing the
number of deaths occurring between the years 1886 and 1889 in countries
having compulsory vaccination, and those without such provision:
Population.
1886.
Smallpoj
1887.
c deaths.
1888.
1889.
Average
of
deaths.
Average
per
million
of popu-
lation.
>. . f Sweden, 4,746,465 .
^f Ireland, 4,808,728 .
B<'3 -1 Scotland, 4,013,029 .
a§ Germany, 47,923,735 .
5 ** l England, 28,247,151 .
Switzerland, 2,922,430 .
Belgium, 5,940,365 .
Russia, 92,822,470 .
Austria, 23,000,000 .
Italy, 29,717,982 .
Spain, 11,864,000 .
1
2
24
197
275
182
1,213
16,938
8,794
1
5
14
17
168
505
14
610
25,884
9,591
16,249
1
9
3
112
1,026
17
865
1
2
6
200
28
3
1,212
1
4
5
12
169
458
54
975
21,411
11,220
15,925
11,425
1 1
1 1
3 1-
3.5 1
16 J
18.5
164
231
14,138
18,110
14,378
12,358
13,416
8,472
510
536
1
963
But a glance is necessary to show the striking difference between the
number of deaths in those countries having compulsory vaccination and
those in which there is no such measure. The average deaths per
million in the compulsory vaccination countries is eighty tiTues less than
in the others. Furthermore, England is the least vaccinated of the
compulsory countries and her death rate is the highest among these.
The Imperial Board of Health of the German Empire gives the
frequency of smallpox in various European countries between 1893 and
1897 inclusive, a period of five years.^
1 No statistics.
" Quoted by Kiibler, loc. cit.
VA (J(UNA TION ST A 'I'lS'l'IdS
Vll
TlfE FllEQUfiNCY 01'' SmALM'OX FN EUROt'KAN SlATKH HIO'IWKKN IHD.'i-lSO?
rNCI.UHfVK (5 YKARS).
Average yearly
Actual
Country.
I'opulation.
52,042,282
mortality in
every million
fjopulatlon.
1.1
number
Hmallpux
deatOH.
YearH.
Germanv
287
5
Denmark
79»,3:)6
0.5
2
6
Sweden
4,894,790
2.1
41
4
Norway
2,045,900
0.6
5
4
England and Wales
30,389,524
20.2
8,066
5
Scotland
4,155,880
12.3
256
5
Ireland
4,580,5.55
9.9
226
5
Switzerland
3,032,901
5.1
78
5
Netherlands
4,707,249
38.7
929
5
Belgium
6,419,498
99.9
3,208
5
French States
8,253,079
90.2
3,721
5
Russian Empire including Asiatic Russia
118,950,400
463. 2
275,502
5
Austria
23,000,000
99.1
11,799
5
Italy
31,007,422
72.7
11,278
5
Spain
10,596,649
563. 4
23,881
4
Hungary
18,234,916
134. 3
12,241
5
Here, again, the countries which during this period have the most
stringent vaccination laws suffer the least smallpox, namely, Germany,
Denmark, Sweden and Norway.
In well-vaccinated Germany, but one person a year in every million
died of smallpox.
In England and Wales, where vaccination is generally but not univer-
sally practised, 20 persons per million died each year.
In Austria, where the vaccination laws are poorly enforced, 99 persons
per million died each year.
It is, indeed, quite possible to know to what extent vaccination is
practised in the various countries by noting the mortality from small-
pox.
There is an inverse proportion between these factors. It is evident,
therefore, that in Spain and in Russia (including Asiatic Russia) vacci-
nation must be greatly neglected.
The tables teach another lesson, namely, that without vaccination
smallpox is still to be regarded as a dread scourge, as a great destroyer
of human life. For in the five years from 1893 to 1897, in the sixteen
countries mentioned, 346,520 lives were sacrificed to smallpox; of this
number Russia lost 275,502. These figures are the more terrible when
it is recognized that these lives might have been saved by the application
of a prophylactic measure within the reach of all.
Immunity of Physicians and Nurses in Smallpox Hospitals. — If it
can be demonstrated that physicians and nurses in smallpox hospitals
are protected by vaccination, this must be regarded as a crucial test.
For if these persons, living in the same atmosphere with scores or hundreds
of smallpox patients, breathing in their very exhalations, are enabled
to escape the infection, it certainly should be possible for others much
less exposed to acquire similar immunity.
Experience shows that physicians, nurses and others, if recently success-
fully vaccinated, may live in smallpox hospitals with perfect safety. The
128 RELATIONSHIP OF COWPOX OR VACCINIA TO SMALLPOX
immunity of employes (when properly revaccinated) is a uniform
experience in practically all smallpox hospitals.
In the hospitals of London, from 1876-79, there were admitted 11,412
smallpox patients who had been vaccinated in infancy, but not a single
case was known to have occurred in a person who had been successfully
revaccinated. It was the rule to revaccinate all nurses and employes
before entering the hospital, and the number thus employed amounted
to about 1000; of these only some half-dozen took smallpox, and they,
for some cause or other, had escaped revaccination.
Dr. Marson,^ physician to the Smallpox Hospital of London for many
years, giving evidence in 1871, stated that during the preceding thirty-five
years no nurse or servant at the hospital had been attacked with smallpox.
Since that period one case only has occurred, and that in an unrevacci-
nated gardener. Thus, during a period of sixty years but one case of
smallpox has occurred among hundreds of persons who were in the
closest contact with the disease. Dr. Marson took the precaution of
revaccinating all persons before permitting them to go on duty. Dr.
Collie,^ whose experience is also large, says: "During the epidemic of
1871, out of 110 smallpox attendants at Homerton, all but 2 were
revaccinated, and these 2 took smallpox."
At a meeting of the German Vaccination Commission (1884) Dr.
Eulenburg related "that a manufacturer in Posen had all his workmen
vaccinated except one, who refused. This man alone of the 150 took
smallpox shortly afterward and died."
In 1885 a committee of the Epidemiological Society of London reported
that out of 1500 attendants in smallpox hospitals, 43 took smallpox
and not 1 of the Jj.3 had been revaccinated.^
"The experience of the epidemic of 1876-77 was of the same kind,
all revaccinated attendants having escaped, while the only one who had
not been vaccinated took the disease and died of it."*
In the epidemic of 1881 in London, of 90 nurses and other attend-
ants of the Atlas Smallpox Hospital Ship, the only person who con-
tracted smallpox was a housemaid who had not been revaccinated.^
Dr. T. F. Ricketts,*' the medical superintendent of the Smallpox
Hospital Ships on the Thames, shows that out of 1201 persons in attend-
ance on board the smallpox ships since 1884, only 6 contracted the
disease, and all recovered. None of these persons had been successfully
revaccinated before going on duty.
At the Southampton Fever Hospital all persons employed during the
smallpox epidemic of 1893 were revaccinated before going on duty, and,
although freely exposed to the disease, not a single individual con-
tracted smallpox.^
According to Dr. Hill, of Birmingham, during the epidemic in 1893
over 100 persons were employed at the City Smallpox Hospital, all of
1 E. J. Edwardes, The Practitioner, May, 1896. 2 Ibid., loc. cit.
3 Transactions of the Epidemiological Society, vol. v., new series.
* Dr. Collie, Quain's Dictionary of Medicine.
6 Mentioned by Ernest Hart. Allbutt's System of Medicine.
6 Report of the Metropolitan Asylums Board for 1892. ' Hart, loc. cit.
IMMUNITY OF Vy\(!(; I NAT HI) l>ll YSKHA NS A N I) Nl'llSHS ];>]
jiot rcspoiidiiifi; to vacciiiiitioii after two or three earefiil trials. Of the
entii'e niirnher of students one contra(;te(I srnalljjox, anrl it was suhse-
qiiently foniul that he had never })cen suecessfiilly vaccinated.
Since the present ej)idemi(; he^an, al)Out 200 })ersons, inchjdin^
})hysieians, run-ses, ward niaids, cooks, hiundresses, and the like, liave
been employed in the smallpox department, and not one has contracted
the disease.
These facts are not wondered at by those who are familiar witli
smallpox; they are anticipated. P^vidence of this same nature has
accumulated for nearly a half-century. P>very ej)idemic adds fresh data.
The innn unity of revaccinated nurses and physicians against smallpox
constitutes testimony in favor of the efficacy of vaccination which is
irrefutable.
Further Direct Evidence of the Efficacy of Vaccination.. Much
convincing evidence of the protection afforded by vaccinati(jn against
smallpox never appears in morbidity or mortality statistics. Every
physician who is familiar with smallpox can cite numerous instances of
such protection. Jenner and other early vaccinators established direct
proof of the virtue of vaccination by showing that smallpox could not
be given to an individual recently successfully vaccinated.
Dr. Jenner in 1801 wrote: "Upward of 6000 persons have now been
inoculated with the virus of cowpox, and the far greater part of them
have since been inoculated with that of smallpox, and exposed to its
infection in every rational way that could be devised, without effect."
And Dr. Woodville, in 1802, stated that within two years there were
vaccinated at the Smallpox Hospital 7500 persons, of whom about one-
half were subsequently inoculated with smallpox matter, and in none
of them did smallpox produce any effect.
Smallpox is one of the most highly contagious of all diseases, and
nearly every human being is susceptible to it; we could cite scores of
instances of protection granted to persons by vaccination after admission
to the Municipal Hospital. A few examples which occurred during the
recent epidemic (1901-04) and of wdiich we have notes will suffice.
A child of one year, who had been successfully vaccinated about ten
days before admission, was sent to the hospital with roseola vaccinosa
which had been diagnosed as variola. The child remained in the
smallpox wards about three wrecks and continued perfectly well. Another
child, of nine years, with exactly the same history, returned home
perfectly well after a constant exposure of over three weeks. An un-
vaccinated colored child, about tw^o years old, was brought into the
hospital with a sister who was suffering from smallpox. Immediately
after admission vaccination was performed, and although the child was
constantly exposed to the infection for three weeks he did not take the
disease. Several other children and also some adults, who were sent
to the hospital under erroneous diagnosis, were vaccinated for the first
time after admission and were rendered absolutely immime.
In every epidemic of smallpox that has occurred in Philadelphia
within the past thirty years, instances have been observed of whole
132 BELATIONSHIP OF COWPOX OB VACCINIA TO SMALLPOX
families being removed to the hospital because of an outbreak of the
disease in these famihes. In such instances the unvaccinated children
have suffered and often perished, while those who were vaccinated
remained perfectly exempt, although living, eating, and sleeping in the
infected atmosphere for several weeks. But we have yet to see unvac-
cinated children escape the disease under similar conditions of exposwe.
Furthermore, we have more than once seen a vaccinated infant take its
daily supply of nourishment from the breast of its mother who was
suffering from varioloid, and the infant continue as free from smallpox
as if the disease were one hundred miles away and the food derived
from the most wholesome source. This is evidence of the prophylactic
power of vaccination that does not appear in mortality reports nor in
statistical records.
Ravages of Smallpox in Countries where Vaccination is Neglected. —
In most of the European countries and in the United States smallpox
at the present day is a comparatively rare disease, appearing, as it does,
in epidemics at infrequent intervals. Many physicians who have been
in practice for fifteen or more years have never encountered even a
single case of this disease. In well-vaccinated countries the epidemics
are small and of short duration. In countries, however, in which
vaccination is neglected, the epidemics may attain in extent and mor-
tality the terrible numbers that were reached in the days before vacci-
nation. In the Russian Empire, including Asiatic Russia, there were
275,502 deaths from smallpox in the five years from 1893 to 1898. In
Spain, with a population of only.ten and a half million people, there were
23,881 deaths from smallpox during this period. Hungary had 12,241
deaths, and Italy and Austria each over 11,000 deaths. In Germany,
where there is compulsory vaccination and revaccination the smallpox
deaths during the same five years numbered only 287.
Dr. Jeanselme^ is authority for the statement that smallpox is still
a murderous disease in Indo-China and other parts of the East. He
estimates that a quarter of the infantile population succumbs to this
disease. During times of epidemic recrudescence the death rate is
higher still. In 1900 Dr. Jeanselme saw the population of the village
of Loos almost completely swept away by smallpox, a few old people,
protected by a previous attack, being the only survivors.
Children under the age of five years furnish the greatest number of
victims. The Annamites and Cambodgians regard variola as a necessary
evil, and children who have not gone through it practically do not count
as members of the family. Vaccination is greatly neglected, but inocula-
tion is practised. The blind in Indo-China are numerous, the loss of
vision in large part being due to smallpox.^
The above conditions might readily prevail in all countries if the
opponents of vaccination were successful with their propaganda.
1 Quoted in the British Medical Journal, August 16, 1902. 2 it,id.
UNANIMITY OF OI'INION AS TO VAI.UK OF VAfKJ/NATfON ];>/.>,
UNANIMITY OF OPINION AS TO THE VALUE OF VACCINATION.
There lius j)rol)ul)ly never heeii in tlie history oF iiiiiiikiiid a ^reat
discovery the acceptance of which some men (\'u\ not (Hspute. The
fijreat truth which -lenner j^ave to the world offers no cxcei^tion to this
general statenuMit. There urc (hssenters wlio do not hcheve in vacci-
nation, but tliey are chiefly to he found outside of the inctheal |)rofession.
We know of no eminent physician wito is not conoinced of the efficacy of
vaccination; those physicians who have had a large practical experience
with smallpox are the most ardent advocates of vaccination, for they
have had the best op])()rtunity of notiuji; the behavior (;f vaccinated
individuals in the presence of smallpox. The few physicians who are
found in the ranks of the antivaccinationists are usually men without
practical experience in smallpox; they argue with statistics (often wit-
tingly or unwittingly distorted) and not with facts derived from j)er-
sonal observation.
As a prophylactic remedy against smallpox vaccination was generally
accepted by the medical profession at an early date.
In 1856 the Medical Officer of the London Board of Health, John
Simon, sent circular letters to 542 prominent members of the medical
profession in the United Kingdom and in some of the other European
countries, requesting their opinions as to the value of vaccination.
Five hundred and thirty-nine replies were received and there w^as
absolute unanimity as to the efficacy of vaccination as a protective
measure against smallpox.
The most distinguished medical bodies in every country have time and
time again affirmed their confidence in the protective influence of
vaccination, and the most enlightened nations of the earth have officially
recognized its value and have encouraged its practice.
Thomas Jeflferson's appreciation of the value of Jenner's discovery
may be judged from the following letter addressed to the discoverer
of vaccination:
MoNTiCELLO, Virginia, May 14, 1806.
Sir : I have received a copy of the evidence at large, respecting the discovery of the vaccine
inoculation, which you have been pleased to send me, and for which I return you many thanks.
Having been among the early converts of this part of the globe to Its efficacy I took an early part
in recommending it to my countrymen, I avail myself of this occasion to render you my portion
of the tribute and gratitude due to you from the whole human family. Medicine has never before
produced any single improvement of such utility. Harvey's discovery of the circulation of the
blood was a beautiful addition to our knowledge of the ancient economy ; but on a review of the
practice of medicine before and since that epoch, I do not see any great amelioration which has
been derived from that discovery. You have erased from the calendar of human afflictions one of its
greatest. Yours is the comfortable reflection that mankind can never forget that you have lived ;
future nations will know by history onli/ that the loathsome smallpox has existed, and by you has been
extirpated. Accept the most fervent wishes for your health and happiness, and assurance of the
greatest respect and consideration.
Th. Jkfpkeson.
Thomas Jefferson's prophecy that "future nations will know by
history only that the loathsome smallpox has existed" fails of fulfilment
only because vaccination and revaccination are not universally adopted.
134 RELATIONSHIP OF COWPOX OB VACCINIA TO SMALLPOX
OPPOSITION TO VACCINATION.
It is a remarkable fact that, despite one hundred years of incontrovert-
ible testimony of the value of vaccination, there should still exist at the
present day an organized antivaccination movement. To be sure the
active opponents of vaccination comprise but a very small percentage
of the people, but their influence is none the less noxious. Curiously
enough the opposition to vaccination is most acute in the very country
whence this great discovery sprang; this fact is a sad commentary upon
the common sense of this portion of the English population. The
opponents of vaccination include a number of persons of prominence
in the literary world ; indeed, a large library of antivaccination literature
has gradually arisen.
No great truth is ever promulgated that does not meet with opposition ;
the truth of the value of vaccination has satisfied the pidgment of Tnedical-
men, but a certain number of individuals outside of the profession
dissent therefrom. These persons have, in various countries, banded
together to antagonize the practice of vaccination and to oppose its
compulsory enforcement.
We prefer to look upon these persons as misguided rather than regard
them in a less charitable light. The evidence in favor of vaccination is
so strong and irrefutable that an unbiased student of the subject can
arrive at but one conclusion. There is no truth more clearly established
than that vaccination and revaccination properly performed protect
against smallpox. And yet some antivaccinationists persist in mis-
interpreting facts and figures with a view of discrediting vaccination;
this is often so patent as to clearly establish the effort as wilful perversion.
Antivaccination propaganda have caused many innocent victims to he
consigned by smallpox to a premature grave.
There is but one rational argument for opposition to vaccination,
namely, that the practice of this measure is not entirely devoid of some
danger. But the danger is so slight in any individual instance that it
is almost a negligible quantity. No human act is completely unattended
with risk. When the rare instances of death following vaccination are
compared with the frightful slaughter of thousands by smallpox before
the days of vaccination, and even at the present day in countries
where vaccination is neglected, the benefits of Jenner's God-given
discovery may be appreciated.
CHAPTER I II.
THE VARIOLOUS DISEASES OF LOWER ANIMALS.
A NUMBER of domesticated animals ap[)ear to l)c siiscc|)til)I<' to pock
diseases which are more or less closely allied to human smallpox. Those
affections are, by reason of difference in behavior, divisible into two
natural grou})S. The diseases comprised in the first <(roup are communi-
cable throufi;li the atmosphere; they are accompanied by a generalized
eruption, and may be regarded as death-dealing pestilences; in this
class are to be included human variola and sheeppox. In the second
group the diseases are only capable of transmission by inoculation
(accidental or intentional); the eruption is usually limited to the sites
of inoculation, and death rarely takes place. In the second group
belong cowpox, horsepox, apepox, and other domestic animal pock
diseases presently to be described.
Jenner was firmly of the belief that many of the common farm animals
were subject to eruptive diseases allied to variola. He says:^ "Our
domestic animals are subject to a variety of eruptive diseases — the
horse, the cow, the sheep, the hog, the dog, and many others. Even
poultry come in for their share. Again, there certainly must be a reason
why the term chicken is annexed to a species of pock which infests the
human skin. In the province of Bengal the poultry are subject to
eruptions like the smallpox, which becomes epidemic and kills them by
the hundreds."
Dr. Baron^ says: "It seems certain that there are, at least, four
animals— namely, the horse, the cow, the sheep and the goat — which are
aft'ected with a disorder communicable to man, and capable of securing
him from what appears to be a malignant form of the same disease.
It is, moreover, proved that other animals may take the vaccine disease
by inoculation, and that matter taken from pustules so produced affords
the genuine cowpox in man. The animals on which these experiments
have been tried are the dog, the goat, the she-ass, and the sheep. The
fact as regards the dog was ascertained by Dr. Jenner."
Indeed, Jenner alleges to have found dogs very susceptible of the
variolse vaccinae; he believed that an attack of this disease rendered
the dog immune against the distemper.
Smallpox of Sheep. — Sheeppox, variola ovina, or clavelee, is an acute
contagious and epizootic disease characterized by SNanptoms closely
simulating the manifestations of variola in the human subject.
Variola ovina is supposed to have arisen in Asia, and, like smallpox,
to have extended thence to the continent of Europe. Various countries
1 Manuscript of Jenner, quoted by Baron. - Life of Jenner, p. 243.
136 THE VARIOLOUS DISEASES OF LOWER ANIMALS
have, from time to time, experienced devastating epidemics which have
greatly interfered with the sheep-growing industry.
The period of incubation of the disease is somewhat variable, but
is ordinarily between nine and twelve days. It is stated that sheep may
now and then- remain unaffected for a period of one or even two months,
although intimately exposed to the contagion of the disease. Some
Continental observers state that the eruption is preceded by two or
three days of fever, but Simonds and other English writers affirm that
in their experience they have never noted any illness prior to the appear-
ance of the eruption.
At this time the infected sheep separates himself from his fellows,
looks weak and dejected, lies down and refuses food, although he will
drink water freely. The breathing is quick and short and the heart
beats accelerated. The conjunctivae are reddened, the lids swollen, and
the tears trickle down the face. A mucous discharge issues from the
nose and tends to block the nostrils. These symptoms begin synchro-
nously with the eruption and continue until vesiculation begins, when
there is commonly an abatement of these manifestations.
The eruption appears as florid-red papules, which are firm and
unyielding to the touch. These are usually observed first on the inner
side of the extremities, and on the cheeks and lips, where the skin is
hairy, but not covered with wool. Nude portions of the body, such as
the prepuce, labia, anus, and inferior surface of the tail may be simul-
taneously attacked. The eruption rapidly spreads over the entire
integument, manifesting itself either in a discrete or confluent form.
In certain species the face is profusely involved, in which case the
disease proves extremely fatal.
The duration of the papular stage may vary between two and six
days, averaging three in the majority of cases; this stage is somewhat
protracted in confluent cases. The reddish papules become gradually
converted into whitish vesicles containing a limpid fluid. Many of the
vesicles are small, and nearly all are unilocular, contrasting in this
respect with the multilocular character of the vesicles in human variola.
The transformation of the papules into vesicles is not uniform, some
undergoing this change a day or two after others, while some papules
may disappear without vesiculating at all. The vesicles are not sur-
rounded by an areola at an early stage, but only after they have fully
matured. In the perfectly formed vesicle of sheeppox a central depres-
sion may be seen, but this is far from being constant.
The duration of the vesicular stage is variable. In the milder cases
the eruption may not progress beyond the stage of vesiculation, and
pustules may therefore be absent. In severe and protracted cases,
however, a purulent fluid is secreted and the vesicles are converted
into pustules. Deep ulcerations may develop when a large quantity
of pus is produced; in confluent cases the inflammation may be so
severe as to lead to patches of gangrene, particularly upon the abdomen
and legs.
The stage of vesiculation or pustulation is followed by crusting of
THE VA R fO /. US T) THE A SES O F L W EAi A NIMA LS ] .'J7
the lesions, constituting tlic process of dcsiccidion. 'I'lic scabs arc of
a l)roiwnisli-ycIlow or l)lackisli color, and vary considerably in voluin(;.
When tluvse fall olf jyil.s nvv seen in the skin, which v;iry in dej>tli accord-
ing to the severity of the disease. Two to four weeks may elafxse before
the complete iiealing of the sores. At the sites of the lesions {permanent
defects remain in the wool of the animal.
In confiuent cases the fever remains high, there is rapid respiration,
moaning, frothy discharge from the n)outh, and at times destructive
lesions of the eyelids and eyeball; a severe diarrhrx-a may hasten the
fatal termination. Jn such cases the slightest ap{)lication of force may
cause the wool to separate from the skin.
Captain J. Carr (quoted l)y Simonds) thus describes this malignant
form: "The pulse becomes increasingly rapid, the mouth dry and hot,
the breath fetid, and the eyelids and even head so much swollen that
the creature can scarcely be recognized. The pustules mav produce
malignant ulcers and render the poor animal lame or blind."
Sacco states that "impregnated ewes are certain to al)ort their lamljs."
The mortality rate is high, varying between 25 and 50 per cent. When
death takes place it is most apt to occur during the first week of the
eruption.
That the disease may be conveyed through the atmosphere is evidenced
by the fact that sheep that have never come in contact with infected
anim.als, but have been kept in neighboring pens, have contracted the
disease.
Youatt states of sheeppox that "if it broke out in a flock, it was almost
sure to be communicated, sooner or later, to all that were within a few
hundred yards of it."
The disease may also be conveyed by inoculation , or ovination, as it
has been termed. Ovination has been extensively employed in order
to mitigate the ravages of natural sheeppox. The disease under such
circumstances commonly develops after four to eight days, and when
performed with special precautions usually produces a milder malady
than when contracted in the usual manner. D'Arboval records the
fact that of 32,317 sheep inoculated, 32,121 took the disease, of which
31,851 recovered and 270 died. The inoculated sheep to the number
of 7697 were subsequently exposed to the infection of sheeppox without
any of them contracting it. Inoculation was not so successful in the
hands of Simonds and of Ceely, who lost in their first experiments
almost 20 per cent, of their sheep. ^
It has been stated that ovination of pregnant ewes will subsequently
protect the newborn. This is denied by D'Arboval, who says that the
lambs born of sheep which had been affected wdth the natural clavelee
(sheeppox), or those which were inoculated during pregnancy, do not
acquire an immunity thereby from the malady.
Some difference of opinion exists as to the prophylactic power of
vaccination against variola ovina. D'Arboval contends that inoculation
' These experiments were conducted on a much smaller scale than those of D'Arboval.
138 THE VARIOLOUS DISEASES OF LOWER ANIMALS
of a large number of sheep with virus from the cow failed to protect
them against sheeppox. Sacco, on the other hand, declares that "he
has fully satisfied himself by repeated experiments of the power of
vaccination to destroy the susceptibility of sheep to contract variola
ovina."
Human Ovination. — Sacco inoculated about 300 children with the
virus of sheeppox and claimed that the ovination protected them against
smallpox. He states: "I subsequently determined to inoculate two
children with ovine lymph on one arm and vaccine on the other; the
vesicles were so similar in appearance that had I not marked the arms
I should not have been able to distinguish the one vesicle from the
other. A few days after the desiccation of the vesicles the children
were inoculated with the virus of human smallpox, but no consequences,
either local or general, resulted therefrom."
The successful inoculation of sheep virus in the human subject is,
however, much more difficult than would appear from the above state-
ment, inasmuch as Simonds, Ceely, and Marson all failed in similar
attempts, although the two latter investigators performed no less than
250 inoculations. D'Arboval also failed in conveying ovine lymph
to the human subject, for he states that he successfully vaccinated a
number of children after ovination had been tried. He also remarks
that efforts to communicate sheeppox by inoculation to horses, oxen,
goats, deer, pigs, dogs, monkeys, rabbits, and various birds were likewise
unsuccessful.
We believe the conclusion may be drawn that while the smallpox of
sheep and that of man resemble each other clinically, and are doubtless
closely related to one another, the two diseases are not identical. It
would appear that sheeppox may at times be inoculated into the human
subject, but there is no reason to believe in the intercommunicability of
human and ovine variola by ordinary infection. No one has ever
observed the smallpox of sheep give rise to smallpox in man, nor has
the reverse route of infection ever been recorded.
Goatpox. — The existence of a primary goatpox is doubted by most
authors, the view being held that this animal, which is zoologically closely
related to the sheep, contracts the disease from the sheeppox. The
goatpox is accompanied by high fever and a generalized eruption.
The disease is extremely rare.
That the goatpox is similar in its nature to cowpox appears probable
from information contained in a letter written by Prof. Heydeck to
Dr. Dunning, and quoted by Baron. The letter reads: "The King
ordered in September that all the children in the Foundling House
should be inoculated with the goatpock, which did its effects."
Variola Equina, Horsepox, Grease or Eaux aux Jambes.— The
various appellations here mentioned have been applied to a pock disease
in the horse which bears a close relationship to vaccinia and variola.
The term grease, Jenner tells us, was employed by farriers to designate
this disease upon the heels of horses. It is regretted by some writers
that Jenner used this term instead of variola equina, for the employment
77//'; VMiioLous i>isI':asi<:s of low/'JH, animals ]'.>/.)
of this name has given rise to some conriision. iyii|jtoi)' in ISOf) pointed
out that the true analogy of eowpox in the liors(; was not tin- f/rea.fe
nor any form of (jrcase, hut a disease regarded ijy the neighhoring
farmers as widely different from it, and caUed by them "serateiiy heel."
Loy in 1801 (listinguish(>(l two forms of grease, the aente and the
ehronie, the former of whieli alone was capable of imparting the disease
to the bovine of human sj)eeies.
llorscpox, unlike the variolous disease in man and in sheep, d(jes
not seem to arise through the action of a volatile contagiurn, but practi-
cally always results from inoculation, either accidental or intended, '^rhe
disease is ushered in with fever, but this in many cases is slight and
often al)sent. The eru})tion exhibits a decided preference for the fetlock
joints of the hind legs, perhaps because these parts are most subjected
to traumatisms. The eruption is in many cases limited to this region,
but a more general eruption may exist either primarily or result second-
arily from autoinoculation. Perhaps the not infrequent presence of
lesions in the nasolabial region may be explained upon the grounds
of autoinoculation. Occasionally, more particularly in certain epizootics,
an extensive eruption may be present, involving the head, belly, and
legs. Such profuse eruptions may be primary or may appear after
the ordinary local symptoms have manifested themselves. The lesions
begin as firm papules, which soon become flattened and are often
umbilicated. By the eighth or ninth day there are seen pea-sized, round,
notably elevated vesicles, which on rupture give exit to a viscid, yellowish
fluid. The surrounding skin is reddened and tumefied. The pocks
may now be transformed into superficial, slowly healing ulcers, or may
be covered with crusts, which fall off from the fifteenth to the twenty-
fifth day.
Jenner briefly refers to grease in the following words: "The skin of
a horse is subject to an eruptive disease of a vesicular character, which
vesicle contains a limpid fluid, showing itself most commonly in the
heels. The legs first become oedematous, and then fissures are observed.
The skin contiguous to these fissures, when actually examined, is seen
studded with small vesicles surrounded by an areola. These vesicles
contain the specific fluid."
It will be seen from the above description that equine and bovine
variola closely resemble each other. The disease in the horse distin-
guishes itself from that in the cow principally by the locality of the
eruption — usually the heels and the nasolabial mucous membrane, the
occasional tendency to generalization of the eruption, and by attacking
the male as well as the female.
The Relation of the Equine Disease to Cowpox.— Great interest
attaches to this subject inasmuch as Jenner regarded grease as the
progenitor of cowpox. Jenner informs us that in dairy counties in
England it was frequently the custom for farm hands to dress the sores
on horses and subsequently, without due attention to cleanliness, to
1 Medical and Physical Journal, November, ISOO, vol. iv.
140 THE VARIOLOUS DISEASES OF LOWER ANIMALS
milk the cows. In this manner infectious matter was carried to the
teats of cows, producing the cowpox. From this source other cows and
many of the dairy hands became infected.
Numerous experiments have proven the correctness of Jenner's
assertion that' cowpox results from inoculation with matter from the
grease. Woodville took exception to this view, basing his contentions
upon the negative experiments of the veterinary professor, Coleman ; the
latter, however, after many unsuccessful results, succeeded in producing
cowpox from the grease. The horsepox has been artificially produced
in the horse and other animals by inoculation. This can be done with
equine lymph directly transferred from horse to horse, with equine
lymph that has been successfully passed through the cow (in other words,
with vaccine virus of equine origin), and finally with pure cow lymph.
In horsepox produced by inoculation, the eruption, almost without
exception, is limited to the site of the introduction of the lymph.
The belief entertained by Jenner, that the grease was the invariable
source of natural cowpox, is not concurred in by most observers. There
are many modern writers who are of the opinion that horsepox is noth-
ing more than a variola or vaccinia accidentally derived from the human
or bovine species. That the latter theory is correct is rendered probable
in view of the fact that both cowpox and human variola may be trans-
planted to the horse with the production of horsepox.
Chauveau injected vaccine lymph beneath the skin and into the
bloodvessels and lymphatics of colts, and produced ageneralized eruption
of horsepox.
Copeman remarks that in all probability Jenner was mistaken in his
assumption that "grease," in the sense of horsepox, was a necessary
antecedent to cowpox; but at the same time there can be little doubt
that the two diseases are very closely allied, if, indeed, they be not
identical,"
We may assume that the two diseases have a common ancestry,
without unavailingly attempting to adduce proof as to the priority of
either. There is equal reason to believe that the hands of the groom
may carry the infection from the cow to the horse as well as from the
horse to the cow.
Human Equination. — Horsepox has been successfully inoculated into
the human subject, with the production of vesicles similar to those
observed in cowpox, and with the effect of conferring immunity against
smallpox.
J. G. Loy^ succeeded in transferring lymph from cases of equine
variola to the teats of cows, producing in them typical cowpox. From
the vesicles thus formed he inoculated children and secured beautiful
vaccine lesions. He furthermore inoculated horsepox directly into the
human species. We quote his description of the results : "Some grease
matter, obtained from the same horse, was inserted in the arm of a
child. On the third day a small degree of inflammation surrounded
1 Experiments on the Origin of the Cowpox, England, 1801, pamphlet of 29 pages.
Till: VA/i/(}fJ)IIS DISICASKH OF LOW Ell ANIMALS \\\
tlui wound. On (,li(^ roui'lJi (liiy tin; iiiociiljilcd phicc was iniich elevated,
and a vesicle oi" a purple color was fornied on tlie fil'lli day; on the sixth
and seventh (hiys the vesicle increased and the inflannruition ext<;nded
and became of a deeper color; on the san)e day a, chilliness came on,
attended w^ith nausea and some vomiting. 'J'hcse w(;re soon succeeded
by increased heat, pains in the head, and a frerjuency of breathirif^;
the feverish symptoms soon abated and disapj)cared entirely on the
ninth day. On the sixth day smallpox virus was inserted into the same
arm in which the matter of grease had been placed, but at a considerable
distance from it. On the fourth and fifth days of the smallpox inocu-
lation some redness appeai-ed al)out the wound, and on the sixth a
small vesicle. '^Fhe inflamniation now decreased and on llic tiinlli day
the vesicle was converted into a scab."
From this child, on the sixth day, before the smallpox firus was
inserted, matter was procured and inoculated int(j five other children.
A vesicle was produced in each case. Ten days after the insertion of
the lymph the children were all inoculated with smallpox virus, but
nothing developed save a little inflammation at the site of the punc-
tures.
The Italian investigator, Sacco, in a letter written to Jenner in ISO'3,
describes similar experiments: "A coachman came to the hospital
for an eruption which he had on his hands. It was immediately recog-
nized that he had contracted horsepox in caring for and dressing horses.
I made nine inoculations (from the sores) on as many children. Three
of these contracted an eruption exactly like that of vaccinia. I made
other inoculations with the material from these children, and it has
already been reproduced in four generations, with the same effect as the
vaccine disease. I inoculated several of these individuals with smallpox,
but without any effect. I also finally obtained, with the virus of grease
inoculated into six other children, two lesions exactly like vaccine
lesions."
Martin, of Boston, observed a case of casual horsepox in 1881, and
obtained typical vaccine vesicles therefrom. He was "called to a man
of about sixty, in bed with considerable headache and febrile reaction.
He presented vesicular sores, two upon the right hand and one upon
the nose, surrounded by areolae, and very painful. These lesions had
existed for about five or six days. The patient was employed as a
groom in a horse-car stable in which were a large number of horses
suflfering from sore heels, and his duties obliged him to constantly
handle these heels. The lesions in the groom closely resembled vaccine
vesicles, and the exuding lymph was therefore collected upon ivory
points and inoculated into several children and a number of heifers.
In every case a typical vaccinal result was obtained. This '"stock'
was continued through cows for some time." It is interesting to note
that Martin discovered casual cowpox at Cohasset during the same
month.
A number of other competent observers have confirmed the above
experiments; so that it may be accepted that human beings can be
142 THE VARIOLOUS DISEASES OF LOWER ANIMALS
equinated with virus taken from the horse, and that such inoculations
protect against smallpox.
Retro-equination has been successfully essayed in horses with bovine
or human virus of equine origin.
Natural Vaccinia, or Cowpox in the Cow. — Cowpox of spontaneous
development is occasionally discovered in members of the bovine species.
The disease in such cases is designated natural cowpox in contradis-
tinction to the affection inoculated by design. Natural cowpox is an
uncommon disease; indeed, it is so rare that to each case attaches an
historical interest. From each cow with spontaneous cowpox a special
strain of lymph is cultivated and perpetuated, so that these first sources
are most highly prized. The disease is most apt to be observed in spring
and early summer, when cattle yield the most milk; while any member
of the bovine family (even the bull) may be attacked, it is particularly
the milch cow in which the disease is found. The eruption is never
generalized, but is circumscribed to the udders or their base. The
location of the lesions constitutes strong evidence that the hands of the
milker are the most important factor in the transmission of the disease.
When the disease once appears in the herd, it spreads with considerable
rapidity from one cow to another.
The disease is described by the older writers as beginning with the
formation of vesicles, although these are doubtless preceded by a brief
stage of papulation. The vesicles are of a bluish color and situated
upon a reddened and swollen base. If rupture takes place the vesicle
is converted into a superficial ulcer with irregular edges, which may
heal with great slowness. Desiccation begins about the twelfth day.
During the suppurative stage there is usually some elevation of temper-
ature, loss of appetite, and a lessening of the milk secretion. Natural
cowpox frequently exhibits a succession of lesions, coming out in crops,
in this respect differing from the inoculated disease. After the termi-
nation of the disease depressed scars are left which may often be dis-
tinguished for years.
Cowpox, both the natural and inoculated form, confers a permanent
immunity against a second attack. No authentic case has been reported
in which a cow has twice suffered from the disease.
Casual or Accidental Cowpox in Man. — It was from observation of
cases of casual cowpox in dairy attendants that Jenner first conceived
the theory of vaccination. These infections result from the contact of
fluid from the lesions on the cow's teats with abrasions upon the hands
of the milkers; one, two, or more lesions are produced, according to the
number of excoriations present. Upon areas of reddened skin there
soon spring up vesicles or blebs, which are of a bluish color, rounded,
flat, and depressed in the centre. These contain a lymph fluid which
later becomes purulent. The surrounding skin becomes reddened and
tumefied, owing to the development of an erysipelatoid areola about
each lesion. The neighboring lymphatic glands become swollen and
painful, and the patient becomes feverish. In severe cases the illness
may be sufficiently pronounced to enforce confinement to bed for a few
77//'; VA/UOLOirS DlSh'ASh'S OF IJ)\V/'JI{, y\NIMALS |.J;>
(lays. In a f(!W days, however, ilien; is an ahalcnieiil, of llie loe;il infhiin-
inatory distiirhanee, and of tlie eonsliint.ional syniplonis, and (lie |>iJS-
tules cither become encrusted or form ulcers which j^radually heal \)y
granulation. In casual cowpox the local and constitutional symptoms
are more severe than when the disease is intentionally inoculated,
probably because in the latter case special precaulions are observed.
Apepox. — ^^rhe monkey aj)])ears to be susceptible both to smallpox
and vaccinia. Zuelzer claims that he produced true variola in monkeys
by inoculation with the blood and crusts of human variola. Cope-
man has also succeeded in inoculating monkeys with the fluid from
lesions of human smallpox. More recently successful inoculations
have been carried out by Magrath and Brinckerhoff."^ Usually the
resulting eruption is limited to the sites of inoculation, but occasionally
a generalized outbreak occurs which may cover the entire surface of
the body. Inoculated smallpox in the monkey is, however, seldom
fatal. The monkey may be rendered insusceptible to smallpox by
previous vaccination.
It is claimed that in the tropics apes sometimes die in large numbers
of natural smallpox.
Anderson, of Glasgow, states that while smallpox was raging with
great violence at St. Jago, on the west coast of New Grenada, monkeys
were attacked with the disease in the forests near David, sixty or seventy
miles away. Dying and dead monkeys were seen on the ground covered
with perfect pustules of smallpox, and several ill monkeys w'ere seen
on the trees, moving about in a sickly manner. In the course of a fort-
night one-half of the inhabitants of the town of David were stricken
with smallpox.^
Smallpox in the Camel. — In the province of Lus, in Beloochistan,
the camels are said to be subject to a disease called "Photoshootur,"
or the smallpox of camels. This disease is said to be communicable
to the camel milkers, and is alleged to protect them against smallpox.^
.' Journal of Medical Resonrcli, February, 1904.
2 Quoted by William Aitlceu, Practice of Medicine, ISGS, p. 258.
^ Quoted by Son ton, Indian Journal of Medical Sciences, October, 1839.
CHAPTER IV.
SMALLPOX.
Synonyms. — Latin, Variola; French, La Petite Verole; German,
Blattern, or Pocken; Italian, Vajuola.
Definition. — Smallpox is an acute infectious disease characterized by
an initial fever of about three days' duration, succeeded by an eruption
passing through the stages of papule, vesicle, and pustule, ending in
incrustation and leaving pits or scars, the fever either intermitting or
remitting in the papular stage and increasing in the pustular stage.
Derivation of Name. — Some difference of opinion exists as to the
derivation of the term variola. It is alleged by some that it was coined
by the monks during the Middle Ages, and that it is the diminutive form
of the Latin word Varus (a papule, pimple, or tubercle), a word found
in Pliny. Other writers, however, believe it to be derived from the
word varius, which means spotted or variegated.
The Saxon equivalent pocca, meaning a bag or pouch, has given rise
to the English pock and the German Pocken. Syphilis appeared in Europe
about 1498 and caused some confusion of nomenclature, so that it
became necessary to prefix the adjective small to the term pock, or pox,
in order to distinguish it from the great pox, or syphilis. The same
change was made in French phraseology; so that at the present day,
variola is designated smallpox, or la petite verole, and syphilis the pox,
or la verole.
History. — It is claimed by some writers that the antiquity of smallpox
dates back to the time of the Tsche-u dynasty in China, at a period not
less remote than a thousand years before the Christian era. It is stated
that temples were erected in honor of the disease, and the goddess of
smallpox was thus glorified. Inoculation, or "sowing the smallpox,"
it would appear was practised in China at a very early period, the result
being crudely attained by thrusting crusts into the nostrils.
Tradition has it also that smallpox existed among the Brahmin caste
of India from time immemorial. Descriptions in some of the ancient
sacred writings of spotted and pustular skin diseases are alleged to
relate to smallpox. Like the Chinese, the inhabitants of Hindoostan
are also said to have worshipped at smallpox shrines and to have offered
sacrifices to the presiding goddess to grant them protection.
That the Greek physicians were acquainted with smallpox is open
to most serious doubt. Some authors have labored diligently to prove
that the great vesicular and pustular eruptions and ''anthrakes" which
Hippocrates (460-377 B.C.) speaks of relate to smallpox. While the
descriptions are somewhat suggestive of this disease, they are far from
constituting satisfactory evidence.
SMyiLLPOX IJo
The first writings of tlu; Roman period ])c,Sirin^ upon I he siilijccl. ;irf;
those of the Jewish y)liilo,sof)her of Alexanfh'ia, IMiilo, wlio lived in the
first c(Mitnry. II !s (l('S('ri|)tion of the Egyptian phij^ue' might witli
greater reason he a,ssnm(>(l to refer to smallf)ox than the writings of
Ilippoerates: "From the great suffering, natural to the fermentation of
festers so extensive, their bodies were tortured and their minds fiJIerl
with horror. The lesions tin-own out soon merged into extensive })listers
filled with pus, as if the ])arts had been burned. It extended over the
whole body from head to foot." This deseription is, as Ilaeser contends,
strongly suggestive of confluent smallpox.
Haeser^ concludes, from a study of the Greek and Roman writings,
"that knowledge of smallpox among the ancient Greeks and Romans
probably existed, although we cannot with absolute certainty either
affirm or deny this assertion."
The word " variola" is first mentioned by Bishop Marius,of Ivausanne,
who employed the term (et variola Italiam Galliamque afflixit) in 570 a.d.
in describing a devastating epidemic that swept through Italy and
France. The same epidemic was doubtless referred to by Bishop
Gregory, of Tours, who, in 582, under the name of "lues cum vesicis,"
described a disease characterized at the beginning by high fever, vomit-
ing, and "back pains," followed by the appearance of a painful eruption
of hard, white vesicles, which occurred most conspicuously over the
face, hands, and feet; the vesicles became pustules, and in many cases
death occurred on the twelfth or fourteenth day.
Procopius, in a chapter "De Bello Persico" (hb. ii., cap. 27), described
a dreadful pestilence which began in Pelusium, Egypt, in the year 544.
It was accompanied by buboes and carbuncles (suggesting bubonic
plague), but was widespread, raged independent of season, spared
neither age nor sex, attacked pregnant women severely, and was a new-
disease but little understood by physicians.
A short time afterward, unequivocal traces of smallpox are met with
in countries bordering on the Red Sea; for we read of caliphs and
caliphs' daughters being pitted and having white spots in their eyes.
In 569 A.D. smallpox appears to have broken out in virulent form in
the Abyssinian army of Abraha, which was besieging Mecca. The
soldiers were decimated by the pestilence, necessitating the raising of
the siege.
Reference to a lost treatise on smallpox (seventh century) by an
Alexandrian physician, Aaron, is found in the w^ritings of Rhazes.
Edwardes'^ says: "The first clear description of smallpox by a
physician, which has come down to us, is by Isaac, the Jew% who lived
in the ninth century. A manusci'ipt latin translation of his work is in
the town library of Mainz (Isaaci Israeliti. . . . opera omnia)."
The most scientific and comprehensive description of smallpox handed
down from these times, however, is from the pen of Rhazes, who wrote
1 Vita Moses, I, C. 22, Ed. Tauchnitz (Bonn, 1S38), tome iii. p. 151.
- Geschiclite der Epidemisehen Krankheiten, Jena, 1S65, p. 27.
3 Smallpox and Vaccination in Europe, 1902.
10
146 SMALLPOX
in about 910. The Bagdad physician was a prohfic writer and a close
observer, and has been called "the Arabian Galen." The following
quotations are of interest:
"As soon as the symptoms of smallpox appear we must take especial
care of the eyes, and then of the throat, and afterward of the nose,
ears, and joints If a severe pain arises in the soles of the
feet, then take care to anoint them with tepid oil, and foment them
with hot water and cotton, .... for these and the like things
soften and relax the skin, and thus facilitate the eruption of the pustules
and lessen the pain."
"All those pustules that are very large should be pricked, and the
fluid that drops from them be soaked up with a soft, clean rag in which
there is nothing that may hurt or excoriate the skin."
"When the desiccation of the pustules is effected, and scabs and dry
eschars still remain upon the body, examine them well, and upon those
that are thin and perfectly dry, and under which there is no moisture,
drop warm oil of sesamum every now and then, until they are softened
and fall off."
. and in order to efface the pock holes, and render them
even with the surface of the body, let the patient endeavor to grow fat
and fleshy, and use the bath frequently and have the body well rubbed."
The above therapeutic suggestions might be incorporated in a modern
treatise on smallpox with but little revision. Rhazes credits Galen with
a knowledge of the disease, and also quotes from Hippocrates, Aaron,
and Masawaih. The last-named writer is cited as saying : ". . . Your
first care should be directed to the eye, for which you should use a
coUyrium made of sumach and rose-water, in order to prevent any
pustules from coming out in it."
Avicenna (980-1037), an Arabian physician, was the first to dis-
tinguish smallpox from measles. In the Canon Medicince he states
of measles "that in it more tears flow." He also conceded the possibility
of second attacks of smallpox.
Franciscus de Pedemontium (1330) referred to red coverings and
warm air as tending to expel the pustules to the surface, for, "according
to Avicenna the sight of red bodies moves the blood."
Constantinus Africanus (1075 a.d.), a Carthaginian, who lectured at
Salerno, the first European medical school, closely followed, as did his
contemporaries, the Arabian doctrines. He restricted the term variola,
which was at that time loosely employed, to smaflpox.
A tenth century Anglo-Saxon manuscript, in the Harleian collection in
the British Museum, contains an exorcism and prayer in which the follow-
ing words appear: ". . . , Geskyldath me vid de lathan Poccas, "
which, rendered into modern English, reads: "Shield me against the
hideous pocks."
A Cottonian manuscript, evidently written in the eleventh century,
contains a prayer to Saint Nicaise, who had the smallpox, and whose
name was to be worn in an amulet to grant protection.
The term pocca, which was the Anglo-Saxon equivalent of variola,
SMALfJ'OX 147
is first encountered in a tenth-century leech-book of f he physician Bald.
The death of Baldwin (1)01), son of the Earl of Flanders, from "variolas
Sive poccas" is set forth in tlu; Jiniitiidii (Hirdniclc.
Smallpox is sup|)osed to have invaded England between the tenth and
thirteenth centuries, llolinshed, describing an e[;ideniic in the reign
of Edward III., writes: "Also many died of small jjoklce.s, both men,
women, and children." According to Ilirsch, Iceland suflVnerl frcHn
smallpox in L30f), having received the infection from Denmark.
John of Gaddesden, physician of Edward II. and author of Ro.ia
Anglica, followed the Arabian treatment of surrounding the patif-nt
with red bed-clothing, hangings, etc. He acquired a great reputation,
but, according to Watson, was a "very sad knave."
During the epidemic of 1694, Queen Mary, the wife of William III.,
died at the age of thirty-three of hemorrhagic smallpox. I>ord Macaulay,
writing of the ravages of this disease, says:
"That disease, over which science has achieved a succession of
glorious and beneficent victories, was then the most terrible of all
ministers of death. The havoc of the plague had been far more rapid ;
but the plague had visited our shores only once or twice within living
memory; and the smallpox was always present, filling the church-yards
with corpses, tormenting with constant fears all whom it had not yet
stricken, leaving on those whose lives it spared the hideous traces of
its power, turning the babe into a changeling at which the mother
shuddered, and making the eyes and cheeks of a betrothed maiden
objects of horror to the lover."
Smallpox was treated in diverse and various manners in different
periods. In 1640 the hot or sweating treatment, by which the peccant
humors were to be expelled, was in vogue. Diemerbroeck, a Dutch
physician and professor, was an advocate of this method. Gregory
remarks that when Sydenham began his medical reform, in 1667, "he
had an Augean stable to cleanse." The "Enghsh Hippocrates," how-
ever, was equal to the task, and succeeded in completely changing the
practice with regard to smallpox. He insisted upon fresh air, and sub-
stituted the cooling for the sweating treatment. He also described the
disease admirably, and was the first to trenchantly distinguish between
measles and smallpox. Boerbaave (1668-1738) was a warm admirer of
Sydenham. He deserves the credit of having maintained that smallpox
was contagious and due to a specific miasm.
Smallpox in America. — It is said that smallpox reached Mexico in
1518, having been brought by a negro slave who accompanied the
troops of Cortez from Cuba. According to Toribio it swept the country,
destroying the lives of three and a half millions of people. De la Con-
damine states that whole tribes of Indians were exterminated, and in
some places no one was left to bury the dead. The disease then reap-
peared at regular intervals of seventeen or eighteen years. In 1633 the
Indians of Massachusetts were attacked by smallpox and slain by the
thousands. The disease first appeared in Boston in 1649.
Referring to the importation of smallpox into America, Gregory
148 SMALLPOX
humorously remarks: "If America gave us, as people confidently say it
did, the great pox, we have more than returned the compliment by
introducing to her acquaintance the smallpox."
In 1707 smallpox reached Iceland, destroying the lives of 16,000
people, almost one-third of the population of the island.
Period of Inoculation. — Inoculation was first practised in Constan-
tinople about the year 1674. Dr. Timoni (1714), Dr. Kennedy (1715),
and Dr. Pylarini (1716) wrote on the subject of inoculation, but the pro-
fession in England ignored the publications. It remained for the
charming and accomplished Lady Mary Wortley Montague, wife of the
British Ambassador to Turkey, to introduce inoculation to the Euro-
pean world. The now famous letter to her friend. Miss Sarah Chis-
well, written in 1717, is here appended:
". . . Apropos of distempers, I am going to tell you a thing that will make you wish yourself
here. The smallpox, so fatal and so general amongst us, is here entirely harmless by the invention
of engrafting, which is the term they give it. There is a set of old women who make it their business
to perform the operation, every autumn in the month of September, when the great heat is abated.
People send to each other to know if any of their family has a mind to have the smallpox : they
make parties for this purpose, and when they are met (commonly fifteen or sixteen together) the old
woman comes in with a nutshell of the best sort of smallpox, and asks what vein you please to have
opened. She immediately rips open that you offer to her with a large needle (which gives no more
pain than a common scratch), and puts into the vein as much matter as can lie upon the head of
her needle, and after that binds up the little wound with a hollow bit of shell, and in this manner
opens four or five veins. . . . The children or young patients play together all the rest of the
day and are in perfect health to the eighth. Then the fever begins to seize them, and they keep
their beds two days, very seldom three. They have very rarely above twenty or thirty on their faces
(sic), which never mark, and in eight days' time they are as well as before their illness. Where they
are wounded there remain running sores during the distemper, which I do not doubt is a great relief
to it. Every year thousands undergo this operation, and the French Ambassador says, pleasantly,
that they take the smallpox here by way of diversion, as they take the waters in other countries.
There is no example of anyone that has died of it, and you may believe that I am well satisfied of
the safety of this experiment, since I intend to try it on my dear little son. I am patriot enough
to take pains to bring this useful invention into fashion in England, and I should not fail to write
to some of our doctors very particularly about it, if I knew any one of them that I thought had virtue
enough to destroy such a considerable branch of their revenue for the good of mankind. But that
distemper is too beneficial to them, not to expose to all their resentment the hardy wight that
should undertake to put an end to it. Perhaps if I live to return, I may, however, have courage to
war upon them. Upon this occasion admire the heroism in the heart of
"Your friend," etc.
The daughter of Lady Montague was the first person ever inoculated
in England (1727), although her son had previously been inoculated in
Constantinople. In the following year, after six condemned criminals had
been successfully inoculated, the two daughters of the Princess of
Wales submitted to the new process.
During the first ten years of its career inoculation met with great
opposition. Later it became more firmly established, and was exten-
sively practised in England up to 1800. It never, however, became
popular on the Continent. The average death rate from inoculation
was about one in three hundred cases, although it often rose above this.
In 1798 Jenner announced his discovery of vaccination. In 1808 the
inoculation of out-door patients was discontinued at the London Small-
pox Hospital, and fourteen years later inoculation of in-door patients
was abandoned. In 1843 Gregory wrote: "In 1840 the practice of
inoculation, the introduction of which has conferred immortality on
smaIjIjPox 140
the name of Lady Montague, which had been sanctiouc*! hy the College
of Physicians, which had saved the lives of many kings, (queens, and
princes, and of thousands of their subjects during the greater part of
the preceding century, was declared illegal by the Knglish J'arliarnent,
and all offenders were sent to j)rison with a gf)od flianre of the tread-
mill. . . . Such are the reverses of fortune tf) vvhicli all siibhjriyry
things are doomed."
Inoculation was first practised in America in 1721 . It was introduced
into this country, at the suggestion of the Rev. Cotton Mather, by Dr.
Zabdiel Boylston, of Boston, who first inoculatecl his only son anrl then
two negro servants. Before the practice was generally aecept(;d, how-
ever, it was necessary to overcome here, as in England, niueli \io!ent
opposition.
The principal advantage claimed for inoculation was that smallpox
thus produced was much milder in type than when the infection was
received in the natural way; while the death rate from smallpox was
one out of every three or four persons attacked, it was, at the highest
from tlie inoculated disease, not greater than one out of fifty, and some-
times as low as one out of three hundred, the average death rate being
somewhere between the two. Not only the number of deaths, but the
marred visages of persons in every community, testified to the frequency
of smallpox before the days of inoculation. Indeed, it was so preva-
lent in the Middle Ages as to lead to the common saying that "from
smallpox and love but few remain free." The disadvantage of inocu-
lation was that smallpox produced in this manner, although milder in
type, was just as contagious as when contracted naturally; hence inocu-
lation had the effect of keeping the disease almost constantly in existence.
Prevalence of Smallpox in the Prevaccination Days. — Smallpox was so
universal a disease that Ben Jonson wrote of it:
"Envious and foul disease, could there not be
One beauty in an age and free from thee?"
Smallpox was mainly a disease of children in former times, and
the adult population consisted for the most part of the survivors from
an attack in childhood, therefore permanently pi'otected. The disease
was regarded as universal or almost universal.
According to Dr. Lettsom, most children in London had smallpox
before the seventh year.
Juncker estimated that 400,000 smallpox deaths occurred yearly in
Europe on an average, and that five-sixths of mankind were attacked.
Many writers were of the opinion that every one was attacked sooner or
later. King Frederick William III. of Prussia, in a dispatch dated
October 31, 1803, states that smallpox caused on an average 40,000
deaths yearly in Prussia.^
That smallpox did not respect royalty is evidenced by the formidable
list of kings, queens, and princes who died of the disease: William II
of Orange, Emperor Joseph I. of Austria, Louis XV. of France, two
1 The above statements are quoted from Edwardes' Smallpox and Vaccination in Europe, 1902.
150 SMALLPOX
children of Charles I. of England, a son of James II. of England, his
daughter Queen Mary, and her uncle, the Duke of Gloucester; the son
of Louis XIV.; Louis, Duke of Burgundy; the dauphin, his wife, and
their son, the Due de Bretagne; Peter 11. , Emperor of Russia; Henry,
Prince of Prussia; the last Elector of Bavaria, two German empresses,
six Austrian archdukes and archduchesses, an Elector of Saxony,
and the Queen of Sweden (174L) The following were attacked with
the disease, but recovered: Queen Anne of England, Peter HI. of
Russia, Louis XIV. of France, William of Orange (afterward Will-
iam III.), and Queen Maria Theresa of Austria. George Washington
was "strongly attacked by the smallpox" during his early manhood,
while on a visit to the West Indies.
THE ETIOLOGY OF SMALLPOX.
That smallpox may prevail in the frigid climes of Greenland and in
the torrid regions of Africa is evidence of the fact that conditions of soil
or climate exert but little influence over the disease. Practically no
civilized country on the globe has been exempt from the ravages of
smallpox. It follows, like other transmissible diseases, the channels
of trade and human intercourse. W^hen the contagium of the disease
is brought to an unprotected community, there the malady takes root
and spreads.
Susceptibility to smallpox is almost universal; but few persons can
boast of natural immunity from this disease. Yet this individual pecu-
liarity is occasionally encountered, as may be seen by reference to the his-
tory of the disease during the prevaccination period. Persons have been
known to go through life constantly exposed to the infection without
suffering from any manifestation of smallpox. It is said that Morgagni,
Boerhaave, and Diemerbroeck enjoyed this privilege. It is not impos-
sible that such immunity may have resulted from a mild attack of
smallpox, from which such persons may have suffered in utero, even
without their mothers having presented any manifestations of the
disease.
Instances are recorded in which persons have resisted the infection
when exposed in the usual manner, but have yielded to the disease by
inoculation later in life. Gregory gives an example of this kind in the
case of a lady who brought up a large family of children, many of
whom she nursed through smallpox without receiving the infection
herself, but at the age of eighty-three she took the disease by inoculation.
While but few are naturally insusceptible to smallpox, through the
agency of vaccination, individual susceptibility at the present day, is
greatly changed; absolute immunity, indeed, is enjoyed by the greater
part of the population.
Instances are met with, under rare circumstances, of apparently
healthy persons resisting the infection of smallpox at one time and
yielding to it at another. We will relate a case in point: In 1874 a
colored man of thirty years came under our care suffering from con-
THE ETIOLOd Y Oh' SMA LLI'OX 151
fluent variola. He stated that vaccination had \ntvA) \n-YU)vu\i-A at
difi:'erent times during his life, but never successfully: In 1871 he
belonged to the crew of a sailing vessel in v^^hich several cases of smallpox
occurred, and his duties required him to fre(|ii('ntly come in ffjiitact
with those who were ill, yet he did not take the disease. He was vao
cinated at that time, but, as before, without result. When he fell ill with
variola three years later he was unable to account f(;r the source of the
infection. The attack proved fatal.
In the days when inoculation was extensively practised it was noticed
that some persons exhibited a temporary insusceptibility to the infec-
tion. Gregory informs us that Woodville found one out of every sixty
children, and one out of twenty adults, to be temporarily insusceptible
to inoculation. Experience demonstrates that the susceptibility to
smallpox may at one time be diminished and at another greatly increased.
The existence of acute and chronic infectious diseases is said by some
writers to temporarily lessen the susceptibility to the infection of variola.
Curschmann asserts " that for an individual suffering from scarlet fever,
measles, or typhoid fever, there is during the entire duration of the
affection only a very slight susceptibility to an attack of variola." He
observed in the hospital at Mayence (where the smallpox building was
near the general wards) that variolous infections never took place during
the course of the typhoid process. A considerable number of typhoid
convalescents, however, were attacked after their temperatures had
become permanently normal. He was led to this conclusion from the
fact that the interval between the time of the subsidence of the fever
and the beginning of the initial stage of variola corresponded to the
longest period of incubation that is encountered — namely, fourteen to
nineteen days. There is no doubt, however, that the variolous infection
does frequently occur during the existence of an acute disease, only
the incubation period in such cases is often greatly prolonged. Smallpox
has been known to exist with the acute exanthemata, particularly scarlet
fever and measles. We have seen unprotected children, while suffering
from measles in its most acute stage, exposed not longer than two
minutes to the infection of variola, sicken with the disease after the
usual incubation period. We have also observed this sequence of events
to develop in connection with a diphtheria patient. In at least a half-
dozen instances we have noted the coexistence of smallpox and scarlet
fever. Chronic infectious maladies, such as syphilis and tuberculosis,
not infrequently exist in individuals who are attacked by smallpox.
Recurrent Smallpox (Second Attacks). — The susceptibility to small-
pox is removed by vaccination, but frequently reappears to a greater or
less degree in a variable period of time. So also one attack of smallpox
does not invariably protect the individual for the remainder of his life
against a future attack. It is undoubtedly the rule that a person does
not suffer from the disease more than once, but well-authenticated
cases of second attacks are recorded. Indeed, some writers allege that
the predisposition to smallpox in some persons is so strongly marked as
to render them susceptible to the infection more than twice, even as
152 SMALLPOX
often as five or six times. The authenticity of reported cases of this
kind, however, is not to be taken for granted, but accepted with extreme
caution, as there are many sources of error.
As to the frequency of secondary or recurrent smallpox, there is some
difference of opinion on the part of authors. Many of the cases reported
in the olden times were doubtless based upon an error of diagnosis, for
the second attacks appear to have occurred almost exclusively in children.
Some of the more practical writers of the early part of the last century
hesitated very long before believing that it was possible for the disease
to recur. The infrequency of such cases was accurately observed during
the time inoculation was in vogue.
Jenner, who closely studied casual and inoculated smallpox for more
than thirty years, was very positive in his views as to the permanency
of the protection which one attack of the disease conferred, and it was
doubtless his positive convictions on this point that led him to announce
his oversanguine belief in the permanency of the vaccine influence.
Gregory, who enjoyed unusual opportunities for studying variola, was
very incredulous on the subject of recurrence of the disease. Most of
the reported cases which he was called upon to examine he found
incorrectly reported. Echthyma, pustular syphilis, and particularly
varicella, he states were fruitful sources of error. But few patients
claiming to have had smallpox previously came under his care as
physician to the vSmallpox Hospital of London for more than twenty
years, and of these few only a very small fraction could stand the test
of rigid scrutiny. Koch states that in the great epidemic of 1871-72,
among 12,000 cases of smallpox in South Germany, no second attack
occurred.
Marson is responsible for the statement that during the one hundred
and nineteen years since the founding of the London Smallpox Hospital,
there is no record of a patient having been admitted twice, suffering
from smallpox. He reports, however, the following interesting instance
of recurrent smallpox: "An Irishman, the son of a medical officer
of the army, who had been vaccinated in infancy by his father, and
who had a large cicatrix remaining from the vaccination, and who
was attended by his father for smallpox in early life and bore decided
pits of the disease, in 1844, at twenty-three years of age, was admitted
to the Smallpox Hospital with severe confluent smallpox, of which he
died." Marson believes that exposure for a time to a great change of
climate, either hot or cold, seems to predispose the constitution to
receive a second attack of smallpox.
It is said that Grossheim observed a light form of variola in a patient
three months after the first attack, but this peculiar case was the only
instance of recurrence which he noted among 22,641 in the German
Military Hospitals.
In regard to the historic case of Louis XV., Gregory has the following
to say: "The most remarkable case of recurrent smallpox on record
is that of Louis XV., King of France, who died of it in the year 1774,
at the age of sixty-four, after having, as it is alleged, undergone that
77//'; ICTIOLOdY OF SMAfJJ'OX 1 Tjf}
disease casually in 1724, wlicn Ik; w;is foiiitccn years of a^c. 1 liavo
been at soitk; pains to iiiv(\stij)carcd to favor the
spread of smallpox were:
(1) Absence of sunshine; (2) presence of the sun aboNc tlx; horizfju
for less than eighty hours a week — i. e., less than eleven hours j>er day;
(3) temperature of the air below 50° F. ; and (4) humidity above 75°
(the saturation point being taken as 100°).
The Infection of Smallpox.— No one would deny at the present day
that smallpox is due to a specific micro-organism. There is, further-
more, no doubt that the disease is spread by means of this orgam'sm,
which is reproduced in every patient. A small quantity of the fluid
from a pustule inoculated into an unprotected person gives rise to the
disease; this is conclusive proof of the fact that the germ is resident in
the pustules. It is also present in the exhalations from the patient and
in the blood. Ziilzer proved that it is contained in the blood by success-
fully inoculating a monkey with blood taken from a smallpox patient.
It would appear from the experiments of the older waiters that the
physiological secretions and excretions, the saliva, sputum, urine, feces,'
etc., are not in themselves infectious; w^hen, however, they become
contaminated with particles derived from the skin and mucous-membrane
lesions, they doubtless acquire an infectiousness.
The contagium emitted by a patient is most intense in his immediate
vicinity, but it may be transported in an active state for some distance
by the atmosphere. If a susceptible person should enter a poorly
ventilated small apartment containing one or more severe cases of
smallpox, infection would almost certainly occur, while if the apartment
were large and well ventilated and the cases few and mild, the risk of
infection would be diminished; if he should approach equally near the
same patient in the open air, the risk would be still less.
Infectious Period of Smallpox. — Smallpox is undoubtedly infectious
in all stages characterized by symptoms. It is alleged by some that
the disease is even infectious during the period of incubation, but we
think there is very little reason to believe that such is the case. It is
possible, however, that the blood of an individual at this stage might
convey the infection if it w^ere introduced into the system of a susceptible
person.
Schafer, quoted by Cursclimann, reports an interesting case in this'
connection: "In the Charity Hospital of Berlin small pieces of skin
were taken for transplantation upon other individuals from the ampu-
1 Medical Times and Gazette, March 11, 1S71. = Abstract in Lancet, October -l,. 1902.
158 SMALLPOX
tated arm of a person who, before and at the time of the amputation,
did not manifest the shghtest symptoms of general disease. Several
hours after the amputation the patient was attacked with violent fever,
followed two days later by the eruption of smallpox. One of the indi-
viduals upon whom the transplanted skin had been placed was attacked
by variola on the sixth day after the operation. The three others
remained exempt.
The disease is least infectious during the initial stage and most highly
so during the suppurative and early period of the desiccative stages.
The scabs are unquestionably infectious, and as long as these remain
on the skin the patient should be regarded as dangerous to the com-
munity. Apart from the experience of modern observers, evidence of
the infectiousness of the crusts is found in the ancient custom in vogue
among the Chinese of inoculating smallpox by inserting the crusts in
the nose.
Even after death the body retains the power of transmitting the
contagium. This fact has been demonstrated more than once where
public funerals have not been interdicted, and where bodies of persons
who have died of smallpox have by accident found their way into
dissecting rooms. It is said that a corpse may retain the infection in a
condition to transmit the disease for an indefinite period — even for the
almost incredible period of several years. ^
Austin Flint records an interesting case in which the disease was
spread by a cadaver:
"During the winter of 1848-49, a young man, a member of the
Medical Class of the New York University, died suddenly and un-
expectedly in the night under the care of a physician who had not
thought him seriously ill. I was invited to the autopsy, and observed,
when the corpse was uncovered, a few dark-red spots on the surface,
which were supposed to be petechial, the principal symptoms of his
attack having been gastric, with great debility, as we were informed.
The coffin was taken to a New England village for burial, where at the
funeral some of the relatives approached and opened it to see the face
of the deceased before it was inhumed. Of this number eight were
attacked with smallpox, no other person in the neighborhood being
assailed."
The infection of smallpox may be conveyed in the following ways:
1. Through direct exposure to the patient, or to infected secretions
and excretions.
2. Through contact with objects which have been infected by the
patient — for example, sick-room articles.
3. Through infection carried in the clothing or on the person of
healthy individuals.
4. Through air transmission.
5. Through transmission by insects and domestic animals.
Infection through Direct Exposure to the Patient. — The vast majority
of cases of smallpox result from exposure to individuals suffering from
1 Vide Nouveau Dictionary, article Contagion.
77//'; i<:r[()ij<)() v of sma ijj'ox 1 5U
the disease. Smallpox is the most typical exam[>lc oi the fontagious op
catching disease. The briefest possible exposure on the part of a
susceptible person will suffice to fjroduce the disease. Many victims
never discover the source of their infection; this is not sl(r
of surcharging the a,tmos|)here of the sick-room. The older writers
believed that the sphere of contagious influence of small[)ox was ex-
tremely limited.
Haygarth, quoted by Gregory, was of the opin'on that it did nf^t
extend "more than a few feet from the patient's })ody."
Ilirsch says that the small{)()x contagion "can be spread by atmos-
pheric currents within a small range," and that there is "no mathe-
matical expression to be found for the extent of that range; at the
utmost it extends no farther than the immediate surroundings of the sick."
English physicians have within recent years devoted considerable study
to the determination of the striking distance of the disease.
In the epidemic of 1881, Mr. W. H. Power,* after excluding all
possible infection through ordinary intercourse, formulated an hypothesis
of atmospheric convection of the smallpox poison. He assumerl that
smallpox infective material was "particulate," and that certain favorable
conditions could disseminate such particulate matter over an area of a
quarter or half a mile.
The particulate matter, or infectious dust, may be held in suspension
in the water particles in the air, in fog and mist, and may be driven l)y
air currents and deposited at some distance. During periods of still-
ness of the air about the hospital the infection is taken up and then
wafted by the winds. The absence of ozone in the atmosphere is also
said to be favorable to spread of infection. Periods of small move-
ment of air and absence of ozone are said by INIr. Power to have
preceded each of the more notable epidemic extensions in the neigh-
borhood of the Fulham Hospital.
Parkes^says: "The exceptional incidence of smallpox in the immediate
neighborhood of some of the London Smallpox Hospitals can admit
of but one explanation, viz., that when a sufficient number of cases in
the acute stages are collected together in one building on a small area
of ground, the hospital becomes a centre of infection to the surrounding
neighborhood." (See Fig. 20.)
"As regards the number of cases aggregated in a hospital necessary
to enable it to exert an influence on the surrounding neighborhood,
Dr. Power's reports of 1884-85 show that this influence was exerted
when the number of acute cases had been restricted to twenty, while
on one occasion he found the excess of smallpox in the neighborhood
of the Fulham Hospital was quite remarkable at a time when the total
admissions to the hospital had not exceeded nine, only five of these
being cases in an acute stage."
1 Supplement to Local Government Board, lSSO-81, also 1SS4-S5.
- Hygiene and Public Health, London, 1901.
11
162
SMALLPOX
Mr. A. W; Blyth^ remarks. "The usual spread of smallpox is from
person to person, but, from inquiries which have taken place as to the
influence of smallpox hospitals upon a surrounding population, it is
certain that the infection can strike at a distance.
Special area around Fulham Hospital divided into sections of li,%, ^, and 1 mile radii, show-
ing in the different areas the number of houses (out of every 100) invaded by smallpox from May
25, 1884, to September 26, 1885.
Between N. and W. the hospital was greatly isolated from traffic because of few roadways.
Belt of houses between W. and S. comparatively narrow.
Between N. and E. houses few within 34 mile ; beyond they completely encompass the hospital.
The so-called special area was within 500 feet from the hospital centre.
The influence of the Sheffield Hospital in the epidemic of 1887-88
could be distinctly traced for a circle of four thousand feet : the following
percentages of households attacked at successive distances from the
hospital are given in the original reports by Dr. Barry,^ inspector of
the Local Government Board for England:
to 1000 feet 1.75 1
1 " 2000 " 0.50 j
2 " 3000 " 0.14 \
3 " 4000 " 0.05 I
Elsewhere 0.02 J
Percentage of houses attacked
at varying distances from
Sheffield Hospital.
The possibility of smallpox spreading by aerial infection increases
greatly both the hospital difficulty and that of individual isolation."
1 Manual of Public Health.
2 Report of an Epidemic of Smallpox at Sheffield, 1887-88 ; London, 1889.
nil': KTioLodY of smalIjI'ox
163
Evans,' from ohscirvatioii of r;i(lfon!, came
to the .same eoricliisioii ;i,.s l>;irry. I)iiriiioi.sf>n iuu\ tlie rjiifhrcak
of the disease can oc(;asionally he detennined witli a fonsidcrahh;
degree of accuracy, ^riiis is more easily accomph'shed in sj)oradic
cases, where an indivi(hial has l)een exposed bnt once and for a brief
period of time. Where the exj)osure is frccjnent or extends f>ver a long
period it is (hfficult to (h'vine the exact moment when the infection is
received. When the (hsease prevails in epidemic form it is not impos-
sible for an unknown exposure to precede the one of which the indi-
vidual has knowledge; in such cases the com])nted [X'riod of incubation
would appear to be unusually short. Erroneous calculatif)ns f)f tlie
duration of the period of incubation have (ioul)tless arisen from fnihire
to recognize this fact.
In the majority of cases in which we have had the opportunity of
carefully studying the incubation stage, we have found it to 1>P t*^" j^}
twej^g, dia.yS7 xind we would, with other writers, regard this as the normal -
period. In a few instances it is true we have known persons to fall ill
with smallpox after the raising of a two weeks' quarantine of the houses
in which they were confined and in which smallpox had existed. W^e
have also been able in a few cases to reckon with tolerable certainty
a period of incubation of sixteen days, the eruption appearing on the
eighteenth. Some writers have recorded instances in which the incu-_
bation period has been prolonged to twenty days. On the other hand,
we have known a young physician, exposed to smallpox, to develop the
first symptoms at the end of five and a half days, and the eruption at
the termination of ten and one-half days. Ordinarily, however, the .
period is seldozii, less. than eight days or more than fourteen.
The incubation period is ordinarily not characterized by any active
symptoms. Patients usually pursue their daily occupations ignorant
of the fact that there is developing within them a dread disease. There
are, however, frequent exceptions to this rule. It is not rare for patients
to lose their appetite and complain of lassitude, chilliness, headache,
gastric uneasiness, etc. These symptoms, when they occur, are com-
monly noted during the last few days of the incubation period.
They may, however, develop as early as a week before the invasive
chill. Now and then a patient will complain of slight sore throat
during the last days of this stage.
The Stage of Invasion, or Initial Stage. — This stage is frequently
ushered in with suddenness and with considerable violence. The
earliest symptom is most frequently a chill. This may be severe enough
to be accompanied by chattering of the teeth, or it may consist of a
succession of creepy sensations scarcely sufficient to attract the patient's
attention. Synchronously with the chill or immediately following it
the fever appears. The temperature on the first day often rises to
103° or 104° F., and on the second and third day, with perhaps the
exception of slight morning remissions, it rises still higher, frequently
reaching 105°, and in some cases even 107° F. The elevation of
temperature is usually sudden; in but few diseases does it rise so quickly
from the normal to a high degree. Even in varioloid the early sjTiip-
168 SMALLPOX
toms are not infrequently equally severe, although occasionally they
are so mild as to escape attention. But the eruption of unmodified
smallpox seldom if ever appears without being preceded by a well-
marked invasive stage. ,
During the continuance of the fever the skin is hot and sometimes
dry. Profuse sweating, however, is by no means uncommon; this is
apt to come on in the evening.
The pulse, as a rule, is full, tense, and rapid, its frequency generally
corresponding with the temperature curve. In adults it varies between
100 and 130, while in children it not infrequently reaches 160. In some
cases the pulse during the initial stage will be found to be relatively slow
and entirely disproportionate to the height of the fever. We have on a
number of occasions noted a pulse of 90, 80, and even 70, with a tem-
perature of 104° or 105° F. These cases were seen in the hospital on
the first and second day of the eruption ; consequently we are not able
to state whether this pulse rate was present at the onset of the initial
symptoms.
The respirations -are almost always increased in frequency, espe-
cially when the temperature is excessively high. Prostration is often
extreme, being out of all proportion to the length of the illness. Strong
and robust patients are frequently unable to stand without support, and
when in the upright position soon become pale and liable to be attacked
by vertigo or syncope. Thirst is great, the lips and tongue are parched
and dry, and there is complete loss of appetite.
Constipation is a common symptom and is apt to persist throughout
the course of the disease. The tongue is usually coated with a thick,
yellowish covering, and the breath is heavy and offensive. iVccording to
some authors, the odor from the body of a patient at this stage of the
disease is so peculiar and distinctive as to make it possible for the diag-
nosis of smallpox to be made by this symptom alone. We must confess
that our olfactories have not acquired the degree of acuteness to detect
such an odor.
Irritabihty of the stomach is a very frequent manifestation. Occa-
sionally the first symptom noted by the patient is severe and persistent
vomiting. In such cases the disease has on more than one occasion
been regarded as gastritis. The vomiting often continues for two or
three days. It is apt to be accompanied by marked tenderness and
pain in the pit of the stomach. The irritability usually ceases when the
eruption appears. When it continues longer it should be viewed with
some soHcitude. Especially in hemorrhagic smallpox is this symptom,
together with epigastric pain, apt to be distressing and prominent.
Nausea and retching are present in some cases without actual emesis.
_ Headache is the,moat.prominent-amongthe..early nervous symptoms.
It usually follows shortly after the chill, but in a certain proportion of
cases it precedes it, being not infrequently the earliest evidence of ill-
ness. Its intensity varies greatly, corresponding in a measure with the
height of the febrile action. At times it is so excruciating as to cause
even self-restrained individuals to cry aloud. The face is often flushed,
77//'; S YMPTOMA TOIJX! V OF SMA L/J'OX 169
the carotids visibly pulsating. Restlessness and sleeplessness are com-
mon symptoms diirino- this stage. Children, on the contrary, are some-
times drowsy and sl('cj)y. When the temj)erature is high, delirium is
prone to supervene. This usually takes the fonn of talkative incoher-
ence, although some patients become! (|uite violent. Coma is rare in
adults, but not uncommon in children. Convulsions are frequently
seen in children, more so ])erhaps in this disease than in any other of
the exanthemata. They may be severe and repeated, and may contimie
even after the appearance of the eruption.
Pain in the back is a symptom so commonly observed that it is believed
to be of special diagnostic value. It is nol ;is (onstant as some of the
otlier symptoms, yet it occurs in more than one-half of the cases. In
perhaps one-third of the cases it is sufficiently severe to cause the patient
to volunteer information concerning it. Its diagnostic import, therefore,
is due rather to its infrequency in the other acute infectious diseases
than to its constancy in smallpox. The lumbar and sacral regions are
the parts to which the pain is usually referred, although it may extend
to the dorsal region. As a rule, it is more severe in unmodified sma]l})ox
than in varioloid, yet this rule is subject to many exceptions. In hemor-
rh agic cas.e.s th e pain is often of an excruciating violence. Lumllaf pain
is more constantly seen among female than male patients, owing to the
fact that the menstrual function is very liable to be excited by the initial
illness of smallpox. In the vast majority of women who are stricken
with smallpox the menses appear out of their regular period. This is -
true of mild as well as severe cases. The premature onset of the men-
strual flow occurs with more striking frequency in this disease than in
any other of the infectious maladies. Pregnant women are exceedingly
liable to suffer from abortion or premature delivery. The pain in the
back owing to these causes is given greater .prominence in women-
General aches and pains are frequently complained of, appearing at
the same time as the headache and backache. These may occur any-
where, but are usually referred to the lower extremities, particularly
about the knees. Thk-S-oreness of the general muscular system may
Isaxi-to^ confusion of diagnosis with ia griffe. Veriigo, which is
particularly manifest upon the patients assuming the erect position, is
a common early symptom. It is often well marked, even in mild cases,
for these patients are more apt to rise from their beds. Syncopal attacks
may occur in weak individuals.
•"¥r©^iisseau records having seen during the initial stage patients who
suffered from temporary loss of power in the lower extremities, asso-
x^olaiecl in a few instances with retention of urine. When this condition
occurs, it is, in our experience, most likely to be encountered at a later
period of the disease.
There is a considerable deg^ree of variation in the character and
sequence of the symptoms constituting the initial stage of smallpox.
This is shown in the following analysis of ICO cases occurring
in the epidemic of 1901 and 1902: The patients, who were taken
without selection, were closely interrogated as to the nature and chrono-
170 SMALLPOX
logical development of the various symptoms. The number includes
28 cases of confluent smallpox, 15 with very profuse and semiconfluent
eruptions, 29 with eruptions of moderate severity, and 29 cases of mild
varioloid. Of this series of 100 patients, 22 died. Headache was the
most constant of the initial symptoms. The various symptoms men-
tioned were present in the following percentages: Headache, 86 per
cent.; chills or chilKness, 78 per cent.; backache, 70 per cent.; vertigo,
57 per cent. ; vomiting, 55 per cent. ; nausea without emesis, 10 per cent.
In some of these cases the symptoms were of marked severity, while
in others they were extremely mild. An effort was made to determine
the earliest symptom observed by these patients. It is recognized that
some inaccuracy must arise from an attempt to chronologically arrange
the symptoms from histories thus obtained.
Chilliness or a decided, chill was the first symptom in
Headache was the first symptom in . . .
Backache ■< " " " ....
Vomiting " " " "...
General aches and pains were the first symptoms in
Vertigo was the first symptom in .
35 eases.
26 "
16 "
9 "
7 "
2 "
In but 2 patients out of the 100 was Jhei;e. complete absence
^f initial illness; 1 of these was a man, aged twenty-six years, witlfi
a very mild varioloid, and the other a colored woman, aged twenty-
seven years, with an eruption of moderate severity. Upon close inquiry
the latter patient admitted experiencing fatigue upon the day preceding
the eruption. It is possible that some negative histories of this character
may be due to poor memory or lack of intelligence on the part of the
patients.
In the severe cases the initial illness was always well marked, although
the classic symptoms were not invariably present. A man, aged fifty-
five years, who had a fatal confluent attack had merely as prodromes
a severe chill, fever, and prostration; headache, backache, vertigo, and
vomiting were absent. A male patient, aged twenty-nine years, with an
eruption of moderate severity, experienced, during the initial stage,
fever, repeated vomiting, and pain in the stomach, without any other
symptoms. On the other hand, quite a number of patients with very
mild eruptions gave a perfect history of the classic initial syndrome.
A young woman of twenty years, for instance, with only three or four
lesions on the face and a few upon the arms and hands, experienced,
at the onset of the disease, headache, backache, repeated vomiting,
severe chills, vertigo, and aching in the legs.
These observations are in accord with those of most writers, and
seem to illustrate the impossibility of forecasting the extent of the
eruption from the degree of severity of the initial symptoms. We have
frequently seen the most aggravated febrile symptoms followed by a
"perfectly insignificant eruption. Mild initial manifestations are rarely
succeeded by a severe cutaneous outbreak. In general terms it may
be stated that severe initial symptoms may be followed either by a
profuse or a sparse eruption, and that mild initial symptoms are nearly
always followed by a mild eruption.
THE 8 YMPTOMA TO L d V F SMA fJJ'OX 17]
The urine, in the initial staf^e, is usually more or lc.-,s diuiinishcd
aceordin*^ to the (le^rc(^ of tlie fever. 'J'Ik; solid constituents are nf>t out
of their normal proportion, excej)t the chlorides, which are cc>nsiderahly
diminished. In severe cases, especially thos(; about to hecrjuK; hemor-
rhafijic, albuminuria may be present. A high gracJe of fever might be
responsible for a small (juantity of albumin, but if it be present in
great abundance a malignant type of the disease should })e suspected.
Before giving an unfavorable prognosis, however, care should ])t taken
to exclude the possibility of pre-existing (Jisease of the kidneys.
The spleen may be found enlarged in the initial stage of severe small-
pox. In mikl cases no enlargement, as a rule, can be detected.
I'eculiar prodromal rashes often make their appearance during the
initial illness. When they develop it is usually j^ji^ori .the second day of
.Jije invasive fever. They disappear ordinarily in from twenty-four to
forty-eight hours. They may, however, continue several days after the
"appearance of the eruption. The frequency of these rashes appears to
vary in different epidemics. During the widespread and malignant
epidemics of 1871 and 1872 they were very common. Osier noted these
rashes during this period in 13 per cent, of his cases. These eruptions
are not so apt to be observed in smallpox hospitals, inasmuch as they
disappear commonly before the diagnosis is made and the patient
conveyed to the hospital. The most common type is that resemhling
measles, with which disease, indeed, it is liable to be confounded. The
eruption has an irregular distribution, bei-ng at times generalized and
at other times limited to certain regions of the body. It, moreover,
differs from the eruption of measles in that the rash is not elevated
above the level of the skin and therefore scarcely appreciable to the
finger when passed over it. Its ephemeral character is also a differ-
entiating feature. This roseola variolosa, as it has been designated,
has a close analogue in the roseola vaccinosa which occasionally appears
about the ninth to the eleventh day after vaccination.
— JTh fi jcarZajt74^z/orm rash is less common than the measles-Hke eruption.
It may involve a large part of the cutaneous surface, but is more apt
to affect certain areas, as the thighs, inguinal regions, extensor surfaces
of the extremities, and the trunk. Some authors refer to the appearance
of an urticarial eruption in rare cases.
The petechial or hemorrhagic initial rash has a special predilection
for certain regions of the body which were carefully studied by Simon,
of Hamburg. This writer pointed out the frequent occurrence of the
eruption in the lower abdominal, inguinal, and genital regions and inner
aspects of the thighs, constituting a triangle whose base traverses the
neighborhood of the umbilicus (the so-called crural triangle of
Simon). The " axillary triangle," including the inner aspect of the
arm, axilla, and pectoral region is also a commonly affected area. The
petechial rash is also frequently seen along the lateral surface of the
thorax and abdomen. The eruption consists of closely aggregated,
pinpoint to pinhead sized, purplish or clarety spots, which are in such
intimate juxtaposition as to convey the impression of a diffuse redness.
172 SMALLPOX
Being the result of a hemorrhagic extravasation into the skin, the
discoloration does not disappear upon pressure.
Occasionally an erythematopetechial rash is seen, the eruption
partaking of the characters of both the erythematous and hemorrhagic
rashes.
The petechial eruptions may occur in cases which later .prove to be
. quite mild. More often, iioweyer, they arejhe harbingers of severe
smallpox of the-^hemoi'diagic type. The morbijliform eruptions in"mlr~
experience are muchino-re .common -in,,, cases o|]jaHoloM7~aildTE(SF"
" Qccurreuce, therefore,, may ♦be regarded as an auspicous sign. We are
able to recall two cases of smallpox in vaccinated individuals in which
the roseolous eruption was practically the only cutaneous manifestation.
In one of these cases, it is true, about half a dozen small variolous
papules appeared as the initial rash faded away, but they disappeared
in two or three days without becoming in the slightest degree vesicular.
' These cases belong to the class commonly designated variola sine
exantkemate, which is the most benignant form that smallpox may
assume. That such cases are occasionally encountered is evident from
the writings of both ancient and modern authors. Perhaps in every
epidemic patients are seen who give a history of exposure to smallpox
and who, in due course of time, are suddenly seized with chills, followed
by headache, fever, vomiting, prostration, and pain in the back. These
symptoras continue iox three or four days, and.,iheik^;UJ3si4e~jftdth,0Lut.
the development of any eruption except perhaps one of .lhe.4irQ.dromal
^rashes to jvhich reference has been made. It is impossible to explain
such cases on any other supposition than that th^ disease-jy as.. , XMJQ^
without. the eruption. Trousseau refers to cases observed by him in
which the only symptoms characteristic of the disease were a "few
pustules on the pharynx and the pendulous veil of the palate."
It may be of interest to record the histories of two patients under
our observation upon whom but a single variolous lesion appeared:
B. H., aged twenty-six years, suffering from measles, was sent into the
Municipal Hospital under the erroneous diagnosis of smallpox. He
was immediately vaccinated, but this and subsequent attempts failed.
,^_^^,^ At the end of ten days he was seized with high fever (104° F.), headache,
^/^ and vomiting. A few days later^a single papulE ap pearei Lin JJie-rPight
loin. This went onT6""vesTcTe formation, becoming characteristically
iimbilicated, but dried up within a few days. The patient claimed to
have had smallpox at the age of eight years, but showed merely a single
pit upon the- face.
The following case presents a somewhat similar history:
W. G., a colored lad, aged fifteen years, was vaccinated four years
prior to admission; he presents a good vaccination cicatrix. He was
brought into the hospital from a house from which several patients with
smallpox were removed. On admission he had a temperature of 102°
F. and presented other well-marked initial symptoms. On the sub-
sidence of these symptoms he developed a single typical papule on the
trunk. ^--^ "^
77/ /-; S YMI'TO MA TO L CI Y O F SMA 1, 1. 1 'OX ] 7;j
These cases come almost within the flefinition of viiriol.-i wiMioul an
exaiithem. If smallpox may occur with tlic a[)()Ciiruiic<' of hut one
lesion, there is no reason why it should not at times rjevelop witlifjut
any eni|)ti()n whatsoever.
The duration of the initial stage is commonly iorty-ei;i;lil lo seventy-
two hours; it is rarely less, but it may be somewhat prolonged. Trousscair
held that the longer the ernj)tion was delayed in its aj)j)earance, tlu;
more favorable was the prognosis. This is scarcely bf^rne out by exyx-ri-
ence. It is misleading to draw any prognostic conclusions from fli(;
duration of this stage.
It is commonly stated in text-books that u|)on (lie appearance of the
eruption of smnllpox the fever subsides and a general abatement of
the systemic symptoms occurs. In_our_^ejqp£nence a decided rennssion
in the t emperature does- not. take place in unmodified smallpox until
the second, third, or fourth day of the eruption. In very mild cases,
"more particularly in those modified by previous vaccination, the temper-
"atui'e may fall to normal as the exanthem makes its appearance. "\Vith
tlTe fall of the fever there is a cessation of the pains and a general improve-
ment in the condition of the patient. In mild cases of varioloid the
illness of the patient is terminated at this stage. In severe cases the
improvement constitutes but a brief respite, and then the grim struggle
with the disease begins.
Stage of Eruption. ^ — By carefully observing the early stage of the
disease it will be found that the true erujDtion makes its appearance with
remarkable regularity on the third 3ay oi the illness, calculating from
The clay on which the initial chill or rigor occurred. In modified smallpox
deviations from this rule may be noted. The eruption almost always
appears first on the forehead and temples near the edge of the hair,
"ana on the wrists. Not infrequently it is seen first on the upper lip
SLiKTaround the mouth. It rapidly spreads to the scalp, face, neck, ears,
forearms, and hands, always showing a decided preference for the
cutaneous surfaces habitually exposed to the atmosphere. In the course
of twenty-four hours, sometimes somewhat earlier, it extends to the
body and lower extremities. It does not simultaneouslv afifect these
regions, but attacks in succession the back, arms, breast, and finally
the legs and feet. In rare cases the exanthem may be first noted on the
trunk or extremities.
TheJ[i,ill complement of lesions does not make its appearance at once
in_any given part; the eruption continues rather to multiply for two or
three days before its definite limit is reached, ^ii varioloid^iiew lesions
, may continue to appear for a longer period of time. I pon carefully
examining the eruption it is seen that many lesions develop at the sites
of hair follicles or orifices of the sebaceous and sudorific glands.
The eruption begins as small red spots or >Ji£cidcs some of which
may be so small and faint as to be scarcely visible, while others reach
the size of a lentil-seed. The color is at first pinkish-red, later assuming
a deeper tint. In many cases the lesions on the trunk and extremities
present the appearance of flea-bites. The lesions gradually increase in
174 SMALLPOX
size and number, becoming more and more prominent,, so that in twenty^.,
_iau4?-]iQurs they assume the form of elevated papules, with a cEaracteristic
feel. The early papules, particularly about the forehead and cheeks,
may be more demonstrable to the sense of touch than to the eye. They
possess a peculiar induration, and convey to the finger a sensation
similar to that which would be produced by grains of shot embedded
in the skin. The "shotty" feel varies in degree in different cases.
Some papules are extremely hard, while others possess comparatively
little induration. They are at first always discrete, but they may rapidly
increase in number and become confluent, even before the vesicular
stage is reached.
On the third day of the eruption, or the fifth day of the disease, very
many of the lesions which made their appearance first will be found
to contain a little clear serum. Indeed, in many patients, one will be
able to note on the second day a lesion here and there which has become
vesicular in advance of the general eruption. These precocious vesicles
are frequently of diagnostic import, enabling one in doubtful cases to
assert the variolous nature of the disease. By the fourth or fifth day
all of the lesions are converted into vesicles. At this stage they commonly'
have the size and shape of a split-pea. Small vesicles are apt to be
conical or acuminate, while the larger lesions have a convexly flat or
hemispherical appearance. The vesicle of smallpox is extremely firm;
not infrequently it feels harder to the finger than the papule from which
it developed. In no other disease do the vesicles acquire such a degree
of induration and hardness. The color of the vesicle is at first pinkish,
the tint extending to the areola surrounding it. Later, as the fluid
exudation into it increases, it assumes a peculiar opaline or pearly hue.
This, with the shining and glistening surface, imparts to the vesicle a
most distinctive appearance. One of the most characteristic features
of the smallpox vesicle is the so-called "umbilication." In the smaller
acuminate vesicles this is seen as a minute central depression or invagi-
nation, representing in all probability the mouth of a hair follicle or
sweat duct. This form of umbilication may occasionally be met with
in other cutaneous diseases, when the lesions are situated at the mouths
of the pilary or sudoriparous orifices. In the larger, pea-sized vesicles
the umbilication is seen as a round, oval, or slightly irregular indentation.
In this case the depression is flatter and is probably due to the bulging
of the periphery of the pock. This latter form of umbilication is of
important diagnostic value, as but few other vesicular diseases produce
quite the same appearance. The forearms and the backs of the hands
are, perhaps, the regions upon which umbilication is most character-
istically seen. Umbilication is only observed in a certain proportion
of vesicles. It is by no means a constant feature of smallpox eruption-
and, indeed, is not infrequently absent altogether. This is particu-
larly true of cases of varioloid. A^form of secondary umbilication is
commonly seen during the stage of- decline or desiccation, when the
pustules, as the result of rupture or drying, show a depression in the
centre.
Till': S YMI'TOMA TOLOd Y OF AM/.I LLI'OX 175
If one ()l),serv(^s closely ilic lar/^c, clear vesicles of nlioiil iIk- fifili or
sixth (lay, j)ar<,iciiliirly those; situated on tiie dorsal surfaces ot" tin;
hands, one can fre(juently discern jliroii^di (lie epidermal roof srjrriefhing
of the interior construction of the lesions. 'I'hey will \h', seen 1o he
made up of compartments which are divided by vertical septa, very
much Hke the divisions of an orange. The vertical partitions are
formed by the spiiniing out and reticulation of the epithelial cells f)f
the rete mucosuin. This accounts for the nudtilocular chai'acter of the
smallpox vesicle, and explains the inability to completely evacuate its
contents by a single puncture. T^arge, fully developed vesicles frecjuently
show at their central summit a disk of the color of yellowish serum,
and around the periphery a whitish, puriform ring looking not unlike
an arcus senilis.
The predominance of the eruption of smallpox on the face and term-
inal extremities is to be accounted for by the greater vascularity of the
skin in these regions. That lesions are attracted by an overfilling of
Fig. 22
Smallpox eruption showing confluence over an area upon which iodine had been applied before
the eruption appeared.
the cutaneous vessels is seen in the excessive development of the erup-
tion wherever the skin has been irritated or congested. It is a common \
experience in the hospital to see in a discrete case of smallpox a profusion
of lesions over a rectangular area in the lumbar or epigastric region
where a mustard plaster had been applied during the initial stage for
the relief of pain. Fig. 22 shows a marked confluence of the pustules
in the form of a band on the wrist where the patient had applied iodine
for a sprain received before his illness. An intense coalescence of the
eruption upon the forearm is seen in Fig. 23. This was occasioned by
the presence of a sunburn upon these parts.
It is only when mechanical or chemical irritation is applied to the
skin before the appearance of the eruption that an increase in the num-
ber of lesions is produced. We have frequently applied tincture of
iodine and similar applications to the skin in the early days of the erup-
tion without augmenting the variolous crop in the region thus treated.
Some of the older physicians purposely irritated the skin of certain
176
SMALLPOX
portions of the body with the hope of deflecting the eruption from the
face to the regions thus treated. Unfortunately, the eruption was
increased in the manipulated areas without diminishing the number of
lesions on the face.
Pig. 23
Smallpox eruption showing areas of extreme confluence which had been the seat of a sunburn
before the eruption appeared.
Stage of Suppuration. — The contents of the vesicles gradually become
more and more turbid, as the result of the increased exudation of
leukocytes, until the lesions become frankly purulent. This condition
is usually reached in unmodified smallpox about ihe .sixth day of the
eruption, and marks the beginning of the stage of suJ3puration. The
pustules now, in good part, become large and globular, and stand out
prominently from the skin. Their color varies somewhat in different
cases. At times the pustules acquire a distinctly yellowish tint not
unlike the color of ordinary pus. Frequently, they retain until ruptured
a peculiar chalky or grayish-white hue. The reddish areola, which is
observed about the vesicles, develops in this stage into a broader,
deeper-hued, violaceous halo. Where the lesions are closely aggregated
the entire interpustular integument becomes reddened and tumefied.
PLATE XV.
Well-pronouneed Discrete Smallpox in an Unvaecinated.
Subject on the Eighth Day of Eruption, showing the relative
sparsity of the lesions upon the trunk.
THE SYMI'TOMATOIJX; Y OF SMAIJJ'OX
177
On the face and scalp, where the eruption is apt fo be profiis<;, tlie
redness and intninesc;enec are so extreme as to Hinder tli(! features of
the [)atients eoni[)letely unrecogni/ahle. The eyeh'ds, as the result of
oedema of the loose areolar tissue, l)ecome enormously f)uffed and com-
pletely close the palpebral cleft, which is bathed in a puriform secretion.
The patient for a time is unable to see, owinj^ to a complete closure of
the eyelids. The lips, nose, and ears are distorted, the normal contour
of the face is lost, and the entire head swollen beyond human [)ropor-
tions. The patient presents a most revolting and loathsome appear-
ance. One seeino; the disease for the first time in this stage is apt to be
appalled by the horrible spectacle. The patient is sorely distressed by
the inflammation and swelling of the scalp, inasmuch as contact with
the pillow is a source of unendurable pain.
Fig. 24
Discrete smallpox eruption on tbe ninth day, showing marked oedema of the face,
completely closing the eyelids.
As the eruption on the body and lower extremities is later in making
its appearance than that on the face, so also is it later in reaching matur-
ation. When the lesions upon the face have become vesicular, it will
be found that the efflorescence upon the trunk and extremities is still in
the papular stage. In like manner the facial lesions will have advanced
to pustulation by the time that the eruption on the body has become
vesicular. There is noticeable, therefore, this regular multiformity in
the character of the lesions upon the different portions of the body.
About the eighth day the pustules on the face have reached their
greatest (levelopmcMit, and the process of retrogression then begins.
They become yellowish, present a shrunken or shrivelled appearance,
and rupture or collapse. On rupturing the pustules give exit to a viscid,
glairy, dirty-yellow pus, which dries in the form of yello^\"ish or brownish
crusts. A gradual subsidence in the inflammation and swelling takes
place, and the normal outhnes of the face are once more restored.
12
178
SMALLPOX
During the stage of pustulation the lesions which exhibited umbili-
cation become distended and globular, thus effacing the central depres-
sion. The epithelial bands holding down the centre of the lesion, in all
probability become dissolved away, permitting the roof of the pustule
to assume an hemispherical form.
The eruption on the,,trwn4^is-atoee*~a4^way«m-U,ch les
jon other parts of the body^,^ Not m|rgqjufijattyjjbe.i^^^ quite
Jree from pustules, even wheii^ffiemce and hands show a marked degree
of confluence. Exceptions to this rule are, however, occasionally met
with. We have seen patients the skin of whose body was so profusely
covered that it would have been impossible to place the tip of the finger
Fig. 25
Large, full pustules on the seventh day of the eruption.
upon a healthy area of skin. Of course, in such cases the danger to
the patient is correspondingly increased, inasmuch as the gravity of the
disease is, as a rule, directly proportionate to the extent of the eruption.
In a well-pronounced case of semiconfluent smallpox under our care
an approximate count of the number of lesions was made. This was
accomplished by dividing the cutaneous surface into certain areas by
means of a colored crayon and counting the pustules within these bound-
aries. Upon the face and scalp the confluence of the pustules precluded
the possibility of their being counted. A conservative estimate of the
number present was therefore made.
The number of lesions computed upon the different portions of the
body is herewith appended:
77//'; S YM/'TOMA TOIJXl Y OF SMA LLI'OX 179
Total oil (IngerH of one hand •
'I'hiiinb ()1 I
Index finger '.)!
Middle " 05 r ... 392
Ring " 81 I
llorsfil .surl'uce of one hand 3H2
Palmar " " " 129
Total lesions on both hands . I,Wk;
PorearniR ■i,W)
Anns 2,8io
Chest 1.000
Abdomen 17.5
Thighs 4,180
Legs 2,8.')0
Feet 7.50
Back 5,700
Estimated number on face and scalp 3,000
Total 20,701
By evacuating some of the pustules with a pipette we estimated that
the lesions at the height of their development each contained about
three drops of pus. Such a computation developed the surprising fact
that the patient referred to carried in his skin about five quarts of pus.
We have seen large men with more profuse eruptions, who must
have had in the neighborhood of forty thousand pustules. With this
prodigious amount of purulent material in the skin the wonder is that
any patient thus afflicted should recover.
'J^^llfL-pustulcs on the trunk appear to have a more superficial seat in .
JJieL,akm than on cutaneous -surfaces constantly exposed to the air; hence,,
ijtiiey arc not accompanied by the same amount of inflammatory swell-
ing ov ulcerative destruction of the cutis. _ There_ is, _inQreover, vei
iitlle tendency on the trunk and lower extremities to confluence of~lEe~
lesions. We frequently note a coalescence of two or three pustules as a
result of their contiguity, but the vast majority of the lesions remain
discrete.
This statement, however, does not apply to the efflorescence on the
hands and. feet. In these regions the degree of confluence may be intense
and cause the patient great suffering. As a result of the thickness of"
the overlying epidermis on the palms and soles, the pustules do not acquire
as great a prominence as elsewhere. Being bound down by the tense
and unyielding horny layer of skin, pressure is made upon the dehcate
underlying cutaneous nerves, producing distressing pain. In a severe
attack of smallpox the palms and soles, the fingers and toes, and the
dorsal surfaces of the hands and feet are profusely covered. "\Mien the
pustular stage is reached the patient becomes perfectly helpless; he is
unable to feed himself or in any way utihze his hands. It is pitiful to
behold him in bed, with his hands and fingers semiflexed, and his arms
• outstretched for fear of the dreaded contact with the bed-clothing. At
times the pustules on the back of the hands fuse and produce large
bulla?, or even an extensive undermining of the epidermis similar to
that seen in a bad scald.
During the suppurative stage a most penetrating and offensive odor
180
SMALLPOX
emanates from the body of the patient, and from the pus-stained bed
and body hnen. This stench results from the decomposition of the
effete and purulent discharge, and is not peculiar to smallpox. In
neglected cases the odor is most sickening, and may pervade the atmos-
phere of a room or, indeed, of an entire house.
Eruption upon the Mucous Membranes.— Simuhaneous with the
appearance of the smallpox efflorescence upon the cutaneous surface,
or a little earlier, the eruption develops upon the adjacent mucous
membranes. The involvement is almost exclusively confined to those
mucous surfaces which are near the external orifices, or to which
the air has access. The eruption early attacks the lining of the
Fig. 26
Well-pronounced smallpox on the eighth day, occurring during a particularly mild
epidemic, the lesions being very superficial.
mouth, nose, and pharynx, and in severe cases the larynx, bronchi,
and oesophagus. The extent of the enanthem bears a direct relation to
the severity of the eruption of the skin. The lesions, however, are
seldom as profuse upon the mucous surfaces as upon the integument.
If an examination of the mouth and fauces be made at the very begin-
ning of the eruptive stage, small yet distinct red spots may be seen upon
the roof of the mouth, buccal surfaces, and anterior arches of the palate.
These macules are pinhead sized and larger, and of an intense red
color, which contrasts with the violaceous or bluish-red tint of the sur-
rounding mucous membrane. In a short time the spots become slightly
elevated or papular, frequently exhibiting a whitish, glistening centre.
The parallelism with the evolution of the cutaneous pock ceases at this
THE S YMI'TOMA TO LOG Y OF SMA /. LI'OX \ 8 ]
stage of the (l('V('l()[)?iicii(. Ttic riiucous-rnenihr;iiie lesion (l(;c.s not pass
tlu'ongh llic stage of j)aj)iile, vesicle, ainl pustule, l)iit pursues a eliarae-
teristic eoiirst; wliicli is detennined \)y its j)eeuliar structure and its dif-
ferent environment. I'here is perhaps an effort on the part of nature
toward the formation of vesicles, but the thin and delicate e[>ithelium
which serves as a covering is destroyed by the macerating influence
of the moist secretion in which they are constantly bathed. As the
eruption upon the skin becomes vesicular and j)ustular, the lesions in the
mouth assume a whitish or grayish appearance, with but little if any
elevation above the surface. 'Vhv denudation of the ey)itheHfd r-ovcring
of the pocks leads to the j)ro(lu('ti()n of circumscribed cios oii^ or super-
ficial ulcerations.
'~'^^^^txricii'ii of Ike /Aroa/, particularly on swallowing, is one of the most
distressing symptoms of the early eruptive stage. But few patients
with well-marked attacks escape this suffering. Even when the patient
is feeling otherwise well the condition of the throat constitutes a source
of bitter complaint. In severe cases, at a later stage, the mucous mem-
brane of the mouth is so abraded, swollen, and painful that the use of
solid food is rendered impossible, and the patient is forced to subsist
entirely on a liquid diet.
►XJae tongue is often the seat of lesions which seriously embarrass
its movement in speaking and eating. Occasionally an intense form
of glossitis is set up, causing the organ to swell so enormously as to pre-
vent its retention wholly within the mouth. This condition, which was
designated by the older writers as glossitis variolosa, is apt to greatly
interfere with swr.llowing, and is under all circumstances to be regarded
as an unfavorable sign.
Much annoyance is occasioned by the presence of the eruption in the
nasal cavities. The mucous membrane is at first swollen and inflamed,
and later covered with crusts which obstruct the nares and render nasal
breathing difficult and often impossible. This is particularly a source
of distress to nursing infants, who are obliged to release the nipple from
time to time to obtain the necessary amount of air.
The eruptive process may involve both the pharynx ancl l9,r^ix and
cause so much inflammation and swelling as to make deglutition difficult
or impossible, or it may lead to the production of hoarseness and complete
jiutb-On ia. In severe cases an acute oedema of the glottis may develop,
which may seriously or even fatally impede respiration. Trousseau re-
cords several fatal cases of this character: " Three smallpox patients, on
the eighth day of the disease, which had run a perfectly normal course,
were suddenly seized with a fit of suffocation which carried them ofl' in
a few seconds, before there was time for anyone to come to their assist-
ance. In one patient autopsy showed laryngitis, with variolous lesions
below the glottis."
In severe smallpox in children we have found it necessary in four
instances to employ intubation in order to prevent asphyxia. In all of
these cases there was laryngitis with considerable swelling of the mucous
membrane. Although relief was temporarily alYorded, death ultimately
182 SMALLPOX
occurred in all four cases. In one of the children the laryngeal stenosis
came on late after complete decrustation had occurred on the skin,
and at a time when the child appeared to be on the road to recovery.
The mucous membranes of the lower portion of the body may also
be involved. The eruption may attack the vulva and the mucous sur-
faces of the vagina, but the lesions in these parts are not apt to be abun-
dant. The lower part of the rectal mucosa may also be the seat of the
variolous eruption. The meatus urinarius is occasionally involved in
both males and females, but the urethral channel nearly always escapes.
Delirium. — As previously stated, a variable degree of delirium may
accompany the high fever of the initial stage. In our experience the
most violent disturbance of cerebration occurs during the early eruptive
period. This may be, in some cases, merely the continuation of the
earlier delirium, but in others it seems to begin after the exanthem has
made its appearance. Some patients are apparently the subjects of
delusions of persecution and of hallucinations, and imagine that some
one is about to do them bodily harm. Acting on this supposition the
demented patient attempts to escape from the hospital and, what is
quite strange, will almost always prefer to gain egress through the
window. On a number of occasions patients, by the exercise of cun-
ning and the awaiting of a favorable opportunity, have effected their
flight with marvellous celerity, and have gained a temporary liberty
in this manner. In some patients the temporary derangement takes
the form of a suicidal or homicidal mania. One of our patients at-
tempted self-destruction by striking himself on the head with a drinking
mug, inflicting several large and painful wounds.
On another occasion a female, by cunningly embracing an opportune
moment, quickly ran to an open fire-grate, on which she seated herself.
While her clothing was burning around her and her flesh charring, she
violently resisted the efforts of the nurse to extricate her. We recall
another patient who rose from his bed at night, struck the nurse to
the floor, and effected his escape in his night-clothes; he wandered a
considerable distance from the hospital, and succeeded, by a shrewd
and plausible story, in prevailing upon the credulity of a wagon driver,
who conveyed him to his desired destination.
These patients are often able to answer questions coherently, and one,
unprepared, may be completely deceived as to their mental condition.
They are apt to exhibit, however, some injection of the conjunctivae
and a wild expression of the countenance. This form of delirium was
called by the older writers delirium ferox.
Patients thus affected require to be closely watched, and, if neces-
sary, restrained in bed by straps or other means. When a patient com-
plains of persecution or asks to be permitted to attend to some business
at home for a day or two, close surveillance is necessary.
•"^-We^have observed this .active delirium most_pJ[ten_d^
and vesicular stag-e of the eruption. When it occurs it is usually asso-
ciated with the confluent variety of smallpox, yet we have known it to
occur in comparatively mild forms of the disease or when the patient
77//'; S VM/'TOMA TOLOd Y OF SMA IJJ'OX 1 8.*}
had become (|uite a})yr(!l,ic;. The persistence of (lie (Iciiiiiiin for ,'i niimlxT
of days is a symptom of evil portent.
The delirium which is seen later, during tlie (jcclinc of iIk; cruplifjii,
is'oT a d'iff(ifCTt"Char?iLf't;CT. Tt is "then of a low, nmllcriii^ form, and fre-
■ quen'fTy^ssocTated with general tremor, dry t(jiigii(;, quick and tremu-
lous pulse, and a collapsed appearance of the features. These nervous
symptoms are not ])eculiar to smallpox, hut may be seen in the terminal
stage of typhoid and other fevers.
The various forms of delirium, while more frequently observed in
alcoholics, appear to be the result of the poison of the disease acting
upon the nerve centres.
It has already been stated that the jjj^i^yL^^y^ in unmodified small-
^QiX^ acmti nues> high until the third or fourth day of the eruption, when
there occurs either a well-marked remission or a brief period of apy-
rexia. In very mild cases the fever subsides earlier. The fall of the
temperature, at this stage, even in severe cases, is not infrequently very
rapid, so rapid, indeed, as to drop from a high degree to normal or even
subnormal in the course of twelve or eighteen hours. The difference
between the morning and evening temperature is not great, although
the latter, as a rule, is slightly higher. When the temperature falls
there is usually amelioration of all the symptoms. The pulse becomes
almost normal; the respirations are easier; the pain in the back, head-
ache, and irritability of the stomach all disappear, except in critical
cases; the delirium ceases, enabling the patient to rest and enjoy re-
freshing slumber. Even the appetite may return, and tlie patient may
be led to believe that the critical period of the disease has passed and
that recovery has begun. The subsidence of the symptoms is never so
complete in variola vera as it is in varioloid. In the latter variety the
fever and other systemic symptoms frequently disappear, and the begin-
ning of convalescence is established; but in the former the chief danger
is yet to be encountered.
At or sliortly after the cornmencemeut of the stage of suppuration
tTie ten\peratin-e again begins to rise, and continues elevated until the
completion of the eruptive process, or longer if complications arise.
This rise constitutes the so-called secondary or suppurative fever of
smallpox. This latter .pyrexiaas, not apt to equal in. intensity the initial
elevation of temperature. When the disease is of moderate severity
""^le^temperature may not rise above 102° F. or 103° F., but in well-
marked confluent cases it frequently reaches 104° F., rarely exceeding
that point. When hyperpyrexia develops, the thermometer registering
105° F., 106° F., or 107° F., the danger of a fatal outcome is corres-
pondingly increased. The maximum degree of fever is often reached
during the hours which immediately precede dissolution. Wunderlich
reports an antemortem temperature of 109.2° F., and Simon has seen
temperatures of 110° and 112° F. immediately after death,
jrke secondary fever commences ordinarily on the. fifth or. sixth dajx^,
,,,^the eruption, when the vesicles begin to fill with .pus.. It is of indefi-
nite duration, depending directly upon the extent and severity of the
184
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THE SYMPTOMA TO/.Od Y OF SMA IJJ'OX 1 85
cutaneous oulhrcak. In a well-marked, discrete, or semiconflueiit
,sTnall])()x the pyrexia is apt to last froui three to six days. In severe con-
(liicut cases it may continue for eif^ht to tw(;lve days or IfMi^er. It is
not uncommon U)Y the secondary fever to nier; tcmj)crature is apt to e(|ual one or two dcffrees. The max-
imal elevation usually occurs, in severe cases, between the seventh and
tenth days. I^ater, when boils and abscesses develop, the diurnal
variations are most pronounced, the evenin<^ fever not infrefjuently
reaching 104° or 105° F., while the matinal temperature registers only
99° F. The pulse and respiration correspond in a general way with the
temperature curve. The pulse, however, is apt to be higher in propor-
tion to the temperature than during the initial stage. With a tempera-
ture of 104° or 105° the cardiac pulsations not infrecjuently reach 140
or 150 to the minute. When the morning remission occurs there is a
considerable slowing in the pulse rate. As is quite to be expected, the
patient experiences more comfort in the mornings than later in the day.
During the pustular stage the chief complaint of the patient is the gen-
eral soreness of the skin. The couch upon which he lies is metaphor-
ically, if not actually, "a bed of thorns;" whichever way he turns he
makes pressure upon the sensitive and inflamed pocks. Nervous appre-
hension, restlessness, and sleeplessness are prominent symptoms of
this period. The patient is conscious of an increasing degree of pros-
tration, and is frequently much concerned as to the outcome of the
illness. It becomes necessary to allay the nervousness of the patient
and induce sleep by the administration of an anodyne. At the end of the
eighth or ninth day a sudden improvement in the general condition of
the patient is often observed. The sufferer becomes brighter, volunteers
information that he feels better, and exhibits altoo;ether a lesser dejjree
of prostration. This is usually coincident with the onset of the period
of involution and retrogression of the eruption.
Period of Involution and Retrogression of the Eruption. — The
exanthem of smallpox reaches the acme of its development with the com-
pletion of the pustular stage. This constitutes the turning point not
only of the eruption, but frequently of the disease. The first evidence
of retrogression of the exanthem is noted in the subsidence of the
inflammatory swelling of the skin, more particidarly in the immediate
neighborhood of the pustules. The abatement is first seen on the face,
where the redness and oedema have been most conspicuous. The eye-
lids become less swollen, permitting the patient to again perceive the
grateful light of day. The tumefied features gradually assume their
normal contour, and the patient begins to acquire some semblance of his
former self. Synchronous with the disappearance of the intumescence
the pustules begin to dry; this period is called, therefore, the stage of desic-
cation. The drying of the contents of the pustule is soon followed by
186 SMALLPOX
a casting off of the crusts, when the stage of decrustation is entered upon.
Nature in this manner attempts to rid the surface of the skin of the
effete products which have there collected, and, finally, restore it to its
normal condition.
The involution of the smallpox exanthem does not occur simulta-
neously upon all portions of the body surface, but follows the same
sequence observed during the development of the eruption. It is but
natural, therefore, that the first evidence of desiccation should be found
in the facial lesions. The pustules in this region may dry without rup-
ture, although more commonly the purulent contents of the lesions
exude upon the surface and dry in the form of yellowish crusts. This color
gradually becomes darker until it assumes a brownish tint. In neglected
cases the crusts may become almost black, enveloping the face in an
unsightly, immovable mask. The adherence of the crusts to the subja-
Unusually large and confluent pustules on the ninth day of the eruption.
cent tissues varies in degree according to the depth and intensity of the
involvement of the cutis. Where the pustule is superficially seated
and there is no ulceration of the skin, the crust is readily detached,
exposing to view merely a reddened area of the skin.
At the same time that desiccation is well established on the face, the
trunk and extremities will exhibit lesions distended with fluid pus.
These rupture, form crusts, and then pass through the process just
described. At this period of the disease the offensive odor previously
mentioned becomes most marked; in some cases it is quite unbearable,
especially when the contents of the pustules discharge and decompose on
the skin, or soak into the bed-clothes and there undergo putrefaction.
After the rupture of large pustules the centres frequently dry and
sink in, producing a cup-shaped depression or umbilication. This
secondary umbilication differs from the primary variety in being dis-
tinctly larger, more conspicuous, and occurring at a much later stage
of the eruption. This form of umbilication is most typically seen on
the dorsal surfaces of the hands.
THE SVMPTOMA TOLOd Y OF SMA IJjPOX
180
of the skin and mucous inciiihranes the temperature falls less rapidly,
or if complications arise it continues for a varying period according io
the nature of the associated conditions. Although the; f(!ver is stearjily
pijrative sta^e of the
disease. The patient is irninc^rsed for fifteen or twenty rninut(!S in a
bath eonsisting of a 1 : I (),()()() to 1 : 20,000 sohition of corrosive sub-
Gangrene of the skin complicaUng severe smallpox ; recovery.
Fig. .S7
Uangiene of the skin accompanying a severe smallpox ; ultimate recovery.
196 SMALLPOX
limate. In other cases we have employed a 1 : 500 solution of creolin.
After the bath the patient is dusted with weak antiseptic powders. This
course of treatment has a beneficial influence in drying up the impetigo
sores and in lessening the tendency to deeper infection.
Secondary Toxic or Septic Rashes. — Another secondary eruption in
smallpox, to which but little reference has been made in literature, is the
toxic or septic rash which appears in a certain percentage of cases during
the stage of decrustation. Between the eighth and eighteenth days, and
most commonly on the thirteenth or fourteenth, there develops upon
the trunk, extremities, and at times the face, a peculiar erythematous
efflorescence. In most instances the rash consists of a diffuse, dusky
redness bearing a strong resemblance to the exanthem of scarlet fever
{scarlatinijorm erythema). At times it is mottled and inclined to become
somewhat morbilliform in appearance. The scarlatiniform eruption is
peculiar in that the skin immediately surrounding the drying pocks is
often exempted, producing a sort of anaemic halo. The rash lasts for
two or three days and then fades away. If the erythema has been well
marked it is prone to be followed by desquamation, which may be most
profuse in character. The exfoliation of the epidermis is usually rapid,
and may be out of proportion to the intensity of the rash. Fig. 78 shows
desquamation of the cuticle of the palms in large masses on the sixth
day of the rash. In this patient the eruption was quite indistinguishable
from that of scarlatina. In occasional instances a most inordinate and
persistent desquamation follows. A young lad developed on the four-
teenth day of the smallpox eruption a severe, deep-red erythema, which
was followed by repeated exfoliation of the epidermis. This patient
desquamated four or five distinct times, the whole process extending
over a period of six or eight weeks. Handfuls of scales could be daily
gathered from his bed. The hair of the scalp and eyebrows, and the
finger-nails were subsequently lost. A patient recently in the hospital
passed through an almost identical attack. Such cases merit the desig-
nation of dermatitis exfoliativa variolosa.
In rare instances these secondary rashes may become hemorrhagic.
Hgemic extravasation into the skin is most apt to occur upon the lower
extremities, where the stasis in the vessels is greater owing to gravity.
We have seen a severe secondary purpuric rash, the history of which
is of sufficient importance to warrant its presentation :
H. W., an unvaccinated boy, aged seven and a half years, was admitted
to the hospital on September 28, 1901, on the fourth day of the smallpox
eruption. The attack was severe, the eruption being semiconfluent.
The patient did well for seven or eight days. On the thirteenth day
of the eruption, the face, on which the swelling had largely subsided,
again became tumefied, the temperature rose, and a profuse macular
eruption, rapidly becoming purpuric, and consisting of bluish-red pin-
head to finger-nail-sized ecchymoses, developed over the trunk and
extremities. The patient sank rapidly and died in two days.
The secondary rashes are not infrequently accompanied by rise of
temperature. The temperature may suddenly mount to 104°, decline
PLATE XXIV.
Exfoliative Dermatitis Occurring during tlie Course
of a Severe Smallpox.
THE S VMI'TOMA TOIJX; V OF SMA LIJ'OX ] U7
rapidly, and tlien remain for some days in (lie nei|^lil)0)'liof»d of lOT' oj-
102° F. Jii some palienls, witli rnslx'S of nioder;i(e sev(;ri(y, no [jyrexial
elevation oeeiirs. WliiK; tlie eruption lasts tli(^ |);i(ients are, as a rule,
sonniolent, extremely irritable, and eonsiflerahly prostrated. The
rashes are more eoinmonly ol^served in patients who have had severe
smallpox eruptions.
Durinf)^ the epidemie of 1901-03, we observed these eruptions in
perhaps 5 per eent. to 8 per eent. of all patients admitted. 'J'he
incidence among children seemed to be greater than among adults.
In the severe epidemic of smallpox in 1871-72, such rashes were
much less fre(|uently observed, and in the year 1904 they were distinctly
less frequent than in the two preceding years.
J^e scarlat i niform erup ti on is t he t ype b^^^r most commonly seen.
The resem blance to IKe^rasn oi 'scarlerlever is so strong that in the
beginning the existence of the latter disease was suspected. In a small-
pox hospital in a neighboring town, several patients with scarlatincjid
rashes of the character referred to were believed to be suffering fi'om
scarlet fever and were promptly isolated. The physician, during a
visit to our wards, identified the toxic rashes with the eruption he had
observed.
Perhaps some of the cases of scarlet fever associated with smallpox
reported by the older writers were in reality instances of scarlatiniform
erythema.
In a boy recently treated in the hospital, a severe variolous impetigo
developed, and this was followed on the fourteenth day of the smallpox
eruption by an intense macnlopapular rash,, which was on the trunk
quitejiidisthiguishable from measles; on the face, however, there was
relatively little eruption. The duration of the eruption was brief, and
catarrhal symptoms were absent.
_ The postvariolous rashes., are in all probability septic or toxic in
character, due doubtless to the absorption of some j^oisoii into the'
blood. Our experience in the Municipal Hospital would indicate that
these are more common in patients who have been the subjects of an
abundant impetigo.
As far as we have been able to ascertain, none of the modern text-
books or monographs on smallpox, save the article by Moore, make
mention of these rashes. The earlier writers doubtless regarded the
development of the erythema as evidence of an intercurrent scarlet
fever, and the numerous instances of the coincidence of these two
diseases may thus be accounted for.
Simon,^ in an article on scarlatina and scarlatiniform eruptions in the
course of smallpox, written in 1873, carefully distinguished these two
conditions and reported cases representing both true scarlet fever and
the secondary erythema which resembles it. In the latter cases he
considers the diagnosis of scarlet fever excluded by the date of onset of
1 Ueber Scharlach und Scharlach-aebnliche-ausschlage im Verlauf der Variola, Archiv f. Der-
matologie u. Syphilis, 1873, p. 115.
198 SMALLPOX
the complication, the absence of adequate invasive symptoms, the mild
character of the angina, the absence of or slight character of the des-
quamation, and the non-contagiousness of the condition.
Of thirteen cases of secondary rash, Simon observed nine develop
after the tenth day of the variolous eruption. A few were seen as early
as the sixth day and as late as the eighteenth or twentieth day. Simon
does not seem to have encountered the profuse desquamation which
has occurred in some of our cases. No mention is made by him of
morbilliform rashes.
According to Simon, Fleischmann also saw some of these cases, as
did likewise Bernouilli, who states that in 1865 he saw a case of secondary
erythema in variola which he erroneously regarded as an intercurrent
attack of scarlet fever.
The only other reference to these rashes that we have been able to
find is by Meredith Richards,^ Medical Officer of Health of Chesterfield,
England. This writer refers also to the bullous and pustular eruptions
occurring late in the course of variola. He says:
" Less known, and from a practical point of view less important, are
certain posteruptive rashes, which include (1) a scarlatiniform erythema,
general in distribution, and not differing from that common in various
septic states; (2) a development of the smallpox pustules which appears
to correspond to what Dr. Crocker has recently described as "impetigo
contagiosa gyrata." The smallpox . pustules, instead of drying up and
scabbing on the eleventh day, show signs of spreading peripherally, so
that in a day or two many of the lesions consist of three well-defined
parts, viz., a central scab, a surrounding vesicular ring which rapidly
becomes pustular, and a red areola surrounding the pustular ring.
Unless treated, the areola and pustular ring continue to spread centrif-
ugally until the whole lesion may measure an inch or more in diameter.
When abundant, this rash gives rise to a very remarkable appearance,
and is clinically important because it is often attended by high temper-
ature and other signs of septicaemia. There is no doubt that this is due
to a mixed infection, as it has a tendency to occur in particular wards
and may be accidentally acquired by attendants. It also merits notice
in passing, as, I believe, this variety of secondary infection has not been
fully described. (3) Accompanying the previous rash or occurring in
other cases exhibiting signs of septicaemia, it is not infrequent to observe
cases in which the healthy interpustular epidermis is raised into flaccid
bullae, containing a few drops of foul, mucopurulent fluid. These
bullae are soon followed by profuse desquamation, which may lead to
the shedding of the nails, and are accompanied by severe constitutional
symptoms of a septicaemic character. Many of them are fatal, though
a good proportion appear to owe their lives to boracic baths combined
with good nursing and general tonic treatment."
1 Accidental Rashes Occurring in the Course of the Exanthemata, Quarterly Medical Journal,
1896, p. 31.
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77//'; vmuI':tii<:s 01' sMALLi'ox 199
THE VARIETIES OF SMALLPOX.
The course jnst described relates more particularly to that form of
the disease iu which the eruption is either discre/e or jiiuuMM44rflifYmf:'- In
our ex[)erieuce the yast iuajority of cases met with Ijelon^ to the last-
n ajne d v.-iriety that is to say, the eruption is usually cither partially
or wholly condiiciil on llic face, the.dorsal surfaces of the hauds, and
the lower portions of the f(jrearms, while on the trunk and extremities
"^jt is'HiscrHe, save a few lesions, j)erha{)s, which may coalesce. Varia-
tions'^" the extent of the eruption may reach extreme limits, from a
few small pustules, scarcely characteristic enough to enable one to defi-
nitely proclaim the variolous nature of the disease, to the most extensive
eruption covering the entire cutaneous surface. Between these two
extremes there may occur numerous grades of intermediate severity.
Confluent Smallpox (Variola Confluens).— It can hardly be said that
there is any symptom during the initial stage of smallpox peculiar to
the confluent form of the disease. Inasmuch, however, as the symptoms
preceding this type of variola are, with great uniformity, of a severe
character, this _g£ave. jo rm may be excluded in tlie presence of mild.,
initial manifestations. Most prominent among the early symptoms
-"aTe'severe headache, persistent retching and vomiting, delirium, or, in
children, stupor, violent pain in the back, and high fever. The tem-
perature always rises rapidly, and attains frequently an extraordinary
height. It is not at all uncommon for the fever to reach 105° or 106°,
F. and cases have been recorded in which a temperature of 110° F. w^as
registered. . Qn.the third, fourth, or fifth day of the eruption the tempera-
ture declines, but this remission is never as complete as in milder cases,
'nor does it continue as long. Xl\inng the remission the temperature is
"^iibt far from 101° or 102° F. , at which point it is apt to remain for a period
"ortwo or. three, days, when the secondary rise commences.,. The fever,
^iiring. the stage of suppuration, is not usually as intense as in the initial
stage, yet it may at times rise considerably higher. The chart shown
upon page 1S4 illustrates the temperature curve of a severe case of con-
fluent smallpox, and may be taken as a fair type of the cases of this
class. It may be well to add that the temperature in the suppurative
stage was somewhat influenced by the use of antipyretics.
It is sometimes stated that the eruption of confluent smallpox develops
early, often on the second day of the initial fever. Our experience leads
us to believe that this variety develops less rapidly than in modified ,
"^Torms of the disease, but there is a shorter interval between the time^
"of its appearance on the face and on other portions of the body. So
quickly is the eruption diffused over the whole body that it has been
mistaken in the papular stage for measles. -Indeed, it is the confluent
form of variola which is particularly apt to be confounded with mor-
^ billi. Ordinarily in forty-eight hours the efflorescence has covered the
entire body surface. Owing to the extensive involvement of the skin,
redness and swelling begin early. The face is intensely h}^ersemic
and the seat of distressing burning and itching. The marked suffusion
200 SMALLPOX
of the countenance frequently enables one to prophesy that the disease
will take the confluent form. As the ' eruption progresses it passes
through the usual stages, though somewhat more slowly than in the
milder cases. The papules are thickly set, and even at this stage a
coalescence of lesions may be noted. The skin is thickened and indu-
rated, and feels like embossed leather. Soon the grayish outlines of
the vesicles make their appearance and the confluent aspect of the
exanthem becomes accentuated. With the conversion of the vesicular
contents into pus, great swelling and oedema develop, particularly about
the face and scalp. The eyelids are enormously puffed, and the margin
of the upper lid so greatly thickened that it completely overlaps the
lower. The nose, lips, and ears are swollen and distorted, imparting
to the countenance a most hideous expression. The transformation
of the features is so rapid and complete that nurses and physicians who
are off duty for a day or two are frequently unable to identify such
patients on their return to the wards. The hands and feet are swollen
Fig. 38
Profuse eruption upon hands.
to double their natural size, and are most exquisitely tender and painful.
When full pustulation is established the neighboring lesions coalesce
and form large, flat blebs. In severe cases the walls of the pustules are
completely swept away, producing flat, purulent, pasty-looking infiltra-
tions of enormous proportions. W^hen the pus exudes upon the sur-
face and dries, a most disgusting stench arises from the body.
In favorable cases, with the beginning of desiccation, a subsidence
in the oedema takes place, and the crusts are cast off from the skin. The
decrustation is, however, slower than in the discrete and semicon-
fluent forms of the disease. TJie suppurative proces§uis*de^,grand
iiKJjQe pergigjtsnt, and may lead to the consecutive production inme
same areas of large crusts which are successively thrown off as they
form. Owing to the greater depth of the purulent inflammation in the
integument, more extensive destruction of the true skin occurs and
consequently the scarring is deeper and more conspicuous. Instead
of discrete pits the face may be seamed with scars in a most frightful
manner.
77/ a; va luicri i':s o !<• sMy\ l li-ox 201
In severe cases which are going to (cnniiijii*; i;i(;illy tin- ccjursc pm-
.snTuT isTaTIi('rT!ino'rv"i"iit froin llial, above; (lc.scrilM'pie.s.sed and
•^ccomp;iiii<'il I)) l)nt little swelling. 'J'he face has a peculiar hinrrerl
appeaniiiee. Tlie older writers regarded the swelling of the face as a
favoral)l(! sign, inasmneh as it indicated a certain vigor of the consti-
tution. Physicians who have had cx[)erience with smallpox will rcco'^-
nize the correctness of this observation. ^wplUng of the features is to
be weJcom,ed.-aa., a, favorable indication, and the absence of . jpedema, iii
confluent eruptions must, be regarded with grave foreboding. An
'*ft1ffimo'us sign in these cases is the early development of flat, brownish,
depressed scabs on a few of the vesicles on the forehead and cheeks.
In these suppressed eruptions the vesicles are only partially filled with
fluid, and the features are only slightly swollen; the skin is roughened
and presents a somewhat parchmenty appearance. There is most
profound prostration, and death results in almost every case.
Fig. 39
Swelling of the face on the seventh day in a fatal case of smallpox.
In confluent smallpox: the mucous membrane of the mouth, throaty
and_ nose H always severely involved. The epithehum of these parts
Ti^equently becomes so completely disorganized by the eruptive process
that it presents the appearance of diphtheritic membrane. Swelhng
of the tonsils and soft palate is often so great as to cause the greatest
difficulty in swallowing. It is in the intensely confluent cases that
glossitis variolosa is apt to occur. The parotid gland sometimes becomes
acutely inflamed, perhaps by extension along the ducts of Steno. Pro-
fuse expectoration of saliva is not infrequently noted. The pharvnx
and larynx are almost always the seat of an extensive eruption, giA'ing
rise to dysphagia, hoarseness, and aphonia. Acute oedema of the glottis
is one of the most serious accidents to which this form of the disease is
liable; when it develops the patient's life is placed in imminent danger.
At a somewhat later period serious submucous infiltrations of pus may
develop, producing tonsillar or postpharyngeal abscesses or perichondritis
of the larynx.
202
SMALLPOX
The constitutional symptoms during the suppurative stage of con-
fluent variola are most pronounced. There is marked pyrexia (104° to
105° F.), rapid pulse, frequent cough and expectoration, great restless-
ness, inabihty to sleep, and profound prostration. Dehrium is very
common, but the patient does not become maniacal as he often does
earlier in the disease. At this stage, also, complications are liable to
occur, such as corneal ulcer, keratitis, pleurisy, empyema, suppuration
of the joints, celluhtis, phlegmonous inflammations, and gangrene of
the skin. Vomiting and diarrhoea may supervene, and still further
exhaust the patient's ebbing vitality. In fatal cases the patient sinks
into a comatose condition, the pulse becomes excessively rapid, and
the temperature not infrequently rises to 105°, 106°, or 107° F. Thus
closes the final chapter in one of the most distressing, cruel, and frightful
diseases "to which human flesh is heir."
Fig. 40
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W. F., aged thirty-seven years. Case of smallpox ia an un vaccinated man, showing the rise of
temperature in the initial stage ; the secondary or suppurative fever, and a later irregular fever due
to ai scesses and cellulitis ; recovery.
\
The mortality rate in confluent smallpox varies in different epidemics,
but it is always extremely high. In general terms it may be stated that
_^.le,ast one-half of such cases perish. When this form of the disease
terminates in recovery it is' tmlyafter^ long and tedious convalescence,
interrupted by the development of boils, abscesses, and other compli-
cations.
Hemorrhagic Smallpox. — Of all the forms of variola the hemorrhagic
is the most formidable and mahgnant. .-For. those w-ho contract a-.-Wjellr.
,j3aarked attack ot this type of the disease there is absolutely no hope.
According as the hemorrhage precedes or follows the appearance of
the variolous lesions, two varieties are distinguished: (1) the so-called
\^urpura variolosa, in which the-hemorrbage js the primary exanthem;
(2) variola 'pustulos a hemorrhagica, in which it comes on secondarily.
In certain epidemics a petechial eruption is frequently seen at the
close of the initial stage of the disease, at or about the time when the
eruption should appear. This symptom often precedes the purpuric
77//'; vAniH'i'iKs ()!<• sMMj.rox 20;i
or hemorrhagic; lonii of the disease, and is IIk rcl'orc, as a rule, an early
sign of inaligiiiiMcy. At other tiiDcs pclcchiic and cfc-hymoscs af>)jear
between tlie j)a|)iiles or vesicles, or (h-vclo]) actually in the, bases of
these lesions. The vesicles and [)ustules may contain })nrulent material
or m;i,y fill up witli sanguinopurulent fluid. Consiclerahle diversity
of ;i[)j)(!arance is sometimes manifested in the eruption of a single case.
There is no satisfactory explanation at hand io elucidate the causation
of hemorrhagic small{)OX. It wf)uld aj)pear that the determining factor
is largely resident in the individual, inasmuch as such cases may be
derived from ordinary smallpox, and, on the other hand, may give rise
to the usual forms in other people. The frequency of this form of the
disease varies in different epidemics, being commonest when a more
malignant type of the disease prevails. It is well known, for example,
that hemorrhagic variola was exceptionally common during the virulent
pandemic of smallpox in 1871-72.
Variola Purpurica. — Variola purpurica, or purpura variolosa, is the
gravest and most malignant form that smallpox can assume. Zuelzer
has called attention to the observation that 4h€period,Qf incubation in
hemorrhagic smallpox is not infrequently abridged to^six. or eight days.
The initial stage does not differ essentially from that of ordinary variola.
The patient suffers from chill, fever, and headache, although the temper-
ature is not as likely to reach so extraordinary a height as in confluent
smallpox. The pain in the back is usually violent, and prostration
excessive. Furtheriu7)reV'°ihe':"p^^ siiffers from precordial
"Histfess, and from severe retching and vomiting. The vomiting in this
iorraj)| the disease is a most distressing symptoni, and commonly proves
Miiore persistent than in ordinary smallpox. It not iiifi((|ueiirly eon-
yjmes^QI_seYeral days after the appearance oi the exantliem. Toward
the end of tlie initial stage a diffuse efflorescence appears on various
parts of the trunk and extremities, while the face remains for a time
exempt. The rash is at first scarlatinoid in appearance, and disappears
partially under digital pressure; later it becomes more intense and of
a deeper hue, ancl hemarrhagic., extravasation into the skin occurs.
Petechia^ vibices", and ecchymoses develop upon the chest, axilla^, lower
portion of the abdomen, the groins and legs; the dark-red or purplish
discoloration now present no longer fades away under pressure of the
finger. The discoloration rapidly extends to the face, which becomes
dusky red or livid and swollen. .The conjunctivae are injected, the eyes
bloodshot, and the lids bluish, owing to hemorrhage into the cellular
"tissue. Frequently the extravasation of blood under the conjunctiva
covering the sclerotica is so great as to cause this membrane to project
bgyonalhe lids, like a sac hlled with blood. Under siich 'conditions
"th-e-pfttreTTt^is unable to completely close the eyes. The cornea retains
its normal transparent appearance, but, owing to the elevated conjimctiva
about its periphery, appears to be sunken deeply into the eyeball.
This condition, together with the dark discoloration of the face and the
tumefied features, gives to the patient a peculiarly unnatural expression.
A close scrutiny of the skin usually reveals the presence of small abortive
204 SMALLPOX
i^ vesicles, which may be almost obscured by the purplish ecchymoses
upon which they may be situated. These are most apt to be found upon
the forehead, axillae, groins, or wrists. The vesicles, which are of a plum-
qolgred or -leaden-gray tint, never develop to any extent, I mt, remain
perfectly flat. As the disease progresses the discoloration of the skin
deepens on all parts of the body, giving to the integument a deep-indigo
hue, which at times almost approaches black. In such cases it is difficult
to say, judging from the skin alone, that the patient is not of African
origin. Hence, this form of the disease has been known as black
smallpox, or variola nigra.
,^The- eruptive process does not always present imequivocal evidence^
of smallpox, for there may be complete absence of true va~riele«s-ksiQjiSu__
A young woman was admitted to the Municipal Hospital, during the
spring of 1902, who exhibited upon the skin nothing save a universal
scarlatinoid eruption of dusky hue. No vestige of papulation or vesicu-
lation was present. There was hemorrhagic extravasation beneath the
sclerotic conjunctiva, and bleeding from the mouth, kidneys, and uterus.
The diagnosis was rendered possible in this patient by tlie characfer
of the initial illness, and the prevalence at the time of an epidemic of
smallpox. In another case, observed in a young man some years ago,
the eruption consisted of numerous petechise and ecchymoses, but no
lesions distinctively variolous were present. Such eruptions might
readily be confoupded with those of malignant scarlatina or measles,
or purpura hemorrhagica. Patients presenting manifestations of this
character were not uncommonly seen during the very malignant epi-
demic of 1871-72.
In this, as in other types of variola, the pharynx and upper part of
the respiratory passages participate in the eruption. There is apt to
be more or less cough, with bloody expectoration. The tongue is large
and red and covered with blackish blood crusts, which may also be seen
on the lips. A fa; tor peculiar to this form of the disease is exhaled; it
is of a sickening character, and suggests stale or decomposing blood.
Purplish spots may be seen upon the gums, palate, tongue, and buccal
surfaces, but the general mucous membrane is usually pale. Hemor-
rhages are quite certain to occur from the nose, bronchial mucous
membrane, kidneys, rectum, and uterus. Vomiting of blood occurs in
quite a large percentage of cases, and bloody stools are by no means
infrequent. Indeed, blood may issue from any or all of the mucous
surfaces of the body; we have even seen a sanguinolent fluid ooze from
the eyes. Women almost always suffer from severe metrorrhagia, and,
if pregnant, commonly abort. The temperature is seldom high, usually
100° F. or thereabouts; the pulse, however, is rapid and compressible.
In our experience this type of smallpox occurs most commonly in
young and vigorous persons. It is rare in young children and in adults
of advanced years. The majority of victims are included between the
ages of fifteen and forty years. Un vaccinated pregnant women seem
particularly susceptible to this dreadful form of the disease.
One of the most extraordinary features about this hopeless malady
TIIM VA filEri/'JS OF SMA LIJ'OX 206
is tliat i.li( ;_j;i(Mi l;il < nmlilioii of the paticuL j'ciuaiiiii clear almost until
the last mouKMit oi life. There may he delirium or stupor, hut usually
the hapless vietim faces death with his mind unohscured and his intellect
unimpiu'nMl. On one oecjision, one of the writers, sfandin^ Ijy fhe
hedside of a most malignant case of purj)uric variola mid not thinking
that the patient was conscious, remarked to the residcmt physician that
there was absolutely no ground for hope in this case. The patient,
although his face was of livid hue, immediately rose in bed, and in a
husky voice exclaimed, with surprise, "J)octor, do you m(;an to say
that I cannot get well?" In less than twenty-four hours the patient
was a corpse.
The course of this type of smallpox is extremely rapid. JJeatli usually
takes place fypn;i tk a-third-io. llie sixth day of the eruption, common! v
as a result ot sudden heart-taikire. Instances have even l)een reconled
in which the patient has succumbed during the initial stage, but such
cases must be of excessive rarity. No more terrible disease exists than
black smallpox, for from this malady there is no hope of recovery.
Variola Pustulosa Hemorrhagica. — Hemorrhagic extravasation into
the skin may develop at any time during the course of the variolous
exanthem. Various types of hemorrhagic smallpox may exist, inter-
mediate between variolous purpura and the pustular hemorrhagic form.
Htemic effusion may take place during the papular stage of the disease
and may occur in the papules themselves or in the intervening areas
of skin. Or the cutaneous hemorrhage may first appear during the
period of vesiculation. In this case the vesicles, instead of containing
clear serum, fill with a sanguinolent fluid. In other cases the extravasa-
tion of blood may be delayed until the pustular stage is reached. The
later the hemorrhage is postponed, the more conspicuous are the variolous
lesions. The earlier it develops, the more will the true smallpox eruption
be suppressed. The amount of swelling and oedema is proportionate
to the extent and development of the smallpox exanthem. ^Vhen
petechia? and ecchymoses develop early the skin has a peculiar livid
appearance, and there is not much swelling. Scattered here and there
between the flat, poorly formed vesicles are seen non-elevated, pea-
sized or larger, bluish, ecchymotic spots.
The hemorrhagic condition of the pustules may be limited to certain
localities, or it may extend over the entire body. Inspection of the legs
will often affard the first evidence of this mahgnant tendencv. During:
the papular or vesicular stage it will be noted that some of the lesions
upon the lower extremities are surrounded by a lialo of the tint of
dilute claret wine. Ai a later period scattered pustules in this region
will be seen to have centres of the color of indigo blue. Bv degrees
others take on the same appearance and the color gradually deepens,
until at last in severe cases the pustules on all parts of the body become
distinctly hemorrhagic. At the same time Mxid spots may be seen upon
the mucous membrane of the mouth and fauces. The gums are spongy
and disposed to bleed. Hemorrhages occur from the nose and internal
mucous surfaces, as in purpuric variola.
206 SMALLPOX
The temperature hovers about 100° F., but rises higher in the event
that the eruption progresses to pustulation. The pulse is rapid and out
of proportion in frequency to the moderate febrile movement. As in
the primary hemorrhagic type, the mind commonly remains unclouded
almost until the end.
This form of hemorrhagic smallpox is more protracted in its course
than variolous purpura, but offers scarcely more hope for the patient.
The severity of the prevailing epidemic influences the prognosis to a
certain extent. In the malignant epidemic of 1871-72, patients present-
ing even mild evidences of the hemorrhagic tendency almost invariably
succumbed to the disease. At other times we have seen recovery take
place in a few cases, but only among those in whom the hemorrhagic
condition of the pustules was limited to a small number of lesions and
appeared at a relatively late period of the disease, and in whom hemor-
rhages from the mucous membrane were not excessive nor long continued.
In June, 1902, a woman, aged twenty-four years, was admitted to
the hospital with a most severe smallpox. She had never been success-
fully vaccinated, although she stated the attempt had been made six
times. On admission her appearance was such as to lead us to regard
her case as practically hopeless. The eruption was extremely profuse
and of a dusky-red color. Upon the legs some of the vesicles showed
distinctly bluish centres. On raising the upper lids an extensive sub-
conjunctival hemorrhage was visible in both eyes. The patient was
expectorating blood, and was bleeding from the uterus and kidneys.
On the following day the hemorrhagic symptoms began to subside and
the variolous lesions to develop more conspicuously. The hemorrhages
gradually ceased and the pustules filled up with a yellowish, puriform
material. From this time on the case pursued the, usual course of a
severe confluent smallpox, the patient finally recovering after a most
desperate illness. Special mention is made of this case inasmuch as it
is a remarkable exception to the general rule.
We have never known recovery to result where all or nearly all of the
vesicles assumed the hemorrhagic character at an early stage, and where
there were well-marked epistaxis, haematuria, conjunctival hemorrhage,
and bloody stools, together with rapid and feeble pulse and the peculiar
livid, purplish, or indigo color of the skin. Pustular hemorrhagic small-
pox is more apt to develop in aged and debilitated subjects, in pregnant
women, and in those addicted to the free use of alcohol.
We have occasionally seen distinct hemorrhage into the pustules in
the lower extremities of individuals who had a smallpox modified by
a remote vaccination. Most of these cases pursued the course of a
varioloid and did not appear, to any great extent, to be unfavorably
influenced by the bloody extravasation into the lesions.
The prognosis in these cases depends somewhat upon the character
of the prevailing type of the disease. Modified eruptions associated
with hemorrhage might with propriety be termed hemorrhagic varioloid.
Exceptionally Mild Smallpox.^ — In every epidemic of variola there
are seen patients who, though unprotected by previous vaccination,
TIIM VAItlETII'^H, OF SMAfJ.POX
207
present remarkably mild manif(!stalions of the- disease. 'J'lie exantliem
in such cases may amount to merely a half-dozen or a clfjzen lesions, or
in rare instatices there may be even a complete absence of the eruption.
The mildness of the constitutional synijjtoins and the paucity of the
eruption in these cases may, with r(;ason, be attributed to a certain
degree of natural insusceptibility to the disease.
, We desire to call attention to the fact that smallpox, under certain
circumstances, may depart from its usual life history and, during
epidemic prevalence, exhibit in a more or less iiiiifonn iiuniner an
Example of a remarkably mild type of smallpox which has been prevailing for some years in
various sections of the United States. Patient unvaccinated.
extraordinary mildness. Such an epidemic has been prevailing in
various sections of the United States for the past five or six years. It is
said to have been imported into this country from Cuba, "vvhere it had
existed during the Spanish-Cuban war. From the South this form
of smallpox gradually became disseminated throughout the Middle and
Western States. The disease was recognized as contagious, as it was
seen to spread from one person to another and from town to town.
But wherever it appeared it was observed to exiiibit the same mild
type, rarely resulting in death. On account of its aberrant symptom-
atology there was considerable diversity of opinion among physicians
208 SMALLPOX
as to the nature of this disease. Many regarded it as chickenpox;
others contended that it was smallpox. Still others, not being able to
reconcile the picture with the symptomatology of either of these two
diseases, regarded the new form as impetigo contagiosa, or as a cutaneous
disease of a new and strange variety.
During the years 1898, 1899, and 1900 there were treated in the
hospital under our care 162 patients suffering from this mild type of
smallpox. Of this number 138 were unvaccinated, and yet not a single
death resulted; 12 of the patients were white and 150 were negroes.
(The disease appeared to start among the Southern blacks, but later,
in other portions of the country, the whites constituted the great majority
of the patients.)
The onset of this type of smallpox does not differ greatly, except in
degree, from that commonly seen in the severer forms of the disease.
According to information obtained from many of the patients the
entire initial illness was often so mild that they were not obliged to remain
constantly in bed; some even stated that they had scarcely been ill at
all, and yet on close interrogation it was found that all had suffered to
some degree from the usual symptoms. In a few patients the initial
stage was marked by its usual severity.
The vast majority of patients would not remain in bed after the
eruption appeared. They preferred to don their clothes and indulge
in various games. It was a novel sight to see these unvaccinated small-
pox patients engage in a game of baseball on the eighth or tenth day
of the eruption, by which time desiccation was often well advanced.
Not more than two or three patients during this epidemic showed
symptoms which were at all serious. In some of the mildest cases it
was impossible to count as many as a dozen pustules upon the entire
cutaneous surface. As a rule, the exanthem was discrete and the lesions
sparsely distributed. A few patients, however, exhibited more copious
eruptions, even to the extent of producing confluence on the face. In
very mild cases the eruption pursued a short, abortive course. Even
in the more pronounced cases the duration of the disease was con-
siderably abridged. The course of the disease was identical with that
seen in varioloid, and yet in the vast majority of the patients there was
no known modifying influence operating such as results from vaccination
or a previous attack of the disease.
Why smallpox in the unvaccinated should present itself so generally
in such an exceptionally mild form is a problem most difficult to solve.
It has been suggested that this form of variola originated in Cuba and
that smallpox in the tropics is less severe than in cold climates. We
are not sure that this is true, but, even if it were, there is no reason why
the disease should not resume its old and familiar form when transferred
to temperate or colder regions. It has furthermore been suggested in
explanation of the mild type that the modification is due to hereditary
vaccinal influence. That this is not true is evidenced by the fact that
the disease in the South prevailed largely among negroes, and it is a
notorious fact that this race most flagrantly neglects vaccination.
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PLATE XXIX.
Same Patient as in Plate XXVIII.
Photograph taken 48 hours later indicating the rapidity of the stages of
desiccation and decrustation.
THE VAUIF/ril<:H ()[<' SMAhhI'OX 209
Indeed, wc wore able to ascertain l)y iii(|iiiry tliiit I lie parculs of many
of our patients had never been vaccinated. A^:i\u, a similar milfl
epidemic occurred in the days of Jcinicr, before there would fiave been
an opportunity for an hereditary iulhicnce to become; manifest. Jenner
in 1798 wrote:
"About seven years ago a species of smallpox spread through many
of the towns and villages of this part of (Jloucesterslu're. It was
of so mild a nature that a fatal instance was sc-arcely ever heard of,
and consequently so little dreaded by the lower orders of the com-
munity that they scrupled not to hold the same intercourse with each
other ks if no infectious disease had been present among them. I never
saw nor heard of an instance of its being confluent. The most accurate
manner, perhaps, in which I can convey an idea of it is, by saying that
had fifty individuals been taken promiscuously and infected by exposure
to this contagion they would have had as mild and light a disease as
if they had been inoculated with variolous matter in the usual way.
The harmless manner in which it showed itself coidd not arise from
any peculiarity either in the season or the weather, for I watched its
progress upward of a year without perceiving any variation in its general
appearance. I consider it, then, as a variety of the smallpox."
Sydenham is said to have described a prototype of the mild variety
of smallpox in 1771.
Van Swieten, the great Dutch physician of the eighteenth century,
wrote in 1759 as follows:
"The primary fever is often little more than a febricula, and the
pustules seldom exceed more than from one to two hundred. The form
is so mild that secondary fever is not manifested and constantly is want-
ing, convalescence coming on on the eighth day of the eruption."
The mildness of the type of smallpox under discussion may be compre-
hended from the following figures: During the year ending June 30,
1902, there were in the United States 55,857 cases of smallpox w4th
1852 deaths (a mortality rate of 3.31 per cent.), and in the year previous
38,506 cases and 689 deaths (a mortality rate of 1.79 per cent.). These
figures include the smallpox in certain sections of the country where
the type was of normal severity.
It is reasonable to presume that in such an epidemic the causative
germ of smallpox has become attenuated in its virulency, as a result
of certain unknown influences. By no other method of reasoning could
we account for the singular and uniform mildness which has character-
ized this extensive and widespread epidemic. We believe, furthermore,
that the infectivity of this mild variety of smallpox is considerably less
pronounced than that of classic variola. We have noted that this type
of the disease has frequently failed to spread where there appeared
abundant opportunity for its diffusion.
Varioloid (Variola Benigna; Variola Modificata ; Modified or Miti-
gated Smallpox). — The term varioloid, from an etymological point of
view, would indicate a disease merely bearing a resemblance to variola.
The impression thus conveyed is, of course, a false one, for varioloid
14
210 . SMALLPOX
is true smallpox in a modified form. This is evident from the fact that
the infection arising from this milder form of the disease gives rise to
variola vera in unprotected persons. Since the introduction of vac-
cination varioloid has become much more frequent than in former
times. Indeed,, in well-vaccinated communities modified smallpox is
apt to numerically exceed the cases of ordinary variola.
It is well known that the immunity conferred by vaccination, although
complete at first, becomes in the course of time more or less impaired
in the vast majority of individuals. The protective influence from this
procedure diminishes very gradually for a variable period of time and
may ultimately become entirely extinguished. It is readily compre-
hensible, therefore,. that we may encounter vaccinated persons in whom,
on the one hand, there is almost complete protection against smallpox,
and, on the other, individuals whose susceptibility to smallpox has quite
fully returned. TW farmgrj.^jdien they co smallpox, will exhibit
the mildest sort of symptoms, with an insignificant eruption, while the"
latter may develop the most severe confluent or even hemorrhagic
Tariola. Between these two extremes one may encounter almost every
possible intermediate grade. It should be stated, however, that it is
exceptional for the vaccinal protection to be completely lost. Usually
a modifying influence upon the course of the disease will be exerted,
even when it appears at the outset that the patient is going to suffer
from confluent smallpox. ^,The vast majority of vaccinated persons
who contract smallpox have the Qpurse of the resulting disease favorably
influenced.
We class as varioloid all vaccinated cases in which the eruption is
markedly abridged in its course and in which there is but little if any
secondary rise of temperature. To be sure, cases in which a second
attack of smallpox is favorably influenced by an antecedent one would
also deserve this designation. We regard as variola all un vaccinated
cases and all those vaccinated cases in which the eruption pursues its
regular course, and is attended with secondary or suppurative fever.
There are certain unprotected individuals who possess more or less
natural immunity against smallpox and in whom the disease is mild
and of short duration. Some writers would include these cases in the
category of varioloid, but we prefer to regard them simply as mild
forms of variola vera.
We not infrequently meet with cases of smallpox in vaccinated indi-
viduals which are so near the dividing line that the determination of
the class to which they belong must be postponed until the suppura-
tive stage has passed.
Varioloid cannot always be distinguished in the initial stage from
variola vera, since the train of symptoms may be the same and of equal
severity in each. In many cases, however, the invasive manifestations
in varioloid are extremely mild and will warrant a prediction of a
sparse exanthem. Unmodified smallpox is so seldom ushered in with
mild symptoms that the likelihood of its occurrence after shght consti-
tutional disturbance is remote. It is important to remember, however,
Tlll<: VAh'f/^
4
5
5
1
8
4
3
8K
Stage of disease
at which abor-
tion occurred .
Discharged
carrying foetus.
Aborted 19th day
of eruption.
Died 7th day
without abort.
Aborted 7th day
of eruption.
Aborted 1st day
of eruption.
Discharged
carrying fcetus.
Aborted 6th day
of eruption.
Aborted 1st day
of eruption.
Died without
aborting.
Discharged
carrying fcetus.
Aborted 6th day
of eruption.
Aborted 4 th day
of eruption.
Aborted 23d day
of eruption.
Discharged
carrying foetus.
Died without
aborting.
Delivered 21st
day of eruption.
Aborted 1st day
of eruption.
Discharged
carrying foetus.
Aborted 17th day
of eruption.
Aborted 18th day
of eruption.
Discharged
carrying foetus.
Discharged
carrying foetus.
Aborted 33d day
of eruption.
Delivered 2 days
before eruption.
Discharged
carrying foetus.
Aborted just be-
fore death 3d
day.
Discharged
carrying foetus.
Delivered on 9th
day.
Discharged
carrying fcetus.
Discharged
carrying foetus.
Result.
Remarks.
Recov-
ered.
"
Foetus had well-marked
variolous vesicles scat-
Died.
tered over body.
Died
7th day.
Died
1st day.
Recov-
ered.
Died
6th day.
Died
Infant infected in utero,
4th day.
exhibiting eruption on
9th day of life ; died on
14h day.
Died
Ceesarean section per-
8th day.
formed immediately
after death, but infant
found dead.
Recov-
Delivered at term.
ered.
<.
Infant vaccinated at
birth ; vaccination
"
took; later contracted
,.
varioloid and died.
"
Delivered at term.
Died.
Post-mortem Csesarean
section ; foetus dead.
Recov-
Child vaccinated three
ered.
times, but without suc-
cess remained well.
"
Child was successfully
vaccinated, but soon
developed smallpox
eruption and died ; in-
fection in utero.
.<
Delivered at term.
*'
Delivered at term.
"
Delivered at term.
«
Child at birth was dead
and covered with a dis-
crete smallpox in the
pustular stage.
"
Baby vaccinated, but
without success ; devel-
oped smallpox erup-
tion and died.
"
Delivered at term.
Died.
Recov-
ered.
"
Child was successfully
vaccinated ; smallpox
appeared on 7th day.
and child died ; infec-
tion in utero.
"
Delivered at term.
**
Delivered at term.
THE VARIETII'JS f)/'' SMALLPOX
22J
No.
Age
23
Character
ot
disease.
Variola.
Whether vac-
cinated, and if
so, character
of cicatrix.
Not vaccinated
Month of
progn'cy
wlicii
attacked.
8^
Stage of disease
at, vvliii'li ii,l)or-
tioii occurred.
Result.
Recov-
RernarkB.
101
Aborted 1st day
of eruption.
Aborted Utii day
of eruption.
ered.
102
23
"
1 poor scar.
8
«
Child at birth healthv ;
successfully vaccinat'd;
12 days later a half-
dozen small jK^x paiiules
api>eared; child died
of erysipelas.
103
21
Varioloid.
1 fair "
8
Delivered Ist day
of eruption.
"
Smallpox eruption ay)-
peared on child 10 days
104
24
"
1 good ' '
4
Discharged
carrying fuetus.
"
after birth ; infection
in ulero.
105
23
"
2 good scars.
8
Discharged
carrying fa;tus.
Delivered at term.
106
42
Variola.
1 fair scar.
2K
Discharged
carrying fcctus.
1
107
26
Varioloid.
2 poor scars.
9
Delivered at term
"
108
29
"
1 fair scar.
4
Aborted 37th day
of eruption.
Foetus showed a sparse
vesicular eruption.
109
25
"
2 good scars.
6
Discharged
carrying fcetus.
110
35
"
2 fair "
6
Aborted 28th day
of eruption.
111
32
"
2 good "
6
Aborted 1st day
of eruption.
112
22
Variola
(hemor-
Not vaccinated
6
Aborted 5th day
of eruption.
Died
5th day.
113
27
rhagic).
Varioloid
Vaccinated
2
Discharged
Recov-
(mild).
16 days before
eruption.
carrying foetus.
ered.
Smallpox in the Foetus.— During an attack of smallpox the causative
germ, in all probability, circulates in the blood stream of the patient.
Therefore, when a pregnant woman suffers from variola, we would
naturally expect the foetus to be likewise attacked and to pass througli
all of the phases of the disease simultaneously with the mother. Strange
to say, however, this is but seldom the case. In a minority of instances
the foetus does become infected, but not synchronously with the infection
of the mother. Indeed, in most cases in which the fatus develops
smallpox it passes through a period of incubation in the same manner
as if it were in the outer world ; that is to say, about two weeks elapse
from the time the mother shows symptoms until the disease appears in
the child. From this observation, which is quite generally the experience
of most writers, it would seem that the infant in utero ordinarily becomes
infected, not through the maternal circulation, but through contact or
proximity. If the blood of the mother were the infecting medium the
disease in the foetus should be of constant occurrence. There are rare
cases in which the foetus contracts smallpox after an exposure to the
disease by a mother who happens to be an immune. In such cases it
is difficult to understand how the causative agent could reach the
infant in utero save through the maternal blood.
Smallpox may be communicated to the foetus in utero at any time
between the fourth month of gestation or possibly earlier and the full
term. When infection takes place in the earlier stages of intrauterine
life, the foetus usually perishes and is expelled in three or four days,
or it may be retained for three or four weeks after hfe has become
222
SMALLPOX
extinct. There are well-authenticated instances in which the child
suffers and recovers from an intrauterine attack of smallpox, and is
born at term with variolous scars.
When the infection takes place during the later periods of pregnancy
the child at birth may be covered with the eruption, which may represent
any stage of development. This occurrence is so well authenticated
that it is unnecessary to quote any cases from literature. We have
ourselves met with four or five instances of this character. In one
case a six months' foetus presented a few red spots which evidently
resulted from a mild vesicular eruption. In another instance an infant
was born at the eighth month, on whose body at birth the eruption
Fig. 43
Smallpox contracted in utero and appearing nine days after birth ; the vaccine lesion seen upon
the arm resulted from vaccination on the second day after birth.
was just appearing. In a third case a four months' foetus was
expelled on the thirty-seventh day of the maternal eruption. The
eruption on the child was rather sparse, consisting of two whitish,
variolous pocks on the sole of the right foot, one on the heel of the left
foot, one on the chest, one on the back, and two firm lesions upon the
palm of each hand.
The fourth case occurred in a colored child (Fig. 44) born at eight
months, on the thirty-third day of the mother's eruption, the latter
suffering only from a very mild varioloid. The infant had evidently
been dead for some days, as the epidermis was detached from the under-
lying corium in large areas. Smallpox lesions in the pustular stage
(about fifth or sixth day) were present upon the face, extremities, and
body, but not profusely. It was calculated that the exanthem in the
Tim vAfin'■ mci \\\\\\ as a
sefjiiel of variola, especially in llic lower exireniities, \i\\\\\\!i^ rise to
phlegmasia alba dolens.
Joint Disease — Joint disease occasionally occurs ;is ;i eornpliejition.
or sef(uel ot" siTia,llj)ox, particuhirly in children. One or iu(M-e of the
joints may become swollen and painful. The elbows ap})ear most
likely to suffer. Chondritis and osteitis may occur, followed by suppu-
rati(m and destruction of the joint and fre(|uently by death. Neve has
reported a number of cases of joint and bone disease following smallpox
in children, and we have likewise met with a few such cases.
Abdominal Complications. — Smallpox is singularly exempt from
abdominal complications. Diarrhcva not infrefpiently occurs as the
result of some derangement of the digestive function. While this
symptom is usually controllable, it may occasionally be so severe as to
precipitate a fatal issue in those greatly weakened.
Peritonitis is a rare complication, and when it occurs may be attrib-
uted to some local cause.
Orchitis. — We encountered this complication in perhaps six or eight
patients during the first two years of the epidemic of 1901-04. The
swelling may involve the entire scrotum or may be limited to the testicle
and epididymis. One or both organs may be affected. The parts often
become extremely firm to the touch. The enlargement commonly per-
sists for a few weeks and then gradually subsides, although a variable
amount of infiltration may continue for a much longer time. A young
man recently under our care had a severe confluent smallpox, complicated
by gangrenous inflammation of the arm, iritis, and orchitis. The right
testicle was swollen to three times the size of the left. The swelling
was firm and not very painful. The infiltration, which extended along
the spermatic cord to the external abdominal ring, reached the diameter
of an adult thumb. It is said that the analogue of this condition,
ovaritis, may develop in the female. We have never observed any
symptoms during an attack of smallpox pointing to acute disease of the
ovaries.
Phimosis. — Phimosis not infrequently occurs in the pustular stage
of smallpox as a result of the swelling of the areolar tissue of the prepuce
occasioned by the presence of the eruption. This is seen most commonly
in young children.
Nervous System. — Psychic disturbance in the form of delirium is not
uncommon in the early eruptive period of smallpox. Tt may in some
cases supervene at a later period of the variolous process. The delirium
may persist for some days and then disappear, or in rare cases it may
develop into a confusional insaniti/. The following cases of insanity
after smallpox have come under our observation:
E. M., aged tw^enty-eight years, was admitted to the ^Municipal
Hospital on November 29, 1903, wdth smallpox. She bore one good
scar from a vaccination in infancy and had a well-marked, discrete
variola. On December 6th she was observed to be tlelirious at times.
The mental excitement increased and the patient became maniacal
238 SMALLPOX
and had to be strapped in bed. From this time on there were occa-
sional lucid moments, but for the most part the patient was delirious.
She would sing and cry and appeared to be completely demented.
Despite the fact that the variolous symptoms had quite subsided, the
patient continued to lose weight and strength and died in an insane
condition, apparently from exhaustion, on January 24, 1904, two months
after the onset of the attack of smallpox.
Mrs. A. C. was admitted to the Municipal Hospital on March 10,
1904, with a modified attack of smallpox. She bore two good vaccination
scars from infancy. The patient had never exhibited any mental
disturbance before the attack of smallpox. Family history negative.
On admission the patient exhibited evidences of mental disturbance.
She spoke at times rationally, but for the greater part talked inco-
herently and almost exclusively upon religious topics. I^ater she
became maniacal, jumped from the bed and through an open window;
she had to be strapped to her bed to prevent violence. At times refused
to eat or drink. She later, when released from her bandages, made
several more attempts to jump through the window. She was removed
to her home on April 9th, her mental condition having remained
unchanged.
Another patient, L. E., aged thirty-seven years, who had recovered
from a mild attack of smallpox, developed religious mania after con-
valescence. He was transferred to a hospital for the insane. It was
subsequently ascertained that he had, before his attack of smallpox,
suffered from a similar mental disturbance.
Several cases of insanity after smallpox are reported by Seppilli and
Maragliano. Of three instances referred to, one remained permanently
insane, the others recovering after appropriate treatment. The authors
also record the remarkable case of a violent maniac, who had been
confined for about six weeks in an asylum, who during an attack of
confluent smallpox was restored to his senses and after convalescence
from variola was discharged from the asylum as a sane man.
Brain symptoms sometimes appear during the stage of decline. We
cannot recall a single instance where we have observed clear and indub-
itable evidence of acute inflammation of this organ, yet we have seen
a few cases — perhaps not more than three — lapse into a state of lethargy
or coma, when desquamation had almost completed, without evincing
any preceding symptoms of inflammatory action. We have met with
a few cases in which there were peculiar psychic changes, followed by
aphasia. This condition we attributed to the presence of a circum-
scribed encephalitis. Westphal has called attention to cases of similar
nature. In 1872 he presented before the Berlin Medical Society a
patient, who during smallpox had had attacks of delirium or coma,
followed by a curious disturbance, characterized by slow, measured,
scanning speech, and ataxia of the upper and lower extremities, similar
to that seen in tabes.
Paralysis. — Various paralyses may develop during the course of
variola. During the past few years we have observed eight instances
COMPTACATI()NHlANI> SPJQUELjE OF SMALLPOX 289
of paralysis among about 3000 cases of smallpox. Of this niirnher
five died and three recovered.
In an infant, one year and four months of age, we observed a hemi-
plegia occur upon the first day of the (Tuy)tion. This succeeded repeated
convulsions which took place immediately before and after the appear-
ance of the exanthem. It is probable that this conchtion was not inti-
mately connected with the variolous process, but resulted from a brain
hemorrhage excited by the convulsive paroxysms.
In another patient, a woman, paralytic symptoms appeared during
the initial stage of the disease. She was brought into the hfjspifal in
a stuporous state, barely able to articulate. There was great difficulty
in swallowing and impaired power in the arms and legs; the loss of
power in these members subsequently became almost complete, but
later a gradual restoration of function occurred. The patient had a
most pronounced scanning speech, which was still ])resent when she
was discharged from the hospital. The reflexes were markedly exag-
gerated.
The third patient, a young colored man, had a severe attack of
smallpox, complicated by extensive gangrene of the scrotum and penis.
At the end of about ten weeks from the onset of the disease he developed
partial loss of power in the legs and arms. He could walk with great
difficulty with a cane. This condition persisted to the day of his
departure from the hospital.
Sometimes the spinal cord is preponderantly or exclusively affected,
the symptoms being those of a paraplegia. We have observed a half-
dozen or more instances of this serious complication, of which the
following are of especial interest:
Case L— C. M., aged thirty years; unvaccinated ; was seen in con-
sultation on April 22, 1902, on the first day of the smallpox exanthem.
The eruption was confluent on the face and hands, and covered thickly
all parts of the body.
The pustides began to shrink on the eleventh day; the secondare' fever
was not high, and there was no delirium. The patient was progressing
favorably until May 4th, when it was found that he was unable to void
his urine, necessitating catheterization. On the following day paralysis
of the lower extremities was noted, sensation being, however, preserved.
There was also complete loss of power over the bowels and bladder.
Immediately preceding the paralysis, there were hebetude and drowsi-
ness, which persisted for several days. A week later, on ^Nlay 12th,
slight motion returned in the legs. A gradual improvement in all of
the symptoms then set in. By June 23d the patient was able to walk
a few blocks without difficulty, although control over the bladder and
rectum was not quite perfect. Complete lecovery ultimately resulted.
Case II. — INIrs. N., married, aged nineteen years, was admitted to
the hospital with a smallpox of considerable severity. She was progress-
ino; well when durina; the third week of the disease she became unable
to move her legs. Sensation was impaired, but not entirely lost. She
had loss of control of the bladder and rectum. Within a few davs
240 SMALLPOX
partial motion was restored in the lower limbs. Later diarrhoea set in
and the patient died.
Case III. — J. W., a man aged thirty-eight years, was admitted to
the hospital on January 13, 1903. He had a scant, modified eruption,
having been vaccinated in infancy. About a dozen lesions were present
upon the anterior surface of the body, a few were scattered sparsely
over the extremities, and on the face there were about fifty lesions.
On the eighth day of the eruption the patient developed loss of power
in the legs so that he was unable to raise them from the bed. Sensation
was impaired, but not lost. There was no pain. The mental condition
was good. Later, retention of urine developed, followed after some
days by incontinence of urine and feces. The patient died on the
thirty-sixth day of the disease, after ten days of high and irregular
fever.
Autopsy disclosed the existence of a number of abscesses in the
kidneys. A culture from the intradural fluid in the spinal region
revealed the presence of staphylococci.
The cord from this patient and from Case II. were sent for study
to Prof. W. G. Spiller,^ of the University of Pennsylvania. The spinal
cord from Case II. had been hardened in alcohol and the microscopic
study was, therefore, unsatisfactory, although nothing distinctly abnor-
mal could be detected in the cord.^
In regard to Case III., Prof. Spiller states: "Strictly speaking, the
case was one of diffuse myelitis, but with the exception of a part of
the thoracic cord the myelitis was almost confined to the anterior horns
and was an anterior polyomyelitis, and probably of vascular origin."
Grave Lesions of the Nervous System Complicating Smallpox with but
Scant Eruption. — It would appear that in rare cases the poison of small-
pox is largely expended upon the nervous system, the skin escaping
with very few lesions. These cases are an exception to the general
statement that the gravity of smallpox is proportionate to the extent
of the eruption. A remarkable case of this character came under our
own observation during the year 1902.
E. M., a burly negro, aged twenty-seven years, was admitted to the
hospital on April 7, 1902. The patient had never been vaccinated.
According to the history, the initial symptoms had been well marked —
headache, vomiting, fever, and backache having been present. The
entire eruption consisted of about a dozen small papules, scattered
over the face, forearms, hands, and trunk. These were arrested in
their development and dried up in a few days, as occurs commonly in
cases of varioloid. The patient fell into a state of hebetude after admis-
sion, although he had walked to the ambulance. He became progres-
1 Prof. Spiller reported the full findings in these cases in a paper entitled " A Report of Two Cases
of Paraplegia Occurring in Variola, One heing a Case of Anterior Poliomyelitis m an Adult." Other
cases in the literature of the subject are referred to. Brain, Autuinn, 1903, London.
2 Since the above chapter was written an article on ' ' Nervous Complications and Sequelse of Small-
pox," by Dr. Charles J. Aldrich, has appeared in The American Journal of the Medical Sciences,
February, 1904. The author reports three interesting cases of aphasia after smallpox, and carefully
reviews the entire subject, giving a full and extensive bibliography.
COMPIJCATIONS AND SMQf/h'f.A': OF SMALLI'OX 241
sively more sfiiporoiis, had difriciilty ii) swallowiiij^, and pailial ana-s-
thesia and loss of power in the legs. Later, complete paraj)lcf,n"a wifli
incontinence of nrine and feces developed. He died on the fourteenth
day of the eru|>lion. The temperature on admission (third day of
eruption) was 00.2° V.; it later fluctuated for nine days hcfwccn this
point and 101° ¥., rising to 104° F. just before death.
The diagnosis of smallpox, owing to the poorly developed lesions, was
not entirely certain until about ten days later, when the wife and child
of the patient were brought into the hospital with variola. Autopsy
showed great softening of the spinal cord in the region of the lower
dorsal and upper lumbar vertebne. When the dura over this area was
punctured the softened cord ran out like pus. From this portion of
the cord a micrococcus w^as grown on culture. The brain showed no
gross changes save an intense congestion of the pia mater.
It is interesting to note that in one of the cases of paraplegia reported
by Westphal the patient had an extremely scant eruption and the
"disease was so mild that the patient did not go to bed." MacCombie
has also called attention to serious disease of the nervous system develop-
ing in the course of mild cases of smallpox.
Peripheral Neuritis. — Peripheral neuritis is encountered as a complica-
tion or sequel of smallpox with great rarity. In the case of paraplegia,
to which we have already referred, in which no microscopic changes
were foimd in the cord, the lesion may have been a peripheral neuritis.
Combemale believes the disorders of speech occasionally complicating
smallpox to be due to paralysis resulting from the action of toxins
upon the peripheral nerves.
Disseminated Spinal Sclerosis. — An interesting case of typical infectious
disseminated sclerosis is reported by Sottas. A young man, aged eighteen
years, with a discrete smallpox eruption, presented during his illness
most severe nervous symptoms. The patient was semicomatose, had
a slow dragging speech, nystagmus, general paralysis, atrophy of the
muscles of the trunk and limbs, and later contractures. At a subsequent
date there were characteristic tremors, exaggerated reflexes, inco-
ordination of voluntary movements, and great mental excitability.
Septicaemia and Pyaemia. — Septicaemia is commonly observed in the
stage of decrustation in confluent smallpox. In severe cases there may
occasionally be seen during the third week a high and irregular fever,
rapid pulse, low delirium, and great prostration, without there being
discoverable any pus collection to account for these s}Taptoms. Pyaemia
is more rare than would be supposed from the writings of the older
physicians. Abscesses in the liver, kidney, and lungs have been
revealed by autopsies, but with great infrequency.
16
242 " SMALLPOX
THE PATHOLOGY OF SMALLPOX.
The Histopathology of the Pock. — The microscopic structure of
variolous lesions has been studied by Barensprung/ Auspitz and Basch/
Ebstein/ Rindileisch/ Unna/ Weigert/ Touton/ Renaut,^ Leloir,^
Buri/" and others.
Weigert regarded the primary changes in the epidermis as necrobiotic
and diphtheroid, due to the local effect of the smallpox poison. He
claims to have found analogous alterations in the liver, spleen, kidneys,
and lymph glands, which he believes to be specifically variolous.
Nearly all of the other writers mentioned describe the early changes
in the skin as inflammatory in character.
According to Barensprung, cited by Curschmann, the red spot, which
represents the first clinical evidence of the pock, is produced by a
circumscribed hypera3mia of the papillary and deeper bloodvessels.
The papule is formed by peculiar changes in the cells of the mucous
layer or the rete Malpighii, which become cedematous, enlarged, and
granular. The vesicle is explained by an exudation of clear fluid from
the papillary bloodvessels, separating the cells above referred to. It is
evident from later studies that other important processes (subsequently
to be described) enter into the formation of the vesicle.
The older writers believed the umbilication to be due to a hair follicle,
sweat duct, or epithelial strand holding down the centre of the roof
of the pock. Auspitz and Basch first pointed out that it was in reality
due to the periphery of the pock swelling more rapidly than the centre.
This view is corroborated by Unna, of Hamburg.
Unna has carefully studied the structural changes in the skin, employ-
ing the most modern histological technique." The following description
is condensed from Unna's detailed account:
The development of the variolous vesicle is the result of certain
peculiar degenerations of the protoplasm of the epithelial cells. The
main features which differentiate the vesicle formation in smallpox
from that in chickenpox are the slowness of growth and the prompt
addition of suppuration to the epithelial degeneration.
The changes in the protoplasm of the cells of the mucous layers of the
epidermis are of two chief varieties. These have been designated, by
Unna, reticulating and ballooning colliquation (softening). Both are
special forms of fibrinoid degeneration.
Reticulating colliquation occurs as follows : As a result of the poison
of the disease the protoplasm of the cells becomes cedematous and
I Die Haut-Krankheiten, 1854. 2 virchow's Archiv, Bd. xxviii., S. 337.
^ Ibid., Bd, xxxiv., S. 598. * Handbuch der pathol. Gewebslehre, 1871.
5 Virchow's Arctiiv, Bd. Ixix., S. 409.
6 Anat. Beitriige zur Lehre von den Pocken, Breslau, 1874, Helt 1.
7 Vergleichende Untersuch. liber die Entwick. von Blaseu in der Epidermis, 1882.
8 Archives de la dermat. et de syph., 1881.
"^ Archives de la physiol. norm, et pathol., 1880, p. 307. '
w Monatshefte f. prakt. Dermat., 1892, Bd. xiv., 1892.
II Histopathology of Diseases of the Skin. Translated from the German by Dr. Norman Walker,
1896.
77//-; I'M'IIOLOCV <>/<' SM.MJJ'OX 24'i
midcr^'oes jKirliiil oi- coiiiplcU; li<|iicr;u:(,i«)ii, Uiiis (.unwvvUw^ IIk; coll
body into a lar^e cavity. (Coagulation of the albuminoid bodies set free
from the protoplasm now tnkes place, ksading to the formation of a
line griundiir prccipiliiic; which lies on the well-jjreserved nucleus or
the tliiri, disixMided cell wall. The nucleus at first renuiiris healthy, but
later shows fibrinoid degeneration. When the li(juci'action of the cells
is partial, protoplasmic tral)ecu];c form which coagulate into a network,
often radially arranged, and hold the nucleus and cell mantle together.
The name "reticulating" collicpiation is given to this degeneration
because of the net-like character of the structure.
Fig. 47
Microphotograph of smallpox pustule showing reticulating epithelial bands. Magnified
80 diameters.
This form of degeneration corresponds with the "alteration cavitaire"
described by Leloir and Renaut. Leloir maintained that the cavity
formation invariably began with a dilatation of the nuclear cavity; in
other words, as a result of the liquefaction of the endoplasm.
In the second form of fibrinoid metamorphosis — that designated
ballooning colliquation — the whole protoplasm of the cell swells up and
becomes cloudy and opaque. The prickle projections are withdrawn
and the cell becomes rounded. The shape of the cell is largely deter-
mined by its position and external pressure, and may be round or
flat, biscuit-shaped, pointed, or drawn out into septoe, or bands.
Most of the cells, however, have the form of hollow spheres or balloons,
the predominance of which gives rise to the name " ballooning colli-
quation."
244 ^ SMALLPOX
The reticulating degeneration mainly attacks the older cells, or those
in the upper strata of the Malpighian layer, and the ballooning degen-
eration the younger cells, or those in the lower strata. This is accounted
for by the fact that the younger epithelia contain a homogeneous proto-
plasm which readily undergoes homogeneous swelling and coagulation,
whereas in the older cells a marginal layer separates from the rest of
the protoplasm in its preparation for cornification.
Formation of the Smallpox Vesicle.- — During the papular stage the
cavity formation begins in the upper prickle-cell layer of the epidermis
by a reticulating colliquation of the oedematous epithelium. Owing to
the slow advance of this process some of the cells are compressed and
thus part of the cavity is, from the commencement, divided by septa
into a series of segments, the bands running perpendicularly in the
centre and being directed outward at the periphery.
At the same time the cells of the lower prickle layer undergo ballooning
colliquation. The cells lose their prickles and become detached from
one another.
As the pock spreads peripherally the differentiation of the process
in the upper and lower strata of the prickle layer becomes more marked.
In the upper part the cavity extends laterally, many of the marginal
cells liquefying and communicating with the general cavity. In the
lower part, on the contrary, ballooning and swelling of the cells develop
slowly.
At the height of the development, therefore, the pock has the shape
of a mushroom, the main cavity formation taking place in the upper
projecting parts, while the under half is sharply constricted.
The cavity is completed by extension of the reticulating degeneration
downward, particularly upon the periphery, and by the ballooning and
detachment of the deeper cells; the latter subsequently become trans-
formed into the compressed bands which traverse the lower portion
of the pock.
Umbilication. — Exceptionally a sort of umbilication may result from
the accidental piercing of the centre of the pock by a hair follicle, the
cornified neck of which limits the swelling of the prickle cells. The
characteristic depression in the centre of the vesicle is due, however,
to another cause. It is the result of the reticulating degeneration and
oedematous swelling of the cells. These occur chiefly at the periphery,
whereas the ballooning degeneration which occurs slowly and gives rise
to less swelling takes place in the centre. The umbilication is, therefore,
due rather to a bulging of the periphery of the vesicle than to a retraction
of the centre.
The pressure of the lateral oedematous cells is so great as to lead to
obliteration of the underlying papillae, while in the centre of the pock,
before suppuration begins, they not only persist but project into the
cavity of the pock.
During the vesicular stage the dilatation of the papillary bloodvessels
beneath the pock is slight and the emigration of leukocytes is strikingly
small. A dense collection of plasma cells is seen in the sheaths of the
Tiii<: PAT 1101/ )(:y of ,smaijj>ox 24r>
vessels and increases in niiniherjis (Jic vcsific mnliircs. 'I'liis jilxind.'ince
of plasma cells is remarkable, considering the acuteness of the process,
and is otdy foniid among the pock-lik(^ processes in variola itself.
After the fiftli day, the bloodvessels, snpcrficial and deep, become
distinctly dilated and a stream of leukocytes is poured out, doubtless
attracted by the dead germs in the tissues. The margin between the
corimn and epidermis is so densely packed as to be scarcely recognizable.
'I'he cavity of the pock gradually fills uj) completely with these white
l)l()od cells. If the horny roof holds, the mass is converted almost
into solid tissue; if it ruptures, there is morcor less profuse suppiinition,
leading to the formation of crusts.
The primary pustulation is due to the variolous j)oisoii, but pro-
longed suppuration must l)e ascribed to secondary ])yogenic infection.
Healing. — Even before the contents of the pustule are completely
dry, a thin layer of epithelial cells lying close on the connective tissue
extends from all sides under the pustule.
When the scab is thrown off there is displayed a persistent trough-like
depression. Where the scab does not to any great extent depress the
base of the pock, the papillary layer is not completely flattened out, and
the scar is not so deeply excavated.
" The depth of the scar consequently depends on the degree and
duration of the flattening of the base of the pock beneath the pustule
and the scab, and we see therefore that the rational treatment to avoid
scars should be mainly directed to the aborting of the pustular stage
and the rapid removal of the scab by profuse epithelial new-growth.
. . . . Suppuration alone causes no necrosis of the papillary body,
but it may, if profuse, lead to a more rapid casting off of the scab, and thus
indirectly to the freeing of the base of the pock; the profusely suppurat-
ing cases of smallpox are not those which leave the worst scars. No
doubt prolonged suppuration, coupled with inappropriate treatment,
scratching, etc., may lead in many cases to a purulent sequestration of
parts of the cutis and thus to distinct scar formation."
For a long time the bloodvessels and all the lymph spaces of the cutis
are dilated, and wandering cells and pigment are more abundant than
normal.
The pocks upon the 'palms of the hands and soles of the feet develop
in a somewhat difi^erent manner from those elsewhere. The reticulating
and ballooning degenerations are only imperfectly seen here.
The "pock body" is usually fan-shaped, undergoes a drier degener-
ation, and has a horny character. It is usually more superficially situated
in the epidermis.
Stokes^ believes that "the primary exudation of plasma cells has not
been sufficiently emphasized by Unna. These plasma cells are probably
derived in part from proliferation of the endothelial lining of the
lymph spaces and bloodvessels. In some sections made from very early
cases, the epithelial cells do not show any great injury, but the cutis
1 The Palliology of Smallpox, Johns Hopkins Bull., Xo. 1-19. Aug., 1903.
246 SMALLPOX
is swollen and there is increased number of plasma cells in the lymph
spaces and around the small bloodvessels. The condition resembles the
response to some injury and seems to be the first change in the skin,
since the various changes in the epithelial cells are not yet present."
In a hemorrhagic case Stokes found the capillaries and lymph spaces
greatly distended and numerous hemorrhages present in the connective
tissue.
Quite recently careful and extended studies of the pathology and
etiology of variola have been carried on by Prof. Councilman/ of Harvard
College, and a number of his associates.
The anatomy and histology of variolous lesions were investigated
by Councilman, Magrath, and Brinckeroff. Eight sets of complete
serial sections were made through typical vesicles and pustules. In the
main Unna's findings are confirmed, but some new facts concerning
the histology of the pock are presented.
The earliest form of degeneration is said to take place in the nuclei
of the cells of the rete mucosum. They become swollen, more vesicular,
and exhibit an increased central clumping of the chromatin. In the
lesions leading to vesicle formation there is a reticular degeneration of
the cytoplasm, with a more advanced degeneration of the nucleus. The
nuclei may lose their form and become irregular and shrivelled, assuming
peculiar shapes. Advanced forms of cytoplasmic inclusions are common
in the nuclear space and in vacuoles in the protoplasm. The proto-
plasmic processes connecting the cells disappear, but the periphery of
the cells remains and undergoes condensation.
It is this degeneration which causes the peculiar reticular appearance
of the early vesicle. It is always better seen in the periphery than in
the centre of the vesicle. With the increase of the exudate coming from
below, the spaces within the cell enlarge, finally rupture, and a network
is formed by the coalescence of the cell borders. The typical small
vesicle is always fan-shaped, with the handle of the fan seated upon the
corium.
A later form of degeneration, the ballooning degeneration of Unna,
may best be regarded as a hyaline fibrinoid degeneration. The Mal-
pighian cells become swollen, lose their granular character, become
homogeneous and refractile, and stain more intensely with the acid
dyes.
The fluid exudate begins early, and in most cases simultaneously
with the degeneration. In the smallest visible papule the swelling is
due chiefly to the presence of exudate; in no case was degeneration
found without evidence of exudation. The early exudate is clear and
contains no admixture of cells. Indeed, a conspicuous feature of the
smallpox process everywhere is the paucity of cells in the exudate.
The cells appear only at a late stage of the process, and are much less
than in other deo:enerations and exudations due to bacterial infection.
1 Studies on the Pathology and Etiology of Variola and Vaccinia ; from the Sear Pathological
Laboratory, Harvard Medical School ; published in the Journal of Medical Research, February, 1904.
THE IWTIIOI/XIY OF SMALLPOX 247
It seems probable that tlie cells appear when the ^m-W'w cli.'inu-ter
of the process is passed, they being then attracted to the necrosis.
Did'erent viirictics of leukocytes are present, but the polynuclcir neutro-
nhilcs prcaler than normal. Nearly all writers refer to degenerative changes in
the liver varying from cloudy swelling to a more or less intense fatty
deceneriition. Weigert descrihes areas of local coagidation necrosis
in which are seen nuclear detritus and many degenerated cells without
nuclei. Siderey says there is intense congestion with migration of white
blood corpuscles and swelling of the endothelial lining of the capillaries;
later the liver cells swell and undergo fatty degeneration.
Roger and (larnier' made a microscopic study of the liver in seventeen
smallpox cases. They conclude that variolous hepatitis is usually total
and may affect the interstitial or parenchymatous tissue. P'atty hepatitis
is said to be the most common, having been found in six out of eleven
cases of coherent or confluent smallpox. In hemorrhagic smallpox, it
is, according to these investigators, constant. Necrotic hepatitis is more
rare and is characterized by cellular necrosis in limited foci or diffuse
bands. This condition was observed alone in two cases, and in two
others associated with fatty degeneration. A third variety, hemorrhagic
hepatitis, was found in one case in a child with congenital variola.
Ponfick and Curschmaim both state that in purpura variolosa the
liver is normal in size and color and does not exhibit the degenerations
above referred to.
According to Ponfick,^ the spleen in those who die early is swollen,
soft, and of a light-red color. It later resumes its normal appearance
except in purpura variolosa, in which variety it is small, hard, and dark
red, with prominent follicles.
Roger and WeilP found the spleen hypertrophied in every one of
sixteen fatal cases of confluent smallpox. Among twelve hemorrhagic
cases it was enlarged in four instances. The most interesting micro-
scopic changes are the presence of nucleated red blood corpuscles, and
a predominance of mononuclear leukocytes among the white cells.
Perkins and Pay^ noted hemorrhages into the splenic pulp in six out
of forty autopsies; three of these were cases of purpura variolosa.
The kidneys, like the liver, show changes var^nng from cloudy swelling
to fatty degeneration. Arnaud^ made histological examinations of the
kidneys in thirteen cases of smallpox. The changes were briefly of
two types — an interstitial cell infiltration and lesions of the epithelium
of the tubules.
Stokes" has recently made a careful study of the kidneys in variola.
' Etude aiiatom. et cliim. du foie dans la variole, Archiv. de mOd. exper., September, 1901.
- Ueber die Auat.Veriinderungen der iiinern Organen bei bemor. u. pust. Variola, Berl. klin. Woch.,
1872, No. 42.
^ Les maladies infectieuses, Paris, 1902.
■* Tbe Etiology and Pathology of Variola, Journal of Medical Research, October, 1903.
6 Revue de m^d., 1S9S, tome xviii. p. 392. ^ Loc. cit.
250 SMALLPOX
Extensive changes were found in every kidney examined. In one case
an acute interstitial nephritis such as described by Councilman in
diphtheria and scarlet fever was found. In one very malignant case
the changes noted Avere as follows: In the glomeruli the capillaries
contained clear hyaline material within the lumen. This was due to
an actual degeneration of the endothelial lining of the glomerular
capillaries. At times the hyaline material formed a large crescentic
mass of homogeneous clear material in the capsular space. The epithe-
lium of the convoluted tubules was swollen and the cytoplasm of the
cells contained numerous granules. In many of the cells the cytoplasm
had completely degenerated into a mass of clear droplets which pro-
duced hyaline casts in the lumen a of the tubules. The clear droplets
took Weigert's stain for fibrin. The adrenal bodies were found by
Perkins and Pay^ to frequently show well-marked fatty degeneration of
the cells of the medulla.
The heart in fatal cases of confluent smallpox is usually relaxed, soft,
and somewhat enlarged. Microscopically the changes are those of
cloudy swelling and fatty degeneration; fragmentation of the muscle
fibres is commonly seen.
In purpura variolosa, according to Ponfick, the organ is firm, con-
tracted, and of a brownish-red color.
The Lymphatic Glands. — Roger and WeilF state that hypertrophy
of the glands in variola follows the same rule as splenic enlargement;
it is very marked in the pustular variety and slight or absent in the
hemorrhagic form. Microscopically the cells found are similar to those
seen in variolous bone-marrow; neutrophile myelocytes are notably
present and in addition there are some basophile myelocytes and occa-
sionally eosinophiles. Giant cells are also seen, and in hemorrhagic
smallpox nucleated red blood corpuscles.
Stokes examined the cervical and bronchial glands in smallpox and
found extensive focal necrosis containing an abundance of streptococci.
Bone-marrow. — In 1873 Golgi^ made a study of the bone-marrow
in ten cases of pustular and twenty-five cases of hemorrhagic smallpox.
In the pustular form he found a great increase of the white cells, while
in the hemorrhagic variety he found a great increase of nucleated red
cells, a distinct diminution of the white cells, some of which were in
process of fatty degeneration, and diffuse hemorrhages in the medul-
lary spaces. The medullary tissue was red and almost as fluid as
blood.
Chiari* found a condition which he designated "osteomyelitis vario-
losa" in 72 per cent, of twenty-two cases examined. This process is
characterized by pea-sized, whitish, grayish, or yellowish nodules, widely
disseminated in the marrow substance. These consist of epithelioid
cells derived from proliferation of the marrow cells. An early necrosis
1 Loc. cit. - Maladies infectieuses, p. 721.
■* Sulle Alterazioni del Midollo del ossa nel variola, Rlvisla clinica di Bologna, 1873, p. 238.
* Osteomyelitis Variolosa, Ziegler's Beitriige z. pathol. Anat. u. allgemein. Pathol., 1893, Bd. xiii.,
S. 13 ; and Zeitschrift f. Heilkunde, Bd. vii., S. 385.
77//'; PATIIOhOaV OF SMALLI'OX 251
sots in. C-liiiiri rcf^iii-ds these focjil nenr()S(!S us (lu(; to tlic sj;ccifi(; vari-
olous ])oisoii.
(!oiinnont and Montiii/)aY of smallpox 261
vaccine lesions, the lyni])h of which gave tyj)ical vesicles when tnms-
I'erred to children.
C'opeman admits that the results of these interesting exjxuirnents are
rendered inconchisive by the fact that the calves cin[)loycd were inocu-
lated elsewhere upon the body with ordinary vjiccinc lynijjh; every
precaution, however, was taken to prevent c(jntaniination of the defined
area inoculated with the egg cuUure. In later experiments Copeman and
IJlaxall succeeded in growing the small bacillus on other culture media.
In 1900 Nakanishi^ isolated a bacilhis from liuman and bovine
vaccine lymph to which he gave the name of "bacillus variabihs Iym[)ha'
vaccinalis." This organism belongs to the pseudodi})hthcria group and
exhibits great variations in size and form. Inoculation of the cornea
of rabbits with cultures of this bacillus produced bodies in the epithelial
cells which were said to closely resemble the cytorrhyctes variola; of
Guarnieri.
In the same year Levy and Finkler^ independently described a l^acillus
found in vaccine lymph which they designated "corynebacterium
lymphse vaccinalis." This organism belongs to the pseuflodiphtheria
class and is probably identical with that described by Nakanishi.
Cause of Pustulation in Smallpox. — It is quite definitely estalilished
that the suppuration of the variolous pock is the result of the causative
agent of the disease and is not due to secondary infection with pyogenic
organisms. In the vesicular and even in the early pustular stage of the
eruption the lesions will commonly be found to contain no bacteria
cultivable upon ordinary media. In an investigation of the contents
of smallpox vesicles and pustules' we found 33 out of 34 cultures of lesions
before the seventh day sterile. Frequently a drop of pus from a lesion
was placed upon a nutrient medium and incubated without any visible
growth developing whatsoever. In all, cultures were made from 82 lesions
in 51 cases of smallpox; of this number 64 cultures remained absolutely
sterile.
This work is in accord with most of the investigations upon this
subject.
Perkins and Pay* made 30 cultures from typical variola lesions at
all of the various stages from the beginning vesicle to the full develop-
ment of the ripe pustule. These were all negative with the exception
of 4 — 1 on the eighth day, 1 on the ninth, and 2 on the tenth days of
the eruption.
After the seventh or eighth day of the eruption various bacteria,
chiefly streptococci, may be found in the lesions.
The Streptococcus Pyogenes in Smallpox. — The streptococcus is
commonly found in the late pustules of smallpox and in many of the
cutaneous complications, such as boils, impetigo, abscesses, erysipelas,
gangrene, etc.
1 Centralbl. f. Bakt. u. Parasit., 1900, Bd. xxvii. - Deutsche med. Woch., June 2S, 1900.
3 A Preliminary Study of the Contents of Variolous Vesicles and Pustules, Journal of the Ameri-
can Medical Association, 1903.
* Journal of Medical Research, October, 1902.
262 - SMALLPOX
After death streptococci are found in the cutaneous lesions and in
the blood and internal organs in nearly all cases. There would appear
to be in many cases an agonal or post-mortem diffusion of streptococci
throughout the, tissues. In 40 autopsies on smallpox patients made
by Perkins and Pay streptococci were found distributed throughout the
body of 38.
Ewing^ found streptococci present in about 90 per cent, of the skin
lesions cultured at autopsy. He also noted the presence of streptococci
in the blood after death in every one of 29 cases examined. In 10
cases of varying severity in which the blood was cultured during life
the results were negative.
Ai'naud^ found streptococci in the blood during life in 2 cases of
hemorrhagic smallpox.
Perkins and Pay^ examined the blood in 20 cases of smallpox and
found streptococci in 11 cases, before or just after death.
Omitting the varioloids and convalescents and considering only the
more serious cases, a total of 16, with streptococci in 11, or 69 per cent.
It is evident from the above investigations that the streptococcus is
almost constantly found in fatal cases of smallpox. While no one can
seriously entertain the idea that its role in smallpox is causal, it is so
uniformly present that some writers believe it bears a peculiar relation
to the disease differing from most secondary infections. It should be
remembered, however, that the same statement might be made with
equal force in referring to the relationship between the streptococcus
and scarlet fever.
Many writers regard the streptococcic bacterisemia as the most frequent
cause of death in smallpox. Councilman* says: "As the result of the
study of the disease, both by culture of the lesions and organs and by
microscopic examination of tissues, we are inclined to regard bacterial
infection as a more important agent in bringing about a fatal termination
than the specific parasite The bacteria are chiefly strepto-
cocci."
Perkins and Pay, and likewise Councilman, suggest that the strepto-
cocci gain entrance to the circulation through the bronchial and pul-
monary mucous membranes.
Perkins and Pay found that the pathogenicity of the streptococci
isolated was markedly different. Some of the strains killed rabbits in
two or three days, while others were without effect. The writers suggest
that the failure of antistreptococcus serum prepared from one variety
of streptococcus may be thus accounted for.
Protozoa in Variola and Vaccinia. — Griinhagen^ in 1872 appears to
have been the first to call attention to the presence of protozoa in variola
and vaccinia. He described in vaccine lymph, clear, refractive, sharply
contoured bodies both free and attached to leukocytes.
1 Proceedings of the New York Pathlogical Society, May, 1902.
2 Rev. de m^d., 1900, p. 303. ^ loc. cit.
* Journal of Medical Research, February, 1904, p. 358.
5 Bemerkungen Ueber den InfeclionstoflF der Vaccin Lymphe, Arch. f. Dermat. u. Sylph., 1872,
p. 150.
77//'; i:.\(;ti<:i!I()I.(i(;v of smallpox 2r;.'i
Renault in JSSI described j)e('iiliur Ixxiics which he hchc\cd lo lic
parasites in the epithelial cells of variola and vaccinia.
In ](SS7 Van ^qv LoefP found in a han^inf^ drf)p of clear vaccine;
lymph numerous small, round bodies endowed with arno-bf^id nu>vement;
later he discov(!r('d the s;ime bodies in smallpox pustules.
L. Pfeill'er pul)lished a series of papers be^^iiminf; in 1887, desciibin^
the presence in variolous and vaccine lymph of the "monocystis epithe-
lialis," a small, unicellular, rounded body which he re<^jirfled as the
specific cause of smallpox. These bodies were also found in the epithelial
cells of the Mal|)i<^hian layer and were said to multiply by division ann-
founded with smallpox. The eruption at times may appear rather sud-
deidy and j)ass throufijh the stages of papule, vesicle, and pustule in a
surprisingly brief period of time. The lesions may be quite firm to
the touch and in other respects closely simulate those seen in smallpox.
In syphilis one can fre(|uently obtain (1) a hittory of injcrtion and a
description of the initial lesion. Indeed, the chancre or its remains
may still be detected. Not uncommonly there are present associatfjd
evidences of syphilis, such as mucous patches, flat condylomata, ulcer-
ation of the tonsils, alopecia, glandular enlargement, etc. The variola-
form syphilide may develop after the disappearance of one of the
earlier syphilitic eruptions.
2. The onset of the two diseases is, as a rule, quite different. The
syphilitic subject will usually give a history of having felt weak and
debilitated for some weeks. If fever precedes the eruption it is ordinarily
not very high and is not accompanied by severe prostration. When
the eruption appears the patient usually calls upon the physician at his
office or at the hospital. We do not note that sudden illness which
precedes unmodified smallpox. In the latter disease, two or three days
before the efflorescence appears, the patient experiences a chill followed
by a rise of temperature, often to 103°, 104°, or 105° F. There are
severe headache, backache, vomiting or nausea, vertigo, general pains,
and severe prostration. The patient, instead of calling upon the
physician, sends for him.
It must be remembered, however, that in varioloid the initial symp-
toms may be mild or absent. On the other hand, in rare cases, syphilis
may present an initial illness which strongly counterfeits that of
smallpox.
3. The development of the eruption in smallpox is rather sudden.
Ordinarily in twenty-four to forty-eight hours the full complement of
lesions has appeared. In syphilis the eruption may continue to come
out for quite a number of days in successive crops. It must be admitted,
however, that in modified smallpox three or four days may sometimes
elapse before the complete appearance of the exanthera.
4. The distribution of the variolaform syphilide may be identical with
that observed in smallpox. Frequently, however, variations may be
noted. The pustular syphilide may involve the trunk more copiously
than the face; this would be exceedingly rare in well-marked smallpox.
The dorsal surface of the wrists and hands are nearly always involved
in smallpox, but may escape entirely in syphilis. The palms of the
hands and soles of the feet are always involved in severe smallpox;
in moderate eruptions they nearly always present some lesions, and in
varioloid they may or may not escape completely. The pustular syphilide,
on the contrary, attacks the palmar and plantar surfaces with the
greatest rarity. The writers have observed in one case a single lesion
272 SMALLPOX
upon the palm of one hand, and in another instance a deep-seated
pustule upon the lateral surface of the sole.
5. The character of the eruption in syphilis and smallpox may, in
the beginning, be so nearly identical as to make a diagnosis from
the eruption alone quite impossible. It will be noted, however, that the
efflorescence of smallpox presents a much greater uniformity in the
character and development of the lesions over the body than does
syphilis. Syphilis is characterized by an essentially multiform erup-
tion; it is not uncommon to find small pustules, large pustules, and
papules interspersed, and these in varying stages of evolution and invo-
lution.
The vesicles and pustules of syphilis are usually conical and involve
merely the summits of the elevations; they never become full and
globular, and fill the entire lesion as do those of smallpox. Beneath
the syphilitic crusts considerable ulceration not uncommonly occurs;
according as this is slight or severe there will be seen, upon detachment
of the crusts, a small, reddish-brown pigmented stain or an excavated
ulcer. The latter heals with the production of a depressed scar.
6. The course of the syphilitic eruption is relatively chronic compared
with that of smallpox. The lesions of variola undergo a striking change
in a few days. The syphilitic efflorescence is indolent, and presents, as
a rule, no decided alteration of appearance within this period of time.
By the sixth or seventh day in smallpox the lesions develop into those
large, full, round, hemispherical pustules which are so characteristic of
the disease.
Finally, to the physician who has seen much of smallpox, there is a
something in the picture, an impression given by the ensemble, which,
while not definable in language, is, nevertheless, of subtle aid in the
diagnosis.
Roseola Vaccinosa. — Vaccination with animal virus sometimes causes
an erythematous or rubeoloid rash, known as roseola vaccinosa, to
appear from the eighth to the twelfth day of the vaccine disease. We
have occasionally known this rash to have been mistaken for the
eruption of variola, especially during epidemic visitations of the disease.
The distinguishing features are that it accompanies vaccinia, that it is
not preceded by a very high temperature, and that it consists of macules
rather than papules.
Acne. — Mild cases of varioloid exhibiting but a few papulopustules
about the face may bear a close resemblance to acne. The history of
exposure, the existence of an initial stage, and the progressive evolution
of the lesions will speak for the variolous nature of the eruption, while
the presence of blackheads, a history of previous outbreaks in the
individual, and the absence of preceding illness will decide in favor of
acne.
Drug Eruptions. — Drug eruptions, particularly those resulting from
the ingestion of the iodides and bromides, may simulate the exanthem
of smallpox. The history and absence of an invasive stage will usually
suffice to make the diagnosis clear.
77//'; I'lKXlNOhllH, OF SMALIJ'OX 275
variola,. C'ontrariwise, in (lie ah,sciif;o of an cpidfinic miM fasf.s of
,sinall|)ox are very likely to be overlooked.
Whenever the diagnosis between smallpox and a disease simulating
it is in doubt, observation of the progress of the eru[>tion for a perifKl
of twenty-four to thirty-six hours will tisnally make elear the nature
of the disease.
THE PROGNOSIS OF SMALLPOX.
Since tlie introduction of vaccination the presence or absence of a
typical vaccine scar on a })atient is an important factor in the question
of prognosis in smallpox. Formerly, smallpox was not only more
common, but uniformly far more fatal, and therefore nnich more
dreaded than at the present time.
During the last century but few diseases claimed a greater number
of victims than variola, but at the present time, especially in countries
where vaccination is carefully and systematically practised, the pro-
portion of deaths from this malady is not greater than 0.7 per cent, of
the entire mortality, and where revaccination at the proper age is also
enforced, this proportion is even much less. In the prevaccination
period one-tenth of all the children born died from smallpox; now the
mortality from that disease among young children where vaccination is
compulsory is almost nil. According to Juncker smallpox killed in the
prevaccination days on an average 400,000 persons every year in
Europe. In 1803 King Frederick William III., of Prussia, stated that
the average yearly mortality rate from smallpox in Prussia was 40,000.
In Prussia, where vaccination and revaccination are rigidly enforced
at the present day, smallpox is almost unknown.
Age. — The age of the patient is of the greatest importance in con-
sidering the prognosis of smallpox. It is comparatively rare for an
infant under one year of age to survive an attack of unmodified small-
pox. So also at the other extreme of life the death rate is excessively
high. In children of from one to five years of age the disease is also
very fatal, but among those of from five to fifteen years the chances
of recovery are rather better than in adult life.
Smallpox Patients Treated in the Municipal Hospital, showing
MoETALiTY According to Age.
series i.
Age. Cases. Died. Percentage.
Under 1 year 60 37 61.66
1 to 15 years :-30 187 35.28
15 " 25 " 1362 402 29.51
25 " 45 " 1215 365 30.04
45 years and upward 227 88 38.77
Total 3394 1079 31.79
276 SMALLPOX ' ]
SERIES II.
(Similar table with somewhat different age classification )
Age. Cases. Died. Percentage.
Under 1 year 57 29 50.87
1 to 5 years 159 50 31.45
5 " 10 " 130 20 15.38
10 " 15 " 66 8 12.12
15 " 25 " 371 55 14.82
25 years and upward 1096 172 15.69
Total 1879 334 17.80
The above tables give the smallpox mortality according to age, and
include both the vaccinated and the unvaccinated cases. All of the
patients under one year of age were unvaccinated except a few who
were vaccinated after infection — i. e., during the incubation period.
Likewise, practically all of the children under five years of age were
unvaccinated.
In Series I. are included the statistics of the large and malignant
epidemic of 1871-72, and of a subsequent severe epidemic; while in
Series II. are included the statistics of the recent and much milder
epidemic of 1901-02.
Race. — When smallpox prevails among aboriginal tribes the mortality
is extremely high. It is commonly stated that the death rate of variola
among negroes is much higher than among whites. This statement
has scarcely been borne out by our experience. Negroes are extremely
negligent as regards vaccination, and the number of unvaccinated blacks
received in smallpox hospitals is apt to relatively exceed the number
of unvaccinated whites. A truer comparison of mortality rates will
be obtained, therefore, in contrasting the unvaccinated of both races.
In the tables here shown, the mortality rate among the negroes is
somewhat higher than among the whites, although the difference is
not great:
Negroes and Whites Admitted to Municipal Hospital.
Cases. Deaths. Percentage.
White 6131 1530 24.95
Black 1073 407 30.79
Total .... 7204 1937 2689
Unvaccinated Negroes and Whites.
Cases. Deaths. Percentage.
White 2036 910 44.69
Black 637 315 49.45
Total .... 2673 1225 45.83
Sex. — Sex influences prognosis to little or no extent.
Among women the mortality is somewhat increased on account of
their liability to suffer from metrorrhagia, or, when pregnant, from
miscarriage or premature delivery. The occurrence of either of these
accidents or the presence of the parturient state strongly predisposes
the patient to the hemorrhagic form of the disease. The mortality
77//'; rnoaNosrs of sma LLpr)X 277
in men is, on the other hand, considerably increased by intemperance.
Drunkards or constant imbibers seem particularly prf»nc to suffer
Itoiu licmorriiiif^ic; sniall])OX. We have found jdrnost all forms of the
disease more severe amonff bartenders, "^'lie powers of resisfanrc
against the exhausting influence of variola are often so diminished
by chronic alcoholism that death results from a form of the disease
from which a |)ati(Mit with more healthy organs would recover.
Mania a, polil constitutes, of course, a very serious foniplif.'ition. In-
temperate persons are apt to be badly nourislu-d, .'ind Ihis conrliliou is
always unfavorable in smallpox.
It will be seen from the subjoined Ijible (iiiil I he inorljility rate jimf»ng
males and females in our experience has been almost the same:
Cases and Mortality According to Sex.
Cases. Deaths. Percentage.
Male 4593 1207 27.45
Female 2606 670 25.71
Total .... 7204 1937 26.89
Unmodified smallpox is an exceedingly fatal disease, the death rate
varying in different epidemics from 15 to 60 per cent. The epidemic
which swept over this and other countries in the years 1S70 to 1872 was
everywhere characterized by unusual malignancy, and the mortality
among the unvaccinated cases was, in some places, as high as 64 per
cent. The following table shows the mortality rate among vaccinated
and unvaccinated cases treated in the Municipal Hospital during the
three largest epidemics experienced since its foundation:
Mortality Eate of Vaccinated and Unvaccinated Cases in
Different
Epidemics,
Cases.
Deaths.
Percentage.
1871-1872.
Unvaccinated .
. 697
449
64.41
Vaccinated
. 1629
276
16 94
Total .
. 2326
725
30.74
1881-1885.
Unvaccinated .
. 447
252
56.37
Vaccinated . . .
. 551
81
14.70
Total
. 998
333
33.36
1901-1904.
Unvaccinated .
. 1943
636
32.73
Vaccinated
. 1844
124
6.72
Total .... 3787 760 20.06
It will thus be seen that different epidemics vary very greatlv in
malignancy. In 1901-04 the mortality rate among the unvaccinated
was just one-half that observed in 1871-72, and almost one-half less
than the death rate in 1881,
Indeed, smallpox may occur in epidemics in which the death rate
reaches as low a figure, even among unvaccinated cases, as 2 per cent.
Such a remarkable epidemic has been prevailing in various sections of
the United States during the past few years.
In the absence of an epidemic influence, smallpox is usuallv much
278 SMALLPOX
less fatal. It is believed by some authors that the disease is more fatal
at the beginning and during the maximum of an epidemic than when
it is declining, but we are not sure that such is always the case. Certain
seasons of the year are also believed to exercise some influence over
the mortality from the disease. It is probably true that a patient is
less able to bear the depressing effects of confluent variola when the
weather is excessively hot than when the temperature is cooler.
Type of Disease. — In considering the prognosis in individual cases
various circumstances are to be taken into account. The type of the
disease and the extent and depth of the eruption are among the most
important factors. The hemorrhagic form of smallpox is frightfully
fatal. Indeed, it may be laid down as a rule almost without exception
that recovery never takes place from the graver types of this disease.
Of 152 cases of hemorrhagic smallpox observed during the epidemic
of 1871-72, 146 died. The 6 cases that recovered belonged to the
milder variety of this type; 1 had slight bloody vomit, and the other
5 exhibited an eruption which on some parts of the body was purplish,
while a number of vesicles contained a dark-blue spot in the centre,
showing that blood was exuded into the vesicles.
The next most fatal form of smallpox is the confluent variety. When
it is comprehended that in such cases there may be forty thousand or
more pustules present, the reason for the high death rate is apparent.
Of 211 cases of confluent smallpox accurately observed during the
epidemic of 1871-72, 168 died, showing a mortality rate of 79.62 per
cent.
Semiconfluent cases are correspondingly less fatal than the confluent;
while in cases with discrete eruptions the mortality falls to a compara-
tively low level.
Thus it will be seen that the prognosis in any particular case is influ-
enced to an enormous extent by the character of the eruption. In
varioloid or smallpox so modified by vaccination, inoculation, or previous
attack that the secondary fever is slight or absent, the mortality is
almost nil, as will be seen from the appended table:
Vakiola and Varioloid Treated in the Philadelphia Municipal
Hospital.
Cases. Deaths. Percentage.
Variola 4156 1906 45.93
Varioloid 3048 31 101
Total 7204 1937 26.89
The fatalities in' varioloid result, as a rule, from some complicating
condition. It must be remembered that attacks in adult patients who
were vaccinated in infancy and showed no appreciable protection are
classed under the head of variola.
The stage of the disease at which death occurs in smallpox will
depend somewhat upon the character of the attack. Patients suffering
from hemorrhagic variola usually succumb on the fourth, fifth or sixth
day of the eruption. Considering all types of the disease the largest
77//'; f'U()(,'N()SlS OF SMALLPOX 270
number of fatalities occur during the second week of the eruption and
particularly upon the ninth, tenth, and eleventh days. As will be seen
in the accompanying table, of 1019 fatal cases of sn)all[)ox, 575, or
50.42 per cent., died during the second week, and .'M7, or .':)4.05 percent,,
of these exj)ired on the ninth, tenth, and eleventh days. Basing the
assertion u[)()n these figures, it may be stated that over one-third of
the fatalities occur upon the critical days mentioned, and over one-half
of the deaths during the second week.
We have occasionally observed death to take place as late as five or
six weeks after the onset of the disease, but in these cases the unfavorable
termination has been brought about by some complicating affection.
Showino the Period of the Disease at which 1019 Cases of Smali.i-ox
Proved Fatal.
First week :
Isl day of ernptinn 1
2d "" " 4
3d " '• 14
4th " " 31
5th " " 63
6th " " 90
7th " " 90
— 293
Second week :
8th day of eruption 84
9th " " 122
10th " " 114
11th " " 101
12th " " 75
13th " " .49
14th " " 30
— 575
Third week :
15th day of eruption 28
16th " " 22
17th " " 12
18th " " 9
19th " " 5
20th " " 8
21st " " 7
— 91
Fourth week and after:
22d day of eruption 7
23d " " . 8
24th " " 6
25th " " 3
26th " " 4
27th " " 3
28th " " 5
29th " " 4
30th " " 4
31st " " 2
32d " " 4
33d " " 1
34th " " 2
35th " " 1
36th " " S
37th " " I
39th " " 1
44tll " " 1 '
— 60
Total 1019
280 SMALLPOX
Vaccinal Condition. — ^The vaccinal condition of the individual is a
most potent factor in influencing the course of the variolous disease.
The degree of protection conferred by the vaccine process can be, in
most cases, approximately estimated by the character of the vaccine
cicatrix. Every now and then we encounter patients with good vaccina-
tion scars from an infantile vaccination, in whom the protection against
smallpox has been almost completely lost; and, on the other hand, we
may see patients with poor scars who still enjoy considerable protection;
but these may be looked upon as exceptions to the general rule.
The existence, therefore, of good cicatrices in a patient who is attacked
with smallpox may be regarded as of favorable prognostic import.
Of 8893 cases of smallpox treated at the Municipal Hospital, 2335
presented good scars; of this number, 152 died, constituting a mortality
rate of 6.5 per cent.; 1105 patients with fair scars were treated, of whom
135 died, showing a death rate of 12.21 per cent.; 1524 cases were
admitted with poor scars, of whom 345 died, giving a death rate of
22.64 per cent.; 3687 unvaccinated cases were admitted, of whom
1542 died, giving a mortality rate of 41.82 per cent. Thus it is seen
that the danger of attacks of smallpox can be measured with a con-
siderable degree of accuracy by the vaccinal condition of the patient.
Vaccinal Condition and Mortality Rate.
Admitted. Died. Percentage.
Vaccinated in infancy (good scars) . . 2335 152 6.5
(fair " ) . . 1105 135 12.21
(poor " ) • • 1524 345 22.64
Postvaccinal cases 4964 632 12.53
Unvaccinated " 3687 1542 , 41.82
Unclassified " 242 45 18.18
Total .... 8892 2219 24.95
There is no reliable symptom during the initial stage to indicate
the gravity of the attack. Not infrequently the mildest eruption of
varioloid is preceded by a very severe febrile stage. If, however, the
initial stage be very mild, it is safe to prognosticate a moderate eruption.
Severe lumbar pains may be present both in modified and unmodified
smallpox, yet if they be extremely severe there would be some reason
to anticipate a hemorrhagic form of the disease. Inasmuch as the
initial morbilliform exanthem {roseola variolosa) is most often seen in
varioloid, we would regard the presence of this rash as an indication
that the true eruption will be of modified form. When the rash is
of the scarlatiniform type, the ensuing eruption may be moderate or
severe; when, however, the prodromal rash is purpuric, it is a symptom
of evil portent, preceding as it does the hemorrhagic form of the disease.
There are, however, exceptions to this last statement; we have occa-
sionally seen erythematopurpuric prodromal rashes in persons who
have made perfectly good recoveries.
It has been already stated that the quantity and character of the
eruption are accurate guides as to the gravity of the disease. The
riii<: I'ttOGNOSis of sma/jj'hx 281
condition of the nnicous membrane of the [)[),'uynx, hirynx, and traeliea
should he regarded as only second in in)j)(jrtance to the skin lesions in
estimating the degree of danger in variola. If these parts become
severely im])licated by the variolons f)rocess, giving rise to a fliphtheritir
condition of the fances, (lys[)hagia, difhculty of res})iration, or ademji
of the glottis, the case shonld be viewed with grave ap|)rehensif>ii.
Even hoarseness at the early period of the rnaturative stage shonld be
looked npon with suspicion.
Favorable Symptoms. — As has })een stated, mild initial manifesta-
tions and the occurrence of a roseolous rash are favorable, inasnnich
as they precede, as a rule, mild forms of the disease. Even in profuse
eruptions, if the pustules become prominent and acuminate well, and
are accompanied by considerable swelling, and if those on the extremities
are surrounded l)y a pinkish areola, and the patient takes nourishment
freely, there is good ground for hope. At a more advanced ])eri(Kl of
the disease, if the state of the nervous system be tranquil and the patient
passes quiet nights, has a contented disposition, and entertains a confi-
dent hope of recovery, the probal)ility of a favorable termination of
the disease is greatly increased, even though the eruption be severely
confluent.
Unfavorable Symptoms. ^ — Among the symptoms which indicate the
approach of a hemorrhagic attack are: excruciating backache during the
initial stage, a petechial prodromal rash in the axilla and groins, sub-
conjunctival ecchymoses and hemorrhages from the various mucous
membranes, a claret-colored areola about the lesions upon the extremi-
ties, and a bluish or lead-colored discoloration of the centres of the
vesicles. The prognosis in a case presenting such symptoms would be
almost hopeless.
An excessive degree of confluence on all parts of the body renders
the prognosis extremely grave. It is an unfavorable sign in confluent
cases if the pustules on the face be flat, milky-white in color, and pasty,
and if there be absence of sweUing. It is also ominous to see here and
there on the face vesicles desiccating prematurely and producing flat,
brownish scabs.
During the early period of maturation the patient's condition should
be regarded as extremely critical if the progress of the eruption be
suddenly arrested and the swelling of the face and hands subside,
leaving the skin between the pustules pale; if the pustules themselves
shrink and collapse; if the pulse be rapid, dicrotic, or feeble; if the
delirium and restlessness increase; or if nourishment be refused or
taken very reluctantly.
Valuable information may often be gained by observing the nervous
symptoms, especially at an advanced period of the disease. Great
restlessness, insomnia, despondency, constant moaning and grindmg
of teeth in children, are unfavorable symptoms. Violent and protracted
delirium, convulsions, or coma usually preclude all hope of recovery.
Even after the patient has passed safely through the perils of the
regular stages of variola, his life may again be placed in jeopardy by
282 SMALLPOX
certain complications. Fortunately, those which are most frequent —
furuncles and abscesses — rarely lead to a fatal issue. The occurrence
of pneumonia, pleuritis with effusion, erysipelas, or abortion should be
viewed with deep concern. But the most fatal of the complications
liable to arise are suppuration within the joints, pyaemia, and empyema.
Gangrene of the scrotum and glossitis variolosa arising earlier in the
course of the disease usually portend a fatal outcome.
THE TREATMENT OF SMALLPOX.
The treatment of smallpox may be considered in its relationship,
first, to the patient himself, and, second, to the community at large.
The latter aspect of the subject concerns the prophylaxis or preventive
treatment of the disease. This may be conveniently classified under
the following captions — notification, isolation, surveillance or quarantine,
disinfection, and vaccination.
Prophylaxis. Notification. — It is important in the interests of public
health that the existence of a case of smallpox should be promptly
made known to the proper health authorities. It is usually the duty
of the physician in attendance to transmit this intelligence. Every
practitioner of medicine should feel himself called upon to aid and
sustain the sanitary authorities in their efforts to prevent or stamp
out a pestilential disease and should willingly comply with any arrange-
ments whose object is the attainment of so desirable an end.
Most large communities have enacted laws making compulsory the
notification of smallpox and other pestilential diseases, under pain of
fine or imprisonment. It is only through a knowledge of the distribution
and extent of smallpox in an infected district that the health authorities
are enabled to intelligently and efficiently inaugurate measures toward
its suppression.
Isoiation.^ — It is of paramount importance, when smallpox appears
in a community, to prevent the dissemination of infection; to this end
the isolation of the patient — the source of the infection — becomes
essential. This can only be accomplished with any degree of certainty
by having the sick removed to a well -organized hospital. General
hospitals and other public institutions cannot, with justice to the other
patients or inmates, harbor and treat those suffering from smallpox.
Even the caring for such patients in isolated pavilions in general hospitals
is open to the objection of multiplying the foci of contagion in the
city or town. It follows, therefore, that every city and large town
should be provided, either temporarily or permanently, with a special
institution for the treatment of this disease in the event of its outbreak.
It should be located in a healthful district, sufficiently removed from
the thickly settled portions of the city to preclude the possibility of
transmitting the contagion to inhabited domiciles, but not so remote
as to interfere with its accessibility. It is also of importance that such
institutions should be constructed in a modern manner, with a view
to making the unfortunate patients as comfortable as possible.
TIII<: TliNATMHNT OF >SMALLPOX ^HP,
Of course, a special hospital of this character should he rnanagefi
under strict quariuitine regulations. No person, however well protef:ted,
should be allowed to visit a patient in the institution (;xce[)t under
extreme circumstances, and then only after every possible precaution
shall have been taken to prevent his carrying away the infection. The
nurses and attendants should not be allowed to leave the hospital, nor
come in contact with other persons, until they have had an antiseptic
bath and have chanfrcd their infected clothing. In j)roviding nurses
and other employ(5s for the hospital it need not be required that they
shall have had smallpox, but they should invariably be vaccinated or
revaccinated before entering upon duty. When delay is possible it
is wise to await the result of such vaccination before the individual
is brought into the infected atmosphere. The hospital should be
supplied with closed ambulances for the transportation of patients.
Private or public vehicles should never be used for this purpose. Indeed,
this is regarded as so important a matter that in some large cities in
this country the use of any kind of public conveyance for carrying
persons afflicted with smallpox is prohibited by law, and its infringe-
ment is made punishable by fine.
Lest infection be spread by the ambulance itself it should be dis-
infected and provided with clean bedding, blankets, etc., every time
it is used. In order that the public may know the character of the
disease that it conveys, it should bear the name of the hospital to which
it belongs.
If the smallpox patient is to be treated at home, every possible effort
should be made to seclude him from all persons, excepting only such
as are required to act as nurses, and they should be protected by recent
vaccination. In selecting the apartment for the patient, a room most
completely separated from all other parts of the house is to be preferred.
If this is not practicable — which is usually the case in the ordinary city
residence — the uppermost room of the house should be preferred. It
should be well ventilated, and, if possible, have an open fireplace in
which fire should be kept constantly burning. All unnecessary articles
of furniture, such as drapery, upholstery, carpets, etc., should be
removed. Every precaution in regard to cleanliness and disinfection of
bedding, clothing, and everything in use in the room should be exercised,
so that the danger of spreading the infection shall be reduced to the
minimum, A sheet wrung out in a strong solution of carbolic acid,
Labarraque's liquid, or some other disinfectant, and suspended across
the doorway may aid in preventing the infection from being disseminated
to other parts of the house. The spaces around doors that are not in
use, which communicate with parts of the house to be protected, should
be sealed by pasting strips of wrapping paper over them.
Surveillance or Qaarantine. — When smallpox appears in a house, the
question arises. What shall be done with the exposed but well members
of the household ? If the patient is treated at home, the other inmates
as well as the sufferer should be quarantined. For, if removed to
another locality, save to a quarantine station or hospital, the disease
284 SMALLPOX pn
might subsequently appear there, and a new centre of infection be
thus estabhshed. To depend upon people voluntarily to curtail their
personal liberty for the public good would be confiding too much, at
the present time, in human benevolence and public spirit. Therefore,
the best results "will be obtained, when the patient is retained at home,
by stationing reliable guards about the house to enforce detention
of the exposed inmates and also all other necessary precautionary
measures.
On the other hand, when the patient is removed to the hospital it
is, in our judgment, not necessary to enforce the above-mentioned restric-
tions. Indeed, we are of the belief that the object desired is often
defeated in large cities by a routine quarantine of the inmates of houses
from which smallpox patients have been removed. To make such
a quarantine effective the individuals should be detained for a period
of eighteen days, the outside limits of the stage of incubation. Segrega-
tion of the inmates of the household for so long a period works a great
personal hardship and prompts them, in many instances, to escape
before the quarantine is placed upon the house. We have known
persons frequently to flee from houses where there existed an individual
suspected of having smallpox, but in whom the diagnosis had not been
definitely made. The settling of these exposed persons in different parts
of the same city and in other cities results in the outbreak of the disease
in these various localities. Thus, instead of limiting the infection rigid
quarantine laws may favor its dissemination. Furthermore, unpopular
restrictive measures tend to provoke evasion of the law and concealment
of the existence of the disease.
When the patient is removed to the hospital we would advise immediate
vaccination of the exposed individuals. To avoid, as far as possible,
failures through imperfect virus or technique, three or four insertions
with different virus had better be made. At the same time there should
be thorough disinfection of the infected articles and apartments. After
this has been accomplished the exposed individuals might resume
their freedom. They should, however, be kept under medical surveil-
lance, and should be daily visited by a physician who should watch for
any symptoms of variola. Such inspection should be continued for
sixteen days from the onset of the disease in the original patient, at the
end of which time the suspected individuals, if well, may be exempted
from further surveillance. During his visits the physician can determine
whether the vaccinations are "taking," and, if not, the procedure can
be repeated, thus giving the patient a still further chance of protection
if vaccinal susceptibility exists.
The above plan is based upon the assumption that smallpox is not
contagious during the period of incubation, and this view is in accord
with the belief held by practically all authorities on the subject. Until
active symptoms manifest themselves the exposed individual is not a
menace to the health of the community, and it is unnecessary and
injudicious to restrict his liberty during this period. Furthermore, a
large experience has demonstrated to us that under a system such as
TTIE TREArM/'JNT OF SMALLPOX 285
outlined, a much larger percentage of exposed individuah v:ill submit
to vaccination and a correfijxmdingly increased numljcr of patients V)ill
consent to he rem,oved to the hospital, for only those who comply with
this advice will be exempted from quarantine.
Apart from these considerations, the system of routine (|n;iniritirie,
during epidemic prevalence of smallpox, will he f(jnn(l to involve the
expenditure of laro;e sums of money.
The quarantining of exposed persons may be practicable and wise
in dealing with sporadic cases of smallpox or with the first cases in a
community, for under such circumstances extraordinary precautions
are justified in an endeavor to limit the outbreak of the disease to the
original patients.
Another means of restricting the spread of smallpox is to apprise the
public of the particular locality in which the disease exists, so that
no one may unknowingly approach within infecting distance of the
place. But how to do this without exciting unnecessary alarm is a
problem not easy of solution. The plan adopted in some cities of
placarding the infected house with a large and conspicuous poster is
believed by many to serve a useful purpose, notwithstanrling the fact
that it frequently meets with much opposition. But whether this plan
be adopted or not, the sanitary authorities should keep the premises
under constant supervision, instituting daily visits by officers qualified
and empowered to advise and direct the observance of proper sanitary
precautions.
Disinfection. — Disinfection is a highly important prophylactic
measure. The infection of smallpox is not only imparted to the atmos-
phere surrounding the patient, but to all articles which have been
used by him or have been near him. It clings to these articles for a
variable length of time, and they are, therefore, not infrequently the
media by which the infection is conveyed to others. Disinfection
consists in the complete destruction of the infecting agent of the disease.
Fresh air and sunlight are nature's disinfectants; when infected articles
are freely exposed to the atmosphere and rays of the sun for some time
the infecting principle becomes less and less active, and finally dis-
appears. Therefore, the house, especially the room, occupied by the
patient should be freely though cautiously ventilated. If the weather
be cool, an open fire upon the hearth would consume much of tlie
infected atmosphere.
Chemical substances, however, furnish the more speedy and reliable
disinfectants, and it is upon such that we mainly depend for the destruc-
tion of the disease germs. Some agent of this nature should be brought
directly in contact with all the excrementitious matter from the patient,
and with everything that has been used by him or has been near him
during the progress of the disease. All discharges, not excepting those
from the mouth and nose, should be received into a vessel containing
some such disinfectant as chloride of lime, carbolic acid, or bichloride
of mercury. Under no circumstances should the excreta be allowed
to flow into the sewer or be cast awav without first l^a^•in£: undergone
286 SMALLPOX
disinfection. In country districts, where disinfectants may not be
readily obtained, the discharges should be deeply buried in the ground
in a locality where there is no danger of contaminating the water supply.
Every handkerchief, towel, and article of bedding and clothing used
by the patient should be steeped for some time before leaving the room
in a solution of two fluidounces of chloride of zinc or four fluidounces
of carbolic acid to the gallon of water, and afterward boiled by them-
selves for half an hour or longer in plain water; all small articles, such
as bits of linen, sponge, absorbent cotton, and the like should be burned
immediately; all utensils used for eating and drinking should be purified
by boiling water; and, in short, nothing should be allowed to leave
the room without having first been subjected to some form of disin-
fection.
The attendants should not be more numerous than the necessities
of the case require. They should be carefully instructed in regard to
the importance of cleanliness, disinfection, and isolation. Not only
should they be instructed to exclude from the sick-room all persons
not having authority to enter, but also all domestic animals, such as
the dog and cat, as they are exceedingly liable to serve as conveyers
of the infection.
The clothing of the attendants should be of such material as can be
readily boiled and washed, and it should be frequently changed and
subjected to this process. No attendant while engaged with the case
should come in contact with other persons. On leaving, either tempo-
rarily or permanently, a bath should first be taken, using freely carbolic
acid soap, and the hair should be washed with a solution of mercuric
chloride. No clothing that has at any time been in the infected atmos-
phere should be worn or carried away from the premises, unless it has
first been disinfected.
Physicians should also exercise care lest they may be the means of
communicating the infection. When called upon to attend a case of
smallpox the physician should not remain in the infected atmosphere
longer than is necessary to make a proper examination ; the prescription
may be written and advice given in another apartment. After each
visit he should carefully wash his hands, face, and hair; his hands
especially should be washed in some disinfecting solution. He should
then expose himself for a considerable time in the open air before
visiting another patient.
The physician should wear in the sick-chamber a long mackintosh
or a linen duster buttoned up to the chin, and a cap to cover the hair,
and these garments should be kept hanging in the open air in the
intervals of his visits. In hospitals where there are many patients to
be examined, and where he is required to spend considerable time in
the wards, nothing short of a change of his entire outer clothing before
leaving the institution should be considered. It is also of importance
for the physician to cover his shoes with rubbers, so that no variolous
crusts which may be upon the floor will be carried out of the infected
house.
THE T UK AT ME NT OF SMAfJ/POX 287
The isolation of a smallpox patient should he continued until all the
scabs are removed. The time necessary to effect their separation varies
greatly in (h'fferent cases. In severe confluent forms of the flisease a
month or more will he required, while in extremely mild and abortive
cases of varioloid the skin may be entirely smooth in a week or ten
days. Upon the palms and soles the inspissated pocks remain embedded
for a long time and recjuire mechanical removal in order to avoid a
long and tedious waiting for spontaneous exfoliation. Even after
removal of the variolous crusts the patient shoidd not be allowed to
associate with the pubHc until he has had one or more antiseptic baths.
Perhaps the most reliable antiseptic bath that can be given is one
containing corrosive sublimate. The safest way one may proceed in
the use of such a bath is by simply sponging the body and carefully
wetting the hair with the solution (1:2000) and then have the patient
freely bathed in plain water with the use of carbolic acid soap, or the
patient may take a full bath in a tub containing a 1:10,000 or 1:
20,000 solution of mercuric chloride. A 5 per cent, solution of Labar-
raque's hquid also makes a very reliable disinfecting bath. After this
he should put on clothing which has not been exposed to the infection,
or, if exposed, has been disinfected, and he may then safely mingle with
the public.
Inasmuch as the body of a person who has died of smallpox is capable
of imparting the infection, some precautions should be observed in
regard to it. For instance, the body should be thoroughly wet with
a solution of corrosive sublimate (1 : 1000) or with a solution of chloride
of lime in proportion of six ounces of the drug to a gallon of water, or
with some other equally powerful disinfectant; besides, it should be
wrapped in a sheet saturated with one of these solutions and buried at
once. The preferable method of disposing of the dead from this disease
is by cremation; but this method is yet perhaps too strongly opposed
by public sentiment to be practicable. It is not advisable to transport
the corpse a long distance or from one city to another for burial, but
if this be really necessary, it should first be placed in a metallic coffin
hermetically sealed. In its burial it should be put at least six feet
under ground, and should not be disinterred unless absolutely necessary,
and then only under sanitary supervision. The vehicle used for con-
veying the body to the grave should afterw^ard be disinfected. It is,
perhaps, unnecessary to say that the funeral should by no means be
public.
After the sick chamber has been vacated, either by recovery or death
of the patient, every article it contains of no great value should be
immediately burned. Everything else which will not be injured by the
ordinary operation of the laundry may be safely and cheaply disinfected
by immersion in boiling water for half an hour. It should be remem-
bered, however, that the water must be maintained at the boiling point
for that length of time. But if it is impracticable to subject such articles
at once to the boihng process, they should be immersed for about four
hours in some reHable disinfecting solution — such as^mercuric chloride
288 SMALLPOX
In the proportion of 1 : 2000, or carbolic acid 1 : 50 — and subsequently
boiled.
The sick-room should be disinfected according to the principles laid
down in the chapter on disinfection. The room should then remain
closed from twelve to twenty-four hours, afterward opened, thoroughly
ventilated, and all surfaces, including the furniture, washed with a
disinfecting solution (chloride of lime, carbolic acid 1 : 50, or mercuric
chloride 1 : 1000) ; afterward the floor and other woodwork should be
thoroughly scrubbed with soap and water. The wall-paper, if there
be any, should be well moistened with the carbolic acid solution and
scraped off and burned. Paper may be reapplied or the walls white-
washed, according to fancy. In addition to all these precautions, it is
advisable to have the room remain unoccupied for three or four weeks,
during which time it should be well aired.
For disinfection of outer clothing, carpets, bedding, and all articles
which cannot be boiled, there is nothing superior to steam under pressure.
The germs of smallpox will certainly perish if exposed for half an hour
to this agent at a temperature of 230° F. There are, however, certain
articles which would be injured by moist heat, and for the disinfection
of these dry heat may be substituted. In this case a temperature of at
least 230° F., continued for two hours, will be required. Formal-
dehyde, however, could be used instead of dry heat.
Vaccination. — Of all of the measures employed to prevent the spread
of smallpox, none is so important and efficacious as Jenner's great
discovery. There is perhaps no single scientific fact better established
than that vaccination, periodically repeated, is capable of effectually
preventing the occurrence of that disease in man. In view of this fact
it does at first sight seem strange that variola should continue to prevail
in civilized communities; and, while nothing appears easier than to
control the spread of this disease, or even to eradicate it altogether,
yet there are diflaculties in the way of accomplishing this end which
seem almost insurmountable. These arise from various causes, but
chiefly from individual carelessness or indifference about employing
vaccination, and from the absence of a general law making it compulsory.
We know that many conscientious citizens are opposed to enforcing
vaccination by law, but as every unvaccinated person is liable to contract
smallpox and disseminate the infection among others, he should be
regarded in the light of a public enemy, and dealt with accordingly.
Surely it is not an unreasonable position to assume that no person
through ignorance or prejudice should be allowed to contravene the
public welfare.
But, in the absence of a statutory law requiring the vaccination of all
persons, very much can be done in the way of enforcing the measure
by restricting the privileges of the unvaccinated. For instance, satis-
factory evidence of successful vaccination should be required of every
child before admission into public and private schools and institutions
for the care of children; no unvaccinated person should be allowed to
serve as a soldier in the army or navy, or in the State militia; and no
Tiii<: tiii<:atmknt of smallpox 280
unvacci Mated iiinnin;ni,nl, slioiild ho jillowcd lo hmd until \;ifciii;itif>M
has been perfoniied.
In view, therefore, of the <,n-e;it importance of lliis prophylactic
measure, it l)ecomes the (hity of all nmiiicipal and Stjde autliorities to
j)rovide gratuitons Viiccination for the ])oor, and, in(h-ed, ff)r all helpless
children of careless or improvident j)arents, no matter to what class of
society they belong. No expenditure of money should be spared by
these authorities in order to protect their citizens against a disease so
loathsome and fatal as smallpox. From a purely monetary ])oint of
view such expenditure is wise, for a single epidemic of this much dreaded
disease in a community may necessitate a greater outlay to care for the
indigent sick alone than would be required to purchase the means of
protection for that community for a decade of years.
If vaccination were universally practised, and repeated from time
to time as circumstances recjuired, there would be little need for other
means of prevention. Whenever a case of smallpox occurs in a family,
the physician's first duty is to vaccinate promptly all members of the
family who have never been vaccinated, and revaccinate all others
without regard to the character of their previous vaccination. It is a
good plan to vaccinate on several successive days those who have never
been previously subjected to this procedure, in order to increase the
probability of obtaining a successful result. If this be done and the
patient sent to the hospital, the disease may be prevented from spreading.
Care of Patient.^ — In order to consider in detail the treatment of
smallpox it seems most convenient to divide the disease into its various
stages, as follows: (1) the stage of incubation; (2) the initial stage;
(3) the eruptive stage; (4) the stage of suppuration; (5) the stage of
retrogression, or stadium exsiccationis.
1. The Stage of Incubation.- — The interval between the reception of
the infecting agent of smallpox into the blood and the earlier manifesta-
tions of the disease is usually unattended by symptoms. There is no
doubt, however, that certain unknown processes take place during this
period. It is very important to know whether an^ihing can be done
at this time to arrest or change these processes so as to prevent or
modify the approaching disease. Drugs, of course, are powerless for
this purpose. Is vaccination at this period capable of exerting any such
influence ?
From the clinical reports of those who have made extensive use of
vaccination at this period of smallpox there seems to be some differences
of experience concerning its efficacy. In commenting on this question
Curschmann says: "Are we able to exert any influence on the disease
in the early stage preceding the eruption? Is it possible in infected
persons, during the stages of incubation and invasion, to cut short the
disease or to modify its course? INIany attempts have been made to
answer these questions affirmatively, but as yet without much result.
The first idea was vaccination, and this was employed by some in the
ordinary way; by others subcutaneous injections of vaccine lymph have
been given, it is said with good results. I must, however, advise great
19
290 SMALLPOX
skepticism regarding these assertions. Of the subcutaneous injection of
lymph I have no experience; but that ordinary vaccination during the
stages of invasion and incubation cannot stay the disease has been proved
to me by chance observations and direct experiments. On the contrary,
I have seen, in cases in which vaccination was practised after infection
with variola, vaccine pustules and smallpox pustules developed side by
side. It is, in my opinion, very doubtful whether vaccination can even
render the course of the disease milder."
The hypodermic use of vaccine lymph is certainly not entitled to any
confidence as a prophylactic measure. Immunity does not result from
the mere presence of vaccine virus in the blood, but from certain unknown
processes which take place in the system in the course of true vaccinia.
It is, therefore, evident that the vaccine disease must reach a certain
stage of development before it is capable of exerting any prophylactic
power whatever. We have had very frequent opportunities of observing
that vaccination during the invasive or initial stage of smallpox is
utterly valueless, and also that it is equally useless when performed
only three or four days prior to the earlier invasive symptoms. A
vaccine vesicle resulting from a vaccination performed at the period
just mentioned, and the variolous pustules, will, it is true, develop side
by side without the one exerting any influence whatever over the other.
But Curschmann's experience seems to warrant the inference that at
no time within the incubation period of smallpox can vaccination be
used with advantage against the approaching disease. If such is his
experience, it certainly differs very greatly from our own. We have
in numerous instances seen smallpox very markedly modified by vacci-
nation performed at this period, and not infrequently have seen it pre-
vented absolutely. In order that protection shall be complete it is
necessary that the insertion of the vaccine lymph should be made
almost immediately after the reception of the contagium; but if made
at a somewhat later date a modifying efl^ect may still be obtained. No
part of the incubation period should be considered too late to make
use of this remedy, since this period is sometimes prolonged beyond its
usual limits, in which case a late vaccination may prove of value.
It is our opinion that vaccinia does not begin to exert its prophylactic
power until the areola commences to form around the vesicle. At this
time the mild febrile reaction, which was regarded by Jenner as a
sine qua non in true vaccinia, becomes apparent. If this stage of the
vesicle be reached before the patient shows any symptoms of smallpox,
the disease may be entirely prevented; if not reached until after the
febrile symptoms appear, but before the eruption occurs, it may modify
the attack. Now, it is well known that in typical vaccinia the areola
appears about the seventh day or eighth day from the date of insertion
of the lymph, and is at its height on the ninth or tenth day; and it is
equally well known that the incubation period of variola is, in the
majority of cases, of ten or eleven days' duration, and that the eruption
does not appear until about three days later. This renders quite obvious
the fact that vaccination, practised shortly after variolous infection has
77//'; rilKATMKNT OF SMAfJ.POX 291
occurred, has an opporditjity in [)()inl of lime to exert more or less
prophylactic iiifhience against (he; incuhaling(Jisease. While no inflexi}>!e
rule can be laid down, it may be said in a general way that if vaccination
be practised on the first or second day after the reception of the infection
into the systetn, the protection may })e perfect; and if errif>loyed betv\(;cn
this date and the fifth day, it may be j)artial. But we would emphasize
the fact that after infection has occurred, every day that is allowed to
pass before resorting to vaccination is so much valuable time lost.
While the appearance of the areola generally indicates the period of
the vaccine process at which its prophylactic power ))egins to }je exerted,
yet this period may vary somewhat in different individuals. For instance,
we have more than once seen, say, two persons exposed to the contagion
of smallpox at the same time in such a manner that there could be no
doubt about infection having occurred, have vaccinated these persons
at once and with the same virus, and the vaccinia in V)oth cases has
pursued an identical course, yet in one the protection was perfect, while
in the other it was only partial. In other similar instances one has
received partial protection and the other none at all. This difference
is doubtless due to some individual peculiarity that cannot be explained.
It is much easier to confer protection against smallpox after infection,
where revaccination is required to accomplish this result, than where
the vaccination is primary. The explanation of this is not difficult. It
is because vaccinia in its modified form, such as results from revaccina-
tion, develops more speedily, arrives at the areolar stage more quickly,
and runs its entire course several days sooner than does the unmodified
or true vaccinia; hence, it is clear that the period of protection in such
cases must be reached earlier.
In endeavoring to confer protection during the incubation stage of
smallpox the quality of the vaccine lymph employed has a great deal
to do with the success. Nothing is of more vital importance at this
period of the disease than that the vaccine virus employed should be
fresh and active. The difference between success and failure in pro-
ducing vaccinia after exposure often means to the patient the difference
between life and death. We know of no virus more reliable or which
will give better results than eighth-day lymph taken directly from a
typical vaccine vesicle on the arm of an infant.
While humanized^ virus has gone out of use in most countries, we
cannot refrain from testifying to its reliability and value in persons
who are exposed to smallpox. The virus of long humanization possessed
the additional advantage of running a rapid course and so bringing
about its protective influence promptly.
The virus resulting from a long series of human transmissions was,
therefore, to be preferred over virus of recent humanization and animal
virus. At the present time, however, we are more concerned with
bovine virus, which has for certain reasons largely superseded the use
of humanized lymph.
1 Humanized virus is still extensively employed in Mexico, where the Iphysicians prefer it to
animal lymph,
292 SMALLPOX
It is believed by some authors that miihiple insertions quicken the
process of vaccinia, and thus hasten the attainment of that stage of
the disease at which its prophylactic poM^er begins to be exerted. Water-
house was of this opinion, and his remarks on the subject are interesting
because they were made a century ago, in the very earliest history of
vaccination. He wrote:
"I think it proper to publish an important fact for which we are
not indebted to Europe, namely. If a person he inoculated with the
kinepock two days after having received the casual infection of smallpox,
the kinepock will predominate and save the patient. Nay, I will go
further and say in some cases three days posterior to infection instead
of two ; for there is a mode of expediting the operation of the kinepock
virus by increasing the quantity of matter thrust under the epidermis;
and it appears, from experiment, that this does not depend so much
on increasing the quantity put into a deep puncture as it does on the
increase of infected surface. In other words, you may expedite the pro-
cess of kinepock inoculation two days if not three, if, instead of two
punctures, you make sixteen or twenty; . . . and on the sixth
day from the operation we shall have the appearance of the eighth
day in ordinary cases; and on the eighth day we shall find the
appearance of the tenth, and so on with the febrile symptoms, in
which commotion the prophylactic power consists."
As there is nothing at this stage of smallpox of greater importance
than vaccinia attended by prompt and speedy development of the
vesicle, it is evident that the virus employed should be selected and used
with the greatest possible care and skill.
It is well under these circumstances to employ an active virus; the
production of a sore arm is a matter of but little importance when the
exposed individual's life is at stake.
In order to ensure success, it is advisable to employ virus, when
possible, from more than one source. It is desirable at this time to guard
as far as possible not only against failure, but also against a vaccine
disease of slow progress. A tardy vesicle, or one that is slow in making
its appearance and late in arriving at maturity, gives no assurance of
safety.
In recent years animal lymph has been brought to a high state of
perfection by the admixture of glycerin. We have found glycerinated
lymph properly prepared and preserved to be more likely to succeed
and also more speedy in its action than the dried virus on ivory points.
Hence, during the incubation period of smallpox glycerinated lymph
may be found almost, if not quite, as effectual as long humanized virus
in preventing or modifying the approaching attack. We have had
extensive opportunities of testing its power in this direction and have
been well pleased with the results. The records of the hospital bear
testimony to the fact that during the recent epidemic of smallpox in
Philadelphia several unvaccinated persons sent in through error of
diagnosis were protected absolutely by the use of glycerinated lymph.
Where the protection was not perfect there was marked modification
Tlll<: TREATMENT OE SMA/JJ'OX 2!i5
proved unavailing, and we can df) notliin^ (norc ;i( this stji^f fli;in ircai.
special symptoms as tliey arise.
The popular though erroneous nolion of piist cfnliiiics, lh;i( if is
necessary to keep the pjitient hot and swejiling, slill prevails to sf>me
extent, and not iid're(|uentiy it is I'oinid very (HffienH to overcome this
prejudice. On the contrary, every effort should Ix; flirecled tf)\vard
keeping the patient as comfortable as possible, and exj^erience shows
that a bedroom well ventilated and having a temperature of from 0')°
to 70° F. is best suited for this purpose. The onjinary febrifuge mixtures,
such as li(pior ammonia' acetatis, litpior ])otassi citratis, tinctura aconiti,
etc., may be given in suitable doses and at stated intervals We are
in the habit of using the following formula:
l;fe— Spirit, ssther. nitrosi,
Syrup. limonis Ctd fSiv.
Liquor, ammonii acetatis fSv. — M.
Sig.— Give 2 to 4 fluidrachms every two hours in a little ice-water.
If there is irritability of the stomach, the effervescing citrate of potas-
sium may be preferable. It sometimes happens that the stomach is
very irritable, especially in children; in this case lime-water, subnitrate
of bismuth, aromatic spirit of ammonia, a little chloroform -water, or
any other drug or agent known to be of service in this condition, may
be used. The swallowing of small pieces of ice will often give relief
when everything else fails. When the skin is hot and dry and the
temperature high, frequent sponging with cool water is serviceable.
Severe headache may call for the application of cold water, iced com-
presses, or an ice-bag to the head. These need not be feared on account
of the popular superstition that they tend to suppress the eruption, for
such is not the case.
Nervous symptoms, such as insomnia, delirium, and convulsions, are
often prominent features of the disease and demand appropriate treat-
ment. Some of the bromide salts, or chloral, given either separately
or in combination, will usually succeed in subduing these symptoms.
For the convulsions of children there is perhaps nothing more effective
than chloral, given either by the mouth or rectum. When given by the
mouth it should be well diluted, since it is very irritating to the throat,
which is liable to become implicated in the variolous process quite
early. Warm baths are also very useful. There is another nervous
symptom commonly present at this stage of smallpox, and that is pain
in the back. This is sometimes so distressing as to call for measures
of relief. When the stomach is retentive Dover's powder may be given,
or some one of the analgesic coal-tar products, now so frequently used
to relieve pain. Sometimes there is much restlessness and general
irritability; in such cases we have found a little morphine, combined
with the febrifuge prescription above referred to, to act most happily.
The common practice of applying mustard to the back for the relief
of pain or to the epigastrium to lessen gastric irritability cannot be too
strongly condemned, since the variolous eruption always appears in
much greater abundance on irritated surfaces. "\Mierever there is an
296 SMALLPOX
ulcer, a wound, or an excoriated condition of the skin, there the pustules
are sure to be found in dense clusters. We have frequently seen the
eruption intensely confluent over regions of the skin where a mustard
plaster had been applied during the initial stage of the disease. Some
have thought that the eruption might in this way be diverted from the
face to other localities, but we are convinced that it is not diminished
anywhere else by reason of its confluence on these parts through the
action of a sinapism; rather is it increased to that extent.
The digestion at this §tage is not vigorous; hence the diet should be
light and easily assimilable. There is nothing more suitable than
animal broths and milk. The best beverages are cold water and iced
lemonade. Acidulated drinks seem to be particularly grateful to the
palate. Gentle cathartics may, of course, be administered whenever
indicated.
3. The Eruptive Stage.— The eruptive stage may be said to comprise
a period beginning with the first appearance of the eruption and ending
when pustulation has fully occurred. The duration of this stage in variola
vera is usually seven or eight days, but in modified smallpox it is short-
ened in proportion to the degree of modification. The great desideratum
for this period of the disease is a remedy capable of diminishing or
modifying the cutaneous manifestations, for there is no doubt that
recovery of the patient almost always depends upon the quantity of the
eruption and the length of time consumed in running its course.
Formerly it was thought that some modification might be brought
about by bloodletting, but experience shows that the most confluent
eruption has succeeded the most vigorous employment of the lancet.
It is, therefore, worse than useless to bleed, for by so doing we expend
power that will be required later on to repair the injury done by the
disease.
The treatment during the eruptive stage of smallpox should be
directed toward alleviation of the subjective symptoms and the correc-
tion of special symptoms as they arise. Usually it is not until the
eruption appears that the disease is recognized and the degree of severity
prognosticated. If the case promises to be at all severe, all flannel
undergarments should be at once removed, and the hair cut close, so
that the head may be kept cool, cleanliness enforced, the risk of cellular
inflammation of the scalp diminished, and a better opportunity afforded
for the employment of cold applications should delirium or more urgent
brain symptoms arise.
The febrile symptoms which usher in the disease now usually remit,
but increase again as the eruption progresses. For this condition the
remedies already mentioned may be continued. It sometimes happens
in a depressed condition of the system, particularly in children, that
the extremities and even the surface of the body are cool, and that the
eruption is too slow in making its appearance. In such cases the appli-
cation of heat and the administration of hot stimulating drinks, such as
hot toddy, may be of service. This condition in children is apt to be
associated with convulsions, in which case there is nothing better than
77//'; THI'IATMKNT OF SMALLPOX 297
a warm batli f()llow(;(l by an envclopineiil, iti vvann blankets. StioiiM
the convulsions continue, however, cliloral, by eitlier inonfli or n;(tnni,
is quite sure to give relief. We repeat here the caution not to fail to
dilute the chloral freely, for the throat is now so much inv(;lve(l in the
variolous j)rocess that an irritating draught may give rise to croupous
symj)toins, or even acute (edema of the glottis.
Tkeatmiont of the TtitioAT. — As the eruption progresses, not only
the fauces, but the soft and hard palate, the buccal mucous membrane,
the larynx, and sometimes the trachea also become more or less involved
in the process, and this is often the source of difficult and painful deglu-
tition. This condition requires the use of mouth washes and gargles,
such, for example, as those containing chlorate of potash, boric acid,
glycerole of tannin, tincture of myrrh, etc. We have found the milder
demulcent fluids made from flaxseed, gum arable, or slippery-elm bark
particularly grateful. Of these none is more relished by the patient
than flaxseed tea, sweetened with white sugar and acidulated with
lemon-juice. Careful and frequent cleansing of the mouth affords
considerable relief. This may be done by the nurse covering her index
finger with a piece of soft linen, dipping it into a solution of boric
acid with glycerin added, and then thoroughly and carefully cleansing
the entire buccal cavity.
During the recent epidemic (1901-04) through which we have passed,
we found orthoform, in one-grain lozenges, useful in lessening the
distressing soreness of the throat and mouth. In severe cases, however,
where the throat was covered with lesions we were obliged to use a
cocaine (1 per cent.) spray in order to lessen the pain in swallowing,
and thus enable patients to partake of sufficient nourishment. Variolous
patients, according to E. Pepper, who advocates cocaine internally in
smallpox, show a considerable degree of tolerance toward this drug.
We have never noted untoward results from the employment of cocaine
internally or in spray form.
The pain in the throat and difficulty in swallowing are often benefited
by having the patient hold in his mouth small pieces of ice, and allowing
these to dissolve slowly. Where there is much glandular swelling the
application of the ice-bag externally will be found useful. Some patients,
however, will prefer the use of poultices or hot fomentations. When
there is much foetor some antiseptic, such as carbolic acid or permanga-
nate of potash, may be added to the mouth wash or gargle. We have
found dilute chlorine water to answer a good purpose. Variolous
glossitis is best treated by mild antiseptic mouth washes and the use
of pellets of ice. Should acute oedema of the glottis or of the ary-
epiglottic folds occur, an emetic may be given if the patient is not too
weak, or local scarification may be practised. When suffocation threatens,
tracheotomy offers the best if not the only chance of recovery.
Treatment of Nervous Sympto^nis. — Toward the latter part of the
eruptive stage of variola persistent insomnia and delirium often occur.
Wlien this condition of the patient is attended by a flushed face and
bounding pulse, an ice-bag to the head and a brisk cathartic may be
298 SMALLPOX
of service. Tartar emetic and sulphate of morphine, in doses of from
one-eighth to one-half grain each, will often produce sleep and quiet
the delirium. Morphine is a most valuable drug in controlling restless-
ness and inducing sleep during the pustular stage of smallpox. To
accomplish this end, it is sometimes necessary to administer a half or
three-quarters of a grain of the drug in twenty-four hours. However,
it is usually well borne and the patients are almost always benefited
by its use. Large doses of bromide of potassium, or chloral freely
diluted, may be given, and repeated if necessary. Some care, however,
must be taken not to push these remedies too far, lest the patient lapse
into coma or a state of profound prostration.
Occasionally the delirium is of that violent kind which the older
writers styled "delirium ferox." This is accompanied by a wild expres-'
sion of the countenance, and such a strong tendency to escape from
the attendant, or to self-destruction, that too much care cannot be
exercised for the safety of both the nurse and the patient. We have
known strong and muscular patients, while in this state of mind, to knock
the nurse down, jump out of the window, and run to some secluded
place, where they would cunningly secrete themselves. We have also
known patients to attempt suicide in various ways while the nurse was
temporarily absent. The necessities of the case, therefore, often require
the use of some artificial means of restraint. For instance, a wide band
of stout webbing or canvas may be placed loosely over the patient's
chest and secured to each side of the bed. Smaller bands of the same
material may be fastened to each wrist and ankle, or leather wristlets
and anklets may be used, the former being secured to the sides of the
bed, and the latter to the foot of the bed, allowing, however, a little
motion of the limbs, so that the patient shall not be subjected to painful
restraint. In the mean time every effort should be continued to quiet
the delirium, and when the patient refuses to swallow, the drugs and
nourishment should be administered by the rectum.
It is deemed appropriate to speak of the treatment of hemorrhagic
smallpox under this head, for the peculiar manifestations of that type
of the disease become strikingly apparent during the eruptive stage; and,
moreover, it is rare for a well-marked case to live beyond the limits of
the vesicular stage. Treatment is of little avail in this phase of variola.
The remedies usually employed are acids, quinine, ergot, and tincture
of chloride of iron; but these, we think, are prescribed more in con-
formity with general usage than with the expectation of obtaining any
real benefit. When hemorrhage takes place in the various cavities
or internal organs of the body, it is recommended that styptics be
employed, together with injections of ice-water, or the use of cold
compresses or tampons, although it is admitted that the beneficial
effect of these agents is very slight. Transfusion and hypodermoclysis
with sahne solution have been tried, but have not given very encouraging
results.
This type of the disease in varioloid is not quite so significant of
danger as in variola. We have seen a few hemorrhagic cases of varioloid
THE TR.EA TMENT OF SMA LLPOX 299
in which the hoin()iThafi;o fi'oiii infernal organs was not very [)rofuse
or protracted, althouf^li tlie purjmric s[)ots were well rnarkecJ, recover
under the free use of iron and stimulants. In these cases nourishment
was freely taken, prostration was at no time profound, and, as the
patients passed favorably tlironS'/lf /I TJ.POX 307
the pustules are opened with uii aseptic needle find their contents
evacuated. The patient is then wrapped in aseptic linen, which is
frequently changed. It is claimed by the author that this treatment
notably diminishes the duration of the eruption, lessens the fever,
prevents severe ulcei'ation and scarring, jind (hus leads to rapid con-
valescence.
Similar results are alleged to have fcjllowcd the use of baths contairiing
permanganate of potassium, the salt being added until the water is of
a rose-red color. Our experience with permanganate baths has been
entirely unsatisfactory. The baths were given daily and, in some cases,
twice daily from an early period of the eruption. They did not seem
to exert any favorable influence upon the course of the eruption or the
disease. Indeed, during the employment of this treatment our mortality
was more than 50 per cent.
Looking back over the literature of the subject, we find that the
antiseptic treatment of smallpox by means of external applications is
nothing more than the revival of an old practice that was employed
and abandoned many years ago. It is true that when these agents
were used a half-century and more ago, it was not because they possessed
antiseptic properties, for the germ theory was not then known; but
ignorance of this fact certainly could have made no difference in the
result. As long ago as 1843, Gregory wrote: "The latest mode of
treating the surface during the maturative stage of smallpox is that of
applying mercurial plasters containing calomel or corrosive muriate
of mercury, or covering the whole surface with mercurial ointment.
In the French hospitals at the present time the latter mode is in fashion.
The reports which have reached us of its success, however, are not
very flattering. I have seen all three plans fairly tried at the Smallpox
Hospital. The ointment and calomel plasters were inefficient. The
plaster of corrosive sublimate converted a mass of confluent vesicles
into one painful and extensive blister, but I am still to learn what
benefit the patient derived from the change."
When the eruption reaches the vesicular stage there is usually experi-
enced considerable burning, particularly of the face, hands, and fore-
arms. For the purpose of preventing or alleviating this symptom, some
ointment or oily substance will be found useful. VaseUn containing
about 3 per cent, of carbolic acid makes an efficacious ointment; or, if
the odor of carbolic acid be objectionable, oil of eucalyptus or thymol
may be substituted. A preparation which we have frequently employed
is composed of equal parts of lime-water and olive oil, to w-hich is
sometimes added an antiseptic and perhaps a Httle cologne water.
This is freely applied with a large camel's hair brush.
When the burning sensation and pain are severe there is perhaps
nothing which gives so much relief as cold applications, such as cloths
wet with cool water and spread over the face and arms. Curschmann
believes that cold and moisture are the most efficient remedies for this
condition. He says: "In severe cases the application of iced compresses
to the face and hands, or to any parts where the eruption is abundant,
308 , SMALLPOX
will diminish the severe pain, lessen the swelling and redness of the
skin, and make the patient more comfortable."
Moore advises the application over the face of a "light mask of lint
thoroughly soaked in a mixture of iced water and glycerin (a table-
spoonful of the latter in an ounce of water) and covered with oiled silk."
The development of the eruption in the thick skin of the palms of
the hands, tips of the fingers, and soles of the feet not infrequently gives
rise to great pain. Cold applications or iced compresses may prove of
service in this condition, although we think we have seen greater benefit
follow the use of luke-warm hand and foot baths. The frequent appli-
cation of flannel cloths wrung out in tolerably hot water, or the use of
hot poultices, is often of great service.
The topical applications recommended for the pustular condition of
the skin are numerous. To assuage the pain, burning, and itching, to
correct the offensive odor, to guard against septicaemia, and to pre-
vent pitting are the principal ends aimed at in the selection of these
measures.
During the period of suppuration the sensation of itching is quite as
intolerable as the pain, so that it is almost impossible for the patient
to refrain from scratching. In consequence of this, or from other causes,
the pustules become ruptured in many localities and their contents
discharged. This purulent material undergoes decomposition and gives
rise to a highly offensive odor. Remedies are demanded to relieve the
itching and correct the odor. Antiseptic and antipruritic washes, such
as carbolic acid (1:100), or corrosive sublimate (1:1000), may be
employed for this double purpose. About the mouth, nose, and eyes a
saturated solution of boric acid in rose-water may be freely used. We
have frequently employed a 5 per cent, solution of either carbolic acid
or Labarraque's solution, directing that both the patient and the bedding
should be sprayed with this solution every two hours.
Very excellent results are said to have followed the use of an unguent
composed of 100 parts of cold cream to 4 parts of salicylate of sodium.
M. Dujardin-Beaumetz reports that this ointment, in his hands, has
not only been successful in destroying the repulsive odor in severe cases
of smallpox, but has actually prevented suppuration. In addition, he
advises that a powder of 100 parts of talc to 6 parts of salicylate of
sodium be dusted over the affected localities.
We have sometimes been able to lessen or modify the horrible odor
by using as a dusting powder, subnitrate of bismuth, boric acid, and,
sparingly, iodoform. To either of these, and especially to the latter,
talc might be added. We have also derived advantage from a dusting
powder composed of 15 to 20 parts of aristol to 100 parts of talc.
MacCombie strongly counsels the early removal of the crusts, which
he asserts can best be accomplished by the use of a linseed-meal poultice,
sprinkled with iodoform. " On the face the method most agreeable to
the patient is to cut a mask of a single thickness of lint, with apertures
for the nose, mouth, and eyes; then to smear a thin layer of linseed-meal
poultice on this, taking care to put on the surface a little vaselin in
Tflli TRMATM/'JNT OF SMAfJJ'OX .'{09
wliich iodoform has been mixed, and to apply this poulficc atients
bear the painting very well, although many complain of smarting for
a time after the treatment. In some patients the skin is so sensitive
that this mode of treatment has to be abandoned, although a tincture of
one-half the usual strength might })e a])plied in such cases. AV)Out the
eighth to the tenth day of the eruption, in unmodified cases, a thin, dry,
parchmenty mask is formed wliich begins to crack and peel off. At
Fig. 53
Showing the eftfect produced by painting the right arm from the elbow to the wrist daily wiih
lincture of iodine. Area painted is free of the secondary impetigo sores seen upon the untreated
arm. Left arm was not painted.
this time it will be found advisable to substitute an unguentous appli-
cation. We believe that the iodine treatment tends to shrink the pustules,
to hasten decrustation, and, to some extent, to lessen the pitting, although
in severe cases it will not prevent it. The liability to consequent pyogenic
complications of the skin appears to be diminished. A notable feature
of this treatment is that it completely destroys the ofi'ensive odor arising
from the areas of skin to which the iodine is applied.
We have also obtained good results from mild emolUent ointments,
with or without antiseptic ingredients. We are not sure that any special
combination is essentially more useful than plain petrolatum or cold
cream. In the early stages of the eruption, these applications are quite
grateful to the skin, and later on they serve to soften the purulent
312
SMALLPOX
debris, which can then be more easily removed from the face. In severe
cases, where the treatment of the face is neglected, the odor is more
offensive, and the ulcerations appear to be deeper and followed by
more disfiguring pitting.
We have frequently incorporated carbolic acid, aristol, biniodide of
mercury, etc., in the ointments applied. As above stated, however,
Fig. 54
Smallpox eruption at a late stage shovviug extensive dark crusting on the face resulting from
neglect of local treatment.
these did not seem to materially increase the efficiency of the applications.
To soften the crusts from the skin, nothing is better than a salve of the
following composition:
p;— Sodii bicarbonatis 5ij.
Petrolati q. s. ad gj.
We have found great benefit to result from the use of baths given
during the stage of pustulation and desiccation. These may be made
TTiE tI{.i<:atmi<:nt of smallpox pap,
antiseptic by tlic addition of (Tcolin (\ :F)(H)) or hicliloride of niercury
(1:J0,()()() to 1:20,000). The piindent accumulations and crusts
are detached from the skin by the baths, and the associated septic fever
is greatly lessened. Furthermore, the liability to [)yogenic skin complica-
tions is diminished. When it is inconvenient or impossible to employ
antiseptic baths, much good will often be derived from oj^ening and
evacuating the pustules, and wasliing the bases with absorbent cotton
saturated with a 1. : 5000 solution of bichloride of mercury.
When extensive impetigo exists we employ a bichloride bath and then
dust the patient with a weak aristol or iodoform talcum powder. An
ointment which will be found useful in treating impetigo pustules is:
1^ — Hydrargyri iimmoiiiati gr. x.
Pulv. amyli,
Pulv. zinci oxidi dd 5ij.
Petrolati Sss.
Treatment of Eye Complications.' — The air in the sick-room or
hospital ward should be changed as frequently as possible. The hands
of the patient should be encased in gloves or protective bandages to
prevent contamination of the eyes. As a matter of daily routine the
eyes should be flushed copiously with warmed, weak, salt or boracic
acid solutions. The edges of the eyelids should be anointed with
vaselin. In all examinations of the eyes great care must be used in
the manipulation, lest the cornea be injured.
In the early stages, when the eyes are hot and flushed and feel heavy,
a douche or spray of ice-cold water often brings relief. In excessive
hyper?emia, frequent bathing with water as hot as can be borne will
have a soothing effect. In other cases, cloths saturated w^th lead-water
and laudanum, or ice-cold compresses may be laid upon the closed
lids.
The conjunctival sac should be frequently flushed with warm boracic
acid solutions. At bed -time the edges of the lids should be anointed
with vaselin, or with yellow oxide of mercur}^ in vaselin, 1 grain to the
drachm, to prevent their becoming glued together.
When conjunctivitis sets in with a mucous or mucopurulent discharge,
mild astringents should be used; saturated solutions of boracic acid,
to which may be added a few grains of sodium chloride, can be employed.
The lids are to be inverted and the mucous surfaces painted with weak
solutions of silver nitrate (1 to 5 grains to the ounce) or protargol
in 5 to 10 per cent, solution may be satisfactorily employed. In some
instances the discharge may be so free that stronger astringents must
be used. Here no more efficient remedy than silver nitrate can be
applied, for in its action it is germicidal as well as caustic. ^Mien the
lids are tense and board-like, however, and their mucous surfaces
covered with a gray film or false membrane, it is not to be used; but
only when the lids are relaxed, the discharge creamy, the conjunctiva
1 The chapter on the Treatment of Eye Complications has heen kindly prepared for us by Dr.
Buiton K. Chance, whom we have frequently called in consultation to advise us iu the treatment
of severe ocular lesions at the Municipal Hospital.
314 SMALLPOX
red, and the retrotarsal folds puckered. After thoroughly cleansing
them the conjunctival surfaces should be brushed daily with strong
silver solution, 10 to 20 grains to the ounce; the excess of the drug
is to be washed away by an abundance of common salt solution.
These washiiigs are to be repeated until the membrane is clear and
red, and as long as the discharge is abundant the use of silver is indi-
cated.
The edges of the lids are to be greased with vaselin, and they are
then to be restored to their normal position. The pressure on the
globe, caused by the swollen lids may be so great as to necessitate the
cutting of the outer canthus. A canthotomy may have to be done also
to facilitate the examination of the conjunctiva and the cornea.
Persistent and increasing chemosis of the conjunctiva demands snip-
ping in order to relieve the pressure on the cornea.
When the lids are tense and the secretion flocculent, the local applica-
tion of cold is most useful. The readiest means of applying it is as
follows: Small squares of lint of several thicknesses of gauze are
placed on a block of ice. When these are cold the excess of water is
squeezed out from them and they are laid on the swollen lids. They
must be changed sufficiently often to maintain a uniform coldness.
In some cases it may be necessary to apply them continuously, while
in others they need be used for short periods only several times a
day.
When the cornea is involved great care must be exercised during any
manipulation, lest pressure be exerted on the globe.
Efforts at cleanliness must be redoubled. Solutions of atropine of
four grains to the ounce are to be used twice or thrice daily, to effect
complete mydriasis, when the ulceration is central. But if the ulceration
be marginal eserine salicylate in weak solution, one-quarter grain to
the ounce, may be used, but with great carefulness, as this drug is
liable to increase the hyperaemia of the iris, with consequent iritis.
Therefore, the use of this drug should be discontinued when the pupil
has become contracted. Ice must be discontinued and hot compresses
are to be substituted. Squares of gauze wrung out of water w^hich is
kept at about 110° F. are to be frequently applied.
Every attempt should be made to remove all of the discharges and
to restore the conjunctiva to its normal condition. The lids are to be
separated very gently and all of the tenacious secretion is to be wiped
off with swabs of cotton. The conjunctival sac is then to be flushed
with warm boric solutions. This attention should be given every hour,
or, if necessary, at even shorter intervals. Although other stronger
antiseptics may be tried, we are of the opinion that the careful and
persistent use of mild boric acid or weak bichloride of mercury
solutions should yield the best results.
Where perforation of the cornea is threatening, the edges of the ulcer
must be cauterized at once. Here a dull hot probe, thoroughly applied,
may end the process. We have used, besides the hot probe, solutions
of carbolic acid, of iodine, and crvstals of trichloracetic acid. If there
TJIli Th'/'JATMKNT OF SMALLPOX 315
1)6 not too Mincli (•oiijiiiictiviil swnitioii, .'i, well-applied rf)llcr hiiiida^^f
may ad'ord the pro|)er sii})])oi't to the already w(;akeried eorii(;al ineirj-
brane.
A low ^ra,de of conjunctivitis may {)er,si.st for a week or even months
after convalescence from smallpox in persons whose illness has fjeen
complicated hy serious conjunctival inflammation. Here the use of
stimulatinfii; astringents like the boroglyceride or the glycerole of tanrn'n
act with signal advantage. Argentamin, 2 to 5 per cent., or largin,
5 to 10 per cent., may be tried.
Formalin, Ir.WOO, or bichloride of mercury, three-quarters of a
grain to the pint, may be used with success in more severe cases with
considerable discharge.
CHAPTER VI.
CHICKENPOX.
Synonyms. — Varicella; formerly, Variola crystallina, Variola nctha,
Variola spuria. English, formerly, water pock, glass pock; German,
Varicellen, Wasserpocken, Wind hldttern, Schafpocken; French, la vari-
celle, la verolette; Italian, Mcrviglicne, ravaglione.
Definition. — Chickenpox is an acute, highly contagious disease,
occurring chiefly in children, characterized by an eruption of vesicular
type, appearing in crops and accompanied by mild febrile disturbance,
which usually begins with the appearance of the cutaneous outbreak.
The lesions dry in a few days into crusts. One attack protects for
life in the vast majority of cases.
History. — Chickenpox is doubtless a disease of great antiquity,
although for centuries it was confounded with smallpox. The Arabian
physician, Rhazes, who lived in the ninth century, made mention of a
mild or spurious eruption which was not protective against epidemic
smallpox. The Sicilian physician, Ingrassias, seems to have been the
first to have described varicella in accurate terms; this appeared in a
work entitled Preternatural Swellings, written in 1553. Vidus Vidius,
an anatomist and physician, wrote some forty years later, employing for
varicella the term crystalli or varioloe crystallines , a designation which
clung to the disease for many years.
Sydenham makes no mention of the disease. An admirable descrip-
tion, which admits of no room for doubt, has come down to us from
the pen of Riverius, who wrote in 1646.
Morton's writings on the subject are of historical value, because,
according to Gregory, he remarks that the disease was vulgarly known
as chickenpox. This appears to be the first mention of this term in
literature. The name chickenpox is said to be derived from the word
cicer, a chicken-pea, the French word for the same being chiche. Morton
(1694) referred to varicella under the title varioloe admodum henigna', re-
garding the disease, as did all of his contemporaries, as a variety of small-
pox. In 1696 Harvey contributed some important writings on the subject.
Although the credit of recognizing the duahty of chickenpox and
smallpox is commonly given to Heberden, it in reality belongs to Fuller,
who, in 1730, expressed his views in the following interesting language:
"The pestilence can never breed the smallpox, nor the smallpox the
measles, nor they the crystals or chickenpox, any more than a hen can
breed a duck, a wolf a sheep, or a thistle figs, and therefore one sort
cannot be preservative against any other sort." ^
1 Quoted by Gee, Reynolds' System of Medicine, American edition, 1879, p. 124.
ciiiCKF.NPnx 317
In 1707 irehordcn rontribiitcd to tlio flrsl, volmrio of (ho. Transactions
of the Royal dollccje of Physicians a carefully [prepared thesis in which
he urged the dissociation of smallpox and chickenpox. He employed,
however, the unfortunate title of variolw, jmsilhr, ignorin/^ the term
varicella which had been introduced a few years before (1704) by
Vogel in Germany. His work, though at first strongly criticized,
became for many years the acknowledged classic on the subject. The
term varicella is a diminutive for varus, a pimple.
In Germany, Sennert in 1676 was the first writer to call attention to
varicella. In Holland, I)iemerl)roek was the physician to achieve this
distinction. In the following century the most important literary
contributions were made by Frank, of Vienna, in 1805; AVillan, of
London, in 1806; Heim, of Berlin, in 1809; and Mohl, of Copenhagen,
in 1817.
In 1820, Thomson, of Edinburgh, obscured the comprehension of the
disease by reasserting the old doctrine of the identity of variola and
varicella, thus leading medical opinion into one of those by-paths which
so constantly cross the road of medical progress.
And again in 1866 there appeared a champion of the doctrine of
unity, in no less a person than Ferdinand Hebra, the great Viennese
dermatologist. Hebra regarded varicella as a mild form of smallpox.
He wrote: "I apply, then, the name variola vera to the most severe
form of this disease, that in which the eruption is abundant and the
fever intense, and in which a fatal result is often observed. On the
other hand, I use the term varicella for cases in wdiich the rash is very
scanty and which run a favorable course and always terminate in
recovery." And, again, "There is positive proof that varicella may
generate variola or varioloid, and, conversely, variola may produce in
another individual varicella."
When it is remembered that mild cases of smallpox were regarded
by Hebra as varicella the above statements need occasion no surprise.
It is difficult to conceive, however, how a close observer like Hebra
could have convinced himself that there was no chickenpox distinct
from smallpox. Hebra's large experience in smallpox and his fame as
a teacher led to an acceptance of his view^s in many quarters. Cursch-
mann, writing in 1875, says: "Concerning the relation of varicella to
variola, no perfect unity of opinion has yet been reached. While Hebra's
view of the close connection of the processes was universally respected
until a short time since, and has its supporters even at the present day,
authoritative voices are again raised in favor of their separation."
Hebra's views were taught by his successor, Kaposi, until his death
a few years ago. Kassowitz, of Vienna, has also tenaciously adhered
to the view of the identity of smallpox and chickenpox.
It is remarkable that a proposition so readily capable of proof as the
distinctiveness of smallpox and chickenpox should be repudiated by
such eminent teachers and observers. The chief explanation of the
astounding assertions they make is the unwarranted use of the term
varicella to designate very mild cases^of infantile smallpox. This and
318 " CHICKEN POX
the failure to recognize chickenpox as a separate disease account for
the discrepancies of these observers as compared with the almost
universal teaching.
With these few exceptions, physicians throughout the world are
agreed that chickenpox is a distinct disease having no relationship
whatsoever to smallpox.
It would be an act of supererogation at the present day to produce
the evidence in support of the duality of these two diseases.
ETIOLOGY.
Age. — Chickenpox is essentially a disease of early childhood. It is
most common between the ag6s of one and seven years. Although it
develops at times in infants at the breast, they more commonly escape
the infection when exposed to it. The statement made by many authors
that chickenpox is excessively rare in adults requires qualification; this
view has been so commonly held for many years that we have deemed
it advisable to discuss the subject of adult varicella under special caption.
We have within a few years seen two score or more cases of chicken-
pox in adults, and similar experiences have been recently reported by
others. The most advanced age at which we have seen the disease is
forty-nine years. The youngest period at which varicella appears to
have been observed is recorded by Senator, who saw an infant of eleven
days with the disease.
The following table, compiled by Gee^ from the records of the Chil-
dren's Hospital of London, shows the age incidence among children:
Boys. Girls. Total.
Under 1 month 2 2
" 2 months 2 6 8
" 3 " 4 9 13
" 6 " 29 28 57
" 12 " 45 52 97
" 18 " 34 28 62
" 2 years 36 39 75
" 3 " 36 42 78
" 4 " ........ 47 53 100
" 5 " 44 52 96
" 6 " 33 25 58
" 7 " 19 11 30
" 8 " 10 19 29
" 9 " 4 6 10
" 10 " 3 2 5
" 12 " 1 6 7
349 378 827
Varicella prevails more at certain times than at others and may occur
in epidemics. In large centres of population, however, the disease is
like scarlet fever, endemic, and to a certain extent always present.
The mildness of chickenpox favors its dissemination, inasmuch as
children frequently attend schools while still in an infectious state.
' Loc. cit.
ETIOLOGY ?AU
Susceptibility is not influencecJ by race, tlic negro and (he C.'aucasian
taking the disease with ecjual facility. Neither does varicella seem to
be influenced by climate or season.
While viiricella, is extremely contagions, its infecting [jower is not as
intense as that of measles or smallpox, and it is an easier disease to
control by isolation. As far as we know, the infection gains entrance
to the individual through the respiratory tract. In the vast majority of
cases chickeiipf)x is contracted by direct exposure to a person suffering
from the disease. It is not impossibl'e that the affection may be carried
by a third person or through the agency of infected objects, but this
is in all probal)ility uncommon. It is possible for the disease to be
transferred before the appearance of the eruption; this is exemy)lified
in the following case:
A physiciaji's daugliter, aged sixteen years, developed a slight sore
throat and a little fever, and was isolated in a room in the upper story
of her home. A small, whitish patch was noticed on the posterior
pharyngeal wall. On the following day the eruption of chickenpox
appeared. An eight-year-old brother who was with the patient on the
previous day was kept in a distant part of the house, out of all communi-
cation with the sister or her attendants. Sixteen days after exposure,
the same having taken place before the appearance of the eruption,
the boy developed chickenpox.
It is not surprising that varicella should occasionally be communicated
before the appearance of the cutaneous outbreak, wdien we remember
that smallpox may be transmitted during the initial stage of the dis-
ease.
How long a patient remains capable of transmitting the infection has
not been definitely determined. Nor is it known whether the infective
agent is present in the crusts, as is the case in smallpox. In the absence
of positive knowledge on this point, it is wise, in order to prevent con-
tagion, to isolate the patient until the skin is entirely free of the original
crusts. Crusts due to secondary infection of the skin are not capable
of transmitting the disease.
Second attacks of chickenpox are of great rarity. Thomas never
observed a second attack, an experience which corresponds with ours.
Gerhardt is said to have treated a child with three attacks, and a similar
observation is recorded by Heim. Vetter states that he saw the child
of a physician who had two attacks of chickenpox within fourteen days.
Neale^ reports a second attack of varicella after an interval of ten days.
Trousseau, Boeck, Kassowitz,Huf eland, and Canstatt have also reported
cases. These isolated instances do not, however, controvert the general
experience of physicians that one attack of chickenpox, in the vast
majority of instances, protects against future attacks.
Inoculability of Varicellous Fluid. — Numerous investigators have
endeavored to determine whether varicella can be communicated by
inoculation. Willan believed that the disease could be thus trans-
1 Lancet, 1S91, ii.
320 CHICKENPOX
mitted, but Gregory remarks that "his experiments are few and, to my
mind, unsatisfactory." Bryce, of Edinburgh, in 1816, made extensive
trials, with negative results. He states^ that he has inoculated with the
fluid of varicella vera, at all periods of the disease, and at all seasons
of the year, children who had never undergone either smallpox or
cowpox, and yet he had never been successful in producing from it
either variola or varicella.
Delpech, in 1843-44, attempted to inoculate patients with varicella
at the Hospital Necker in Paris, but with unsuccessful results.^ Hessa^
compiled data of 113 inoculations with varicellous fluid; in 87 of these
no result was obtained, in 17 there was merely a local manifestation,
and in 9 cases a general eruption ensued. Thomas obtained negative
results in his inoculations and mentions the fact that Heim, Vetter,
Czakert, and Fleischmann. had similar experiences. J. Lewis Smith
in this country likewise failed in his attempts to transfer chickenpox
to children who had never had the disease.
Steiner* obtained results very different from those above referred to.
He claims to have inoculated ten children, eight of whom developed
typical chickenpox. The time elapsing between the inoculation and the
appearance of the eruption in these cases was eight days.
If the possibility of transmission of the disease in the usual manner
was entirely excluded in Steiner's cases, his observations go very far
toward proving that chickenpox can be communicated by inoculation.
In view, however, of the negative results obtained by nearly all other
investigators, future experiment will be necessary to confirm the
successful inoculations obtained by Steiner.
Period of Incubation. — The stage of incubation of chickenpox is
ordinarily longer and more variable than that of smallpox or measles.
Different observers assign rather variant limits to this period, as will
be seen by reference to the following quotations :
Gregory^ says "it does not exceed four days and is certainly less than
a week;" Heberden^ places it at eight or nine days; Trousseau,'^ "fifteen
to twenty-seven days;" Gee,^ "at about a fortnight;" Thomas," thirteen
to seventeen days; Delpech, twelve days; Holt,^° "quite uniformly from
fourteen to sixteen days;" Corlett,^^ ten to nineteen days.
Our experience would lead us to regard fourteen to seventeen days
as the usual period, although we have observed it to extend over nineteen
days and even as long as twenty-one days. It is possible that in rare
cases it may be less than ten days and longer than three weeks.
In 16 cases occurring in an outbreak in the Municipal Hospital we
1 See Thomson on Varioloid Diseases, p. 74, quoted by Gregory.
2 Quoted by Gregory. ^ Ueber Varicellen, Leipzig, 1829.
1 Wiener med. Wochen., 1875, No. 16.
5 Lectures on the Eruptive Fevers. First American edition, 1851, p. 295.
6 Quoted by Gee. Loo. cit.
^ Lectures on Clinical Medicine. American edition. Philadelphia, 1882, p. 136.
8 Reynolds' System of Medicine. American edition, Philadelphia, 1879, p. 125.
5 Ziemssen's Encyclopedia of Medicine.
10 Diseases of Infancy and Childhood, p. 929. " Acute Infectious Exanthemata, p. 165.
H,YMI'T()MA TOLOCIY 321
were able to fix the hiciihation stage quite accurately. Tlie periofls
were as follows:
i:i (lays in . . 1 case. 1« 'lay.s in . .1 case.
14 " . . 7 cases. !'•• " ■ . I "
15 " . . 3 " 'il " . . I "
17 " . . 2 "
Stciiier, who claims to have successfully iuoculatefl varicella in ei^'ht
patients found the incubation stage in these patients to be uniformly
eight (lays. During the incubation period there are, as a rule, no
evidences of disturbed health. Now and then, however, as in some of
the other exanthemata the breeding of the disease may give rise to slight
symptoms, such as loss of appetite, lassitude, and general inclisposition.
SYMPTOMATOLOGY.
Pre-emptive Stage. — In the vast majority of cases chickenpox is not
preceded by a ])rodromal illness. The onset of the constitutional
manifestations is usually coincident with the appearance of the eruption.
The ordinary history elicited from mothers is that the eruption is the
first symptom to attract their attention, and that the children are not
ill prior to this time.
At the Municipal Hospital we have had the opportunity of studying
the temperature records of a number of chickenpox patients before the
appearance of the eruption; these patients were convalescent from
scarlet fever when they developed varicella. In almost every instance
the temperature remained about normal until the chickenpox eruption
appeared and, indeed, in some cases even after the lesions had developed.
In a small percentage of cases some little constitutional disturbance
may be observed a day or two before the appearance of the exanthem.
This consists of slight rise of temperature, anorexia, vague pains, and
chilliness. More common is it to discover these symptoms a half-day
or so before the eruptive outbreak. During the night preceding
the appearance of the exanthem the child may be slightly feverish and
restless. But these mild precursory symptoms should not be regarded
as representing a prodromal illness, for by this term as applied to
smallpox is meant a distinct stage preceding by two or three days the
onset of the eruptive phenomena.
It is important, however, to call attention to the fact that varicella
in adults may occasionally be preceded by a prodromal stage. While
most of these patients give no history of a pre-emptive illness, a minority
of them will volunteer such information. We have seen perhaps a half-
dozen of adults suffering from varicella who had distinct prodro-
mata. These symptoms consist usually of chilliness, lassitude, anorexia,
nausea, slight headache and backache, and some elevation of temperature
(101° to 102° F.). These manifestations may precede the appearance
of the eruption by two or three days, though more often not longer
than twenty-four hours. It is rare to observe high fever, vomiting,
severe lumbar pain, and prostration — symptoms which usher in a well-
pronounced smallpox.
21
322 CHICKENPOX
In general, it may be said that a true prodromal stage in children
suffering from chickenpox is extremely rare; in adults it is by no means
so infrequent. When it does occur it is much milder than the prodromal
illness ordinarily observed in smallpox. A prodromal erythema is, in
rare cases, seen before the appearance of the varicellous eruption, as it
is at times before the eruption of smallpox and measles.
Thomas observed "just before the outbreak of a light case of varicella
with ephemeral though intense fever (105.8° F., rectal temperature) the
appearance of a universal erythema of short duration." He adds,
however, that although he watched carefully for these eruptions this
was the only one he ever saw.
Henoch is also said to have seen and described such an erythema.
A prodromal scarlatinoid rash preceding the appearance of the
varicella eruption was observed by us in a patient admitted into the
scarlet-fever ward of the Municipal Hospital in the early part of 1902.
A girl, aged five years, was sent to the hospital from a large foster
home. She had had vomiting, some elevation of temperature, and on
admission there was a diffuse scarlatiniform rash covering the entire
trunk. This resembled scarlet fever so strongly that an experienced
interne regarded it as the scarlatina exanthem. The rash faded in
the course of twenty-four hours and was followed by the appearance
of a number of varicella vesicles. At the end of five days after admission
to the ward, a rise of temperature to 103° F. occurred, accompanied
by sore throat and a well-pronounced and typical scarlet-fever rash.
It was evident that the child contracted scarlet fever in the ward. No
scarlet fever existed in the foster home from which the child was received.
The Eruptive Stage.- — As has been stated, the eruption is commonly
the first symptom to attract attention to the disease. Synchronously
with the appearance of the cutaneous outbreak, or a few hours before
or afterward, a varying degree of fever sets in. In some cases this
does not reach higher than 99° F. ; in others, however, the pyrexial
elevation may be most marked. Thomas records one case in which
the initial temperature was 105.8° F., and we have on several occasions
observed temperatures of 104° and 105° F. This high fever is, as a rule,
of brief duration, subsiding in twelve or twenty-four hours to 99° or
100° F. High fever does not necessarily presage the development of a
profuse eruption. We have seen a temperature of 104° in a case with
scant and abortive lesions.
The temperature commonly falls to normal in the course of one to
three days. Where the eruption is copious, however, moderate fever
may persist for four or five days. In cases in which the varicellous
lesions become secondarily infected, the temperature may continue
above normal for a fortnight or even longer.
The Eruption. — The eruption of chickenpox usually appears first on
the back or the face, although other regions may be the seat of the
initial lesions. Irregular extension then occurs, new lesions developing
on different portions of the cutaneous surface. The hairy scalp is
nearly always beset with^some vesicles.
SYMPTOM A TOLOaV 323
The distribution of ilic eruption is subjec^t to soino varialioii, hut is
tolerubly uniform in the majority of cases. 'J'fie trunk, particularly the
hack, is relatively more profusely attacked than the distal portions of
the extremities — the wrists, ankles, hands, and feet. The face usually
presents a moderalo iiumhcr of discrete vesicles. It is rare for the
face to escape coiiij)lc(cly, altlioiif^h at times hut two or three lesions
may he present. At other times, in copious eruptions, quite an al)und-
ance of lesions may he seen on the face. The arms and legs are seldom
j)rofuscly attacked except in unusually extensive cases.
It has heen clainicd hy some writers that varicellous lesions do not
occur upon the palms and soles. It is true that in most cases the palmar
and plantar surfaces are free of eruption; hiit it is hy no means rare
Fig. 55
Chickenpox lesions in the crusted stage, about the fourth day of the disease.
to find a few vesicles in these regions, and in severe cases the lesions
may be fairly numerous.
The palms and soles are much less frequently and less abundantly
involved than in smallpox, in which disease some lesions are nearly
always present in these regions. The dorsal surfaces of the hands and
feet are likewise relatively lightly affected compared vnth the general
extent of the eruption. In fact it may be stated that the distal portions
of the extremities usually suffer but little in chickenpox; the eruption
prefers the covered surfaces.
The distribution of the eruption may, to some extent, be influenced
by ixritation of the skin prior to the appearance of the lesions. We
have seen a profuse crop of lesions develop over a rectangular area
on the sternum to which a mustard plaster had been applied during
the pre-eruptive period. Any irritant by increasing the vascularity of
324 CHWKENPOX
the skin may attract lesions to the region thus irritated. It is not so
common, however, to observe an increase of the eruption from this
cause as it is in smallpox. In the latter disease the influence of
cutaneous congestion in determining an increase of the eruption in a
given area is emphasized by frequent experience.
Ordinarily by the time that the physician is called to see a child with
chickenpox vesicles are observable upon the body. If the skin is
carefully examined early it will be noted that the vesicles are usually
preceded by erythematous spots. These are pea to bean sized, rosy
red in color, and in appearance not unlike the rose spots of typhoid
fever, or fleabites. Very soon the centres of the macules become raised
and small vesicles are formed which rapidly increase in size. In some
cases the rosy macules are elevated, somewhat acuminated, and in
reality represent papules.
The duration of the transitional lesions before vesiculation takes
place is extremely variable. At times some of the lesions of varicella
abort in the macular or papular stage and never go on to the develop-
ment of vesicles. Indeed, Thomas mentions a case, the nature of which
was verified by the previous occurrence of varicella in a sister, in which
erythematous spots (roseolse) persisted for thirty-six hours and then
disappeared without the formation of any vesicles whatever. Varicella
without the development of vesicles must, however, be extremely rare.
Varicellous vesicles may spring up so rapidly that they appear to
arise directly from the normal skin. We were enabled to determine
in one instance that vesicles developed in less than four hours. A
trained nurse bathed a child at 11 a.m. and carefully examined the
skin for an eruption v/ithout discovering any. At 3 p.m., four hours
later, we examined the child and found several fully formed, tense,
varicellous vesicles on the trunk.
The lesions often look as if they had been produced by drops of
scalding water sprinkled upon the skin. They are superficially situated,
differing in this respect from the deeper-seated vesicles of smallpox.
The epidermal roof of the vesicle is thin and readily ruptured.
The vesicles of chickenpox vary greatly in size; they may be no
larger than a pinhead, or they may reach the dimensions of a large pea.
They are commonly tense, although rarely as hard as the variolous
vesicle. Slight traumatism, such as is produced by scratching or the
friction of clothing, sufifices to rupture the vesicle. The fluid from an
early vesicle is clear and watery in appearance; later it becomes turbid
or lactescent. The vesicles are round or oval, the shape being some-
what determined by the lines of cleavage of the skin. In the axillary
and lateral costal regions they are commonly oval, the long axis corre-
sponding with the direction of the ribs.
Chickenpox vesicles are commonly surrounded by a reddish areola.
This may be narrow, measuring but an eighth of an inch; in other cases,
however, it may have a breadth of a half -inch or more.
Much diagnostic value has been attributed by some observers to
the comparative degree of evacuation of chickenpox and smallpox
PLATE XL.
A Severe Attack of Chiekenpox, showing Lesions in Various
Stages of Development (fourth day). Relative sparsity of lesions
on the face as coin pared with the trunk.
HYMI'TOMA TOI/XiY ;i2o
vesicles effected by })uncturin^ llicin willi ii nccHlc. While- il is tnie
tliat the varicella vesicle is often coiiiplclctly crnpficd, aiul the variolous
vesicle, owiiif^ to its more niultilociilar striicliire, less cotripletely evao
uated, hut little value should be phu-ed upon this test. There is too
much latitude j)ossibIe in the iiiterprcliilion of the deforce of evacuation
effected. s
The eru|)tion of chickcii])ox ii,j)pcafs in crops-. 'J'he first outbreak
couiinonly consists of a do/en to fifteen lesions. After an interval of
some hours, usually a day or so, a second crop appears which often
numerically exceeds the first. Twenty-four hours later a third out-
break may occur and new lesions may thus continue to appear for four
or five days or even a week. Owinfi^ to the fact that the lesions are
of ditt'erent age, they are seen in varying stages of evolution and invo-
lution. There may be present at the same time small, new, tense vesicles ;
older, drying vesicopustules, and, in addition, dark-colored cni.sts
which represent the remains of the first vesicles. This multifoi-mity
is one of the most distinguishing features of the eruption of chickenpox.
The duration of the individual lesions of chickenpox is brief. The
vesicles, after reaching the acme of their development, become flaccid,
and in from one to three days dry into crusts. The unruptured vesicle
desiccates first at its central summit. Lesions which are ruptured by
mechanical force give exit to a fluid which forms an irregularly shaped
crust.
The fluid contained in the vesicle is at first as clear as w-ater; it later
becomes turbid and finally, if unruptured, quite purulent. During these
changes the vesicle which has in the beginning a "dewdrop-like"
appearance acquires a grayish or yellowish color.
True umbilication, such as is seen in the early smallpox vesicle, does
not occur in chickenpox. There is sometimes seen a pinpoint-sized
invagination of the surface of a vesicle due to the presence of a hair
follicle. Commonly there is observed a central sinking in of some of
the vesicles or vesicopustules due to partial evacuation and central
drying. This is also seen in the late pustular stage of smallpox, and
might be called a secondary umbilication.
As the vesicles of chickenpox begin to dry there not infrequently
develops a flat, vesicular, spreading ring upon the border of the crust;
beneath the raised-up epidermis is a little puriform fluid. The lesions
may, as a result of this process, spread to the size of a silver quarter
or half dollar. This condition is extremely common in smallpox and
has been called "impetigo variolosa." The process being the same
in chickenpox, the condition might be appropriately designated "impetigo
varicellosa." The cause of these spreading sores is an infection of the
varicellous sites with streptococci and staphylococci present upon the
surface of the skin. In extensive eruptions where there is much of
this impetigo, moderate elevation of temperature may develop, giving
rise to a secondary fever.
The extent of the varicellous eruption is extremely variable. The
total number of lesions in some cases mav amount to but a half-dozen;
326 CHICKENPOX
on the other hand, they may cover almost completely the entire cutaneous
surface and number hundreds or even thousands. Thomas says, "as
many as eight hundred have been counted or estimated." In a
copious eruption in a young boy we counted one thousand four
hundred lesions; shortly afterward in an older lad convalescent from
scarlatina we encountered a much more extensive eruption.
A photograph of this boy is shown in Plate XLII. We estimated
that there were in the neighborhood of three thousand lesions upon
the skin.
While neighboring and closely set vesicles may occasionally coalesce,
one never sees a confluence of the lesions such as is observed in smallpox.
Scarring After Varicella. — It is not uncommon for some varicella
lesions to be followed by scars. Indeed, it is rather the rule for patients
to have one or several cicatrices which persist after the disappearance
of the eruption. These are from pinhead to pea sized, rounded or oval,
and excavated to a variable degree. In severe cases the number may
reach a half-dozen or a dozen or more. They are never, however, as
numerous as is seen in smallpox. The scars result from a destruction
of the papillary layer of the true skin; this may be due to secondary
infection as a result of scratching, but it may occur entirely apart from
this cause. Chickenpox vesicles at times break down early and produce
a necrosis of the underlying corium; the ulcer left heals with the form-
ation of a depressed scar. Occasionally a hypertrophic scar or sort of
keloid forms at the site of these losses of tissue.
The mucous membranes are not infrequently the seat of varicellous
lesions. It is quite common to find a few vesicles upon the soft and
hard palate, and these in doubtful cases are of diagnostic importance.
Lesions are also occasionally noted upon the buccal mucous membrane,
tongue, and posterior pharyngeal wall. Situated in these regions the
flaccid roof of the vesicle soon ruptures, leaving at first a grayish peUicle
of epithelial debris and later a circumscribed superficial abrasion,
surrounded by a reddish areola and resembling to some extent the
sore of aphthous stomatitis. The eruption in the mouth is usually scant,
even in cases characterized by an abundant cutaneous outbreak. The
exanthem, as a rule, appears synchronously with the eruption on the
skin, but it may precede it. We know of a colleague who was perplexed
by the appearance of a circumscribed patch on the posterior pharyngeal
wall of his daughter, but who later discovered that it was an early
varicellous lesion preceding the general eruption by about twelve hours.
Henoch has seen varicellous vesicles on the gums and also on the
conjunctival mucous membrane. Thomas observed the latter attacked
only when the contiguous portion of the eyelid was affected. He
likewise under similar conditions noted involvement of the nasal
mucous membrane.
Marfan and Halle have recorded two cases of involvement of the larynx,
one necessitating tracheotomy. The other case succumbed to other
complications and on autopsy the remains of a vesicle were found on
the right vocal cord.
PLATE XLF.
An Unusually Extensive Eruption of Chiekenpox in which the
Lesions -were Estimated to Reach SOOO in number.
,S' Y M I 'TO MA TOfAXl V
327
Varicelloiis lesions arc occasionally found in flic; vc;stil)ule of the
va<);ina Jind upon the prepuce, in wliich regions the accompanying
swelling mjiy cause difficulty in micturition.
As far as is known, chickenpox never attacks the mucous membrane
of the slonKich or intestines. Partridge, in 1SS7, prcscnicd to the New
York l*ii,th()logi(;al Society specimens from a child that hainrnonly
complicates varicella.'
In mild cases but one or several varicellous lesions may undergo
necrosis; in more extensive cases many of the vesicles become involved.
The vesicle may either become converted into a bleb, the gangrenous
process beginning beneatli this epidermal elevation, or the vesicle may
dry into a dark crust and enlarge uj)on th(^ j)eriphcry. I'pori removal
of the crust a sharply marginated, punched-ont, freely discliarging ulcer
is seen. A dusky-red areola surrounds the ulcer or eschar. In extensive
cases the temperature rises to 104° or 105° F., and the patient rapidly
sinks. ■ Ivung complications, particularly pulmonary infarction, are
common. Mild cases of gangrene may recover. The affection is
most common in debilitated infants, more especially those in whom
the varicella is preceded by some other illness. In Griffith's case the
chickenpox was preceded by measles, diphtheria, and pneumonia.
Cases of gangrenous varicella have been reported by Hutchinson,
Demme, Abercrombie, Andrew, Crocker, Biichler, Jamieson, Lowen-
hardt, Payne, Stanifooth, Haward, Vierordt, Griffith, Lockwood, Silver,
Woodward, and others.
We have, on several occasions, observed localized gangrene occurring
at the site of smallpox pustules; these cases all terminated fatally.
Stokes,^ of Dublin, reports a case of vaccinia gangrenosa ending in
recovery.
Synovitis and Arthritis. — Synovitis and arthritis have been reported
as rare complications. Laudon^ and Ferret' have both published
examples of joint involvement in chickenpox. The patient of the
former, a boy aged four years, developed high fever early in the course
of varicella, followed by marked swelling of the left elbow-joint. Re-
covery took place after several weeks.
Semtschenke, quoted by Rille, saw 2 cases of purulent pleurisy and
purulent arthritis in an epidemic of chickenpox in Russia.
Hogyes reports a case of varicella in a seven-year-old girl followed
by nephritis and subsequently by an inflammation of several joints,
accompanied by high fever and ending in recovery.
Braquehaye saw a purulent arthritis of the knee and elbow develop
on the ninth day of a varicella which w^as apparently running a normal
course. Despite incision and drainage death resulted. On autopsy a
septic endocarditis was also discovered.^
Marfan and Halle" describe 2 cases of serous involvement of the larynx
through the presence of varicellous vesicles. In one case, in a boy of
three years, tracheotomy was performed, the patient recovering. In the
other, a child of nine months, with a well-marked chickenpox, developed
1 An excellent description of this afiection is given by Crocker under the title o." "Dermatitis
Gangrsenosa Infantum." Text-book of Diseases of the Skin. American edition, 1903, p. 535.
- Dublin Journal of Medical Sciences, June, ISSO.
^ Deutsche med. Wochenschrift, Leipzig, 1890, xvi. p. 5G7.
* Province mt>d. Lyon, 1SS9, iii. pp. 256-261.
6 Quoted by Brown. Twentieth Century Practice of Medicine.
6 Quoted by Brown. Ibid.
332 CHICKENPOX
stridor and dyspnoea; diphtheria bacilli were absent. Bronchopneu-
monia and diarrhoea supervened and death resulted; the post-mortem
examination revealed the presence on the right vocal cord of a round,
shallow ulcer, evidently the remains of a varicella vesicle.
Nephritis. — Nephritis is one of the most serious of the complications
and sequelse of varicella. While it occurs in only a very minute per-
centage of cases, there are in the literature a sufficient number of recorded
instances to cause physicians to keep in mind the possibility of its
development and to watch the kidneys in the treatment of this otherwise
trivial disease.
Henoch^ was one of the first to mention nephritis as a complication
and reported 4 cases following chickenpox. Janssen,^ Hogyes,^ Oppen-
heim,* Brunner,^ Unger,® Rille,^ Schwab, von Jiirgensen^ and Dillon
Brown'' have all described similar cases.
The nephritis usually comes on during the first or second week
of the disease. It varies in severity as does this complication in other
infectious diseases. In severe cases an abundance of albumin and
tube casts may be present in the urine. As a rule, the nephritis is
mild, recovery taking place promptly. Dillon Brown, however, reports
a case in which the kidney involvement after a mild attack of varicella
ran a chronic course, ending fatally some ten years later. Ildgyes'
case terminated fatally through complication with pneumonia, and
Rille reports an uncomplicated nephritis ending in death and showing
on autopsy parenchymatous changes in the kidneys.
Bronchitis and Bronchopneumonia. — Bronchitis and bronchopneu-
monia are mentioned as complications by Meigs and Pepper, and Rille
reports a peculiar form of pleuropneumonia ending fatally on the
nineteenth day after varicella.
Association of Chickenpox with Other Exanthematous Diseases. —
It is not at all uncommon for varicella to develop during convalescence
from other acute exanthematous diseases, such as measles, scarlet fever,
smallpox, etc. On the other hand, these diseases may develop in
patients suffering from varicella. It is rather rare for these eruptive
diseases to be synchronously present in their acutest stages; usually the
second disease appears as the first is beginning to decline.
Chickenpox has repeatedly broken out in the diphtheria and scarlet-
fever wards of the Municipal Hospital. Under these circumstances the
varicella would naturally appear not earlier than the end of the second
week of the original disease. We have often seen varicella appear in
scarlet-fever patients who were profusely desquamating. We have also
observed these two diseases present at the same time with vaccinia.
1 Berliner klin. Wochenschrift, No. 2, January, 1884. - Nedre. Tijdsch., 1884, B. xx. p. 223.
3 Orvosi hetil., Budapest, 1885, xxix. pp. 11-16.
* Berliner klin. Wochenschrift, December 26, 1887.
5 Aerztl. Mitth. a-Baden, Karls nute, 1888, xlii. pp. 49-52.
6 Wien. med. Presse, 1888, xxix. pp. 1449-1451.
7 Wien. klin. Woch., 1889 ; Deutsche med. Woch., 1891.
8 Nothnagel's Encyclopedia of Medicine. Article on " Varicella."
9 Twentieth Century Practice of Medicine. Article on " Varicella."
(]()MI'IJ(!.\TI()NH AND Sf'Xjff I'JL.f: OF ('II K' K ICS I'OX ,'},'J.^j
Chickenpox may af)|)ciir diiiiiif;- coiivalcsccnfc from smjillprjx. 'I'lif
foll()winox
at an early age.
During the eighteenth century epidemics of scarlatina were observed
in all parts of Europe.
A severe epidemic of scarlatina prevailed in Lon Quoted by Thomas C. Minor, in a report to the American Public Health Association, 1875.
344 SCARLET FEVER
ETIOLOGY.
Despite the fact that the causative agent of scarlet fever has not
yet been discovered, the statement may be made that the disease is
produced by a specific micro-organism. Scarlet fever is so similar
in its behavior and manner of transmission to other infectious diseases
of proven parasitic origin that, reasoning by analogy, we are irresistibly
forced to this conclusion. Not many years ago it was maintained by
writers that cases of scarlet fever could arise de novo, independently
of pre-existing cases. The spontaneous origin of infectious diseases is
no longer credited by medical scientists of the present day. The channels
of infection are often so devious and the manner of transmission so
mysterious as to make the origin of these diseases in individual instances
quite incomprehensible. But the mystery of an infection is dispelled
and becomes as clear as the trick of the magician when the solution is at
hand. The proposition may, therefore, be accepted that every case of
scarlet fever has its origin in an antecedent attack in another individual.
Modes of Transmission of the Scarlatina Contagium.— The germ
of scarlet fever is chiefly if not exclusively conveyed in two ways: (1)
directly from a scarlatina patient to the newly infected subject, and
(2) through the intermediation of infected objects.
The vast majority of cases of scarlatina doubtless result from exposure
to persons suffering from the disease; this is freely admitted. A certain
school of German writers, led by von Kerchensteiner, maintains that
the disease cannot be conveyed hy a third person. The clinical experience
of numerous careful observers is strongly opposed to such an opinion.
Indeed, there are recorded instances of such transmission which appear
quite conclusive.
Dr. Loeb, of Worms, mentions the case of his three-year-old daughter
who developed scarlet fever at a time when there were no known cases
in the city. The origin of the infection was a mystery until it was
discovered that a medical friend and colleague who had been at the
house, and upon whose lap the little girl had sat for a long time, had
some hours previously visited three cases of severe scarlatina in another
city and had not changed his clothes. The disease manifested itself
at the end of two days. The circumstances surrounding the case would
seem to point in the strongest manner possible to the conveyance of
the germs in the clothes of the physician.
Thomas saw a case "in which a nurse coming directly from a scar-
latinous patient communicated the disease in the short space of three
hours to a child who had almost recovered from a tracheotomy." He
also quotes Zengerle to the effect that a healthy woman, after a visit
to a scarlatinous patient, transmitted the disease to her daughter, who
was the first patient affected in the whole city. Murchison was con-
vinced, from the testimony he had received from numerous physicians,
that the scarlet-fever infection was not rarely carried by them.
The infection commonly clings to objects which have come in contact
with the scarlet-fever patient, such as bedding, clothing, books, letters,
ETIOLOGY 345
toys, etc. Numerous instances are recorded in which such articles
have transmitted the infection. IJotli Tiic-htirdson and Peterson traced
cases of scarlet fever to infection transjnilled in letters. It is an important
matter in infectious-disease hospitals that all outgoing mail lie thor-
oughly disinfected.
The scarlet-fever contagium may cling tenaciously and for a long time
to the sick-room and to certain objects contained therein. Murchison,
on the testimony of Richardson, mentions an extremely sad illustration
of this. A child having been seized with a fatal attack of scarlet fever
in a country house, the three remaining children were fjuickly removed.
After a lapse of several weeks one child that was brought home con-
tracted in twenty-four hours an attack of scarlet fever to which he
rapidly succumbed. The house was then thoroughly cleaned and the
walls whitewashed, but the infection was not removed, for a third child
that returned after four months took the disease and died in the same
manner as the others. It is believed that the infection was retained
in a thick layer of straw covering on the children's beds.
Von Hildebrand claims to have contracted the disease from a black
coat which he had worn a year and a half before while attending a case
of scarlet fever in Vienna.
The most remarkable claim of longevity of the scarlet- fever infection
is mentioned by Boeck (quoted by Johannessen, loc. cif.), who relates the
circumstance as follows:
"The children of a colleague of mine had obtained permission to play
with some things in an old writing desk. In a drawer lay some hair that
had been cut from two children that had died of scarlet fever tiventy
years before; since that time the drawer had not been touched. Now
it was opened and the children took scarlatina. These cases were the
first in the city, so that the probability is evident that the infection
was transmitted in this way."
Immunity and Susceptibility.— There is no such universal suscept-
ibility of persons to scarlet fever as is known to exist toward measles
and smallpox. Experience teaches that but few people enjoy a natural
immunity against these latter diseases. Many persons, however, escape
contracting scarlet fever even though freely exposed to its infection.
The contagion of scarlet fever is a most ca'pricious one; it may repeat-
edly spare an exposed individual and lead him to believe that he is
immune against it, only to smite him at some subsequent period.
This temporary immunity against scarlet fever has been repeatedly
noted by various observers. Nurses have frequently been observed
during the closest attendance upon patients suffering from scarlet fever
to remain free from infection, and yet later contract the disease. Such
a case has recently come under our observation:
Mrs. X., aged thirty years, a private trained nurse, was brought into
the Municipal Hospital on January 9, 1903, suffering from a well-
pronounced attack of scarlet fever. She had never had the disease in
childhood. During the past few years she estimated that she had nursed
about fifteen cases of the disease. On November 17, 1902, she com-
346 SCARLET FEVER
pleted her service in connection with a severe case of scarlet fever in the
suburbs of Philadelphia. A little over six weeks later she began to
nurse a patient with puerperal scarlet fever. After being on duty four
days she herself was taken with a scarlatina of average severity, which
ran a typical course and was followed by profuse desquamation.
We recall the case of an ambulance driver at the Municipal Hospital
who came in almost daily contact with cases of scarlet fever, and who
finally at the end of several years contracted a well pronounced attack
of the disease.
On another occasion one of the nurses at the Municipal Hospital
contracted a well marked attack of scarlatina on returning to duty in
the scarlet-fever wards after a year's absence. Prior to her departure
she had nursed mixed cases of diphtheria and scarlatina for a period of
three months.
It would appear in these cases that for some reason or other the
resisting power of the subject is lowered at the time of infection; this
explanation seems to us to be more plausible than the assumption that
the attack is determined by an unusually intense infective agent.
In some instances it would appear that the temporary immunity
against scarlet fever is overcome by infection through unusual channels.
The puerperal state and surgical operations are said to favor the develop-
ment of the disease.
Von Leube^ gives an interesting account of an attack of scarlatina in
his own person following a wound received in making an autopsy upon
a patient who had died of an unusually severe case of scarlet fever.
He states that he had considered himself perfectly immune, having been
exposed as a child, and having attended any number of cases under all
sorts of circumstances. Ten days after the post-mortem wound upon his
finger he developed sore throat, and on the following day he vomited,
had a "decided fever," and the scarlatina rash. The course of the disease
was one of medium severity.
The susceptibility to scarlatina commonly disappears in adult life;
at any rate, many adults who have never had the disease escape infection,
although freely exposed. Patients suffering from scarlet fever have on
numerous occasions been placed in the wards of general hospitals
without appearing to disseminate the disease among other occupants
of the ward. Such experiences illustrate the very limited suscepti-
bility of persons who have passed the age of puberty.
During the past few years the students of the various medical colleges
in Philadelphia have been conducted through the wards of the Municipal
Hospital in order to study the various infectious diseases therein treated.
About 700 students in all have taken advantage of this bedside instruc-
tion. They were taken into the scarlet-fever wards in which there were
100 or more cases of this disease, and remained from one to two hours
in this intensely infected atmosphere. About one-half of these students,
according to their statements, had never had scarlet fever, and yet not a
1 Specielle Diagnose der inneren Krankheiten, Bd. ii. p. 364. Leipzig, 1893.
ETIOLOGY 347
single one contracted the disease. Tliis is strong proof of (lir; frequent
ahrf)gation of the siisc<>|)lil)iliiy of adults to scarlet f(!ver.
Epidemics Among Adults. — VogI,' of the (j(;rieral Medical Staff of
Bavaria, reports two epidemics of scarlet fever among the Bavarian
troops at Munich. In 1884-S5, during a garrison epidemic covering a
period of ITSdays, 125 out of 7442 soldiers, or 1.07 per cent., contracted
the disease. The mortality rate was 4 per cent. In 1804-95, during a
similar epidemic lasting 155 days, 311 out of OfiOS troops, or 3.23 per
cent., took scarlatina, of whom 1.2 per cent, dierl. The attack rate
among exposed adults is thus seen to be very small.
Murchison estimated that the number of persons attacked with
scarlet fever in England and Wales was considerably less than one-half
of the number of l)irths. It is evident, therefore, that the lessened
susceptibility to scarlatina exhibited in adult life is not entirely due to
protection granted by an attack in childhood.
This is also shown by the figures of scarlatina in virgin countries.
From 1873 to 1875 an extensive epidemic^ of scarlatina raged in the
Faroe Islands. The disease had not been known in this locality for
fifty-seven years and possibly had never occurred at all. From the
carefully collected data of Hoff concerning the town of Thorshavn, the
chief city of the islands, it is seen that of a population of 930 persons,
237 contracted the disease. Among the entire inhabitants of the islands,
of whom none had ever had scarlatina, but 38.3 per cent, contracted
the disease during this protracted epidemic.
Age. — Age is a most pronounced factor in the determination of
susceptibility to scarlet fever. It is a general experience that infants
under one year of age exhibit a lessened disposition to contract the
disease; this is still more true of nurselings under six months, and in
infants under three months of age scarlatina is excessively rare. The
infrequency of the disease at this tender age may be judged by the
statements of experienced observers in reference thereto.
Fleischmann^ saw no cases under six months of age; Eulenberg, none
under eight; Thomas, none under five; Boning saw no cases under one
year; Senfft saw but one patient under one year, and Gaupp only two.
Haller observed a case at five months; Voit, one at two and a half
months; Kiipfer, one at two months; and Veit, one at two weeks.
This represents an extremely scant number w^hen the large number
of cases of scarlatina observed by these men is taken into consideration.
In Johannesen's statistics of scarlet fever deaths in Norway from 1862
to 1878, the number of infantile attacks is considerably greater. He
reports 15 deaths from scarlatina under six months, and 93 under one
year. In our own experience at the Muincipal Hospital we have found
that among 5000 cases of scarlet fever admitted into the hospital, about
1 per cent, consisted of infants under one year of age. We have on a
number of occasions had infants a few months old brought into the
1 Miinchener med. Wocli., 1895, p. 949.
- Mentioned by von Jurgensen in Nothnagel's Encyclopedia of Practical Medicine.
3 Mentioned by Thomas in Ziemssen's Encyclopedia of Practice of Medicine, p. 180.
348 ^ SCARLET FEVER
hospital with mothers suffering from scarlatina, but we have seldom
observed them to contract the disease. We have seen them suckle at
breasts covered with the scarlatinal rash, draw a febrile milk, and yet
remain perfectly well.
The question whether there is a congenital scarlatina is most difficult
to answer. Children are so commonly ushered into the world with a
red rash that but little reliance can be placed upon the existence of an
exanthem. Furthermore, it is not uncommon for the tender epidermis
of the infant to peel off after some days and thus cause a desquamation.
Baillou, Ferrario, Stiebel, Hiiter, and others saw infants that were
alleged to have scarlatina at birth (most of them being born of mothers
suffering from scarlet fever at the time), but the facts do not appear to
us to warrant the unreserved acceptance of the diagnosis. Murchison
saw two pregnant women with scarlet fever, and in each case the child
born at the time was free of the disease. Elsasser also saw a healthy
babe born of a mother with scarlatina.
Children from two to five years of age appear to be most susceptible
to the contagium of scarlatina. From five to ten years the attack rate
is somewhat less, and after the period of puberty is reached the suscept-
ibility to the disease is greatly lessened. No age, however, appears to
guarantee absolute immunity against scarlatina inasmuch as persons
even over the age of ninety-five have been known to contract the dis-
ease.
Murchison's valuable statistics of scarlet-fever deaths in England and
Wales, covering the enormous number of 148,829, will give a fairly
accurate idea of the incidence of the disease in the different age periods :
Under 1 year 9,999 or 6.7 per ct.
From 1 to 2 years 20,975 " 14.1
2 " 3 " . 23,842 " 16.0
3 " 4 " 22,528 " 15.1
4 " 6 " 17,726 " 11.9
5 " 10 " 38,591 " 25.9
" 10 " 15 " 8,676 " 5.8
Total under 5 years 95,070 or 63.8 per ct.
From 5 to 15 years 47,267
15 " 25 " , . 3,871
" 25 " 35 " 1,306
35 " 45 " . . 671
" 45 " 55 " 331
55 " 65 " 185
" 65 " 75 " 88
" 75 " 85 " 30
" 85 " 95 " 4
Over 95 " . ; 6
Total 148,829
It will be seen from the above tables that considerably over one-half
of the deaths of scarlatina occurred in children under five years of age.
Almost 90 per cent, occurred in those under ten years, and over 95 per
cent, under fifteen years of age.
These figures correspond very closely with statistics of scarlet-fever
deaths in Berlin from 1875 to 1891, and with Johannesen's statistics for
ETIOLOGY :W.)
Norway. As showing the fatal cases in cliildrcii.iKKler ouc yrar, the
latter statistics are of particular interest :
Fatal Cases of Scarlatina in CuRisTrANA (Jndkk Onk Ykarch Af;K,
(JOHANNESEN.)
iBt month
2(1 to 3d month .'{
4th " f)th " 12
7th " 12th " 78
The above deaths were out of a total of 1040 fatal cases.
Family Predisposition. — Some families, at times, exhibit an unusual
susceptibility to scarlatina; this is manifested not only by several mem-
bers of the family contracting the disease, but likewise by the severity
of the attack. Thomas^ recognizes "an intense family predisposition,
showing itself by numerous and severe attacks in the family as soon as
one infection has taken place in it." Trousseau says: "Scarlatina
epidemics may be full of danger for an entire population, or they may
assume this character only for a single family. The malignancy limits
itself in a measure to a single hearth, and in such cases the disease is
malignant for all persons that live within its circle." Henoch^ expresses
much the same idea; he says: "Striking to me appeared the fact that if
scarlatina breaks out in a family, very frequently also a second and third
child are taken off under similar conditions, and in this way whole
families can die out."
Copeman,^ during a severe epidemic of scarlet fever in 1844, saw four
children in a family die so suddenly that poisoning was suspected ; a fifth
child went through an ordinary attack of scarlet fever.
A somewhat similar instance has recently come under our observation.
In the winter of 1902 we saw a family in which four children were
smitten with scarlet fever. All fell suddenly ill with vomiting, which
was attributed by the mother to free indulgence in candy. Soon the
scarlatinal rash manifested itself. The eldest daughter, a girl of seven-
teen, died in five days; a second one had a temperature of 105° F.,
with intense prostration, and recovered, as did a third child, only after
a most desperate illness. The infection in these cases was most viru-
lent, and yet the prevailing type of scarlatina in the city at that time
was quite mild.
These severe family epidemics are difiicult to account for. Henoch
presupposes a mixed infection in such cases. Thomas does not seek
an explanation in an unusually intense infection, for he says "the
infecting cases are frequently of a mild character."
Epidemics of this character are happily uncommon. In some instances
there is a tendency to family immunity, the members thereof exliibiting
an almost complete insusceptibility to the disease.
Climate. — Accordingto INIinor,^ who has in a most painstaking manner
studied the prevalence of scarlatina in the United States, climatic con-
ditions influence the spread of the disease. He says:
1 Loc. cit, p. 175. - Vorlesungen iiber Kinderkrankheiten, p. 654. third edition.
3 Jahresbericht, etc., der Gesammteu Medicin. E. Virchow and A\\%. Hirsch, vi. Jahrgang, 1S71,
vol. ii. p. 247. 4 Loc. cit., p. 13.
350 < SCARLET FEVER
1. "The zone of comparative immunity in the Eastern Hemisphere
extends from 10° south latitude to 20° north latitude." (In this zone
are found Sumatra, Borneo, India, and most of Africa.)
2. "A zone of comparative immunity in the Western Hemisphere
extends from the equator to 10° north latitude." (In this zone are
found Venezuela- and the States of Colombia.)
3. "Another zone of comparative immunity in the Western Hemisphere
extends from 30° to 35° north latitude." (In this zone are found South
Carolina, Georgia, Alabama, Mississippi, Louisiana, Texas, and the
northern part of Florida.) According to the vital statistics of the United
States for the year 1900 these States, with the exception of Texas, had a
remarkably small scarlatina mortality compared with other sections of
the country.
4. "In times of pandemics, occasional epidemics occur at points
within the zones of comparative immunity." The disease in these
regions, however, attacks by preference the Caucasian race.
Minor furthermore says that in these countries, "lying for the most
part in the tropics and near the equator, exposed to the direct rays of
the sun, a high mean annual temperature is of course noticeable."
This author, after discussing the climatic influences, concludes that
"a very high temperature, combined with periodical humid atmos-
phere, is unfavorable to the development of any scarlatinous ten-
dency."
Season. — Hirsch has studied the seasonal incidence of 435 epidemics
of scarlet fever occurring in Norway, Sweden, Russia, Germany,
Holland, France, Italy, Spain, and North America. Most of the epi-
demics occurred in autumn, as will be seen from the following figures:
autumn, 29.5 per cent.; winter, 24.7 per cent.; summer, 24 percent.,
and spring, 21.8 per cent.
In England, since the days of Sydenham, it has been recognized that
scarlatina prevails most in the fall; 55,956 deaths in London from
scarlatina during a period of twenty-four years gave the following
percentages: autumn, 35.54 per cent.; winter, 23.85 per cent.; summer,
22.75 per cent.; spring, 17.87 per cent.
In the United States scarlatina is most prevalent during the latter
part of winter and during the ea^'ly spring months. The vital statistics
for 1870 show the largest number of deaths in March. The first five
months of the year exhibit a considerably greater mortality than the
rest of the year:
Scarlatina Deaths by Months in the United States in 1870.
January
. 2205
February
. 2393
March
. 2726
April .
. 2294
May .
June .
July .
. 2146
. 1826
. 1216
August
. 1096
September
. 927
October . .
. 1000
November
. 1281
December .
. 1705
Unknown .
5
Total . . . 20,320
I'lTIOUXlY
351
Arranged according to seasons, (Ik^ figures read as follows:
Spring
Summor
710(1
3038
Aiilnrnii
Winder
.",208
0303
Tlie- vital statisfics of the United States for the year 1000, although
somewliat ditrerently j)resented with reference to scarlet-fever mortality,
give similar results:
Scarlatina Deatuk by Months i-ek 1000 of Deaths from Ali, (Jaijsrs
IN THE United States in 1900.
January .
. 118.3
AugUHt
50.3
February .
. 112.8
September
52.5
March
. 1008
October .
69.4
April
. 105.7
November
84.8
May .
. 98.4
December .
98.7
June .
. 50.0
July . . .
. 40.3
Total actual deaths
6333
Here again it is seen that the greatest mortality from scarlet fever
is in the late winter and early spring months.
According to Murchison, epidemics of scarlet fever in France occur
more frequently in the spring and summer months.
Johannesen classifies as follows 65,785 cases of scarlet fever occurring
in Sweden from LSGT to 1878:
January
February
March .
April
May
June
11.3 per ct.
9.2
9.1
6.9
July .
August
September
October
November
December
6.6 per ct.
0.3
5.7
8.0
10.4
10.7
It is seen that the greatest number of cases occurred in November,
December, and January.
In Berlin, from 1877 to 1883, there were 5428 deaths from scarlatina,
with the following monthly mortality:
January .
. 6.7
per ct.
July .
. 8.0 per ct
February
. 5.3
August
. 8.5
March
. .5.8
September
. 10.7
April
. 6.1
October .
. 13.8
May . . .
. 7.0
November
. 10.9
June
. 8.1
December
. 8.5 "
The greatest number of deaths occurred in autumn — September,
October, and November, the maximum being reached in October.
From the various statistics presented it is seen that season apparently
has some influence on scarlatina prevalence. The same months in
different countries show, however, Avidely divergent figures.
The different character of the climate in the countries mentioned may
account for the discrepancies in the monthly morbidity incidence. It
will be necessary to carefully compare the climatic and meteorological
conditions by month in the various countries before an^-thing can be
definitely said as to the influence of season upon the spread of scarlatina.
Minor^ studied the influence of temperature on the prevalence of
1 Loc. cit.. p. 51.
352 SCARLET FEVER
scarlatina and came to the conclusion that the colder weather seemed
to favor the scarlatinous tendency. He states that:
1. The scarlatinous tendency is but slightly, if at all, modified by a
temperature ranging from zero to 65° F.
2. The scarlatinous tendency is decidedly modified and lessened
by a temperature ranging from 75° to 80 ° F.
3. The scarlatinous tendency is almost entirely destroyed where there
is a prolonged high temperature ranging from 80° to 85° F.
Influence of Urban and Rural Localities. — As would be naturally
expected, the prevalence of scarlatina is greater in city than in country
districts. This is to be accounted for by the more extensive intercourse
between cities and by the greater crowding and more intimate contact
of the people. The vital statistics of the United States for the year
1900 show a very distinct difference between the city and rural death rate
by months:
Death Rate from Scarlatina by Months in Cities and Rural Districts,
PER 1000 OF All Deaths.
Cities. Rural.
January 1.6 0.8
February 1.8 0.9
March 1.5 0.9
April 1.4 0.8
May 1.4 0.7
June 1.0 0.4
July 0.6 0.3
August 0.5 0.3
September 0.4 0.3
October 0.8 0.4
November 0.8 0.8
December 1.2 0.8
Scarlet fever is practically endemic in the great centres of civilization ;
the disease in the large cities of the world increases and decreases from
time to time, but never dies out completely.
Altitude. — Minor^ says in regard to altitude that " scarlatina prevails
at all altitudes, epidemics occurring at New York, Providence, and Bos-
ton, on the Atlantic coast; at Pittsburg, Cincinnati, Chicago, Detroit, and
St. Louis, in the interior of the continent; finally, among the mountains
of Nevada, and at San Francisco on the Pacific slope. In order to
determine whether altitude seems to modify or lessen the tendency to
scarlatina, we shall group the States as follows: First group. States
having average altitudes ranging from 150 to 600 feet, are Tennessee,
Vermont, Kentucky, Georgia, North Carolina, Texas, Massachusetts,
Maine, Maryland, Alabama, South Carolina, Arkansas, Connecticut,
Mississippi, New Jersey, Rhode Island, Delaware, Louisiana, and
Florida. Total population of this group, in 1870, was 14,597,384.
Second group, States having average altitudes ranging from 600 to 1000
feet: Iowa, Wisconsin, Missouri, Michigan, New York, Pennsylvania,
Ohio, Virginia, Indiana, Illinois, and New Hampshire. Total population
1 Loc. cit., p. 54.
i<'/ri()[/)GY 353
of this grou|), In IS70, was 21,500,509. Thirrl group, States having
average altitudes ranging from 1000 to 5400 feet: Nevada, California,
Oregon, Nebraska, Kansas, Minnesota, and West Virginia. 'J'otal
population of this group, in 1.S70, was 2,i:i3,:j]6. In these three groups
of States, 20,15!) deaths from scarlatina occurred — i. e., 3833 in th(! first,
15,351 in the second, and 1475 in the third. If we analyze these
figures, the following is the result:
Altitude. JJcaths.
150 to 600 feet 1 death to every 4380 of population.
600 " 1000 " 1 .. » u 1401 " "
1000 " 5400 " 1 ' 1447 " "
" NoviT, taking into consideration the density of population in the
second group as compared with the third, together with the fact that
scarlatina, being a contagious disease, should be more prevalent where
it has the largest and densest population to prey upon, we conclude
that altitude rather favors an increase of the scarlatinous tendency."
A striking difference in the prevalence of scarlatina in certain of the
European capitals has been observed. In London,^ from 1868 to 1872,
there were nearly 115,000 cases of scarlet fever. In Berlin, from 1877
to 1883, scarlatina caused 5428 deaths. On the other hand, during a
period of five years in Paris, the total deaths from scarlet fever were
only 67.
It is quite inexplicable why London and Berlin should suffer so
severely from this disease while Paris possesses a comparative immunity.
Race. — There is strong evidence that negroes are less susceptible to
scarlet fever than the whites, and, furthermore, that the mortahty rate
among the former is very considerably lower than in the Caucasian race.
Minor,- writing in 1875, says: "The total number of blacks d\4ng of
scarlet fever in the Southern States was 107 out of a total black popu-
lation of 3,713,327; so that 1 out of every 34,704 of the aggregate
black population died of scarlatina. The total number of whites d>ang
of scarlet fever was 446 out of a total white population of 4,811,962;
so that 1 out of every 10,790 of aggregate white population died of
scarlet fever. It will be at once noticed that the disease is much more
frequent among the whites than among the colored population. During
epidemics the whites have seemed to be the sufferers, and there is
reason to believe that there is a certain immunity from epidemic scar-
latina existing among the negroes of the South."
During the Civil War^ 378 whites took scarlet fever, of whom 70
died, and 118 negroes contracted the disease, of whom but 2 died.
Comparing the number of the white and black troops it is seen that the
attack rate was 54 in the black race to 26 in the white; on the other
hand 70 deaths occurred among the whites and only 2 among the
negro soldiers.
The United States census of 1870 demonstrated the fact that the
1 Meutioned by Forchlieimer. Article in Twentieth Century Practice of Medicine.
2 Loc. cit. 3 Medical and Surgical History of the Kebellion, vol. iii.. part i.
23
354 SCARLET FEVER
foreign-born population of the country was 5,567,229, and that 1
out of every 6105 died of scarlet fever. The population of the native-
born whites was 28,120,788, of whom 1 out of every 1473 died of
scarlet fever. The negro population was 4,880,009, of whom 1 out of
every 16,886 died of the disease.
It is thus seen that scarlet fever destroyed, relative to the population,
over ten times more whites than negroes. The census statistics of 1850
give somewhat similar results.
The United States census report of 1890 shows a scarlatina death rate
among the whites of 14.2 per 1000 deaths from all causes to 2.7 among
negroes. The figures of the 1900 census are almost identical — 12.0
death rate among the whites as compared with 2.6 among the blacks.
These statistics would indicate that the Caucasian race in the United
States is six times more susceptible to scarlatina than the negroes.
Inoculability of Scarlatinal Virus. — Attempts, doubtless based upon
the success achieved by inoculation of smallpox, have been made to
induce a mild form of scarlet fever by this process. These experiments,
though often contradictory, have thrown some light upon the etiology
of scarlet fever.
In 1834 Miquel reported to the French Academy that he had inocu-
lated a number of children with the fluid of scarlatina vesicles. The
rash was localized to the region of inoculation. Miquel alleges that
complete immunity against scarlet fever was conferred. The reported
facts made it very doubtful that scarlatina was actually transmitted.
In two cases inoculated by Rostan the rash appeared seven days after
inoculation. According to the statement of Guersant,^ Petit-Radel made
unsuccessfid attempts to produce scarlatina by the introduction of
epidermal scales beneath the skin of previously unattacked persons.
On the other hand, Stoll is reported to have produced the disease by
rubbing into the skin scales from a case of scarlet fever. These experi-
ments are seen to be contradictory and permit no conclusions to be drawn.
A much more convincing case is the accidental inoculation of Dr.
Rupprecht^ with mucus from the trachea. This physician had per-
formed a tracheotomy on a mixed case of scarlatina and diphtheria.
In insufflating the lungs through an elastic catheter, he received some
mucus into the mouth. Sixty hours later an angina developed and in
seventy-eight hours a chill. The eruption Avas irregular, but the diag-
nosis was said to be certain.
Recently some rather conclusive inoculation experiments were carried
out by Stickler^ in an effort to induce a mild attack of scarlet fever.
Mucus from the mouth and throat of scarlatinal patients was mixed
with a 1 : 600 solution of carbolic acid and injected subcutaneously
into ten children. Scarlet fever occurred in each child. The period of
incubation varied between twelve and seventy-two hours, and averaged
thirty-two hours. The author found that the attacks were too severe to
1 Quoted by Thomas. Loc. cit.
■■' Ein Fall von Scharlach. Wiener med. Woch., 1862. Hauptblatt, p. 435.
3 Medical Record, September 9, 1899.
F/nomciY 355
warrant I'nrtlicr inoculations, and, therefore, (lesisted. Incidentally the
fact was proven that the mn(;us of the upper ;iir passaj^es contains the
causa caiuv/n.s of the disease.
From the experiments (juoted we are not justified in drawing any
conclusions as to the presence in the skin of tlif; infectious principle.
A possibility of error, always to be kept in mind, is that persons inocu-
lated with scarlatinal virus may have contracti^d the disease throuf^li
exposure in the ordinary mamier.
Mode of Reception of the Scarlatinal Infection. — 'J'he scarlatinal
poison is ordinarily received into the system through the upper air
passages. It would seem that the genital tract in puerperal women and
cutaneous wounds may also offer a point of ingress for the infection.
IJut in the vast majority of cases the poison is "breathed in" just as
in the other acute eruptive fevers. Whether the virus effects its entrance
into the blood in the lungs, or at some point along the respiratory
avenue, is a difficult question to answer. l)owson, in 1893, endeavored
to prove that the first and essential localization of the scarlatinal poison
was in the throat. Berge,^ following this view, maintains that scarlatina
is primarily a local tonsillar infection, and that the eruption both upon
the cutaneous and mucous surfaces is the result of the action of an
erythemogenic toxin generated in the tonsils. The streptococcus in one
of its virulent forms is regarded as the causative agent of the disease.
The view is advanced that the infection may exceptionally gain entrance
into the system through other channels, as in the case of surgical and
puerperal scarlatina. The author cites a number of cases to show that
in puerperal and surgical scarlatina the primary tonsillitis is absent,
although the buccopharyngeal enanthem may be present.
The theory and facts presented by Berge are of interest, but until
the cause of scarlatina is satisfactorily demonstrated, we will doubtless
remain in ignorance of the site of invasion of the scarlatinal virus.
Period of Infectivity of Scarlatina. — In discussing this subject we
wish to draw a distinction between the duration of infectiousness of the
scarlatinal virus within and without the patient. Reference has already
been made to the longevity of the virus outside of the human subject.
The contraction of the disease from contact wdth infected objects may
constitute a source of error and obscure the proper estimation of the
infectious period.
There can be no question that at the very beginning of scarlatina
the contagiousness is limited. We have frequently known children,
exposed to the disease at the very outset, escape infection only to contract
it when re-exposed a number of weeks later. Children wlio are im-
mediately separated from a case of scarlet fever as soon as it is dis-
covered will frequently remain well; in this respect scarlet fever differs
strikingly from measles, in which disease the contagion is extremely
active even before the appearance of the rash.
Scarlet fever is highly contagious during the period of eruption and
1 Pathogonie de la scarlatiue. Paris, 1S95, p. 126.
356 SCARLET FEVER
usually for some time following the disappearance of the rash. The
view has been generally held that contagiousness persists throughout
the entire stage of desquamation, and that the infectious principle is
resident in the epidermal scales. There have always been some dissenters
from this view and the doubt as to the contagiousness of desquamating
epithelium is becoming more generally entertained.
Scarlet fever is not only contagious before desquamation begins, but
not infrequently after it has completely terminated. It is obvious,
therefore, that the infection must reside somewhere in the body apart
from the cutaneous surface. Experimental and clinical evidence both
point to the throat and adjacent cavities as the probable lurking places
of the infectious organisms. It is, therefore, of importance to continue
the isolation of patients until discharges from the nose and ears have
ceased.
It is probable that the prolonged infectivity manifested by certain
cases of scarlatina is due to the presence of the scarlatinal contagium in
the secretions of the throat or in the nasal and aural discharges.
It is practically impossible to state just at what period a case of scarlet
fever ceases to be infectious. The more remote the time from the onset
of the disease, the greater is the likelihood of the infection having been
extinguished. Probably for this reason the isolating of the patient for
the full period of desquamation has been found to be a good working
rule.
Physicians connected with scarlet -fever hospitals not infrequently see
patients who have remained in the hospital from eight to twelve weeks,
give rise, upon their return home, to other cases in the same household.
And this occurs despite the most careful disinfection of the body and
the clothing.
These return cases occur in the experience of many hospitals in from 2
to 4 per cent, of the patients. We have seen patients at the end of eight,
nine, ten, and eleven weeks, after every vestige of desquamation had
disappeared, give rise to the disease in others. In a case recently
observed by us we learned that, after the dismissal of the child from the
hospital, the ear began to discharge again; shortly afterward a second
case developed in the family.
Some years ago the following sad case came under observation at the
Municipal Hospital: A child with a well-marked scarlet fever came to
the hospital at an early stage of the disease, the eruption just appearing.
The patient remained in the hospital nine weeks. Desquamation had
completely ceased. An antiseptic bath was given in a room disconnected
from the hospital building, and the child was dressed in clean clothing.
The patient had had a discharging ear which had gotten well, but during
the last bath slight moisture in the ear was noticed. A few days after
the child's return, the mother and two other children were brought to
the hospital with scarlet fever. The attack in the mother was severe,
the disease terminating fatally in a short time. The mother had been
exposed to the child before the latter was first admitted to the hos-
pital.
The Contagiousness of Desquamating Epithelium. — Almost thirty
years af^o Thomas wrote: "'J'lie eonta^ioiisiiess oi" the; postexanthernatic
period is usually ascril)e(l to th(; scales of e})i(h^ririis wliieh separate
during the process of desfjuamation; hut it seems to me that there is
not the shadow of evidence to prove that the contagion is contained n
them either exclusive'y or even chiefly; for it may be presumed that the
contag on enters from the l)lood into all secretions and excretions of the
patient. Volz, in fact, totally denies the contagiousness of the epidermal
desquamation."
Von Kerchnsteiner states that "the most favorable conditions for
contagion exist during the stage of eruption and acme of the exanthem ;
the most unfavorable dui'ing desquamation."
(This subject is more fully discussed in the chapter on treatment.)
There is no evidence to indicate that the scarlet fever contagium is
disseminated by aerial transmission. The immediate vicinity of scarlet-
fever hospitals appears to be as free of the disease as other .sections of
the city. In this respect scarlet fever differs from smallpox, in which
disease the territory immediately surrounding the hospital is apt to
show a disproportionately large number of smallpox cases.
The following figures are taken from the Medical and Surgical Reports
of the Boston C a y Hospital, 1897:
Radius of one-eighth of a mile from scarlet-fever hospital . . cases.
" " one quarter " " " " " " " . . 6h
" " one-half " " " " ■' " " . . 71 "
" " three-quarters " " " " " " " . . 75 "
" " one " " " " " . . 72 "
Within one mile of the hospital 2^6 "
Beyond the one-mile limit 756 "
It is seen from the above figures that no cases developed within the
one-eighth mile limit about the hospital.
Our experience at the Municipal Hospital would lead us to believe
that the striking distance of scarlet fever is extremely limited.
It has been exceedingly rare for families in the immediate vicinity of
the hospital to become attacked with scarlet fever, although they have
not escaped smallpox.
The fact that scarlet fever is not carried beyond the confines of the
hospital walls rather militates against the view of the infectivity of
scales, for in a scarlet-fever ward the air contains myriads of minute
particles of desquamating epithelium.
Scarlet-fever Infection in Milk. — The transmission of the infection
of scarlet fever in milk has attracted the attention of physicians for
some years.
Thomas, wa-iting in 1875, referred to two epidemics reported by
Bell and Taylor in which the dissemination of the disease was ascribed
to infected milk. In the latter epidemic one of the first cases of scarlatina
occurred in the family of a milkman whose wife milked the cows. The
milk was supplied to twelve families, in six of which scarlatina appeared
in rapid succession, without contact with the milk server, and at a time
358 SCARLET FEVER
when the disease was not epidemic. The milk had been kept in a
kitchen in which scarlatinous patients had been treated.
In 1886 Power^ observed in London a severe epidemic of scarlet fever
which appeared to attack in particular the patrons of Hendon Farm,
whose cows were, suffering from a peculiar malady. This disease was
studied by Klein/ who came to the conclusion that the animals were
suffering from scarlet fever, and that the infection was conveyed in the
milk to human subjects. The malady was introduced among the cows
by an animal which had elevation of temperature, cough, faucial and
oculonasal catarrh, a red rash about the eyes and on the inside of the
thighs, followed two weeks later by desquamation and loss of hair.
Vesicopustules were present upon the udders, which later gave rise to
ulcers. The animal had recently given birth to a calf. Klein found
streptococci in the serum from the vesicles which he inoculated into
animals. He likewise found streptococci in the blood of some scarlatina
patients. This organism he regarded as the specific cause of scarlet
fever.
In the same year Crookshank and Brown^ noted an epidemic among
cows analogous to that observed by Klein. After carefully studying
the same and making further inoculations from an accidentally received
sore on the hand of a dairyman, they proved that the disease was cowpox.
The same streptococcus was obtained by culture. i
In 1885 an epidemic of scarlet fever occurred in Rostock, Germany,
apparently from milk infection.* A very striking increase in scarlet fever
occurred in June, in which month 36 cases developed. It was dis-
covered that the families (with two or three exceptions) were supplied
with milk from a farm in the village of Gehlsdorf, where 6 cases of
scarlet fever and a number of cases of sore throat existed among the
farmers' families and employes. Some of those who were taken ill had
milked the cows and had handled the milk. According to the investiga-
tions of the Rostock physicians, 8 of the 36 cases could with certainty
be attributed to infection from the milk. As indicating the presence
of the infecting agent in the milk, it was noted that those who drank
boiled milk escaped; this was the case in two children, two and four
years of age, who remained free, although other children in the same
household who drank raw milk contracted the disease.
Freeman^ has made a careful study of the transmission of various
diseases through infected milk. He states there is conclusive evidence
that contaminated milk has caused certain epidemics. In 26 recent epi-
demics of scarlet fever in England traceable to milk, 15 were found to
be due to the disease in man.
Epidemics due to infected milk have within recent years been reported
1 Milk Scarlatina, London. Report of the Medical GfiBcer of the Loral Government Board, Feb-
ruary, 1885 and 1886, No. 8, p. 73.
- The Etiology of Scarlet Fever. Proceedings of the Royal Society of London, 1887, xlii.
3 Communication to the Pathological Society of London, 1887.
< Quoted by von Jiirgensen. Loc. cit., p. 413.
5 Medical Record, March 28, 1896. Quoted by Northrup in von Jiirgensen's article on "Scarlet
Fever." Loc. cit., p. 414.
i<:ti()L()(1 y 359
in this country. In Plainficld, New Jersey, an epidemic wastra eed to a
farm hand who had a mild attack of ,s(;arlet fever ntifl who liandled the
milk (hirinfij this tinu^
More rec(Mitly iin ontl)r(>a,k of scarlet fever occurred ainf)n^ .'>o students
of Purdue University, Lafayette, Indiana. The i^o cases wen; fed at
eleven different boanhng houses, all of which were supplied with milk
by the same dairyman. Five private families supplied with the same
milk had one or more cases of the disease in their househftids. The
infec'tion was attributed to winter c-jothin^ which had just been f)ut on,
and which had been laid away the March before, at which time the
"dairyman's family ran through a course of scarlet fever."
From the now extensive literature upon the subject, we may conchule
that scarlatina may be conveyed through a contaminated milk supply.
The proposition is not proven beyond the peradventure of a douljt, but
the chain of circumstantial evidence is so strong as to render this con-
clusion almost irresistible. It would, furthermore, appear that the
milk is contaminated through contact with an individual suffering or
convalescent from the disease. The view advanced by Klein that the
cows themselves suffer from scarlatina remains unproven and is not
generally credited.
Hall,^ in reviewing the subject of milk infection, makes the following
interesting statement: "While scarlet fever occurs in epidemic form in
those countries where cows' milk forms a staple article of food, espe-
cially among children, it does not occur in countries where cows' milk
is not used as a food, or where children are raised upon mothers' milk
only." In Japan cows' milk is not used, and scarlet fever is practically
an unknown disease there. In India, cows' milk is used, but children
are kept at the maternal breast until they are three or four years of age.
Scarlet fever is a rare disease in India, seldom occurring in epidemic
form.
Pregnancy and the Puerperium, — It cannot be said that pregnancy
increases the predisposition to scarlet fever, for, according to Senn,
Tourtual, and Trousseau, no case of scarlet fever in pregnant women
was observed by them during extensive epidemics of the disease. That
scarlet fever is an excessively rare occurrence during pregnancy is
evidenced also by the statement of Olshausen that he was able to
find only seven cases in medical literature. When scarlet fever does
complicate gestation it is prone to lead to abortion or premature delivery.
Great diversity of opinion is expressed, in the extensive literature^
on the so-called 'puerperal scarlatina, as to the real nature of this affection.
Malfatti^ in 1801 published an account of a malignant scarlet fever
epidemic which prevailed among puerperal women in confinement in
Vienna. The symptoms were: offensive lochial discharge, abdominal
tenderness, with later (between the second and seventh days after
1 New York Nfedical Record, November 11, 1S99.
" An admirable collation of the literaiure on this subject is presented by Marcel Durand in a
Paris thesis entitled " Etude hislorique et critiqne sur la scarlatina pnerperale." Pp. 3J5. Paris, 1S91.
'■> Journal der prakt. Heilkunde, by C. \V. Uufeland, Bd. xii., part iii. p. VJO. Berlin, Ungar, ISOl.
360 SCARLET FEVER
delivery) chills, headache, ringing in the ears, hot skin, nervousness,
and moderately rapid pulse; then a diffuse reddish exanthem, which
on the third, fourth, or fifth day became bluish, accompanied by marked
nervous symptoms, failure of the vital powers, and death.
In 1875 Braxton Hicks read before the London Obstetrical Society a
paper in which he' stated that of 89 puerperal cases under his care that
had febrile symptoms, he regarded 37 as suffering from scarlet fever.
Very few of these patients had an angina of any severity and 17 did not
have an eruption. In 2 instances scarlet fever developed in children
who were exposed to the puerperal women. In the discussion that
followed, some endorsed but many repudiated the diagnosis of scarla-
tina in these puerperal fevers.
Olshausen^ combats the contention of Hicks and mentions the argu-
ments which led Helm and subsequent writers in Germany to regard
puerperal fever with scarlatiniform rash as puerperal septicaemia: (1)
these epidemics occur in maternities and not synchronously with
outside epidemics; (2) the malady has a malignity more in accord with
puerperal septicaemia; (3) it is often complicated with peritonitis and
other manifestations analogous to those seen in puerperal fever; (4)
origin in the early days of the post-partuvi as is observed in septicaemia;
(5) in the majority of cases it has been impossible to establish contagion.
Olshausen collected 141 cases of scarlatiniform rash occurring during
pregnancy and the puerperium; these were reported by Koch (3),
Schneider (5), Clemens (2), Simpson (2), Hardy (2), MacClintock (34),
Brown (9), Johnston and Sinclair (2), Winkel, Halahan (25), Hicks (18),
Lange, Denham (8), Senn (7), Dance (1), Trousseau (1), Gueinot (4),
Hervieux (7), and Olshausen (5). Of this number only six occurred
during pregnancy. Eight developed immediately after confinement, 62
from the first to the second day after confinement, 27 the third day, and
22 from the third to the eighth day afterward.
Winckel,^ in expressing his incredulity concerning the scarlatinal
nature of Hicks' cases, mentions the fact that lying-in women in England
more frequently exhibit an erythema upon the cutaneous surface than
in Germany.
Martin^ is of the same opinion and regards true puerperal scarlatina
as a rare occurrence. Indeed, in 38,000 accouchements he observed this
complication but three times.
Von Jiirgensen, after a careful study of Malfatti's cases, does not
regard them as true scarlatina, but as puerperal septicaemia. He
believes that scarlatina, in the strict meaning of the term, is of slight
significance as a factor in the mortality of the puerperium.
The fact is recognized that puerperal septicaemia may be attended
with a rash which cannot be distinguished from that of scarlet fever.
The lying-in woman may develop after confinement either a true scarlet
fever or a puerperal fever with a septic scarlatiniform rash. There can
1 Archiv llir Gyntikol. und Obstet. de Cred(§, 1876.
2 Die Pathologie und Therapie des Wochenbettes, third edition, p. 350. Berlin, Hirschwald, 1875.
3 Zeitschr. fiir Geburtsh. und Gynitkol., 1876, vol. ii.
ETIOI/XIY 301
be no doubt that in the past many instances of the IjiUcr ffjitflition have
been regarded as puerperal srarlatina. Tlie fliflereiilial diaj^nosis is
often extremely difliciilt. The following points would indicate a puer-
peral infection rather tiian scarlet fever:
1. The absence of an epir a
septic rash may he (jiiite indisliiif^iiishiihle from that, of s(;arlet fever.
The general symptoms must he considered and the condition of the
throat, tongue, glands, ears, and kidneys determined in order to throw
the full(\st light n])on these diriicult cases.
The diiignosis of scarlatina is sometimes indnhitahly confirmed hy
the unfortunate transmission of the (hsease to another subject.
THE SYMPTOMATOLOGY OF SCARLET FEVER.
Period of Incubation. — By the period of incubation is meant the time
elapsing between the reception of the scarlatinal poison into the .sy.stem
and the first manifestation of symptoms of the disease. It is well to
bear the fact in mind that the reception of the contagion is not invariably
coincident with the exposure to the disease.
The breeding stage of scarlatina is briefer and at the same time more
variable than that of the other acute exanthemata. Within its com-
paratively narrow hmits, a considerable degree of variation occurs.
The incubation stage of smallpox, although extending over a longer
period, is strikingly uniform and reliable; to be sure, there are some
variations, but these constitute exceptions. Measles, too, has a com-
paratively constant period of incubation.
The various writers on scarlet fever, in giving expression to their
views as to the duration of the incubation stage, are guided largely l)y
their individual experiences. Apart from actual differences in the
clinical experiences of physicians, some of the widely divergent incubation
periods may possibly be attributed to differences in the discriminating
judgment of the observers. The more conservative writers are in
general agreed that the most common period of incubation of scarlet
fever is between three and seven days; the narrower these limits are con-
tracted as a general proposition, the greater is the liability to error.
Thomas regards "four to seven days as the most frequent interval,"
and looks upon shorter or longer periods as exceptions to the rule.
Von Leube and Forchheimer both subscribe to this estimate. Vogl
believes that the exanthem appears three or at most five days after
infection.
While these intervals cover the vast majority of cases, there have been
recorded occasional authentic instances of much shorter and longer
periods of incubation. Trousseau's case of not more than twenty-four
hours' incubation is of interest. He writes: "A London merchant had
taken one of his daughters to the Eaux Bonnes in the Pyrenees, and had
passed the winter with her at Pau. On his way back to London he
stopped at Paris, where he wished to remain some days. His eldest
daughter was keeping house for him in London. Impatient to embrace
her father and sister, she started for Paris. When crossing the channel,
she was seized with fever and sore throat, and seven or eight hours later
364 ■ SCARLET FEVER
arrived at Paris in the middle of a very serious attack of scarlet fever.
She alighted at the hotel, almost at the very moment when her father
and sister arrived from Pan. The two sisters remained together in the
same room, and in twenty-four hours the sister who had come from Pau
showed the first symptoms of a mild attack of scarlatina. In London
the disease was then epidemic, but there were no cases at Pau."
Trojanowsky, Forster, Sorensen, Murchison, Alonzo Clark, Raven,
Hagenbach-Burkhardt, and others have recorded periods of incubation
of twenty-four hours or even less; so that it may be accepted that in
rare cases the infection may give rise to symptoms almost immediately
after entrance into the system.
As to long periods of incubation, there is much divergence of opinion.
Veit claims it may be twelve to fourteen days; Paasch published a case
in which it was twelve days; Gerhardt and Reinhold credited periods
of eleven to thirteen days. Bawy records an instance of twenty-one
days and Trojanowsky one of twenty-eight days.
Murchison, in his wide experience, has only been able to collect a
series of 13 cases in which he could be sure of the incubation period;
in not a single one of these cases was the period longer than six days.
On the other hand, Hagenbach-Burkhardt^ reports 57 cases in which
he has been able to study the incubation period. Of this group the
remarkable number of 35 had incubation stages of over seven days.
Under eight days there were 4 cases; nine days, 2 cases; ten days, 1 case;
eleven days, 5 cases; twelve days, 1 case; thirteen days, 4 cases; fourteen
days, 2 cases; fifteen days, 5 cases; seventeen days, 2 cases; eighteen
days, 1 case; nineteen days, 2 cases; and over twenty days, 6 cases.
This is certainly a most remarkable array of long incubation periods to
come within the experience of any one observer.
Some of these instances and others exhibiting long periods of incu-
bation may possibly be explained upon the grounds of a temporary
immunity retarding the susceptibility to the scarlet-fever poison. While
unprotected individuals are almost invariably susceptible to the con-
tagion of smallpox and measles, the same is not true of scarlet fever.
Certain individual conditions about which little is known seem to make
some persons immune at one time and susceptible at another to the
infection of scarlet fever.
We have recently had the opportunity of watching a protracted
epidemic of scarlet fever in a home for children in this city. For a
period of over three months, children contracted the disease two or .
three at a time and were sent to the Municipal Hospital. About 40
out of 100 were thus gradually attacked. It would seem that in many
of the children the individual susceptibility was temporarily in abeyance
or that the infection was not received by them in the beginning in
suflflciently intense or concentrated form.
It is alleged by some writers that a virulent contagium may shorten
the period of incubation, and that a similar abbreviation of this stage
may result when the scarlatina occurs in a surgical or puerperal subject.
1 Ueber Spital iafectiouea, Jahrbuch fiir Kiaderheilk., Bd. xxiv. p. 105.
Tim SYMPTOM A TOLOflY OF liCAHLF/r FKVRH
365
Holt/ has tabulated records of the incubation periorj in 113 cases,
some of which were ol).served by him, but most of which have been
abstracted from the literature of the subject:
iNfJur.ATioN Pkrioo.
24 hours or
lesK .
. 6 cases.
7 flays .
8 cajeR
2 days
. 15 "
8 " . .
. 2 "
3 "
. 28 "
9 " . .
. 5 "
4 "
. 2.') "
11 "
1 case.
5 "
. 6 "
14 "
. 1 "
6 "
. 15 "
21 "
. 1 "
It is seen that in 87 per cent, of these cases the incubation period was
between two and six days.
Simple, Usual, or Normal Scarlatina (Scarlatina Simplex).
Period of Invasion. — During the stage of incubation no symptoms,
as a rule, are present, the morbid process being entirely latent. The
Fic
. 59
MONTH
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Temperature and pulse record of scarlatina simplex. J. B., aged six years ; mild case of scarlet
fever terminating in recovery.
onset of the disease is sudden. The earliest symptoms are : indisposition,
fever, headache, vomiting, and sore throat. Chills are usually absent
1 Piseases of Infancy and Childhood, Xew York, 1896, p. 889,
366 SCARLET FEVER
except in severe cases. In children vomiting is the earhest as wel as
the commonest of the invasive symptoms, and is, therefore, of suggestive
diagnostic import. Not infrequently children in the full bloom of
health are quite suddenly seized with vomiting rapidly followed by
the other symptoms of scarlatina. Billington observed this symptom in
about 80 per cent, of his cases. We have obtained a history of the
occurrence of emesis in 76 out of 155 cases, or about 50 per cent. We
believe that the average frequency of this symptom is greater than
would be indicated by these figures. The evacuation of the contents
of the stomach may be accompanied by diarrhoea, although usually the
bowels are constipated. In severe cases in infants convulsions are not
uncommon. There is loss of appetite and the tongue is furred. Adults
and older children who are able to appreciate the sequence of the
symptoms often indicate sore throat as the first.
Temperature. — The temperature rises rapidly, often reaching 102° to
104° F. or more in the course of a few hours. The pulse increases in
frequency and, compared with the temperature, is often disproportion-
ately rapid. The radial pulsations may number in children 140 to 160
per minute, and in adults 120 to 140.
Headache and vertigo are common, and the patient may be alternately
somnolent and restless. The thirst is often intense. The patient is
greatly prostrated and presents the facies of a very sick person. The
skin is hot and dry, the eyes dull and listless, and the face flushed.
The fever in scarlatina is subject to great variations, being influ-
enced by the severity of the epidemic and the nature of the accom-
panying complications. The pyrexial curve is by no means as constant
as is seen in the other two important exanthematous diseases — smallpox
and measles.
Wunderlich^ gives the following as the average febrile course: The
temperature at the onset of the disease rises rapidly, and after a few
hours reaches 104° to 105° F. or higher. With slight morning remissions
the fever still increases from the appearance of the eruption until its
complete diffusion over the surface. When the eruption has reached
its height, the temperature begins to decline by gradual steps, with
slight evening exacerbations.
It is thus seen that the fever is a continued one during the invasive
and early eruptive period, and that the pyrexia subsides by lysis con-
currently with the fading of the exanthem.
In well-pronounced cases of what might be called the normal form
of scarlet fever the early rise of temperature is seldom below 104°, and
it not infrequently reaches 105° or 106° F. The high temperature
persists ordinarily for four or five days and then a decline sets in.
The intensity and the duration of the fever depend much upon the
type of the prevailing epidemic. We have determined the duration of
the fever in 265 cases of scarlatina which we treated in the winter of
1902-03, at which time the type of the disease was distinctly mild.
1 Eigenwarme in Krankheiten,
77//'; H^YMPTOMATOLOCY OF SCAULh'/r /''/'JVh'ii
Wl
Tetn[)()riuy ri.ses of tern[)eratiire occurring late and resulting fio
recognized c()iiif)li("itioii,s or .s('f|U(!lir' were not consifjcrefj.
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R. B., aged seven years ; case of scarlet fever with an intense rash and severe early symptoms,
terminating rather unusually by crisis.
DuEATiox OF Fever in 265 Cases of Scarlet Fevfr Treated
Municipal Hospital in the Winter of 1902-03.
AT THE
Lasting
1 day
. 2
2 days
. 3
3 "
. 17
4 "
. 19
5 "
. 32
6 "
. 40
7 "
. 35
8 "
. 29
9 "
. 22
10 "
. 14
11 •'
. 14
12 " . .
. 10
13 " . .
. 4
14 " . .
4
Lasting 15 days
16 "
17 "
18 "
19 "
20 "
21 "
22 "
23 "
24 "
25 "
26 "
Total .
5 cas
4 '
3 '
1
2 '
3 '
'
'
1 '
*
2t5
It will be seen from the above table that in the largest number of
cases the fever terminated upon the sixih day of the disease. In 15S
cases, or 60 per cent., the fever lasted from five to nine days. It must
be remembered that the prevailing form of the disease was mild and
the mortality low.
Jamieson states that of 200 cases observed by him the maximum
temperature was reached— in 11 cases on the first day, in 76 on the
368 SCARLET FEVER
second day, in 75 on the third day, in 36 on the fourth day, and in 2
cases on the fifth day/
Deviations from the pyrexial curve above mentioned not infrequently
take place. Instead of declining by lysis the temperature may fall by
crisis. On the third or fourth day a sudden decline of the fever to
normal or subnormal may take place. The temperature may then
continue for some days at or slightly above normal. Henoch, Fiirbringer,
and Jiirgensen have described such cases and Litten has reported
instances of high initial fever followed by an apyretic course. Henoch
noted 4 cases out of 175 with normal morning temperature and evening
elevation. Litten observed similar cases.
Ordinarily, high fever accompanies severe cases with well-marked
eruptions, but there are numerous exceptions to this rule. Leichtenstein
mentions a case with marked delirium and intense eruption running an
almost afebrile course. Cases of a malignant type may be entirely
unaccompanied by elevation of temperature, and, indeed, the temper-
ature may even be below the normal line.
It is not rare for very mild cases to be unaccompanied by pyrexia.
We recall an afebrile case developing in the hospital whose temperature
record we were enabled to observe for several days before the attack.
Fiirbringer^ describes a secondary fever in scarlatina that is inde-
pendent of and unaccompanied by any discoverable complication.
Wunderlich, quoted by Trousseau, observed a considerable elevation
of temperature during the stage of desquamation. Gumprecht and
Jiirgensen have also recognized this secondary fever. Thomas^ describes
irregular cases of scarlatina with protracted fever. He writes: "When
the fever is irregular it fails to defervesce after the normal progress and
disappearance of the eruption and angina, but continues for weeks,
sometimes with the same intensity and a typhoid character like that of
a variety of scarlet fever presently to be described; sometimes with
increasing intensity, especially if it is to prove fatal, and at other times
it declines gradually as in protracted defervescence. In such cases the
pulse is often very rapid, the heart's action violent, and the first sound
of the heart diffuse or even replaced by a distinct murmur." And,
again, "Not infrequently there occurs still another form of the disease
in which there are not only local affections of moderate, perhaps even
trifling importance, but also disproportionately severe fever of long
duration which characterizes this variety as a typhoid scarlatina."
Thomas remarks that in these cases the fev,er is the chief symptom and
that it may be protracted for weeks.
Hyperpyrexia is more frequently observed in scarlet fever than in the
other exanthematous diseases. It is not so rare for 107° F. to be reached ;
such cases usually terminate fatally, although when the hyperpyrexia
is not protracted recovery may take place. In rare cases the fever may
mount to an extraordinary height. Wunderlich records a temperature
1 Quoted by Forchheimer, loc. cit.
2 Realeacyklopadie, Bd. x., 5, p. 472. Quoted by Jiirgensen, loc. cit.
3 Loc. cit., pp. 254 and 269,
THE SYMPTOM A rOLOav OF SCA RfJ':!' FEVER 369
of 110.8° K.; Thomas, 111.2° F.; I>oiclit(;ii.sl(;in, 100° and 100.0° F., and
Dr. Currie, according to (ircgory, 112°F\ These rises of temperature
were, as might be expecte(], shortly followed by death.
Throat S'i/mpf<)7ns. — Throat symptoms are, as has been stater), early
complained of by adidts. On ins})(;ction, general fancial redness is
observed, involving pjirticnlarly the uvnhi, tonsils, and soft j)ahit(;. ^^'hen
the cutaneous eruj)tion begins to manifest itself the redness increases
and there develops oedema and swelling of the mucous tis.sues. At times a
thin, grayish or yellowish film of exudate may be seen on the swollen
tonsils. Often the soft palate, uvula, and buccal mucous membrane
show a punctated redness similar to that later ol^served ujjoji the
skin.
The stage of invasion is brief, not lasting ordinarily more than twenty-
four hours. In some cases the eruption appears before twelve hours
have elapsed.
In a series of 84 cases of scarlatina, Barthez and Rilliet observed the
eruption appear as the first symptom in 4; in the majority of the cases,
however, the eruption manifested itself at the end of twenty-four hours.
Trousseau saw a severe case of scarlatina with marked brain symptoms
in which the rash was delayed until the eighth day. It is, however,
distinctly exceptional for the stage of invasion to last much longer than
twenty-four hours.
Stage of Eruption. — The exanthem of scarlet fever usually begins
upon the neck and subclavicular regions, then spreading rapidly to the
chest, face, abdomen, arms, and legs. A variable time elapses in different
cases before the acme of the eruption is reached. The milder efflor-
escences reach their height earlier than those of greater intensity. In
severe cases the rash may take until the third or fourth day before its
greatest intensity is attained.
The color of the scarlatina exanthem varies in different individuals
and is extremely difficult to depict in words. It has been variously
designated by writers as scarlet, bright red, boiled-lobster tint, raspberry-
juice color, rose colored, wine colored, etc. These terms are permissible
because they convey a definite impression to the mind, but when these
tints are compared with the exanthem at the bedside the terms are seen
to be inaccurate. The color of any inflammatory eruption is due to the
blood appearing through the texture of the skin. The amount of blood
in the skin as determined by the calibre of the cutaneous bloodvessels,
the character of the blood, and the complexion of the individual all
influence the coloration. It is a matter of daily observation that the
rash in fair-skinned persons is brighter than in those of swarthy com-
plexion, whose skin contains a greater amount of epidermal pigment.
In general, the scarlatinal rash is reddish, sometimes bright, but more
often dull or dusky red. Sometimes the eruption is so brownish-red,
particularly in dark-complexioned individuals, as to almost approach
a bright terra- cotta color. IMore rarely the element of blue is so well
marked, particularly in dependent areas of skin, as to be quite purplish
owing to the venous congestion. The color varies not only in different
24
370 SCARLET FEVER
persons, but at different periods in the same individual. A bright
eruption commonly becomes dusky before it fades.
When the scarlatinal exanthem is viewed at a little distance it gives
the impression of a uniform reddish blush. When, however, the skin
is closely scrutinized it is seen that it is made up of innumerable reddish
points or puncta. These are of a deeper tint than the skin intervening
between them.
At tunes eruptions are seen in which the skin between the puncta is
of normal coloration. This appearance may occasionally be noted
during the coming out or evolution of the exanthem. Ordinarily the
points of greatest color intensity are surrounded by areolae of somewhat
brighter hue. When these coalesce, as is usually the case, a diffuse
eruption is presented, the puncta being scarcely distinguishable through
the obliteration of contrast. At times the areolae are narrower, exhibiting
a little intervening normal skin and giving the eruption a more or less
speckled appearance. In other cases with larger pale areas a mottled
appearance is noted. Finally, there may exist large, irregular patches
of healthy skin, particularly on the arms, legs, and buttocks, producing
so marked a blotchiness of the exanthem as to suggest a strong resem-
blance to measles.
The scarlatinal eruption frequently exhibits small pinpo"nt to pin-
head-sized, reddish elevations, which occur most commonly at the sites
of hair follicles. These are frequently seen upon the extremilies,
particularly the lower, but may also appear upon the trunk. This
condit on was called by the older writers scarlatina papulosa.
In addition to these elevations a general goose-flesh condition of the
sk n is not infrequently observed. This is best marked upon the abdo-
men and chest, and is characterized by immerous pinhead-sized papules
bearing a close resemblance to the "cutis anserina" evoked in the
normal skin by exposure to either extreme of temperature. These
papules may be faintly red or of the normal skin hue. They differ from
ordinary goose-flesh in that they persist usually for some days. At
times this condition is so pronounced as to impart to the skin a "nutmeg-
grater" feel and appearance.
In the older descriptions of scarlet fever one reads of the occurrence
of sudamina at the height of the efflorescence. Inasmuch as during this
stage the skin is hot and dry with no tendency to sweating, one would
not expect to find sudaminous sweat vesicles. It is extremely common,
however, to find in well developed rashes innumerable miliary vesicles.
To this condition the term scarlatina miliaris or scarlatina vesicularis
has been given. The vesicles are conical, epidermal elevations, pin-
point to pinhead sized (size of millet-seed), with turbid or lactescent
contents, and usually disseminated, although occasionally occurring in
groups. They are commonly situated on the abdomen and chest and
to a lesser extent on the extremities. The region in which they are
frequently most copiously present is the mons veneris, for here the ery-
thema is often intense. In this region they are prone to develop into
minute but well-marked, yellowish pustules.
Till': HYMI'TOMATOLOdV ( )!'' SCA ItLICT i'lCVI'lit ."J]
Rarely, f()iiii'i;iioiis vcisielcs iiuiy coalesce, fonninjj; hlc^fts of the size of
a ])ea or larger, ccni.stitutiiig tli(! .scarlatina jHnri/ph'Kjoidca f>f the older
writers.
Miliary vesicles may be seen in nearly all well-pronounced scarlet-
fever eruptions. They are much more fref|uent than is generally
sup])()sed, l)eing often overlooked on account of their minute proportions.
A niagiu'fyiiig glass will often ))riiig them into view wh(;n they are not
clearly perceived by the unaided eye. In perhaps 20 per cent, of all
cases and 50 per cent, of well j)ronounced eru|)fioiis, vesicles are readily
Miliary vesicles with lactescent contents appearing about the axilla with the rash of scarlet fever.
visible if looked for; lesions of this size, however, do not intrude them-
selves upon one's vision upon cursory inspection of the rash. The
vesicles are more conspicuous in severe eruptions than in mild rashes.
In decidedly exceptional instances they may be so pronounced as to
overshadow the general scarlatinal exanthem and puzzle the physician
in the diagnosis. Dr. J. P. C. Griffith, of this city, has reported several
such cases.
Gee, Squire, Bohn, Rilliet and Barthez, D'Espine and Picot, Moizard,
Baginsky, Vogel, and others believe that miliary vesicles are determined
by an excessive degree of inflammatory action of the skin. Thomas, on
372 SCARLET FEVER
the other hand, thinks that the miHary vesicles are produced by a
pecuhar disposition of the skin of patients. He states that in some
epidemics this condition has been noticed so often and in such abundance
that the normal eruption was observed only in a minority of cases.
Griffith^ fully coincides with the latter view. He cites cases in which
extensive miliary eruptions accompanied mild scarlatinal rashes. He
feels that it is perfectly possible in occasional cases to have the presence
of an abundant miliarial eruption cause decided difficulty in the diagnosis
and even lead to error.
In a large experience with scarlet, fever we have found miliary vesicles
to be much more frequently associated with intense rashes than with
mild eruptions, although they may occasionally be seen in the latter.
The older writers seemed to think that this miliary eruption accom-
panied certain epidemics of scarlatina, and they fancied that these
"miliary epidemics" represented a peculiar infection rather different
from ordinary scarlet fever.
During the period of the fading and decline of the eruption, pea-sized
or larger, flat, epidermal elevations are often noted. These are whitish
and suggest sudamina the contents of which have been absorbed, for
one seldom, if ever, discovers fluid in them. They may be readily
opened with a needle, and resemble empty pea-pods. The exfoliation
of the summits of these lesions and of the miliary vesicles constitutes
the beginning desquamation on the trunk, but this will be later referred to.
The character of the eruftion on the face varies somewhat. In some
cases this region remains entirely free. More commonly the temples and
cheeks are the seat of a deep -red flush; it is probably that this flushing
is often associated with the true rash, for it is not rare to see the face
desquamate profusely. The forehead often shows redness, but this is
usually less intense than on the lateral aspects of the face. The tip and
alse of the nose, and the upper and lower lips and the chin, commonly
appear preternaturally pale. This circumoral pallor defined by the
marked flushing of the cheeks gives the patient a most curious appear-
ance, which, if not peculiar to, is always strongly suggestive of scarlet
fever.
On the arms and legs the rash exhibits no peculiarities save its likeli-
hood to early involve the flexures of the joints (groins, popliteal spaces,
and elbow flexures), and its greater tendency to be blotchy. Upon the
palms and soles the eruption is usually diffusely red without any puncta.
When pressure is made upon the scarlatinal rash a momentary pallor
is produced, then a return of redness and flnally a gradual paling again
which persists for some minutes. We have seen on the legs pale bands
persist where garters had previously been worn.
Indeed, one may inscribe a name upon the efllorescence with a blunt
instrument and in a few moments note the white letters stand out upon
the red background. This is the reverse of the ordinary dermographism
and might be termed ancemic dermographism. This is a vasomotor
1 Scarlatina Miliaris, Jacobi's Festschrift, 1900, pp. 182-186.
77//'; HYMI'TOMATOl/XlY OF SnAUL/'/r /''HVER
873
peculiarity, biii it is douhtful whether it possesses any reliable diagnostic
value.
Itching is not infr(H|ij(',ntly cxpcricnccrl by scarlet-fever patients.
While in most cases it is insi^nii(i( ant or entirely absent, it is occasionally
quite severe. It may be noted during the early evolution of the eruption,
at its height, or during the decline just before desquamation sets in.
In intense eruptions there is often some adema and swelli7if/ of the
skin accompanied by an exaggeration of the lines of cleavage. The
skin under such circumstances is thickened and shows wrinkling of the
epidermis.
On the other hand, the eruption may be so mild as to make the
diagnosis difficult and even impossible. Indeed, in rare cases the
eruption may l)e absent altogether.
Fig. fi2
Ansemic bands at the sites of the garters during the height of a scarlet-ltx t-i ti upi i^n, li.i^ is
vasomotor phenomenon similar to the white bands following digital stroking.
The eruption persists at its maximum intensity but for a brief period
— from a few hours to a day or two, and then gradually fades. ]\Iuch
variation is shown as to the entire duration of the exantbem; ordinarily
the eruption lasts from three to seven days, but its life may be shorter or
longer than this period. Cases doubtless occur in which the eruption
is of such brief duration as to escape notice entirely; instances of scarlet
fever without eruption, but followed by desquamation, are probably to
be accounted for by evanescent undiscovered eruptions.
In some cases a temporary fading or recession of the rash occurs. It is
not rare for the exanthem to be more vivid in color at certain times.
The rash is not infrequently brighter in the evening than during the
day. It is more rare for the eruption to recede completely and later
reappear.
The Enanthem, or Mucous -membrane Eruption. — As has already been
stated, sore throat is not infrequently among the earliest of the s\Tap-
374 SCARLET FEVER
toms ushering in an attack of scarlet fever. In the very beginning
there are commonly seen congestion and swelling of the tonsils, uvula,
and soft palate. A punctated redness is often visible on the soft and
hard palate. During the eruptive stage the gums and buccal mucous
membrane usually exhibit some redness and swelling.
If the gums are inspected from the second to the fifth day there will
oftentimes be seen milk white 'patches which look much as if they had
been produced by the application of pure carbolic acid. These represent
a desquamation of the epithelial covering of the gingival mucous mem-
brane, and can readily be peeled off by slight friction. This process
occurs at times in measles and perhaps also in other affections in which
there is congestion of the oral mucous membrane.
The tongue is, as a rule, heavily covered with a grayish fur at the
onset of an attack of scarlatina. Soon the tip and edges assume an
angry, reddish coloration, and a roughened or granular appearance.
At this time also the fungiform papillae on the dorsal surface of the
tongue become swollen and prominent and peep through the surface
coating. Usually by the fourth day or thereabouts lingual desquamation
takes place and the coating is cast off, disclosing to view a red, raw-
looking, often glazed surface studded with enlarged papillae.
At times the papillary elevations are numerous and small, looking
like the granulations in a wound. At other times they are scattered and
more prominent. This condition of the tongue is of considerable
diagnostic importance and has been variously described as the "rasp-
berry," "strawberry," or "cat's tongue." It should be remembered,
however, that mild cases of scarlatina occasionally exhibit no abnor-
mality of the tongue whatsoever.
During the eruptive stage the condition of the throat undergoes
aggravation. The tonsils are usually enlarged, reddened, and covered
with a layer of mucopus or actual pseudomembrane. The uvula,
anterior pillars, and soft palate are intensely reddened and oedematous.
The patient complains of much pain in the throat, particularly on
swallowing.
Desquamation. — Exfoliation of horny epithelium begins during the
decline of the eruptive stage. Desquamation occurs first upon those
parts of the cutaneous surface which were first the seat of the exanthem.
(Fig. 63.) Where the face has presented much eruption or even
intense flushing a branny desquamation will often be noted as early
as the fourth day. Almost simultaneously a similar epidermal exfolia-
tion occurs upon the neck and the upper portion of the chest. This
process is commonly inaugurated about the sixth or seventh day of the
disease.
If one watches for the first evidence of desquamation on the trunk,
it will be noticed as a number of discrete, pinpoint-sized, powdery scales.
These represent the desiccated summits of the miliary vesicles. In a
day or two these small scales are cast off, leaving minute, jagged rings
of desquamation. The horny layer is now lifted off by centrifugal
extension of these rings, which grow progressively larger. On meeting
Till': SVMI'TOMATfJLor/Y OF HCAULKT VKVKii
370
intestines, etc. On iliis iiccoiinl HawU^y lias suggested \\v,\\. flif; terin
lymy)h;i,ti(; fever he siihslitiitefl I'or searlet fever.
(^iiil(^ early in the conrse of searl(;t ff'ver do we w^Av. ;in iif)j)rcfiahle
ttunefaclion of tlu; suJHMitaneous lyni[)h "[hinds, more j)!irlinij;irly those
sitiuitoul ahoiit the angles of the jaws.
The following presentation of the eondition of the glands in 100 eases'
will give an adecpiate idea of tin; cxicnl of (he lyniphiiOf iii\olvement
in searlet fever.
Fk;. G7
Pronounced desquamation in large lamellEe.
The various lymphatic glands were enlarged in the following pro-
portion of cases:
Inguinal glands 100 per ct.
(a) pea-sized ' 23 per ct.
(6} beau-sized 77 "
Axillary 96
Maxillary 95
Posterior cervical 77
Anterior cervical 44
Submaxillary 36
Epitrochlear . . . ' 26
Sublingual 25
The inguinal glands were in the main enlarged to the size of a pea
or bean, although occasionally they would reach the dimensions of an
almond.
The epitrochlear glands vary from the size o" a lentil to a pea. Not
infrequently the enlargement occurred but upon one side. Occasionally
there is a second enlarged gland just above the epitrochlear gland.
1 A Clinical Study of the Lymphatic Glands in One Hundred Cases of Scarlet Fever, by J. F.
Schamberg, Annals of Gynecology and Pediatry, December, 1899.
380 SCARLET FEVER
The axillary glands vary in size from a pea to an almond. They are
usually enlarged in clusters rather than singly.
The sublingual gland is scarcely ever larger than a lentil seed. The
submaxillary lymphatic glands were found to vary in size from a pea
to an almond. In one case a gland reached the dimensions of an orange,
broke down, and suppurated.
The maxillary glands, or those just behind the angle of the jaw, reach
the largest size of any of the lymphatic glands and are the commonest
to undergo suppuration. In the above cases they varied from the size
of a bean to that of an orange. The average was perhaps represented
by the dimensions of an almond or hickory nut.
The anterior cervical glands, or those lying in front of the sternocleido-
mastoid muscle, were usually pea to bean sized, as were also those
posterior to the muscle.
The glands were examined at various stages of the disease, as early
as the second day, and as late as the fifteenth. In the cases studied
upon the second and third days the glandular enlargement was so well
marked as to suggest the probability that the glands are already some-
what tumefied on the first day of the illness.
The duration of the enlargement doubtless varies in different patients.
In several cases, examined at intervals of a few days for three weeks,
the glands were found to gradually diminish in size, but at the end of
this time they were still slightly enlarged.
Statistics are frequently misleading, and those presented above are,
perhaps, no exception to the rule. While it is true that the inguinal
glands were enlarged in every one of the 100 cases of scarlet fever
examined, it is more than probable that in some of them the enlarge-
ment antedated the attack of scarlet fever. The percentage of appar-
ently healthy children with pea-sized or larger inguinal glands must be
very considerable. Still the effort was made to eliminate this error as
far as possible. It is in most cases not difficult to distinguish between
an old and a recently enlarged gland. The former has a decidedly
sclerotic feel, with the resistance, say, of cartilage. The latter presents
a peculiar resiliency with the consistency of liver.
The enlargement of the glands about the jaw and neck is ordinarily
proportionate to the amount and intensity of throat involvement. There
are, however, occasional exceptions to this rule, and it should be recog-
nized that extensive lymphatic swelling may occur with but slight
throat symptoms.
When the glandular swelling is of moderate extent and of early
occurrence, it usually undergoes gradual subsidence. When the swelling
is very great, and particularly when it develops late, from the second
to the fourth week of the disease, it is extremely prone to suppurate and
form a glandular abscess. This will be further referred to under the
subject of complications.
Respiratory Symptoms. Laryngitis. — Despite the intense inflam-
mation of the pharynx in scarlatina there is but little tendency to involve-
ment of the laryngeal structures. Trousseau's epigrammatic saying,
77//'; HYMPTOMATOI/XIY OF SCARLI'/r FKVER 381
"Scarlatiriii has no likitifi; for tlic, hirynx," is hornc out, hy (•x})f'ri('r)ce.
He fiiHlier r(Miiarks: '"rriio scarliilinou.s sorf^ tfiroat, tlicri, is pJiaryn-
geal, (lillV'i-iii^f in this respect from tlic; sore thrfnit of measles, whieh is
laryiin-eiti, and from that of smallpox, whieh is hofh [)haryngeal and
laryn^ciil."
It is only when the inflammation of the throat in scarlatina is severe,
with tendency to f>;}ui/Trenoiis ehan^^
^'^^
^:^
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^^
*
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•V* .
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''*-i^
■S^^a,
■'V^-v^,"V 'V •''^^ ''.^^ - . -.,- > ^1
0. S., aged twenty-five years. Woman with the anginose form of scarlet fever, treated at the
Municipal Hospital. Subsidence of temperature on the fifteenth day. Recovery.
The glands at the angles of the jaw become rapidly swollen; they
commonly attain the size of a walnut or even a small apple. The
surrounding cellular tissue participates in the general inflammatory-
process, producing great cervical intumescence and often causing the
child's head to be bent backward.
Upon inspection of the throat the tonsils, arches, uvula, and soft
palate are, during the first couple of days, seen to be intensely reddened
and oedematous. Even at an early date there is a hypersecretion of a
viscid, stringy mucus, which adheres to the tonsils and soft palate, and,
becoming dry as a result of the mouth breathing, occasions much
annoyance to the patient. Commonly by the third or fourth day a
membranous exudate appears upon the tonsils, uvula, and soft palate,
384 SCARLET FEVER
extending often to the pharynx and posterior nares. The occlusion of
the nasal channels further obstructs the ingress of air and distresses the
already harassed patient. The buccal and alveolar mucous membrane
is greatly congested, and often the seat of ulcerations from which blood
oozes. The teeth, gums, and lips are covered with sordes, and an
offensive, at times fetid odor is emitted from the mouth. The tongue
is of an angry-red color and occasionally ulcerations, covered with a
grayish exudate, are seen upon the edges. As has been stated, the nose
discharges a purulent material and commonly shows ulcerations of the
mucous lining. The eyelids may also become inflamed, the conjunctiva
congested, and a purulent discharge issue from the palpebral cleft.
The child is often unable to swallow, water or milk being ejected
through the nose. The nasal and faucial respirations are of a rattling
character and painful to behold.
The extension of the morbid process along the Eustachian tubes leads
to a purulent inflammation of the middle ear on one or both sides.
Rupture of the tympanic membrane occurs with the evacuation of the
purulent accumulation. The external auditory canals become infected
by this discharge, and often develop ulcerations which may eat quite
deeply into the tissues.
The child with a bad anginose scarlatina is a pitiable object — it lies
with the head back to prevent the pressure of the swollen glands from
compromising the breathing; the neck is greatly tumefied, the overlying
skin stretched and glazed, the commissures of the mouth fissured and
covered with blood crusts, the nose discharging a sanguinopurulent
matter, the eyelids swollen, and the ears expelling a thin, ichorous pus.
Indeed, every orifice of the face gives issue to a putrid and foul-smelling
discharge, which contaminates the atmosphere about the patient with
the stench. The general symptoms are those of a profound septicaemia.
In extremely bad cases, and in our experiences more particularly in
mixed cases of scarlet fever and diphtheria, extensive ulceration and
sloughing of the tonsils or soft palate may take place. The necrosis in
such instances involves the entire thickness of the tissues, and leads
commonly to perforation of the soft palate. We have in a number of
cases seen these perforating ulcers of the soft palate; they may be bilateral,
or occur only upon the one side. The accompanying symptoms are pf
a septic character, and the prognosis is unqualifiedly bad; death takes
place in almost every case.
In fatal cases of anginose scarlatina death may occur as a result of
the severe primary blood poisoning, or through the development of the
later complications, such as nephritis, pneumonia, endocarditis, etc.
Bronchopneumonia is more frequent than is commonly believed, the
symptoms being masked by the severe angina and the grave toxaemia.
The urine is diminished in quantity and nearly always contains
albumin. The microscope will often discover the presence of tube
casts and also red blood corpuscles.
A fatal termination is preceded by rise in the temperature to 106°
or 107° F., an increasing prostration and stupor, and a progressive
77//'.' HYMPTOMATOI/XIY OF SCARfJ'/r FHVHIt 385
weakening and augmented frc(|ii(iicy i)\ I he juilsc. Fatal cases usually
succumb during the first or scscond wc(;k of the illness.
In severe cases of angiiiose scarlatina the lym})halic glands and
adjacent tissues, under the influence of intense inflanimatif)n or, y>erfiaps,
a special infection, may inulergo f/anr/rene, leading to gr(;at sloughing
and even alarming or fatal hemorrhage from the erosion of some large
bloodvessel. Trousseau speaks of a case in a boy of fourteen " in whom
the gangrene condition was so extensive that tlie muscles of the neck
were dissected, as occurs in diffuse phlegmonous inflammations, showing
the carotids pulsating at the bottom of a horrible wound."
In cases that end in recovery the temperature at about the end of a
week or ten days begins to decline, the pulse slows and acquires Ijetter
volume, the marked nervous symptoms gradually disappear, and the
throat and adjacent cavities show a lessening in the intensity of the
inflammatory process. The decline in the temperature is slower and
lesS regular than in the usual type of the disease, and the normal is
seldom reached before the end of the third or fourth week. Con-
valescence is apt to be complicated by nephritis and in some cases by
rheumatism and endocarditis.
Scarlatina Maligna.
Malignant scarlatina, a fortunately rare form nowadays, is char-
acterized by such a sudden overwhelming of the vital forces as to cause
death in a few days, or, indeed, within twenty-four hours. The symp-
toms, consisting of extremely high fever, severe brain symptoms, and
profound prostration, with or without hemorrhages into the skin and
from the mucous membranes, develop with fearful rapidity, and the
patient sinks under the dread influence of the poison.
The abruptness of the onset of the disease in these cases is remark-
able. Children in the enjoyment of apparent perfect health may be
smitten while at play. The child has a severe attack of vomiting, which
may be accompanied by purging, and is followed by convulsions or
stupor. The temperature rises rapidly to 107° or 108° F., the pulse to
140 or 150. Great restlessness and delirium may alternate with stupor.
Excruciating headache and violent pains in the extremities are some-
times present.
The eruption is usually irregular, appearing often on the hands and
feet before it is seen on the body. At times it appears only about the
flexures of the joints. The rash may recede after a brief presence, only
to appear a few days later. It is sometimes partial, assuming an er\'sipe-
latous aspect on the face or legs. It has commonly a h\dd hue, being
beset with petechise and vibices.
The local symptoms in malignant scarlatina are severe. The throat
is so intensely swollen that swallowing is often impossible. The glands
are greatly enlarged, and, if the patient hves long enough, the nose and
middle ear become involved.
Prostration and collapse may occur so suddenly that no eruption
25
386
SCARLET FEVER
appears. The skin is pale or livid, the lips blanched, the eyes glassy
and sunken with partial closure of the lids, the surface cold, the pulse
weak and fluttering, and death imminent and inevitable. This choleraic
type at times cannot be diagnosed without the presence of other cases
of scarlet fever in the same household.
These rapidly fatal cases are rare, but well-authenticated instances
are recorded. Morris^ speaks of a child that was taken out apparently
in perfect health for its morning airing and brought back within an hour
with stupor and general muscular relaxation, cold surface, feeble pulse,
and total insensibility; death occurred in twelve hours. Within a few
days two other children in the same family were seized with scarlet
fever which ran a regular course. Dr. Rush reported "a few instances
of adults, who walked about, and even transacted business, until a few
hours before they died." Such a case is mentioned by Morris; "A judge
Fig.
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the fifth day of the disease.
of one of the courts was seized with nausea while on the bench and
retired to his home, where for two days he remained, scarcely willing
to admit himself to be sick, and reluctant to confine himself to his
chamber, though the rapid, feeble pulse and an imperfect eruption too
plainly indicated the nature of the affection; on the third day he died
while in the act of shaving himself." A near relative stood beside the
corpse and contracted a similar fatal illness.
Gregory^ in referring to malignant cases says: "In some extreme
cases ... all the ordinary appearances of scarlet fever are masked;
petechise, coma, and a sloughy state of the throat alone appear." And
further he remarks there are cases "where no affection of the skin
takes place at all." As an instance thereof he attended a woman and
two grown-up daughters, in all of whom "the nervous system was utterly
prostrated, or in the state of collapse. There was no violence, no
delirium, no struggling for breath, no rash; but the pulse was small,
1 Pathology and Therapeutics of Scarlet Fever. Philadelphia, 1858.
2 Loc. cit.
77//'; HVMI'TOMATOLOdY OF SCMfLhri' [''KYHIi. 387
the skill cold, iuxl (Ik; whole; syslcm depressed hy llu; inlcnsily reratnre hoverefJ
between 99° and 101° F. until the eif^hteenth day, when it rose to 105° F.
Accompanying this rise there were headache, abdominal pain and
diarrlux'a, and a recurrent, very bright rash; no throat symptoms.
Urinary examinations were n(!gative. 'i'lircc; chiys hiter a second desqua-
mation began. 'Vhe temperature jk^w grachially d(;cl ned, reaching
normal on the twenty-seventh day of the disease. The patient was
believed to be well, when on July 6th, or the thirty-second day of the
disease, the temperature again rose to 101|° F. The patient com-
plained of a sliglit sore throat, and a rash, followed by a fine desfjuama-
tion, appeared on the face, arms, and trunk. The tem})erature declined
quite promptly; the patient made a good recovery and was discharged
from the hospital on July 26th.
Fig. 70
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Scarlet fever ; two relapses. A. D., aged twenty-one years.
It is seen that the first relapse occurred upon the eighteenth dav of
the disease, and the second upon the thirty-second, or just two weeks
later.
Complications and Sequelae of Scarlet Fever.
Throat.^ — Angina is an essential feature of the symptomatology of
scarlet fever and cannot be regarded as a complication except where it
is excessively developed. The most moderate expression of the scar-
latinal sore throat is a uniform congestion of the uvula, anterior pillars,
and tonsils. This form has been designated as erythematous angina.
In more severe cases the mucous membrane is greatly swollen, and there
is extension of the catarrhal inflammation posteriorly to the pharvngeal
wall and anter'orly over the soft palate; these parts are of a deep-
red color and bathed in a profuse mucoid secretion. The swelling of
396 SCARLET FEVER
the soft palate may be so intense as to seriously interfere with swallowing
and to cause the regurgitation of liquids through the nose, The tonsils
may also exhibit great increase in size and embarrass both deglutition
and respiration.
In the membranous variety of angina the mucous membrane of the
tonsils is covered with an exudate, which is usually of a yellowish or
brownish tint and thinner and softer than the membrane of true diph-
theria. While in most cases the pseudomembranous deposit is limited
to the region of the tonsils, it is not uncommon for it to be present upon
the half- arches and also scattered in patches upon the soft palate. It
may likewise spread by way of the pharynx into the posterior nares
and, in rare cases, to the tongue and buccal mucous membrane. Exten-
sion of the process along the Eustachian tube gives rise to inflammation
of the middle ear, a most frequent complication of anginose scarlet fever.
The glands about the angles of the jaw undergo inflammation and
tumefaction and commonly suppurate. Pronounced constitutional
symptoms accompany this variety of the disease. The temperature
hovers about 104° or 105° F., and there is marked disturbance of the
nervous system. Intense restlessness, delirium, stupor, coma, or con-
vulsions may be present. The pulse is extremely frequent, often reach-
ing 140 or 150 beats per minute. There is profound prostration, the
urine contains albumin, and the patient is completely overwhelmed by
the poison of the disease.
When there is extension of the process to the nose a purulent rhinitis
is set up. There is a profuse discharge of a thin mucopurulent and
often blood-stained material, frequently containing shreds of membrane.
This irritating discharge inflames the nostrils and the upper lip and
gives rise to impetiginous sores. The nose is swollen and the nostrils
obstructed, causing considerable difficulty in breathing. An offensive
odor is given off which can be detected some feet from the bedside.
The nasal inflammation is attributed to the action of the streptococcus,
the extension of whose pernicious activity may give rise to infection of
the nasal sinuses.
French writers have called attention to the bad prognosis in these
cases of early purulent coryza. The mortality in the Aubervilliers
Hospital was over 50 per cent., and this complication was feared more
than the most malignant forms of angina.
The membranous inflammation may extend to the larynx and produce
serious difficulty in respiration. As has already been stated, however,
laryngeal involvement is extremely rare in scarlet fever.
In normal scarlatina the larynx is exempted, and the mucous mem-
brane, being in a healthy state, is not particularly susceptible to the
noxious influence of the streptococcus or the diphtheria organism. In
measles, on the other hand, the larynx is primarily involved and the
soil is rendered favorable for the implantation of these micro-organisms.
The gangrenous variety of angina is fortunately rare, and is, for the
most part, observed in hospitals. The gangrene may begin upon the
tonsil, at the site of the rupture of an abscess. The necrotic process
77//'; (JOM/'fJCATfONS OF SCAUfJ'/r F/CV/af Pjij-J
may involve the eiiiiro ton.sil, which .sloughs out enmassc. In soine cases
the gangrene is hinited to the tonsillar tissues; in others it spreads
beyond, attacking and destroying the palatine arches, the uvula, and a
considerable portion of the soft palate. The affected parts are at first
covered with a grayish-blac-k, puhaceous de[)osit, which, when thrown
off, discloses to view frightful loss of tissue. The odor cmitfcd frf)m
these cases is foul and penetrating. The nose and ears are commonly
involved and give exit to an ichorous discharge. The glands of the neck
are greatly swollen; the constitutional depression is profound. In our
experience tlie most common form of gangrenous angina has been
characterized by circumscribed necrosis of the soft parts, particularly
the soft palate, leading to irregular or rounded perforations about a half-
inch in diameter. This condition may develop early, or may be po.st-
poned to the second or third week of the disease. We have observ^ed
this complication much more often in mixed cases of scarlet fever and
diphtheria than in scarlet fever alone. The prognosis in this circum-
scribed gangrene is very unfavorable, although patients occasionally
recover with considerable deformity of the soft palate.
In extremely rare cases gangrene may commit frightful ravages.
The connective tissue of the neck may become involved, the overlying
skin destroyed, and the muscles and large bloodvessels laid bare. Where
the patient does not die of hemorrhage from erosion of the carotid
artery, jugular vein, or other large bloodvessels, he is sure to succumb to
the blighting influence of the septic poisoning. Recovery can only take
place where the gangrene is limited to small areas.
Secondary Angina in Scarlet Fever. — The throat involvement thus
far described occurs early in scarlatina and influences to a considerable
degree the course that the disease takes.
A secondary angina may develop late in the disease; indeed, at times
after convalescence is established. It is not rare for the tonsils to
become the seat of a severe inflammation, increase greatly in size, and
after a few days undergo suppuration. The neighboring soft palate
becomes reddened and greatly tumefied. There is distressing pain, and
speech and swallowing are difficult. W'^e have here the usual symptoms
of a suppurative tonsillitis or quinsy. In some cases the tonsillitis
subsides without pus formation. We have observed these late anginas
in hospital wards, a circumstance wdiich suggests a second infection
from without as the cause. Similar attacks of tonsillitis have occurred
in ward maids and nurses, a fact which renders this view all the more
plausible.
Postscarlatinal Diphtheria. — Before the days of bacteriology all
cases of membranous angina were regarded as diphtheria. It is now
recognized that the membranous deposit frequently seen in the throat
early in the course of scarlatina is nearly always due to the streptococcus.
Diphtheria is, as a rule, a complication of the stage of convalescence.
Caiger^ gives the date of "onset of 408 cases of postscarlatinal diph-
theria :
1 Article on Scarlet Fever iii AUbutt's System of Medicine, p. 161.
398 SCARLET FEVER
Time of Onset of 408 Cases of Postscablatinal Diphtheria (Caigee.)
Percentage
Weeks. Cases. of total cages.
One 11 2.69
Two 36 8.82
Three " 55 13.48
Pour . . ' 77 18.87
Five 54 13.23
Six 46 11.27
Seven 38 9.31
Eight 27 6.61
Nine 18 4.41
Ten 13 3.18
Eleven ........... 9 2.20
Twelve 9 2.20
Over twelve 15 3.67
It is seen from the above figures that the susceptibihty to diphtheria
is most pronounced from the third to the sixth week of scarlet fever.
Cases of postscarlatinal diphtheria are much more common in
hospital than in private practice. In large hospital wards it doubtless
occasionally happens that a secondary diphtheria remains undetected
and exposes other patients to the infection. The mortality of mixed
cases of scarlatina and diphtheria is, as would naturally be expected,
higher than that of primary diphtheria.
There is nothing in the clinical or pathological picture of postscar-
latinal diphtheria to distinguish it from primary diphtheria. It is
usually limited to the tonsils and adjacent half -arches, although it
may exhibit greater extent and spread to the posterior nares or to the
larynx. The thick, grayish-white exudate contrasts strongly with the
thin, smeary, yellowish or brownish deposit seen in the early stages of
scarlatina. Paralyses, such as are seen after diphtheria, are excessively
rare after scarlet fever. This observation is so well attested that when
paralysis occurs after scarlatina there is a reasonable ground for the
suspicion that a mixed infection has been present.
The diagnosis will, in large measure, rest upon the bacteriological
findings. The presence of the Klebs-I.(OefHer bacillus in a throat which
is the seat of exudate indicates the existence of diphtheria.
Since the specificity of the diphtheria bacillus has been established,
numerous examinations of scarlatina throats have been made to deter-
mine the character of the membranous angina. Chabade,"^ of St.
Petersburg, made cultures of 214 scarlatinal throats; of these, 98 had a
catarrhal angina, 33 had a lacunar angina with a pseudomembrane
in the tonsillar crypts, and 83 had a pseudomembranous angina involv-
ing the tonsils and adjacent soft tissues.
In the catarrhal group no diphtheria bacilli were found, but strepto-
cocci and, at times, staphylococci were present. In the lacunar anginas
the Klebs-Loeffler bacillus was found twice. In the pseudomembranous
cases the diphtheria organism was found eleven times, thrice almost in
pure culture, and in eight cases associated with the streptococcus.
1 De 1' Association de la scarlatina avec la diphth(Srie, La semaine m6d., 1899, p. 184. Quoted by
Northrupln von Jiirgenseu's article on Scarlatina in Nothnagel's Encyclopedia of Practical ^Jledicine,
77//'; COMI'LldATIOSH OF SdAltLHT I'l'lVhlK ,'}li9
Variol jukI I )ev6' examined (lie iliroats of 525 cases of scarlatina.
Of this nuiiilx'r ()2 liiul exudate in the tliroat, 'M) of whifh proved fo l;e
true dij)htlieriii,.
Garret and Waslihourn,'' from cultures of the tliroat of fJOO patients
treated in the r.ondon Fever Hospital from 1890 to J SOS, foinid that
over 1 per cent, showed Klebs-LoefHer bacilli on admission.
For tlu^ |)nst few years we have made cultures of all scarlatina [)atients
admitted into the Municipal Hospital. The (;ulturcs were made at the
home of the patient, in the ambulance, or after entrance to the ward.
In one series of cases, in which cultures were made after the admis.sion
of the patients to the ward, there were 1G7 negative results and SO po.si-
tive, or 32.85 per cent.
In a second series of over 500 cases, in which the cultures were taken
either at the home of the patients or immediately after their reception
into the ambulance, the results were as follows:
Negative cultures
. 74
Positive
cultures . 26
. HS
. . 17
. 77
. . 23
. 65
" M not recorded) 34
. 81
. . 19
. 10
. . 3
390
122
Percentage, 23.8
A further series of 500 cases, some cultured before admission to the
wards and some shortly after, gave the following figures:
Negative cultures . . 87 Positive cultures . . 13
.84 " " . . 16
.80 " " . . 20
.86 " " . . 14
.80 " " . . 20
417 83
Percentage, 19.9.
The aggregate of these figures gives a total of 1259 cases, of which
285, or 29.25 per cent., yielded positive cultures.^
The throats in many of the positive cases showed merely evidences
of catarrhal angina. Subsequent cultures in the positive cases would
at times be negative, but in not a small number of instances three or
four positive cultures were obtained. There were comparatively few
patients in whom the diagnosis of diphtheria would have been made
from the clinical appearances.
The diphtheria patients are treated in a building which is quite apart
from that occupied by scarlatina patients. i\Iixed cases are treated in
the same building, but in a distant wing.
Ears. — Inflammation of the middle ear is, perhaps, the most com-
mon complication of scarlet fever.
1 SoG. m6d. des hop., 1900, xvii. p. 1025 ; quoted by Norttirup, loc. cit.
2 Ann. de mtJd. et chir. enfant, 1899, t. iii. ; quoted by Northrup, loc. cit.
s These cultures were examined and reported upon by the City Bacteriological Laboratory, which
Is under the supervision of Prof. A, C, Abbott, of the University of Peunsylvania,
400
SCARLET FEVER
Its frequency varies with the character of the epidemic and with the
age of the patient. In the anginose variety of scarlatina middle-ear
disease follows in almost every case. Some epidemics appear to be
characterized , by a much smaller incidence of ear complications than
others. Holt mentions the fact that in an epidemic occurring in the
New York Infant Asylum in the spring and summer of 1889, there were
73 cases of scarlet fever and not one developed otitis. In a fall and winter
epidemic in the same institution, two years later, of 43 cases of scarlet
fever, 20 per cent, developed otitis. The frequency of otitis in different
epidemics is influenced by the degree of angina present, and also to some
extent by season, middle-ear trouble being more prevalent in the colder
months. Infants are more liable to develop otitis media than children
of more advanced years. This may be due to the relatively large size
of the Eustachian tube in infancy.
Finlayson states that otitis was present in 10 per cent, of 4397 cases
of scarlet fever reported by him. Caiger^ analyzed 4015 cases of scar-
latina, and determined that otitis media with discharge took place in
11.05 per cent, thereof. Burckhart reports this complication in 33 per
cent, of cases. In attacks with severe throat involvement otitis occurs,
according to Holt, in fully 75 per cent, of cases.
Bader and Guinon^ report 33 per cent, involvement in the form of
mild or catarrhal otitis, and purulent otitis in but 4.5 per cent, of cases
of scarlatina.
Middle-ear disease results from direct extension of inflammation
from the nasopharynx and doubtless through the action of the bacteria,
chiefly the streptococcus. This complication may develop at any time
during the course of scarlet fever, even as late as during convalescence.
It is apt to develop early in bad cases with severe throat involvement.
In 18 cases of otitis media recently observed by us the discharge
appeared upon the following days:
Day of Scarlet-fever Illkess upon which Eighteen Cases of
Otitis Media Developed.
1 on the
6th day. 1 on the .
. 18th day
1 " "
8th " 2 " " .
. 19th "
2 " "
9th ■' 1 " " .
. 20th "
1 " "
10th " 1 .. <. .
. 21st "
1 " "
nth " 1 " " .
. 22d "
1 " "
13th " 1 " " .
. 23d "
1 " "
16th " 1 .. .< _
. 32d "
1 " "
17th " 1 <. » _
. 35th "
One or both ears may be affected; when both are attacked the dis-
charge does not, as a rule, appear simultaneously, an interval of four
or five days or a week separating the two attacks.
When the ear complication develops early in the course of the disease,
while the temperature is high and nervous manifestations still present,
the symptoms thereof are apt to be obscured by the general condition
of the patient. When the otitis appears^at a later date, after the scar-
1 Scarlet Fever, Allbutt's System of Medicine, New York, 1897, vol. iii, p. 150.
' See Moiisard, Scarlatine, in Traits des mal, de I'enfance, Paris, 1897, vol. i.
77//'; COMI'IjIdATION'H OF .ST.l /,'/./<; 7' FKVKli 401
latinal fever has declined, ils df-vclopincnf, is acicornpanicd by a sharp
rise of tcirij)erature. The fever is usually preccicled hy pain, alfhfjugh
this symptom is extremely variable.
Infants will often carry their hands to their cars and uftcr shar[)
shrieks. \w some cases there is eiilar^(;m(Mit and tenderness of lyiiij)ha.fic
glands about the (^ar. The otitis may be a simj>lc caiarrhal irdlamination,
or it may be furulent or suppurative. In the formc^r variety the duration
of the affection is much shorter and of a less serious character. The
fever, pain, and tenderness subside rapidly after spontaneous rupture
or incision of the tympanic meml)rane.
Purulent otitis media pursues a much more protracted course. A mucr)-
purulent discharge may continue for weeks or, indeed, the condition
may lapse into a chronic suppurative otitis. The immediate dangers
associated with this condition are extension of the purulent inflammation
to the mastoid cells or meninges of the Ijrain, the erosion of bloodvessels,
with the production of serious hemorrhages, and finally the development
of septictemia or pysemia.
Cases are on record in which the erosion of large bloodvessels has led
to fatal hemorrhage. Baader^ reports the case of a three-year-old boy
suffering from a purulent otitis complicating scarlatina, who developed
on the eleventh day of the disease a severe and uncontrollable hemor-
rhage from the . ear which caused death on the third day. Autopsy
disclosed a perforation of the posterior wall of the tympanic cavity and
an erosion of the lateral sinus.
Hessler^ records a case in which a fatal hemorrhage resulted from
ulceration of the carotid artery.
A similar case is reported by Hynes,^ in which a sudden and unlooked-
for hemorrhage poured from the right ear in a four-year-old child. The
child later vomited blood in large quantities and died. It was thought
that the bleeding came from the internal carotid artery.
Hliber* reports a case of hemorrhage from an eroded vessel which
caused a haematoma of the neck, the opening of which resulted fatally.
Kennedy has reported three fatal cases of hemorrhage, and ]Moller and
West each one instance.
The following case of septicaemia associated with purulent otitis was
observed by us in the Municipal Hospital in 1SS9:
F. F., a boy aged thirteen years, was admitted to the hospital on
February 2d, with a bad anginose scarlet fever. His condition improved
for a week, the temperature reaching normal. On February 10th the
patient had a chill with a rise of temperature to 104f ° F. On the follow-
ing day another chill and a temperature of 107f ° F. The next day the
temperature rose to 107i° F. For a period of ten days there occurred
the most violent rises and falls of temperature, the extreme limits being
95i° and 107i° F., an excursion of 12 degrees. Chills recurred each day
and on one occasion repeated vomiting. The ear which was discharging
1 Acute Verblutung bei Scharlach, Corres. bl. f. Scbweiz. Aerzte, 1875, Bd. v.
2 Quoted by Forchheimer, loc. cit s Quoted by Forchheimer, loc. cit .
■• Deutsche Archiv f. klia Med., Bd. viii. p. 422.
26
402
SCARLET FEVER
was kept thoroughly clean with a carbolized solution. By February
27th the patient had recovered sufficiently to leave his bed (Fig. 71).
The immediate dangers of purulent otitis having been passed, there
remain severe structural changes which may seriously interfere with the
sense of hearing. There may be partial or complete loss of the tympanic
membrane upon one or both sides ; occasionally the ossicles are destroyed
and thrown off. Ulceration and necrosis of the walls of the tympanum
may occur, with the development of further complications to which
Fig. 71
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Remarkable excursions of temperature due to suppurating otitis media. F. F., aged tliirteen
years, admitted to liospital in critical condition : bad throat and mouth ; ears discharging on second
day of disease. Various rises of temperature accompanied by chills ; ultimate recovery.
reference will be made later. The labyrinth may be attacked in rare
cases. Pye, Phillips/ and others have reported cases in which laby-
rinthine structures were necrosed and discharged en masse. These
patients were, of course, left completely deaf. Bezold^ gives the results
of 185 cases of scarlatinal otitis: "In 30 there was entire destruction of
the membrana tympani, with the loss of one or more bones ; in 59 the
perforation comprised two-thirds or more of the membrane; in 13 there
were smaller perforations; in 44 there were granulations or polypi; in
1 Quoted by Holt, loc. cit.
2 Quoted by Holt, loc. cit.
TIIK COMPLICATIONS OF HCAIfLh'/r FEVhlli 403
15 there was total loss of liearing on one side, and in f»f the cases on
both sides; in 77 of the cases the hearin^^ distance U)V low voice was
less than twenty inches."
Burckhardt-Merian' reported XS cases of ear corn[)hcations of which
72, or 84.7 per cent., involved both ears. Of 4'MY.) cases of acrpiircd
deafness and dumbness, 445, or 10. .'i per cent., were due to scarlet fever.
May, of New York, has collected similar statistics; of 5613 cases of deaf-
mutism, 572 were traceable to attacks of scarlet fever.
Purulent otitis may, in rare cases, give rise to disease of the mastoid
antrum. This may occur during convalescenc;e from scarlet fever or
may develop after the otitis has become chronic. The mastoid region is
painful and tender and acquires a characteristic appearance — the great
postauricular swelling causing the ear to stand out prominently from
the head. The temperature rises to 103° or 104° F., and, unless there is
operative interference, brain symptoms may manifest themselves. On
incision a mastoid abscess is found present. At times a superficial
abscess is found in the region of the mastoid, without actual involvement
of the mastoid cells.
Thrombosis of Lateral Sinus. — Thrombosis of the lateral sinus is
occasionally encountered in cases in which cerebral abscess or meningitis
subsequently develops. The onset is sudden, with chills and high and
irregular fever.
Facial Palsy. — Facial palsy is by no means a rare complication of
scarlatinal otitis. We have observed this paralysis in a number of cases
of severe middle- ear disease. It is due to an extension of inflammation
from the tympanum to the facial nerve, where it passes through the roof
of the cavity. The symptoms do not differ essentially from facial palsy
occurring from other causes.
Abscess of the Brain. — Abscess of the brain may result from extension
of the suppurative inflammation from the middle ear. The petro-
squamous suture being patulous in children, an avenue of infection to
intracranial structures is readily offered. The periosteum of the tym-
panum is continuous with the dura mater, and extension of inflammation
may occur along this membrane. In addition, the infection may be
carried to the brain through the medium of the veins.
Purulent Meningitis. — Purulent meningitis is an extremely serious
complication that may arise from a suppurative otitis. It may have its
origin in thrombosis of the lateral sinus or may develop from necrosis
of the roof of the tympanic cavity. There are usually high fever, stiffness
of the neck, retraction of the head, vomiting, and, at times, parahiic
eye symptoms. Death occurs ordinarily in about a week. The following
case will illustrate the symptomatology of this complication:
W. J., aged three years, was admitted to the INIunicipal Hospital on
April 9, 1903, with a severe attack of scarlet fever. On the sixth day
of the disease the right ear discharged. Fever was protracted, the
temperature not touching normal until the thirtieth day. Later the
1 Ueber den Scharlach in seinen Beziehungen zum Gehurorgan ; Volkmann"s Sammlung klin.
Vortriige Chir., No. 54.
404 SCARLET FEVER
temperature rose as the result of a cervical abscess. There was no
fever from the forty-fourth to the fifty-fourth day. At this time the
temperature began to rise and the patient vomited. He cried out sharply
upon being disturbed. A gradually increasing stuporous state developed.
The neck was rigid and the head retracted. The pupils were equal
and reacted to light. The patient gradually lapsed into complete coma.
The temperature rose to 106f ° F. and the patient died on the ninth
day of the complication and the sixty-fourth day of the scarlet fever.
When the skull was opened at autopsy a foul odor was immediately
noticed. A purulent exudate was found covering the entire base of the
brain, but involving chiefly the left side. The pia mater under the
left cerebellum was infiltrated with pus, and there was free pus in the
various fossae. There was no discoverable caries of the petrous portion
of the temporal bones, and on opening these no pus could be detected.
Cultures from the purulent material demonstrated the presence of the
staphylococcus pyogenes aureus.
Complete Deafness .^ — Complete deafness not due to middle ear
disease occurred in a boy, aged five years, at the Municipal Hospital,
during convalescence from a well-marked attack of scarlet fever. The
patient had been out of bed for a number of days, when he was suddenly
taken ill with high fever, vomiting, heavily coated tongue, and delirium.
This was shortly followed by pronounced mental hebetude; vomiting
persisted for several days, nothing being retained upon the stomach.
Mental dulness continued for several days, after which, upon the clearing
up of the mental faculties, it was noticed that the patient was absolutely
deaf. There had not been any discharge from the ears nor any other
evidence of otitis. The mastoid region was normal. The temperature
for a week or ten days was markedly irregular, fluctuating rapidly
between 99° and 104° F. About the same time that deafness was noted
there was a paralytic strabismus. The patient left the hospital absolutely
deaf. The internal ear was doubtless diseased in this case, perhaps as
the result of a localized meningitis.
Eyes. — In cases of severe scarlet fever, particularly where there is
a purulent rhinitis, extension of the inflammation may take place and
a severe conjunctivitis set up. More often the conjunctivitis that
develops is of a mild character, with injection of the bloodvessels of
the sclera and lids, increased lacrymation and photophobia.
The lacrymal duct and gland may become involved through the
infection that has its origin in a purulent coryza. Through this channel
other ocular structures may subsequently be attacked.
Primary Keratitis. — Primary keratitis with its unfortunate train of
symptoms develops at times, particularly in scrofulous subjects. We
recall a corneal ulcer in a colored child, who had previously suffered
from keratitis, in whom perforation with prolapse of the iris occurred.
Leichtenstern reports 2 cases of corneal ulcer and 1 of hypopyon keratitis
occurring in a severe epidemic in the hospital at Cologne. Thomas
quotes Schroter as saying that the cornea may be affected primarily
and independently, usually in the way of rapidly progressing abscesses
Till'] aOMI'LldATIONS OF SCA/ifJ'JT FJ-JVJ'J/i 405
or suppurating ulcers or pernicious keratomalacia, in wliicli tfie cornea
of one or both eyes, witliout any marked symptoms, hecfjmes turl^id in
a few (lays, is transformed in its totality info a turhid, dirty, grayish-
white membrane, and exfoliates piecemeal. The inflammatory |)rocess
may travel thence over the uveal tract and cause a panophthal-
mitis.
Choroiditis. — Choroiditis may, in rare cases, com[)licate scarlet fever.
In the epidemic already alluded to TiCiclitenstern saw a case of choroiditis
which ended in phthisis bulbi.
In those cases in which a severe nephritis is present ophthalmoscopic
examination may reveal the existence of an alhuminuric retinitis. Both
eyes are usually equally and simultaneously affecterl. After a protracted
course more or less complete restoration usually results.
Temporary blindness, or amblyopia, may complicate the kidney con-
dition; after some days complete visijDn is usually restored. We have
personally observed such cases. Porter' saw a young girl with severe
complications, develop temporary blindness with exophthalmos from
infiltration of the cellular tissue of the orbit. DuvaP saw a similar
case of exophthalmos lasting ten days, the sight being subsequently
fully restored.
Within the past few years we have observed in the Municipal Hospital
two cases of orbital cellulitis complicating scarlet fever and leading to a
fatal termination. These cases were seen and studied by Dr. Burton
K. Chance,^ Assistant Surgeon to the Wills Eye Hospital, Philadelphia,
to whom we are indebted for careful notes of the cases:
Case I. was a boy, aged seventeen years, who during a protracted
convalescence from a severe scarlet fever developed a sudden diffuse
cellulitis of the right orbit. A chill and sharp rise of temperature were
followed by an effusion of fluid into the areolar tissue, with protrusion
of the globe. The eyelids were red and excessively oedematous. The
fundus was at first pale, but later intensely red, with fine hemorrhages.
There was marked swelling of the disk, an overdistention of the veins,
and contraction of the arteries. A day or two before death the cornea
became necrotic and the eye was lost. High fever, delirium, and coma
preceded death, which took place one week after the development of
the complication. The examination of the orbital structures after death
revealed only a diffuse serous infiltration; there was no evidence of
intraocular suppuration.
Case II. was a boy, aged ten years, who was convalescing from
scarlet fever, when there developed in the right orbit an acute congestion
with infiltration of the tissues, producing proptosis between the intensely
oedematous lids. The local symptoms were similar to those in the first
case. Throughout the course of the process the cornea remained
unaffected. Deep incisions were made into the periocular tissues,
evacuating a quantity of blood-tinged serum, but no pus. On the eighth
1 Quoted by Thomas. 2 Quoted by Thomas.
3 Dr. Chance reported his findings in a paper read before the Philadelphia County Medical Society,
May 27, ]903. This was published in American Medicine, June 13, 1903, p. 960.
406 SCARLET FEVER
day after the onset of the complication the patient was seized with con-
vulsions and died. Permission to make an autopsy was refused.
In rare cases failure of vision may be due to atrophy of the optic
nerve or to detachment of the retina. O'ptic neuritis may occur with
meningitis or without such involvement, as in a case reported by Putnam.
Heart. — The heart may suffer in scarlet fever from (1) the scarlatinal
toxin, (2) as a result of nephritis, and (3) from secondary infections,
such as rheumatism, pyaemia, etc.
That the scarlatinal poison has a direct influence upon the heart is
seen in the early tachycardia, the heart beats being out of all proportion
to the temperature. Furthermore, in mahgnant cases that are over-
whelmed at the onset by the poison of the disease, the symptoms are
those of an acute cardiac failure; the pulse is rapid, small, and irregular;
the extremities are cold, and pallor and cyanosis are often present. In
severe cases of the disease, the scarlatinal toxin, according to Romberg,^
may early cause a pronounced dilatation of the heart.
The occurrence of nephritis in scarlet fever naturally leads to changes
in the cardiac muscle. Whenever the kidney involvement is at all
pronounced there will be found a hypertrophy and dilatation of the heart.
The changes are apt to be present upon both sides, but the preponderant
enlargement is nearly always found upon the left side.
RiegeP states that in most, if not in all, cases of scarlatinal nephritis
there is an increased arterial tension from the very beginning. After
the blood pressure has persisted for some time, the heart enlarges as
a consequence. In some cases the increased size of the heart may be
noticed a few days after the onset of the nephritis. It is readily seen
how this form of cardiac disease is produced. The development of
nephritis by raising the arterial tension throws an extra burden upon
the heart; if the heart has already been injured by the influence of the
scarlatinal poison, the strain may be too much and acute dilatation may
result. If the heart muscle has more recuperative power a compensatory
hypertrophy may take place.
If the left heart develops a pronounced insufficiency, a dilatation of
the right side will usually occur. When this results we see the usual
symptoms of cardiac insufficiency — dyspnoea, rapid pulse, enlargement
of the liver, etc. A murmur may or may not be heard over the mitral
orifice. It is important to recognize the fact that the bruit is not due
to an endocarditis, but to cardiac dilatation. This murmur will be
found to disappear as the heart improves.
Myocarditis. ^ — ^Myocarditis is the heart condition which is most
frequently called into existence by the scarlatinal toxin and by the
associated nephritis. The other forms of heart disease are more
commonly associated with secondary rheumatism or septic infection.
Ashby found endocarditis not uncommon with rheumatoid affections
1 Ueber die Erkrankungen des Herzmuskels bei Typhus Abdominalis, Scharlach, etc., Deutsch.
Archiv f. klin. Med., Bd. xlviii. p. 369, and Bd. xlix. p. 413.
2 Ueber die Veriinderungeu des Herzens, etc., bei Acuter Nephritis, Zeitschr. f. klin. Med., 1884,
Bd. vii. p. 260 ; quoted by von Jurgensen, loc. cit.
TffM aOMf'fJdATfO.MS OF SCARLET FEVER 407
devcloj)inf( in the third or fourth week of scarlet fever, hut not witli tlie
early synovitis.
Roger^ has found endocarditis an uncommon complication. Out of
2213 cases of scarlet fever (1727 in adults) examined by him, he saw
but 2 cases of endocarditis. On the other hand, he noted extracardial
murmurs 002 times.
McCollom,^ in an analysis of 1000 cases of scarlet fever, says: "A
mitral systolic murmur was detected in 187 cases; bruit de (jatop in 5
cases; irrcfj^nlar action of the heart in 54 cases; endocarditis in '> and
pericarditis in 5 cases." Many of the murmurs referred to were thought
to be due to lack of tonicity of the heart muscle as a result of the action
of the scarlatinal poison.
Von Jiirgensen expresses the opinion that endocarditis of the cardiac
wall is more common in scarlet fever than valvular involvement. He
further believes that tliis mural endocarditis may slowly extend to the
valves after the attack of scarlet fever is over.
Pericarditis. — Pericarditis occurs from time to time in the course of
scarlet fever, being much more common in association with nephritis,
synovitis, and pyemia than with cases of simple scarlatina. Roger
has observed cases of dry pericarditis, both at the height of the disease
and during convalescence.
In pyaemia endocarditis and pericarditis are commonly present; the
exudate in the latter affection in such cases may be purulent. Roger
saw a child, aged eight years, with a severe scarlet fever complicated
by a purulent otitis media, die on the forty-seventh day of the disease.
At autopsy the pericardium was covered with a false membrane; there
was an ulcerative endocarditis and an abscess in the wall of the left
ventricle. The streptococcus was recovered from these lesions.
In our own experience severe cases of endocarditis have been rare,
and, w^hen present, have been accompanied by joint involvement. We
recall a twelve-year-old boy who during the third week of scarlet fever
had articular swellings which recurred from time to time for several
weeks. He also had a well-marked albuminuria. This patient developed
at a later period an endocarditis which severely damaged the mitral
valve; he subsequently exhibited a presystolic murmur with a pro-
nounced thrill over the mitral region. The murmur had a peculiar
crowing sound of a musical character. After undue exertion he devel-
oped a sudden dilatation of the heart with rapid pulse and a change
in the character of the murmur which now became blowing. He was
tided over this crisis, but a few weeks later he again developed a cardiac
dilatation and died. A rather unusual symptom in this patient was a
geographic erythema which appeared over the trunk from time to time,
recurring apparently with fresh joint involvement and then gradually
fading away.
In another fatal case we observed a vegetative endocarditis attack-
ing the mitral and aortic valves, associated with pleurisy, joint swelUngs,
and extensive purpura.
1 Loc. cit., p. 941. ' Scarlatina, Medical and Surgical Reports, Boston City Hospital, 1899.
408
SCARLET FEVER
Lymphatic Glands. — A generalized enlargement of the lymph glands
constitutes a part of the normal symptomatology of scarlet fever. The
subcutaneous lymph nodes in all parts of the body undergo some hyper-
plasia, but those situated in the neighborhood of the facial orifices
undergo the greatest tumefaction. That this primary lymphatic involve-
ment is due to the scarlatinal toxin is evidenced by the fact that the
lymphoid elements of the spleen, liver, and intestines become likewise
hyperplastic.
It is only when the lymph glands become excessively enlarged or
undergo suppuration that a complication is added that augments the
danger of the disease.
The most aggravated cases of lymphadenitis occur in association with
the anginose variety of scarlet fever.
Greatly swollen and suppurating maxillary glands.
In these cases the glands at the angle of the jaw undergo rapid enlarge-
ment, causing the head to be thrown backward. This complication
increases the suffering and danger of the child, who by this time is
already prostrated by the poison from a sloughy throat and discharging
ears and nose. The temperature is high, the nervous system markedly
disturbed, and death imminent.
By the fifth or sixth day of the disease the maxillary glands may
already have attained the size of small apples. They are hard at first,
but gradually break down and suppurate.
In cases of scarlet fever of less severity, but accompanied by pro-
nounced angina, it is not at all rare for the glands at the angle of the
THE (!(>MrfJC'A7'ff)NS OF SCAUfJ'/J' F/'JV/er ct.
Between 1 and 2 years . . 107 " 5 cases 4.6 "
" 2 " 3 " . . 106 " 12 " 11.3
" 3 " 4 " . . 79 " IC " 20.2 "
" 4 " 5 " . . 80 '• 20 " 23.2
" 5 " " . . 89 " 18 " 21.9
After 6 " . . 300 " 60 " .... . 16.6
While severe cases of scarlet fever are more apt to be followed by
nephritis than mild cases, it is impossible in any individual instance
to prophesy the development or the non-occurrence of this complication,
because the scarlatinal attack may be severe or mild. There appears
to be something in the individual make-up which predisposes one
toward or protects one against a complicating nephritis. Doubtless
each individual has certain organs or tissues whi^ch are more vulnerable
to the noxious influence of the scarlatinal poison than others.
The opinion formerly held, that "catching cold" plays any important
role in the etiology of nephritis complicating scarlatina, is being dis-
credited by most writers on the subject.
Symptoms of Nephritis. — In some patients albumin appears in
the urine for the first time during convalescence ; in other cases albumin-
uria is a reawakening of the nephritic process that manifested itself
early during the acute stage of the disease.
The nephritis with its accompanying symptoms of intoxication
ordinarily comes on insidiously, although in some instances it may
explode with alarming suddenness. The development of albuminuria
is accompanied, or often preceded, by a rise of temperature. A febrile
elevation in the third week of scarlet fever will commonly be found to
be due to nephritis. The character and duration of the fever are
extremely variable. It may persist for a number of days or may drop
to normal at the end of forty-eight or seventy-two hours. The tem-
perature often exhibits striking irregularities, dropping to normal and
suddenly rising again. Ordinarily the pyrexia is moderate in intensity,
but it may rise to great height. We have seen a temperature of 106f ° F.
414
SCARLET FEVER
accompanying a moderate albuminuria which appeared on the twenty-
third day of the disease and disappeared on the twenty-sixth day (Fig.
73). In severe nephritis fever may persist throughout the duration of
this compHcation. In some cases no fever is noted whatsoever.
Before the appearance of the albumin, there is not infrequently noted
a considerable increase in the quantity of the urine voided. As a result
of this polyuria urination is frequent and may wake the patient from
his sleep at night.
Most writers refer to pain in the back as one of the early symptoms
of scarlatinal nephritis; this lumbar pain cannot be frequent or severe,
at least in children, for it is most rare to hear a complaint in reference
thereto. Haematuria may be one of the early symptoms to direct atten-
tion to the kidneys.
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Scarlet fever. F. O., aged six years. Chart showing pronounced rise of temperature coincident
with the onset of albuminuria. Albumin was first found on the twenty-third day.
One of the most characteristic features of scarlatinal nephritis is the
marked pallor of the countenance, with puffiness of the eyelids. In walk-
ing through a scarlet-fever ward one may frequently pick out the
nephritic patients by noting this appearance. GEdema is a particularly
common symptom in scarlatinal nephritis. A peculiarity of this com-
plication is the tendency to rapid anasarca. This appears to be much
more common in the nephritis of scarlatina than in ordinary Bright's
disease. In explanation of this it is stated that the oedema is due not
alone to the condition of the kidneys, but also to changes in the lymphatics
and bloodvessels of the skin.
The anasarca is accompanied by a pale or alabaster-like appearance
of the skin. The swelhng usually begins about the eyelids and the
ankles, but later the legs, genitalia, and lower portion of the abdomen
become affected. In severe cases the entire body may be attacked.
A thin and poorly nourished child may become rapidly metamorphosed
TIII<: C()M/'fJCATfON,S OF SCAUfJ'JT h'EVHIt 41 5
into a plump child within a few hours, as a result of the axlematous
infiltration. Anasarca, according to Troijsscau, is met with in cases
of medium severity, rather than those of the most serious forms of
scarlatina. Its frc(|U(nicy varies !^vv;\\\y in difrcrent epidemics. Barthez
and llilliet observed anasarca in one-fifth of their (;ases. Some writers
have stated that nearly all of their cases were dropsical. Among the
150 cases of scarlet fever referred to above, we did not see a single
instance of anasarca, although UMlema of the face was not an uncommon
symptom.
Anasarca may affect deej) seated structures or the serous cavities.
The fluid may hll up the peritoneal cavity, giving rise to a pronounced
ascites, or the pleural or pericardial sacs may be similarly infiltrated.
The soft palate, uvula, epiglottis and arytenoepiglottidean ligaments
are more rarely attacked, in the latter case giving rise to o'dema of the
glottis. In such cases intubation or tracheotomy may have to be per-
formed to prevent suffocation.
(Edema of the lungs and brain are extremely apt to be present in
cases that terminate unfavorably.
Anasarca may be present in rare cases without all)umin being found
in the urine. This does not indicate that nephritis is not present, for
ursemic symptoms may burst forth suddenly and with great intensity.
Henoch reports the case of a twelve-year old child admitted to the
hospital with oedema of the face and scrotum following scarlet fever.
The urine was scanty, but contained neither albumin nor nephritic
elements. Two days later convulsions occurred and three days after-
ward the child died.
The Condition of the Urine. — In the so-called febrile albuminuria,
the urine contains albumin for a day or two, after which it disappears,
perhaps to reappear at the end of the third week. Microscopic exami-
nation reveals the presence of cylindroids and occasionally a few hyaline
or epithelial casts. Not infrequently red and white blood corpuscles
are present. A cloudiness is often seen in the urine, which is due to
the presence of mucus resulting from the presence of degenerated
epithelium. With the advent of the true scarlatinal nephritis the urine,
as a rule, begins to decrease in quantity, although exceptionally there
may be for a short time an increased secretion. The urine becomes
quite concentrated and contains an abundance of urates, which give
a pronounced ring with the nitric acid test. Albumin is found at first
in small quantity, but later in larger amount. In bad cases it may
constitute half by bulk with the heat test or, indeed, there may be
complete coagulation of the urine. At this time hemorrhage from the
parenchyma of the kidney may take place, causing the urine to look
brownish-red and smoky. Under the microscope will be seen red
blood corpuscles, cylindroids, epithelial detritus, and hyaline, epithelial,
fatty, and blood casts.
When there is much blood present it will settle as a deep red collection
at the bottom of the urine glass. The amount of albumin is corre-
spondingly increased with an augmentation in the quantity of blood.
416 SCARLET FEVER
Exceptionally albumin may be absent for a number of days, although
casts are present; on the other hand, a considerable quantity of albumin
may be present without urinary casts being found.
The specific gravity varies greatly according to the amount of urine
passed. It may be as low as 1004, or as high as 1040 or more; ordinarily
it will be between 1020 and 1035. The amount of urine secreted pro-
gressively diminishes in severe cases, and there may be complete sup-
pression for a period of twenty-four hours or longer. Cases in which
this occurs usually succumb.
The reaction of the urine is almost invariably acid. The quantity
of urea excreted varies with the amount of urine, but is usually under
2 per cent.
When dropsy occurs the urine is extremely scanty, high colored, of
high specific gravity, and contains an abundance of albumin and casts.
It is not at all uncommon for the albumin to disappear every now
and then from the urine, only to reappear in a few days. We have
frequently noted this irregularity in scarlatinal albuminuria. In certain
cases the albumin appears intermittently in the urine. At other times
it is absent at certain periods of the day; this peculiarity has been
observed in a considerable number of patients in certain epidemics.
This occurs independently of those cases in which albumin is absent
while the patient remains in a recumbent position, but reappears when a
sitting or standing position is assumed.
These observations make it a matter of importance to carefully
examine the urine at frequent intervals. If an examination is made
only from time to time, albumin which is intermittently absent or which
disappears at a certain time of the day may be completely overlooked.
It is a good plan to examine the urine every other day up to the fifteenth
day of the disease and then to make daily analyses. The urine should
be examined both for albumin and microscopically, and the amount
passed and the specific gravity should be ascertained. With the use
of very delicate tests small quantities of albumin will doiibtless be
found which are not recognizable by the usual tests employed. For
practical purposes, however, the nitric acid or heat test will suffice.
In cases that tend toward recovery the urine increases in quantity,
the blood and casts disappear, and the albumin gradually diminishes.
In our experience the urine in scarlet fever has given a positive
diazo reaction in about 25 per cent, of the cases examined. This reaction
has little or no diagnostic value.
Aubertain^ and Roger have each reported cases of scarlatinal albumin-
uria in which albumin was absent in the mornings while the patient
remained in bed, but would appear soon after the patient stood upon
his feet. Ten minutes' standing posture in one case would produce an
albuminuria lasting about two hours. Exercise in the horizontal position
failed to excite the presence of albumin. In some of these cases of
orthostatic albuminuria a gradual cure takes place; others eventuate
in a permanent albuminuria.
1 L'Albuminurie orthostatique au cours de la nephrite scarlatinense. La presse m6d., 1901.
TIIK COMPfJCA T/ONS OF SCA HI.KT Fh'VPJfi 41 7
In some cases of severe nephritis, particularly when the urine becomes
greatly reduced in cjuantity, symptoms of uramia are prone to develof).
These usually come on gradually after distinct evidences of kidney
involvement, although tliis is not invariably the case. Indeerl, uncmia
may, in rare cases, supervene without the previous existence of albumin-
uria. Henoch reports such a case; on the twelfth day of scarlatina, in
a four-year-old child, intense right-sided convulsions and stupor devel-
oped; examination of the urine on the previous day had failed to show
albumin. The patient was catheterized on the development of the
symptoms, and a considerable quantity of albumin was then found.
Ordinarily the first symptoms in a patient about to develop uraemia
are vomiting and, at times, diarrhoea. This is doubtless an effort on
the part of nature to eliminate some of the retained poisons through
these channels. Leichtenstern claims that one of the most frequent
modes of onset of scarlatinal uraemia is the development of pronounced
dyspnoea associated with rapid heart action. There is usually some
elevation of temperature, which, in bad cases, may become excessive
and reach 106° or 107° F. But the symptoms referable to the nervous
system dominate the clinical picture. There are frecjuently intense
headache, tinnitus aurium, and somnolence or stupor, with occasionally
sudden loss of vision. These symptoms are rapidly followed by con-
vulsions. The convulsive movements may be partial, that is, limited
to one set of muscles, as those about the jaws, in which event there
may be a tonic contraction; in other instances they are unilateral or
general, affecting the entire body. When the convulsions are limited
to certain sets of muscles consciousness is usually preserved, but when
there is a general epileptiform seizure it is followed by coma, at least
for a time. The convulsive attacks may be of brief duration, lasting
but a few minutes, or they may persist for an hour or more. There may
be a single seizure, although more commonly there is a succession of
convulsions upon the same or successive days.
When the convulsions are severe and protracted, death may result
from exhaustion, cerebral hemorrhage, or oedema of the lungs. In
other cases a fatal termination comes on later, the patient lapsing into
a progressively deepening coma. In some cases a gradual oncoming
stupor may be the only pronounced symptom of urremia.
In favorable cases the convulsions cease, the stupor disappears, the
urine increases in quantity, and the patient emerges from the crisis.
The amaurosis which develops from time to time in uraemia usually
disappears when the convulsions cease, but the blindness may continue
for several weeks, ultimately ending in complete recovery. In some
cases aphasia and hemiplegia may develop during uraemic conMalsions
and disappear when convalescence is established.
In rare instances patients may become maniacal after ursemic attacks.
Wagner^ saw a patient who had eleven convulsive seizures, each one
being followed by the wildest mania; although the temperature registered
107.6° F., the patient recovered.
1 Quoted bv von Jiirgensen, loc. cit.
27
418 SCARLET FEVER
Melancholia may also develop as a sequel of uraemia.
If the urine now increases in quantity, there is but little likelihood
of a recurrence of the severe nervous manifestations. The abnormal
urinary constituents gradually disappear from the urine and the patient
is entirely restored to health.
Prognosis. — The prognosis of scarlatinal nephritis is much more
favorable, both as to life and to functional restoration of the kidneys,
than would be expected from the nature of the symptoms. The vast
majority of patients recover from the nephritic attack, even where
alarming urtemic phenomena have been present. Intense and un-
remitting headache, protracted convulsions, repeated vomiting, and
coma are symptoms of bad omen. The quantity of albumin in the
urine is no reliable guide, as a severe nephritis may exist with but
little albumin in the urine, and the converse may also be true. The
number and character of the casts and particularly the quantity of the
urine are more important criteria. Suppression of urine renders the
situation extremely grave, although recovery may take place if diuresis
can again be established.
The opinion has prevailed for a long time that scarlatinal nephritis
was but seldom followed by chronic Bright's disease. While it is
fortunately true that restitutio ad integrum usually takes place, it is
nevertheless certain that the number of cases of permanent nephritis
following scarlatina has been much underestimated.
We had at the Municipal Hospital, during the winter of 1902, a girl,
aged eight years, who was brought in with a well-marked case of scar-
latina from a hospital where she was being treated for a nephritis said
to date from an attack of scarlet fever five years previously. She had
bloody urine for some days, but made a good recovery from the scarlatina
and left the hospital many weeks later still suffering from a chronic
nephritis.
Aufrecht^ reports a case of nephritis after scarlet fever lasting twenty
years, and terminating in a contracted kidney. Leyden, Litten, Forch-
heimer, and others have reported cases eventuating in chronic Bright's
disease. Holt says that he formerly believed such results rare, but
larger experience has convinced him that this sequel is not uncommon.
Of 77 cases of scarlatinal nephritis occurring in the Southwestern
Hospital of London, in 1892, 6 cases, according to Caiger, were dis-
charged with chronic albuminuria after a prolonged residence.
If delicate tests for albumin were employed and careful microscopic
examination of the urinary sediment were uniformly made for months
after attacks of scarlatina, it would doubtless be found that a larger
proportion of cases eventuate in chronic nephritis than has been
supposed.
Many of these patients have structurally damaged kidneys, which at
some future period, as a result of a variety of causes, may be reawakened
into activity. The practical lesson to be borne in mind is that the
urine of patients convalescent from scarlatinal nephritis should be
1 Deutsche ArchiT f. klin. Med., Leipzig, 1887, Bd. xlii. p. 517.
77//'; aOMr/JCAT/ONS OF SdAlilJ'lT FKVMIl 419
carefully exarniiHul froin lime to time, and tlie did. and uuAc fjf life
rcn;ulat('(l accord inoly.
Scarlatinal Rheumatism (Synovitis Scarlatinosa^. — In tlic absence
of conclusive evidence that acute articular rheumatism is a specific
tnorhid process due always to the same infectious a{2;ency, we are justified
iu adlieriuf^ to the old term "scarlatinal rlieumatism." 'J'he attemy)t tf)
distiiifijuish lu'tween a scarlatinal synovitis and a coini)licatin[( rh(;niiia-
tism is scarcely warranted by our present knowledge of the subject.
Synovitis and arthritis occurring in the course of scarlet fever are
frequently associated with other phenomena, such as endocarditis,
pericarditis, pleurisy, etc., which are common rheumatic coniphca-
tions.
The frequency of joint involvement in scarlatina appears to vary in
different countries and in different epidemics. Trousseau says: "By
minute interrogation, and by carefully examining and applying a certain
degree of pressure to the joints, articular pains are found to be present
in about one-third of the cases (of scarlatina). It is important to know
this; for acute affections of the joints, general arthritis, pericarditis, and
endocarditis frequently occur during the course of the disease."
Ashby observed synovitis to occur 20 times among 900 cases of
scarlet fever. Koren,^ of Christiana, noted scarlatinal synovitis of a
mild type 27 times in 426 cases (6.3 per cent.) of scarlet fever in
the epidemic of 1875-77.
Vogl appears to have observed an unusually large number of cases
of joint complications in scarlatina. He is authority for the statement
that articular involvement occurred in 13.6 per cent, of the cases in the
epidemic of 1884-85, and in 10.6 per cent, in 1894-95.
Hodger^ saw 217 instances of scarlatinal synovitis among 3000 cases
of scarlet fever, or 3.2 per cent.
It is seen from the above figures that the frequency of this com-
pHcation varies from about 3 to 13 in 100 cases. Our personal
experience would lead us to regard the first figure (3 per cent.) as
representing more nearly the average incidence of this complica-
tion.
Two forms of joint involvement are recognized — a simple serous
synovitis and a purulent or suppurative arthritis. The mild form is
fortunately far more common than the suppurative variety. Articular
involvement may occur at any period of the disease, but is most common
during the stage of desquamation in the second or third week of the
disease. The wrists and fingers are the joints most often attacked,
although the ankles and toes not infrequently participate in the process.
Sometimes the larger joints, such as the shoulders and knees, become
involved. The usual symptoms are pain, stift'ness, and swelling.
Redness may or may not be present. Trousseau states that scarlatinal
rheumatism is usually mild and of short duration, is commonly localized,
and when it disappears does not tend to return. We have seen cases
1 See Johannsen, loc. cit., p. 195.
- See Eichhorst's Spec. Pathol, und Therapie, Leipzig, 1897, p. 241 .
420 SCARLET FEVER
in which there were periods of disappearance and of recurrent involve-
ment. Scarlatinal rheumatism is frequently, although not always,
attended with a rise of temperature which commonly reaches 101°
or 102° F.
In mild cases the articular inflammation subsides in the course of
three to five days. In more severe cases it may last for weeks.
Suppurative Arthritis. — Suppurative arthritis is a rare complication of
scarlet fever, and usually occurs late in the course of the disease. The
joint becomes painful, swollen, hot, and reddened; the fever is high, the
patient prostrated, and all of the usual symptoms of pyaemia are present.
One or several articulations may be involved. In the vast majority of
cases a fatal termination supervenes. In rare instances, through surgical
intervention, or even at times without, recovery takes place after a long
and tedious illness, but with serious impairment of the functional
activity of the joints involved.
We have seen scarlatinal rheumatism associated in one case with a
severe endocarditis and a recurring geographic erythema of the trunk
and extremities, and in another fatal case with endocarditis, pleurisy,
and hemorrhagic purpura.
In persons of scrofulous habit a scarlatinal synovitis may, after a
long course, eventuate in tuberculosis of the joint (white swelling).
In rare cases of scarlet fever the sheaths of tendons may undergo
inflammation (tenosynovitis), which commonly terminates in suppu-
ration. In other cases periarticular abscesses may occur and rupture
into one of the large joints.
Cases of periostitis and ostitis have been reported, involving particu-
larly the petrous portion of the temporal bone, the nasal bones, and the
cervical vertebrae.
Briick^ describes a form of scarlatinal myositis, which attacks most
commonly the lumbar, pectoral, abdominal, and intercostal muscles,
and which is characterized by pain and soreness and moderate rise of
temperature.
Purpura Hemorrhagica. — It is important to distinguish between
true hemorrhagic scarlatina and secondary purpura developing during
the course of the disease. The former condition appears, as a rule, at
the outset, and is characterized by constitutional symptoms of great
intensity and malignancy, associated with hemorrhages into the skin
and from the mucous membranes.
Purpura hemorrhagica comes on usually after the subsidence of the
acute scarlatinal symptoms and not infrequently during convalescence.
Most cases develop during the second or third week, and most commonly
from the fourteenth to the twentieth day. The patient loses appetite,
is apathetic, and may have some rise of temperature. Nose-bleed is
often one of the first symptoms; soon pinhead-sized purpuric spots
appear upon the skin of the trunk, extremities, or face; the gums become
swollen and bleed; the urine contains blood, and hemorrhage may take
1 Petersb. med. Presse, 1896, No. 18.
77//'; aOMPfJCATfO.VS OF SCAIILFT FHVI'Ht
421
place from \\\v. stomach and l)()wcls. A inarkcd pallor srjon fjevelops,
the patient l)(!Conies ])ro.strate(l, and, in seven; eases, d(;atii takes place
from loss (^f hlood, Jieniorrhafre into the brain, or (;xhaustion.
AlhiHTiiiniria is usually j)resent, even when the urine is free of Vjlood.
In mild cases the hemorrhages from the various mucous membranes
cease after a short time, and the patient, although intensely ansemic,
recovers.
These secondiiry purpuras are not seen alone in scarlatina, but in
other infectious diseases, such as influenza, rheumatism, smallpox, etc.
They are probably due to some secondary infection which rlestroys
either the integrity of the blood or the vessel walls. We have seen two
cases of heinorrliagic purpura comj)licating scarlatina.
A three-year-old child, suifering from a well-marked scarlatina,
developed late in the course of the disease swelling of the joints, diffuse
Fir,. 74
Purpura hemorrhagica associated with pleurisy, endocarditis and joint trouble, complicating
scarlet fever. Fatal termination.
ecchymotic patches upon the face, trunk, and extremities, and endo-
carditis. The patient after some days' illness died. Autopsy showed
vegetations upon the mitral and aortic valves, a right-sided pleurisy,
and hemorrhages into the mediastinal and peritoneal cavities.
The second case was a girl, aged eight years, who, upon the seven-
teenth day of a scarlatina of average severity, became apathetic, had
slight rise of temperature, and nose-bleed. The following day, small,
pinpoint petechia appeared upon different parts of the body, bleeding
occurred from the gums, and an abundance of blood was found in the
422 SCARLET FEVER
urine. The bleeding continued for a few days, but ceased under treat-
ment and the patient made a good recovery. A pronounced ansemia
persisted for a few weeks. Albuminuria was present even after the
cessation of hsematuria.
Although this complication is uncommon, a number of cases have
been published. Biss^ reports the case of a boy, aged three and one-
half years, who suffered from a severe attack of scarlet fever compli-
cated by double otitis media. On the nineteenth day after admission
to the hospital he developed an extensive eruption of pinpoint hemor-
rhages over the trunk and limbs, vomited a half-pint of blood, passed a
similar quantity by the bowel, and rapidly succumbed. Autopsy showed
the kidneys to be " transformed almost entirely into fat."
Murray^ saw a two-year-old colored child develop scarlatina after an
operation for hernia. On the ninth day of the attack there occurred
bleeding from the kidneys, bowels, stomach, nose, and gums, and
hemorrhages into the skin and conjunctivae. The red corpuscles
numbered 2,000,000 per cubic centimetre. Urine contained blood and
epithelial and hyaline casts. Death took place on the fourteenth day.
De Boinville^ places on record the case of a boy, aged four and one-
half years, who, on the sixteenth day of scarlet fever, had hemorrhages
from the nose and hemorrhagic spots on the scalp and about the knees.
Although the amount of blood lost was small, the epistaxis could not
be checked and the patient died five days later.
Phillips* reports the case of a girl, aged fourteen years, suffering from
scarlet fever, who had a recurrent rash on the fourteenth day, and
swelling of the joints on the twentieth day; six days later petechial
patches on the chest and legs and free bleeding from the nose, gums,
and kidneys. Patient had albuminuria and acute dilatation of heart,
but recovered.
Gangrene. — Mention has already been made of the sloughing of
the tissues of the neck, which occasionally accompanies cellulitis and
abscesses. The muscles and large bloodvessels of the neck may be
exposed by gangrene of the overlying skin.
Gangrenous stomatitis, or noma, is also seen at times after scarlatina,
although it is much rarer than after measles. Apart from these con-
ditions, a form of spontaneous gangrene is, in rare instances, observed
during the course of scarlatina. When seen, gangrene usually develops
during the second or third week of the disease, and usually attacks the
extremities. In most of the reported cases the condition has been
attributed to embolism. There appear first bluish discoloration, pain,
and coldness, and then hemorrhagic extravasation into the skin. In
some of the reported cases the gangrene was so deep and extensive as
to necessitate amputation of the affected member.
1 Lancet, August 2, 1902, p. 286.
- Case of Scarlet Fever with Purpura, Lancet, February 11, 1893, vol. 1.
3 A Peculiar Case of Scarlatina Hemorrhagica, Lancet, August 9, 1903. This case is evidently a
purpura hemorrhagica, and not one of true hemorrhagic scarlatina.
* Scarlet Fever with Relapse ; Acute Rheumatism and Purpura Hemorrhagica ; Recovery. London
Lancet, 1893, vol. ii.
TIII<: COMPLKIATinXS OP' SCARL/'JT FKVI'Hi 423
. Cases of gangrene have been reported by Blanpain/ Hudson,* Kiister,'
and Chapin/
Wood and Arrigoni'"' ?iave reported oases of gangrene affecting the
genitaha, and Wilson" a case of gangrene of the face occurring three
weeks after convalescence from scarlatina.
Pearson and Littlewood^ rey)ort the case of a boy, aged ff)ur years,
who, after an ordinary scarlet fever, on the eighth day developed small,
hemorrhagic discolorations of the skin of both legs. In a few days
the legs became livid, first upon the feet, thence spreading upward.
The femoral pidsation was lost, the legs became cold, intermittent
pain occurred, and lines of demarcation formed about three inches
above the knees. At the same time slight dilatation of the heart was
discovered. On the twenty-third day of the disease the right leg was
amputated, and, a week after, the left. The patient recovered. Embolic
and thrombotic clots were found in the bloodvessels of the amputated
limbs.
Buchan* reports the case of a boy, aged thirteen years, whose
scarlatinal rash on the second day exhibited a bluish appearance on
the legs. A few days later the veins, especially at the apex of Scarpa's
triangle, stood out quite prominently. Hemorrhages occurred into the
skin of the legs, particularly the right; there were also hsematuria,
nose-bleed, and ha?moptysis. The lower part of the right leg became
mummified and a definite line of demarcation formed just above the
knee, where an amputation was performed. The patient made a rapid
recovery.
We recall a child treated in the Municipal Hospital in 1900, who
developed gangrene about the third week of a severe scarlatina. Ecchy-
motic patches developed upon the leg, followed by rather superficial
sphacelation of the tissues. A few days later one hand became blue
and cold, and shortly after this the other hand became similarly affected.
The radial pulse was lost and both hands assumed an indigo-blue
color. Before actual gangrene could take place the child, who was
greatly prostrated, died. The gangrene in this case was doubtless due
to embolism (Fig. 75 j.
Skin Complications. — Reference has already been made to the
various abnormalities of the rash of scarlet fever, including an excessive
development of miliary vesicles. It remains to discuss the occasional
complicating skin disorders which are quite apart from' the scarlatinal
process.
1 Scarlatine ; gangrene spontaneti des membres ; embolies ; autopsie. Aroh. Med. Beiges, Brux.,
1869, 2, ix. pp. 324-334.
- Scarlatina Resulting in Mortification of the Right Limb, and Sacceesful Amputation. Transac-
tions of the Ohio Medical Society, 1858.
^ Spontan. Gangran des Unter-schenkels nach scarlatina: Ampntatio Femoris : Tod., KasECl,
1876 and 1878.
* An Unusual Result of Scarlet Fever; Embolus; Gangrene : Amputation. Medical Age, Detroit,
1884, xi. p. 205.
* Quoted by Thomas. ^ Reviewed in Archiv f. Kinderheilk., 1?98, p. 418.
7 Dry Gangrene of Both Legs ; Double Amputation, 1897, 11, p. 84.
8 Lancet, October 5, 1901, p. 915.
424 SCARLET FEVER
Febrile herpes occurs every now and then during the invasive stage
of the disease. The patches develop usually about the mouth, although
they may be situated about the cheeks or ears. While herpes is not
very frequent in scarlet fever it is more commonly seen than in smallpox
or measles.
Urticaria is not an infrequent accompaniment of scarlet fever, although
it cannot be considered as bearing any special relation to the disease.
It may be seen early or late in the course of the illness, and is usually
neither extensive nor protracted. This complication is doubtless due
to the presence in the blood of some accidental toxin or drug.
Blehs may occasionally develop upon the skin as a result of a coa-
lescence of neighboring miliary vesicles in intense rashes. Thomas says
that they may reach the size of hazel-nuts. Bullae may also occur upon
patches which are destined to terminate in gangrene of the skin. Some
Pig. 75
Gangrene of the skin complicating scarlet fever. Patient developed gangrene of
both hands and died.
authors speak of the occurrence of pemphigus, particularly in certain
epidemics. These are, in all probability, not true instances of pemphigus,
but of bullous dermatitis of septic origin.
We have occasionally seen cases of localized necrosis of the skin in
small areas, a condition analogous to the so-called varicella gangrsenosa,
but better designated dermatitis gangranosa. Fig 76 shows this condi-
tion upon the knees of a young boy.
Eczema may occur as a complication of scarlatina, but is more apt
to develop as a sequel. Intense desquamation may leave the skin dry,
harsh, and fissured, and the seat of eczematoid patches; these may
persist for some time after convalescence. In other cases a purulent
discharge from the ears or nose may give rise to an impetiginous eczema
in the region of these orifices ; the skin becomes moist and covered with
crusts as the result of the irritating and infective discharges.
77//'; aOMI'LICATIONS OF SCA.'i'fJ'JT FFVI-'Ji 425
Cutaneous ahscas.sr.s- may occur iijxjii any portion of ttx; integument.
This compliciition is iincoinmoii, usually occurrinj^ in scplic cases. We
recall an adult })alicnt in whom a, larletely d(;generated.
Respiratory Organs. — The larynx may become involved as a result
of a secondary diphtheria or a membranous inflammation of strepto-
coccic origin, although the latter is much rarer than in measles. CP^Jema
of the glottis results at times from extension of inflammation, and on
other occasions from nephritis.
Perichondritis of the larynx is a rare and fatal complication. Accord-
ing to Kraus^ it occurs about once in 200 to 250 cases of scarlatina.
Rauchfuss saw 4 cases among 903 cases of scarlatina, and Leichtenstern
2 cases among 467 patients. Its development may necessitate the
performance of intubation or tracheotomy.
Pulmonary complications are much less common in scarlatina than in
measles. The bronchial tubes and lungs, are nevertheless, according to
Henoch, much more frequently involved in bad cases than is generally
believed. These lesions are masked by the severe constitutional symp-
toms, and are often not discovered until autopsy. In a series of 98 fatal
cases of scarlatina, reported by McCollom,^ 15 were due to broncho-
pneumonia.
As would naturally be expected, pulmonary complications are com-
moner in infants than in older children and adults. Roger^ gives the
following morbidity and mortality statistics of pulmonary complications
in scarlatina according to age:
Scarlatina. No. of patients. Cases of pneumonia. Mortality.
First infancy ... 56 6 (10.7 per ct.) 5 (8.9 per ct).
Childhood ... 430 6 (1.3 per ct.) 2 (0.4 per ct.).
Adults .... 1727 4 (0.2 per ct.) 3 (0.1 per ct.).
All of the pneumonias in the infants were bronchopneumonias.
Four of the children of the second group had bronchopneumon'a, and
two had apical pneumonia. Bronchopneumonia occurred in two adults.
Bronchopneumonia in severe cases appears usually during the first
or second week. Henoch remarks: "We found bronchitis and broncho-
pneumonia in nearly all the severe cases and also repeatedlv during
life."
Lobar Pneumonia. — Lobar pneumonia may develop dur ng the
height of the disease, or more commonly after nephritis has manifested
itself. The upper lobes are more often affected than other parts of
the lungs.
(Edema of the Lungs. — CEdema of the lungs is by no means a rare
complication when the kidneys are severely affected and a general
dropsy exists. Serous transudation into the lungs may occur rapidly
and lead to sudden death.
Involvement of the pleural cavities in scarlatina is uncommon.
1 Prag. med. Wochenschr., 1899, pp. 29 and 30.
- Quoted by Corlett, loc. cit. s Loc. cit, p. 9?3.
428 SCARLET FEVER
Pleurisy may develop in association with a lobar pneumonia or it may
occur independently thereof. The process may be dry or accompanied
by serous or purulent exudate; scarlatinal pleurisies show a pronounced
tendency to eventuate in empyema, a complication which adds much
gravity to the disease. However, desperate cases may at times terminate
favorably, as is evidenced in a remarkable case of Trousseau, who
drew off from the chest of a fourteen-year old girl 750 grams of pus,
the patient making a complete recovery.
Thomas says all forms of scarlatinal pleurisy are characterized by
rapid development and by but slight local disturbance, even when
the affection is very intense. The effusion is usually present only upon
one side.
Pleural involvement is more frequent in cases complicated by nephritis.
It is especially apt to accompany scarlatinal rheumatism. We have
already referred to a patient treated in the Municipal Hospital, who had
purpura, endocarditis, synovitis, and a fibrinous pleurisy.
Farb ringer regards exudative pleurisy as a frequent complication,
occurring, in his experience, in 5 per cent, of cases of scarlatina. Johan-
nesen, of Norway, found, among 688 deaths from scarlet fever, but
3 that resulted from pleurisy.
Nervous System. — While the onset of scarlatina is attended in severe
cases by pronounced nervous symptoms, these subside if the course is
favorable, and do not add to the gravity of the disease. The early
cerebral manifestations are in part due to the scarlatinal poison and
in part to the high fever. Headache and dehrium may be present in
ordinary cases, but convulsions and coma presage an attack of great
severity.
Later in the disease severe nervous symptoms, such as delirium,
convulsions, coma, sudden blindness, etc., may develop as a result
of uraemia.
Hemiplegia. — Hemiplegia may occur early from a cerebral hemor-
rhage during the invasive convulsions, or it may come on at a later date
as the result of embolism. Taylor^ reports a right hemiplegia resulting
from embolism of the middle cerebral artery; the patient succumbed
later to diphtheria.
Addy^ saw a case of partial hemiplegia with amnesia after scarlatina.
Meningitis. — Meningitis usually results from extension of inflam-
mation and infection from the middle ear or the nasal sinuses. We
have already referred to a case of purulent meningitis of the base of
the cerebellum which we observed after a purulent otitis media. Roger^
saw a twenty-three-year-old man in whom a severe purulent rhinitis
complicating scarlatina was followed by meningitis. At autopsy the
left frontal lobe of the brain was covered with purulent plaques and
the left sphenoidal sinus contained pus. The presence of the strepto-
coccus in pure culture was demonstrated. Similar cases have been
1 Medical Times and Gazette, London, 18S0, ii. p. 686.
2 Glasgow Medical Journal, 1880-85, S. xiii. pp. 463-465.
3 Loc.cit., p. 850.
77//'; COMI'fJdATIONH OF SCARI.F/I' FFVKR 429
reported by other observers. Jiaudelocque' reports a case of meningo-
encepliiilitis characterized by headache, vomiting, and convulsions,
followed by coina and the loss of speech, hearing, and sight. Althous^
reports a case of spinal meningitis with consecutive lateral and pos-
terior sclerosis.
Incomplete Paraplegia. — Cases of incomplete paraplegia have been
described by Dcinange,'' Roger, and others. Roger says that among
22b'3 patients with scarlatina 4 cases of incomplete paraplegia were
observed. Three women liad for al)Out a week great difficulty in
standing up or walking. The fourth patient was a man who on the
second day of the disease had paralysis of the soft palate. Later the
two legs and the right arm became affected ; the palsy passerl off in ten
days. Cultures from the throat excluded the possibiHty of diphtherial
infection.
As has already been stated, facial palsy occurs occasionally from
involvement of the facial nerve in the bony roof of the ihiddle ear.
Insanity. — Insanity has been reported as a complication and sequel
of scarlatina. The mental aberration is usually temporary, but may in
some cases persist after convalescence. Mitchell,* Rabuske, and Wagner
have each reported attacks of acute mania in scarlet fever, the mania
in the last-named case following ursemic convuls ons.
Carrieu'' records a case of dementia and Brill a case of scarlatinal
insanity with epilepsy. Wildermuth," in a report of 1S7 cases of epilepsy,
states that 12 cases followed attacks of scarlet fever.
Multiple Neuritis. — Egis^ reports a case of multiple neuritis following
scarlatina in which there was an ataxic gait and paralysis of both
peroneal nerves. But two other cases of multiple neuritis could be
found in literature.
Tetany. — Steffen^ reports a case of tetany in a young girl suffering
from scarlatina; an attack was noticed after each bath. Kiihn-Ulsar^
mentions a case of tetany in a boy, aged four and one-half years, suffering
from scarlet fever. For six weeks muscular spasms and stiffness were
noted, at times limited in extent and at other times general. Trismus
was present for fourteen days. The patient gradually recovered.
Bones. — Necrosis of the petrous portion of the temporal bone and of
the ear ossicles occurs in severe cases of purulent otitis media. Necrosis
of* other bones sometimes takes place. Brown^° reports a case of necrosis
of the lower maxilla after scarlet fever, and Weickert^^ reports a case
in which both jaws were thus affected.
Neumark^^ reports 30 cases of acute infectious osteomyelitis, of which
5 follow^ed scarlet fever.
1 Gaz. des. hop. de Paris, 1887, xi. pp. 197-199. = Brit. Med. Journal, 1S81, i. p. 50.
3 Bull. Soc. anat. de Paris, 1874, pp. 503-9.
< Edinburgh IMedical Journal, 1881-82, xxvii. pp. 721-24.
6 New England Medical Monthly, 1882-83, ii. pp. 55-58. « Quoted by Holt, loc. cit.
' Archiv f. Kinderheilk., 1900, sxviii. s Jacobi's Festschrift, 1900, p. 83.
9 Berliner klin. Wocheuschrift, 1899, No. 39, p. 855.
10 London Lancet, 1844, i. p. 220.
1' Deutsche Klinik, Berlin, 1854, vi.j). 22. i= Archiv f. Kinderheilk.. Bd. xxii.
430 SCARLET FEVER
Sequelae. — But few words will be devoted to the sequelae of scarlatina,
as they represent merely a continuation of the complications or dis-
abilities resulting from structural damage.
A weakened and anaemic state of the system may develop after
scarlatina as after many other infectious diseases; the patient is thus
lowered in resisting power and rendered more susceptible to the other
infectious diseases. There is, however, no such increased susceptibility
to tuberculosis as exists in patients recovering from measles.
The various organs of sense may bear for a long time and in some
cases forever the marks of a cruel scarlatinal attack. The mucous
membrane of the eyes, throat, and nose may show persistent pathological
alteration.
It is the ears, however, that most frequently exhibit permanent
damage. It is largely because of injury to the sense of hearing that
scarlatina is so feared by the laity. A chronic purulent otitis media
-may persist after scarlatina and lead at a remote date to mastoid or
intracranial disease. Destructive changes involving the middle ear
and the contained ossicles may cause auditory disability, varying in
degree from slight impairment of hearing to complete deafness. When
this occurs very early in life the loss of this sense may lead to deaf-
mutism.
As has already been suggested, the damage to the kidneys is often
more than a transitory one. In a certain proportion of cases albuminuria
will persist and eventuate in a chronic Bright's disease. In other cases
the kidneys are functionally normal, but are rendered more susceptible
to subsequent burdens or infections.
Various cutaneous diseases, such as furuncles, eczema, etc., may
follow in the wake of scarlatina.
Reference has already been m4de to certain psychic disturbances,
such as mania and melancholia, which may persist after scarlatina.
Chorea. — Chorea may develop a few months after convalescence is
established. This sequel is not of great frequency. Carlslaw reports
only 3 cases of chorea following 533 cases of scarlet fever, and Priestley^
13 cases after 5355 attacks of scarlet fever.
THE BACTERIOLOGY OF SCARLET FEVER.
Within the past quarter of a century numerous investigations have
been undertaken to discover the specific cause of scarlet fever. That
the disease is produced by a contagium vivum and that every case of
scarlet fever receives its infection from a previous one are propositions
which command general acquiescence.
The exciting cause of the disease is certainly micro-organismal, but
the identification of the causal parasite is still shrouded in mystery.
As early as 1762, Plenciz,^ of Vienna, attributed the cause of scar-
latina to living corpuscles. Hallier^ in 1869 was one of the first observers
1 British Medical Journal, September, 1897, p. 805.
2 Quoted by Berg6, loo. cit. s Jahrbuch f. Kinderh., N. F., ii., 1868, 1869.
TIII<: liACTKh'IOr/XlY OF SCARIJ'/r F/'JV/'Jk 431
to search for the microscopic cause of the disease. With the crude
magnifying lenses at liis disposal he found a micrococcus in and about
the blood corj)usclcs wliicfi lie ref^arded as the morbific agent of the
disease.
One year later lloilinan examined the sweat of scarlatina patients
and discovered the presence of a micrococcus.
In 1872 Coze and Felt// found in the blood of scarlet-fever patients
bacteria G microns long, which caused the death of nibbits when inocu-
lated.
Riess^ in 1S72 found certain alleged lower forms of life in the blood,
but failed to prove anything by cultures or inoculations.
In 1875 Klebs found, in the substance of an inguinal glanrl of a
patient suffering from scarlet fever, a sphere made up of micrococci
which later changed their form. To this organism he gave the name
"monas scarlatinosum."
Tschamer^ in 1879 claimed that scarlatina was caused by a crypto-
gamic organism, designated by him the "verticillium candelabrum,"
which is foimd upon rotten wood. He regarded this as one stage of
development of the micrococci found by him in the blood cells, scales,
and urine.
In 1882 Eklund* found bodies in the urine of scarlet-fever patients
which he called "plax scindens." He found similar organisms in the
soil, in water, and on mouldy walls. Children living in the vicinity of
such excavated soil were observed to contract scarlatina.
Octerlony observed these same bodies in the blood and urine of
scarlatina patients.
In 1883 Pohl-Pincus^ found cocci in the epidermic scales and also
on the soft palate.
Klamann*^ made similar observations in the same year.
In 1885 Fraenkel and Freudenberg^ isolated a streptococcus from
the liver, kidney, and spleen in three fatal cases of scarlet fever.
Babes found in 18 out of 20 fatal cases of scarlet fever a strepto-
coccus which he regarded as a variety of the streptococcus pyogenes."
Loeffler in 1884 isolated the streptococcus from false membrane in
the throats of scarlatinal patients.
In 1885 Power^ noted a severe epidemic of scarlet fever in London
which began among the patrons of the Hendon farm who were receiving
milk from cows which were suffering from a peculiar disease.
Klein^° investigated the circumstances of the epidemic. He found that
the disease in the cows was transmitted from one to another, and that
1 Recherches cliniques et exporimentelles sur les mal. infect., Paris, 1S72.
- Quoted by Bourges, Les recherches microbiennes dans la scarlatine, Gaz. hebdom. de med. et de
chir., March 28, 1891.
a Centralz. f. Kiuderh., 1878, 1879, ii. * Quoted by Bourges.
' Centrablatt f. die med. Wissen., 1883, xxi. « Allgemeine med. Centralz.. 1SS3, lii.
7 Quoted by Berg6, Pathog(§nie de la scarlatine, Paris, 1895.
s Quoted by Berg6.
9 Milk Scarlatina, Loudon, Report of the Medical Officer of Local Government Board, Febmarv.
1885, 1886.
10 The Etiology of Scarlatina, Proceedings of the Royal Society of London, 1887, xlii.
432 SCARLET FEVER
it began with fever, followed in two or three days by swelling of the
eyes. From the fourth to the sixth day there appeared an erup-
tion, oculonasal catarrh, cough, and rapid breathing. Desquamation
occurred about the third or fourth week, with loss of hair. In severe
cases sore throat and enlargement of the submaxillary glands were
present. On the fifth or sixth days several vesicles appeared upon the
udders, which dried into crusts and fell off about the fifth or sixth
week. Diplococci sometimes arranged as streptococci were found
in these lesions. Klein, in studying the blood of scarlatina patients,
found from the fourth to the sixth day of the disease, in 4 out of 11
cases, a streptococcus of the same character as that obtained from
the Hendon cows. He regarded this as the cause of the disease, and
looked upon the disorder in the cows as bovine scarlatina.
Klein's conclusions were attacked by Duclaux, by C. B. Brown, and
also by Crookshank. Crookshank^ saw an analogous epidemic among
cows in Wiltshire from which no scarlet fever was spread. The disease
was recognized by him as cowpox. Both Crookshank and Thin con-
tended that the streptococcus found by Klein was the ordinary strepto-
coccus of suppuration.
In 1887, Edington,^ working with Jamieson, isolated from the scales
and blood of scarlet-fever patients a bacillus which he regarded as the
cause of the disease. The organism was quite uniformly found in the
blood after the third day and in the scales after three weeks. This
so-called bacillus scarlatinse was motile, grew in long threads, and
fluidified gelatin. Inoculations of rabbits and guinea-pigs produced
fever and an erythema followed by desquamation.
Brown later demonstrated this bacillus in the scales of ordinary
dermatitis. A committee of the Medico-Chirurgical Society of Edin-
burgh investigated the claims of Jamieson and Edington, and was
able to find the bacillus in but 3 of 10 cases of scarlet fever; of nine
blood cultures results were obtained in four; cultures from scales were
negative and inoculation experiments were without result.
In 1889 Madame Raskin' read before the St. Petersburg Congress a
communication in which she described a peculiar micrococcus which
was found in the blood cells at the beginning of scarlet fever. It was
likewise discoverable in the internal organs, skin, and mouth at autopsy.
It killed rabbits and guinea-pigs, but did not induce symptoms of
scarlet fever.
In 1893, Fiessinger^ announced his belief that the streptococcus was
the cause of scarlet fever.
Dowson^ in the same year expressed the opinion that scarlet fever
was due to the streptococcus and that the tonsil was the seat of the
primary infection.
This assumption was later championed by Berge and by Eemoine.
1 Communication to thie Pathological Society of London, 1887.
2 Jamieson and Edington, British Medical Journal, 1887, i.
3 Centralblatt f. Bakt. u. Parasit., 1889, v. •• Semaine m^d., July, 1893.
6 Med. Chron., Manchester, 1893, 1894, xix. p. 217.
77//'; HAdTFjaoinaY of hcaulht f/':vi':r 433
Bergd/ in a l)rocliurc pul)li.she(l in 1S95, disfMisses at length the njitiire
of scarlet fever and fonnnlates the following conclu.sions:
1. Ordinary scarlatina is a local infection of the tonsils. The scarla-
tinal enij)tion (exiuithern and enjinthem) is the resnlt of a toxic erytheni-
agenic action of tlie inicrohic poisons secreted in the infeftterl tonsils.
2. An imposing array of evidence points to the strc})tococcns in one
of its virulent forms as the pathogenic agent of the disease.
Lemoine^ in ISOf) likewise affirmed his belief that the streptococcus
bore an etiological relationship to scarlet fever, and that the point r)f
entrance of the germs was the throat.
Class'* in 1S07 described a diplococcus, sometimes appearing in
short chains, which he found constantly in the pharynx in scarlatina.
It was also found in the blood, but rarely after the first day of the
disease. Intravenous injections of this organism in white swine were
said to produce an aflFection closely simulating scarlet fever.
Schamberg and Gildersleeve,^ in a bacteriological examination of the
throats of 100 cases of scarlet fever, found the diplococcus described
by Class in but 15 cases. They found that, while this organism appeared
as a large diplococcus when first isolated and cultivated on certain
media, it later decreased in size to about 0.6/^, and appeared as a
micrococcus, occurring singly and in pairs, with an occasional short
chain. The organism reacted upon the various media in a manner
similar to the ordinary staphylococci.
In 1900 Baginsky and Sommerfeld^ described a streptococcus almost
constantly found in the throat and blood of scarlet- fever patients. This
organism sometimes appeared in short chains and in pairs. These
investigators tentatively regard the streptococcus as the cause of the
disease.
Protozoa in Scarlet Fever. — In 1887 L. PfeifFer'' described protozoa-
like bodies in the blood of scarlet fever and vaccinia. The significance
of these was not explained.
Mallory^ recently described certain bodies in the skin in four cases of
scarlet fever which he regarded as stages in the developmental cycle
of a protozoon. They form a series which are closely analogous to the
series seen in the asexual development (schizogony) of the malarial
parasite, but in addition there are certain coarsely reticulated forms
which may represent stages in sporogony or be due to degeneration of
the other forms.
These bodies found in the skin fixed in Zenker's fluid and stained
with eosin and methylene blue can be divided into two groups. The
first group consists of round, oval, elongated, and lobulated bodies
1 La paUiog&nie de la scarlatine, Paris, 1895, p. 126.
2 Bull, et m^m. Soc. mM. des hop. de Paris, 1S95 and 1S96
'* New York JVIedical Record, September, 1899, p., 330; Journal of the American Medic&l Associa-
tion, 1900, vol. xxxiv.. No. SI ; ibid., 1900, No. 13, p. 799.
■• Transactions of the Philadelphia Pathological Society ; also Medicine, September, 1904.
5 Berliner klin. Woehenschrift, 1900, Nos. 27 and 2S, p. 688.
Zeitschrift f. Hygiene, Bd. ii., 1SS7.
7 Protozoon-like Bodies Found in Four Cases of Scarlet Fever, Journal of Medical Research, Janu-
ary, 1904.
2S
431 SCARLET FEVER
from two to seven microns or more in diameter. Most of the bodies
seem to be composed of a close-meshed, finely granular reticulum.
The second group of bodies have a striking radiate structure. They
are found in vacuoles and in the protoplasm of epithelial cells, and free
in the lymph spaces and vessels of the corium just underneath the
epidermis. These radiate bodies vary from four to six microns in
diameter. They are usually spherical, contain a central round body
around which are grouped ten to eighteen narrow segments, which in
some cases are united, but in others are sharply separated laterally from
each other. Sometimes the segments are free.
Mallory proposes for these bodies the name "cyclaster scarlatinalis,"
in consequence of the frequent wheel and star shapes of the rosettes,
its most distinguishing characteristic.
These bodies were found only early in the disease, most abundantly
in the skin of a boy who died forty-eight hours after the appearance of
the eruption. A number of cases in the desquamative stage of the
disease were examined with negative results.
The Relation of the Streptococcus to Scarlet Fever.— The finding
of streptococci in scarlet fever by Frankel and Freudenberg, Babes,
Loeffler, Klein, Crookshank, Fiessinger, Dowson, Berge, Lemoine, and
Baginsky and Sommerfeld has already been referred to.
Lemoine, in a study of the throat in 117 cases of scarlet fever, found
the streptococcus alone in 93 cases and present with other bacteria
in 14 cases.
In 1900 Baginsky and Sommerfeld^ published the results of a large
number of bacteriological examinations in scarlet fever. In 411 cases
of this disease streptococci were constantly found in the throat. In a
later series of 290 cases streptococci were found in 285. In this group
they were found alone 21 times, with staphylococci 222 times, with
diplococci 25 times, and with diphtheria organisms in mixed cases 17
times. In 701 cases, therefore, streptococci were absent but 5 times.
Pearce^ found streptococci alone or associated with other organisms
in scarlet fever, in abscessed ears, in the antra of Highmore, in bron-
chopneumonia, serofibrinous pleurisy, empyema, acute mitral endo-
carditis, cervical lymphadenitis, embolic abscesses in the lungs and
kidneys, acute pericarditis, acute diphtheritic endometritis, etc. In 11
cases of general infection the streptococcus was found in 9. Strepto-
cocci have been found at autopsy in the heart's blood, liver, kidneys,
and other organs.
Weaver' found streptococci in the tonsils of 18 cases. Cultures from
the skin of 15 cases disclosed nothing of interest.
Slawyk* in 98 fatal cases found bacteria in the blood of 52; strepto-
cocci were found 39 times, and streptococci and staphylococci 6 times.
Hektoen'^ found streptococci in the blood of scarlet-fever patients,
1 Berliner klin. Wochenschrift, 1900, Nos. 27 and 28.
2 Report of Boston City Hospital, 1899.
s Journal of the American Medical Association, 1903, vol. v. p. 609.
■4 Jahresber. f. Kinderheil., 1901. ^ Journal of the American Medical Association.
77//'; BA(!TI<:iil()l/)(!Y OF SCAUfJ-:T FHVHIi 435
more particiiliirly in (Ik' sov(;re cjisos. 'J'liry wen; ahsent, however, in
some of tli(^ IVUiil cas(!.s.
S('lijunl)er^ and Gildcrsleevc' oxiiinincd, harlcriolof^ically, tlif throats
of 100 patioTils snflVritif»; fi-oiii scarhit fever. A f^reat vari(;ty of
orpjanisins was isohitcd. Strej)toeoeci were found in SS rases and
staphylococ(;i in 73. The staphylococci varied in pathogenic power,
but, as a rule, killed rabbits and guinea-[)igs in a sliort time.
('ultures were also made from the throats of 100 apf)arently well
jKM'Sons and from S2 per cent, of them stre[)tococci wen; f^btained. A
number of these were tested and found to l)e as virulent as tho.se from
other sources.
The almost constant presence of streptococci in throats of scarlet-
fever patients and their activity in the production of such complications
as otitis media, cervical abscess, and endocarditis have led certain
writers to afHrm their belief in the streptococcal origin of scarlet fever.
Dowson, Berge, and Lemoine have, in recent years, particularly cham-
pioned this view. There can be no question as to the constancy with
which the streptococcus is found in scarlet-fever throats, and at autop.sy
in the various organs and tissues. This would constitute a strong argu-
ment in favor of its specific pathogenicity in scarlet fever, were it not
for the frequency with which it is found in other infectious diseases.
For instance, in smallpox it is scarcely less ubiquitous than in scar-
latina.
It is commonly found in the late pustules of smallpox, and in many
of the cutaneous complications, such as boils, impetigo, abscesses,
erysipelas, gangrene, etc. After death streptococci are found in the
cutaneous lesions and internal organs in nearly all cases. There would
appear to be in many cases an agonal or post-mortem diffusion of
streptococci throughout the tissues. In 40 autopsies on smallpox
patients made by Perkins and Pay, streptococci were found dis-
tributed throughout the body in 38. Ewing found streptococci in
about 90 per cent, of the skin lesions at autopsy; he also noted the
presence of streptococci in the blood after death in every one of 29
cases examined.
It is evident from the above and other investigations that the strepto-
coccus is almost constantly found in fatal cases of smallpox. While
no one can seriously entertain the idea that its role in smallpox is causal,
it is so uniformly present that some writers believe it bears a peculiar
relationship to the disease differing from most secondary infections.
Many writers regard the smallpox bacterjiemia as the most frequent
cause of death in smallpox. Councilman" says: "As a result of the
study of the disease, both by culture of the lesions and organs and by
microscopic examination of the tissues, we are inclined to regard bac-
terial infection as a more important agent in bringing about a fatal
termination than the specific parasite The bacteria are
1 A Bacteriological Study of the Throals of One Hundred Cases of Scarlet Fever, etc. : Trausac-
tions of the Philadelphia Pathological Society ; also Medicine, September, 1901.
» Journal ot Medical Research, February, 1904, p. 358.
436 SCARLET FEVER
chiefly streptococci." Perkins and Pay, and likewise Councilman, sug-
gest that the streptococci in smallpox gain entrance to the circulation
through the bronchial and pulmonary mucous membrane.
It would seem that the relationship of the streptococcus to scarlet
fever and to smallpox is quite similar. It gives rise in both to numerous
complications and not infrequently leads to a fatal termination. The
proof that it is not the cause of smallpox is easy of demonstration; the
proposition that the streptococcus bears no etiological relationship to
scarlatina is more difficult to disprove.
It appears to us reasonable that in certain infectious diseases, particu-
larly scarlatina and smallpox, the resisting powers of the tissues are so
weakened against the streptococcus, that this organism invades the
system and works its noxious effects.
Until the streptococcus found in scarlet fever is shown to possess
properties which trenchantly distinguish it from other streptococci, and
until this disease is experimentally produced by inoculation of a pure
culture of such an organism, the belief in the causal relationship of the
streptococcus to scarlet fever cannot be maintained.
THE PATHOLOGY OF SCARLET FEVER.
The Blood. — The older writers contented themselves with a descrip-
tion of the fluidity, coagulability, and color of the blood. At the present
day accurate methods are in use which throw considerable light upon
the changes in the circulating fluid.
Felsenthal and Bernard, from a study of the specific gravity of the
blood, conclude that it is reduced in all cases of scarlet fever. The
reduction in haemoglobin is disproportionately great as compared with
that of the specific gravity.
Hayem was one of the first writers to point out a reduction in the
red blood corpuscles and an increase of the leukocytes. He also called
attention to the frequent increase of fibrin, especially in attacks accom-
panied by bad throats and suppurative complications.
Ewing^ states that the gradual loss of red cells noted by Hayem has
been fully verified by Kotschetkoff, who found a reduction to three
millions or less in nearly every case. Zoppert, on the other hand, found
more than four million corpuscles in 5 out of 6 cases. A number of
other observers have also found in a considerable number of cases but
a slight decrease of the red cells.
Estimations of the hoBmoglohin percentage were made by Widowitz^ in
14 cases of scarlet fever. In all but 1 the haemoglobin was strikingly
high in the beginning, then falling until the commencement of con-
valescence, when it again increased in quantity. When nephritis
develops a more decided fall takes place.
1 Clinical Pathology of the Blood, 1901.
2 Hamoglobingehalt des Blutes Gesunder und Krankerkinder ; Jahrbuch f. Kinderh., N. F.
xxviii. p. 384.
77//'; I'ATiioLodv ()!<' scMiLhrr /<■/':]■ f'ju, 437
Leukocytes.- 'Ili(! white cells have been carefully .studied by a
nurrilxM" of iiivcsti<^ji,t()rs, uotahly Kot.sclietkfjn' and Bowie. 'Jlien; i.s
f^eneral a^eeineiit as to the uniform ;i,nd early a[)})earance of leuko-
cytosis.
Kot.schetkoff .states that leukocyto.sis is influenced hy the type of
the disease; mild cases show usujilly from 10,000 to 20,000 white cells;
tnodcrately severe cases, from 20,000 to .'->0,000 cells; and the severe an(]
usually fatal cases from 30 ,000 to 40,000 cells; in some rapidly fatal ca.ses
over 40,000 leukocytes were present. Yet Rieder's^ cases seldom gave
more than 20,000 cells, although some were complicated and fatal.
FelsenthaP found in six attacks of moderate severity in (-liildren from
1S,0()0 to 30,000 leukocytes.
Bowie^ gives the results of the careful and repeated examination of
167 cases. He concludes that (1) practically all cases of scarlet fever
show leukocytosis; (2) the leukocytosis begins in the incubation period,
very shortly after infection; it reaches its maximum at or shortly after
the acme of the disease and then gradually diminishes to normal; {'S) in
simple uncomplicated cases the maximum is reached during the first
week, and the normal generally some time during the first three weeks;
(4) the more severe the case, the higher is the leukocytosis and the
longer it lasts ; the milder the case, the slighter the leukocytosis and the
shorter time it lasts; (5) a favorable case of any variety of the disease
has always a higher leukocytosis than an nnfavorable one of the same
variety; (6) the temperature has no effect on the leukocytosis. These
observations are in complete accord with those of Kotschetkoff.
Differentiation of Leukocytes. — Bowie states that the poly-
morphonuclear leukocytes are increased relatively and absolutely at
first, and then fall to normal; the lymphocytes act in an inverse manner.
In simple cases this cycle occurs within the course of three weeks.
Kotschetkoff estimates the number of the polymorphonuclears as vary-
ing between 85 per cent, and 98 per cent., according to the severity of
the disease; the highest point is reached on the second day of the erup-
tion, a gradual diminution then occurring. The lymphocytes are at
first diminished, but later increase to normal.
According to Bowie, the eosinophiles are diminished at the onset
of the fever. In simple favorable cases a rapid increase then occurs
until the height of the disease is passed, when a gradual decline to
normal takes place, the latter occurring after the disappearance of the
leukocytosis.
The more severe the case the longer are the eosinophiles subnormal
before they rise again. In fatal cases they never rise, but sink rapidly
toward zero. Kotschetkoff says that eosinophiles in all but severe
cases are normal or subnormal at first; after two or three days they
steadily increase, reaching a maximum of 8 per cent, to 15 per cent,
in the second or third week, and then decline slowly to normal about
1 Quoted by Ewing, loc. cit. s Quoted by Ewing.
* Quoted by Ewing.
* Leukocytosis in Scarlet Fever, Journal of Pathology and Bacteriology, March, 1902.
438 SCARLET FEVER
the sixth week. The eosinophiles may disappear early in the disease
in cases which prove fatal.
While the above quoted results of Kotschetkoff and Bowie are in
striking harmony, certain other observers have noted divergent findings.
Sevestre/ frorn an examination of 13 cases, concluded that "in severe
cases it was found that the percentage of the finely granular eosinophiles
was always high," and "in the majority of cases examined the per-
centage of the coarsely granular eosinophiles was found to be dimin-
ished during the whole period of the disease."
Ewing says that Weiss found no eosinophiles in 1 case at the height
of the exanthem, and Rille observed marked eosinophilia in a fatal
case; Bensaude observed as high as 20 per cent, of eosinophiles in
one instance.
Influence of Temperature, Rash, and Complications. — Kots-
chetkoff states that the grade of the leukocytosis depends upon the
severity of the disease, especially the angina, but not upon the height
of the temperature. Complications such as lymphadenitis, otitis, and
nephritis usually have little effect on the leukocytosis.
According to Bowie, the temperature has no effect on the leukocytosis.
In complications, the leukocytes go through a cycle of events similar
in all respects to that of the primary fever as regards both sum-total
and differential leukocytosis, and the same laws govern the behavior
of the leukocytes in both cases.
Sevestre says that "complications such as otorrhoea, rhinorrhcea, and
adenitis tend to increase the number of white cells." He also states
that a relationship exists between the leukocytosis and the rash; the
former varies with the severity of the latter, and with the fading of the
same the leukocytes show a marked diminution in number.
Rieder and Turk^ have noted a high persistent leukocytosis, especially
in those cases followed by nephritis or other complications. Pee^ found
an increase in the leukocytes in 2 cases during a late adenitis.
Bowie believes that the simple counting of the leukocytes is of but
little diagnostic value. A differential count may, however, be of aid,
for scarlet fever is one of the few acute infections in which one finds
an early increase of the eosinophile cells and a persistence of the
increase for some time.
As regards ^prognosis he says: "In simple, severe scarlatina, if the
leukocytosis be high and rising, a favorable course may be predicted;
if it be low and stationary a tedious course may be expected. If the
eosinophiles show a relative increase the augury is good; if they are
normal or subnormal after the first day or two, then, in all probability,
the case will be severe. The persistence of a relative increase of the
eosinophiles suggests some complication, whereas, if they come down
to normal in the usual manner, one may be free from anxiety as regards
complications."
1 St. Bartholomew's Hospital Reports, 1896, vol. xxxii. p. 225 et seq.
2 Quoted by Ewing. s Quoted by Ewing.
MOiaHI) ANATOMY OF SCAh-U'lT Fl'JVKR 439
MORBID ANATOMY OF SCARLET FEVER.
But lilUc iul'ornuitioii is obtained by {>ost-rii(>rlf]ji (■xuniiiiutiou in
uncomplicated cases of scarlet fever that cannot be foretold by the
symj)tc)iniit()l()(jjy of tlic disease. The fj;ross morbid changes are usually
observed in ilie skin, tongue, throat, and lyniplialit; structun;s of the
body. Indeed, the most uniform j^ross alteratifjn is a hyperplasia of
all of tlic lymj)hoid structures of the body.
After death the eruption commonly fades away completely except in
those cases in whicli the rash has been intense. In the hemorrhagic
forms the |)etecliial S])ots will, of course, remain visible.
Histological Changes in the Skin.^ — Tlie skin has been studied by
a number of investigators, but principally by Klein, Unna, and Pearce.
Klein^ studied the changes in the skin in 20 cases. He found the
epidermis slightly thickened, particularly the mucous layer. Many of
the rete cells showed dividing nuclei. Between the horny and mucous
strata were small spaces containing granules resembling micrococci.
In the rete Malpighii were found lymph corpuscles with deeply stain-
ing nuclei. In the corium the epithelial cells of the follicles and sweat
glands exhibited an increase of the nuclei. The bloodvessels were
distended by corpuscles and occasionally by fibrin. The nuclei of the
lymphatics and of the endothelial and muscular coats of the arteries
were increased.
Neumann^ noted swelling of the rete cells and elongation of the
prickle cells, between which was evident a cell infiltration, occasionally
containing red blood corpuscles. The bloodvessels and lymphatics were
dilated. There was slight cellular proliferation around the sw^eat glands,
hair follicles, and bloodvessels.
Kaposi^ regards the changes in the skin as the result of vascular
congestion with moderate cell infiltration; the papules and vesicles
occasionally seen are due to an excessive exudation and cell proliferation
in the papillfe and in the rete mucosum.
Unna* examined the skin of 7 cases of scarlet fever. His findings are
briefly as follows : There is a marked wrinkling of the whole epidermis
along with the papillary body, which is due to an overstretching of the
epidermis by the sodden, engorged cutis and to subsecjuent distortion,
after excision of the skin, when the cutis contracts. The elasticity of
the cutis indicates that during life it could not have been the seat of
oedema.
The bloodvessels of the true skin are enormously dilated, suggesting
almost distention by artificial injection. This distention, which is
present even after death, is the result of a vascular paralysis. White
blood corpuscles are extremely scant, scarcely more than is found under
normal conditions.
1 Local Government Report, viii. 24, London, 1876 ; quoted by Pearce, loc. cit.
2 Med. Jahrbiicher, 1882, p. 152.
3 Path, und Therapie der Hautkr., Vienna, 1899, p. 243. * Loc. cit., p. 629.
440 SCARLET FEVER
No particular changes are found, at the height of the eruption, in the
prickle layer. There is absence of mitosis, oedema, and of any dilatation
of the interepithelial lymph spaces. Mitoses are found first and pretty
numerously in the stage of desquamation.
In view of the above findings, Unna regards the changes in the
scarlet fever sisin as paralytic and not inflammatory.
Pearce^ examined the skin in 8 cases between the second and sixteenth
days, and 1 on the thirty-second day.
On the second day, beyond a congestion of the bloodvessels and
slight dilatation of the lymphat cs, no changes were observed. In 3
cases examined on the third day, a few leukocytes and lymphoid cells
were seen in and grouped around smaller lymphatics beneath the rete
Malpighii. From the fifth to tenth days the most marked condition
was an nfiltration of the epithelium with polymorphonuclear leukocytes.
The cells apparently leave the bloodvessels beneath the rete and pass
up between the epithelial cells and collect in the superficial layers of
dead cells, with which they are thrown off. In the connective tissue
beneath the epithelium were numerous polynuclear leukocytes and a
few plasma cells. The lymphatics were widely dilated and contained
many leukocytes. By the twelfth and sixteenth days the leukocytic
infiltration had nearly disappeared. In a late desquamating case the
rete contained numerous mitotic figures.
Tongue. — When death occurs early in the course of the disease the
enlarged papillae may be visible at post-mortem. Pearce^ made a
microscopic study of the tongue in 8 cases, all between the second and
ninth days.
The process in the tongue is said to be similar to that in the skin,
but is more marked and begins earlier. The chief changes consist of
a dilatation of the papillary bloodvessels and lymphatics, a leukocytic
infiltration of the epithehal layers, particularly pronounced over the
papillae, and the presence of leukocytes in and around the bloodvessels.
The polymorphonuclear leukocytes wander between the epithelial cells,
collect beneath the superficial epithelium, with which they are cast oft*.
The most pronounced cell infiltration is seen between the fourth and
ninth days. Mast-cells are increased in number and plasma cells are
seen in small numbers about the bloodvessels. Mitoses in the epithelial
cells are frequent. Pearce regards the process as inflammatory and
suggests that the exciting cause of the leukocytic infiltration may be
a positive chemotaxis excited by the presence in the tissues of the
scarlet-fever toxin, or by substances formed by its action on the super-
ficial epithelial cells.
Lymphatic System. — In 1872 Harley^ studied the post-mortem
changes in 28 cases of scarlet fever and concluded that it was a disease
of the lymphatic system characterized by hyperplasia of the lymph
glands, spleen, tonsils, liver, and other lymphatic structures of the
1 Scarlet Feyer, its Bacteriology and Gross and Minute Anatomy, Medical and Surgical Reports ot
Boston City Hospital, 1899.
2 Loc. cit. 3 Med. Chir. Trans., London, 1872, Ix. p. 102.
MOItBIl) ANATOMY OF S(!AlilJ':T h'KVKIi 441
body. Tie, thcnvfore, proposed to .substitute for the riaine, searlet fever
{\w. tenn lyin|)liatic fev(^r.
Then! eaii be no (loii})t tliat proiioiirK;(!(l liyperplasia of \\\c lyjn{>hoifl
tissues is a coiistant {irid eoiiS})ieiioiJS aeeoin})aniiiient of sc;arlct fever.
Pearee' found the mesenteric, retroperitoneal, bronchial, and tracheal
glands enlarged in all cases. The superficial lymph nodes, such as
the cervical, axillary, and inguinal, were also found enlarged. The
glands were quite firm, and, on section, pale and watery.
Klein and J'earce have both jnade histological studies of tlie glands.
Klein^ examined the lymph glands in 8 cases. The centres of the glands
were transparent and composed of large cells resembling giant cells.
There were also large cells with transparent vesicular nuclei. In the
sinuses were small cells and also large granular cells, with one or two
transparent nuclei (endothelial).
Pearce studied the glands, including the mesenteric, cervical, and
bronchial, in 20 cases. The changes observed were similar to those
seen in the spleen, but were not present in all cases. The bloodvessels
were congested, and in 3 cases small hemorrhages were seen. The
lymph sinuses were dilated and contained many large endothelial cells
lyhig loose in their lumena. These cells were frequently observed to
be phagocytic, containing a number of disintegrated lymphoid cells.
Plasma cells, exhibiting numerous mitotic figures, were found through-
out the lymph nodes.
Spleen. — The gross appearance of the spleen, according to Pearce,
permits of a classification into two different groups. There is no increase
in pulp, but a marked enlargement of the Malpighian bodies. In such
cases the spleen is firm, and the capsule smooth but not tense; on
section there is seen a dark-reddish background, dotted everwhere
with regularly or irregularly enlarged Malpighian bodies. This con-
dition was noted in 13 out of 23 cases examined.
In the other class the splenic pulp is greatly increased and the Mal-
pighian bodies indistinct. The spleen is then large and soft. This
condition was seen in 7 cases, in 2 of which, however, there was enlarge-
ment of the Malpighian bodies. In the remaining 3 cases absolutely
no change in the gross appearance of the spleen was visible. The
differences described do not seem to depend upon the age of the patient,
the stage of the disease, nor the intensity of the infection.
Klein^ noted, in 8 cases examined histologically, an enlargement of
the Malpighian bodies. A peculiar pale area, composed of endothelial-
like cells, was observed in the centre of the bodies. The intima of the
bloodvessels exhibited a hyaline degeneration, at times leading to
obliteration of the lumen.
Pearce made a careful histological study of the spleen in 21 cases.
The enlargement of the IMalpighian bodies was found to be due to a
central massing of large endothelial cells in addition to the presence
of numerous plasma cells. These were abundantly present also around
1 Loc. cit. - Transactions of the Pathological Society of London, 1S77 ; quoted by Pearce.
3 Quoted by Pearce.
442 SCARLET FEVER
the bloodvessels, in the lymphatics, and along the trabeculse. The
bloodvessels were greatly congested. A peculiar condition noted was a
collection of cells, chiefly plasma and lymphoid cells, but occasionally
also a few leukocytes, beneath the endothelial lining of the vessels.
Liver. — The gross changes in the liver are not pronounced. It
exhibits usually, although by no means constantly, some degree of
enlargement. The consistence is ordinarily less firm than the normal
liver. In 1 case Pearce noted on the surface a number of minute,
yellowish areas, which were shown to represent necrotic foci. Roger
observed in 2 cases a number of scattered red spots due to subcapsular
ecchymosis, a sort of purpura of the liver.
Histologically, the changes in the liver are those of an acute febrile
infectious disease. In 22 cases examined by Pearce the liver cells in
each instance exhibited the degenerative changes common to fevers.
In 4 cases distinct fatty degeneration was noted, and in 7 cases extensive
fatty infiltration. An infiltration of lymphoid cells with a few poly-
morphonuclear leukocytes was found around the portal vessels in 11
cases. A few eosinophiles and plasma cells were seen, the latter more
particularly in the bloodvessels. Phagocytic endothelial cells were found
in the bloodvessels in 5 cases. Focal necrosis of the liver was observed
in 4 cases. The focal areas seemed to arise from endothelial cells, derived
in part from the capillary endothelium of the liver, and, in part, from
embolism through the portal circulation of cells originating in the
spleen. The changes are similar to those described by Mallory as
frequently occurring in the liver in typhoid fever.
Roger and Garnier^ made histological examinations of the liver in
12 cases. The changes described by them are of different types: one
series concerns the mesodermic elements of the liver — leukocytic infil-
tration, thickening of the capsule of Glisson, etc., inflammation of the
vessels; the other affects the epithelial tissue. The first stage of inflam-
mation in the liver is leukocytic infiltration of the portal spaces. Later,
the epithelial cells are altered; they may merely show unequal coloration
of the nuclei or they may degenerate in considerable number around
the portal spaces, or, finally, a number only may degenerate, forming
a limited focus which may subsequently become infiltrated with leuko-
cytes. At the same time inflammation of the conjunctive tissues may
increase and the cells present may undergo hyaline and fatty degen-
eration or fatty infiltration. When parenchymatous hepatitis is extensive
the interstitial changes also become pronounced.
Gastrointestinal Tract. — The mucous membrane of the pharynx,
tonsils, and soft palate show, under the microscope, the usual changes
observed in inflammation of these structures.
Fenwick^ described changes in the mucous membrane of the stomach
analogous to the desquamation of the cutaneous surface; in severe cases
there was an absolute loss of epithelium. In addition he found a
1 Des modifications anatom. et chimiq. dufoie dans la scarlatine, Rev. de m6d., March 10, 1900, and
Roger, Les maladies infect., p. 1056.
2 Medico.-Chir. Trans, of London, 1862, xlvii.
MOUIill) ANATOMY OF SCARfJ'//' FFVh'fi 443
dilatation of the l)loo(lve,ssels and a filling up of the ga.stric tii};iil<.s witli
a granular and fatty nuitcrial and small cells.
Crooke, in a study of cases, found catarrhal gastritis in all, anrl,
in the severe cases, interstitial and folhcnhir gastritis characteri'/(;d hy
hyperplasia and necrosis of the lymph follicles, and infiltration of the
muscular coat with round cells. Ilesselwarth found 21 instances of severe
gastroenteritis among -SI autopsies.
I'earce examined the stomach histologically in 6 cases. In a case
dying upon the second day the surface of the stomach was covered
with a thick layer of mucus and necrotic epithelial cells, containing
numerous leukocytes and cocci. Polymorphonuclear leukocytes and
granular material were found in the tubular glands, and numerous
plasma cells between the tubules. Enlarged and altered lymj>h nodules
were seen in the lower part of the mucous membrane; 4 other cases
showed similar but less-marked changes.
The intestines exhibit changes very similar to those seen in the stomach.
Virchow described marked hyperplasia and swelling of the lymph
follicles. Crooke says that Peyer's patches at times look like those
found in typhoid fever during the first week.
Bone-marrow.— Pearce^ examined the bone-marrow in 11 cases, of
which 2 were adults. In all the cases the Ijone-marrow was very cellular.
Giant cells and nucleated erythrocytes were seen and eosinophile cells
were found in abundance. Lymphoid cells and neutrophilic leukocjies
were present in fair numbers. The principal cells, however, seen in all
cases were about the size of and closely resembled the plasma cell. They
formed the bulk of the cells found in the bone-marrow.
Roger^ found the bone-marrow absolutely normal in 1 case, and in
another evidence of slight reaction of the medullary tissue.
Heart. — The cardiac muscle suffers in scarlet fever from two chief
causes- — the scarlatinal poison and, secondarily, from involvement of
the kidneys. The most common changes observed are cloudy swelling
and fatty degeneration, processes which are observed in many infectious
diseases.
Romberg^ has pointed out that the interstitial connective tissue, as
well as the myocardial tissue, shows pathological alteration. The muscle
fibres are separated by masses of cells and the arterial bloodvessels
exhibit distinct inflammatory changes.
Pearce, in an examination of 9 cases, demonstrated fatty degen-
eration in 5. Segmentation and fragmentation of the myocardium were
observed in a few instances.
The above changes doubtless result from the poison of the disease.
The heart frequently undergoes hypertrophy and dilatation as a result
of a coexisting nephritis.
Friedlander* states that in children with nephritis the heart increases
1 Loc. cit. : Loc. cit.
5 Ueber die Erkrankungen des Herzmuskels bei Typhus abdom., Scharlach und Diphtheria;
Deutsch. Archiv f. klin. Med., Bd. xlviii. and xlix.
* Ueber Herzhypertrophie ; Du Bois-Reymond, Archiv f. Physiolog., 1891.
444 SCARLET FEVER
in weight on an average about 40 per cent. Jager is of the opinion
that two-thirds of all cases of scarlatinal nephritis are accompanied
by cardiac hypertrophy and often by dilatation. When the integrity of
the heart muscle is compromised in the earlier days of the disease by
the fever and the scarlatinal poison, it becomes unable to withstand
the increased' pressure later when the kidneys become involved, and
thus undergoes dilatation. Silberman^ explains the heart changes as
follows: (1) there is no disease in which the elimination of water is
so suddenly and enormously diminished as in scarlatinal nephritis;
(2) the glomeruli are principally affected; (3) there is extensive involve-
ment of the kidney structure; (4) the oedema compresses the blood-
vessels of the skin and in this way increases heart pressure ; (5) increased
resistance in the aortic system is more readily followed by cardiac
hypertrophy in children than in adults.
RiegeP states that increased arterial tension accompanies all cases of
scarlatinal nephritis, and as a result thereof hypertrophy of the heart
takes place. The enlargement is sometimes observed a few days after
the development of the nephritis. Forchheimer believes that from the
effects of the scarlatinal toxin dilatation commonly takes place, even
if lasting only a short time, with hypertrophy following as compensa-
tory.
A clinically demonstrable pericarditis is distinctly uncommon in
scarlet fever. Slight grades of pericardial inflammation are occasionally
seen at autopsy. When nephritis is present effusion of serum often
occurs, in some cases giving rise to enormous distention of the peri-
cardial sac. When inflammation is present the exudate may be sero-
fibrinous or purulent; in the latter event streptococci and staphylococci
are usually found upon culture.
Endocarditis. — Endocarditis of the cardiac wall is said by von
Jiirgensen,'^ to be more common than valvular endocarditis. Forch-
heimer considers endocarditis as a very common complication of scarlet
fever. The margins of the valvular segments are, in mild cases, the
seat of small excrescences, in severe cases larger ones constituting a
verrucous endocarditis.
Roger in 2213 personal examinations, of which 1727 were in adults,
observed endocarditis but twice, while extracardiac murmurs were
found 692 times. In 1 of the cases of endocarditis there were ulcero-
vegetating lesions and an abscess of the myocardium. The strepto-
coccus was found to be the cause of the abscess.
Antra of Highmore. — Pearce found an inflammation of these cavities
in 3 cases. In 2 both cavities were filled with an abundant purulent
fluid, and the process was a true empyema. In both of these cases
both middle ears were infected, and in one of them the sphenoidal sinus
was filled with a greenish-yellow pus.
1 Jahrbuch f. Kinderheilk., N. F., 1894, xxxvii. ; quoted by Forchheimer, loc. clt.
2 Ueber die Veranderungen des Herzens u. des Gefassystems bei Acuter Nephritis ; Zeitschr. f.
klin. Med., 1884, Bd. vii.
3 Log. cit.
MORIill) ANATOMY Oh' SCAUfJ'/I' F/'JVKR 445
Pulmonary Complication. — In a series of 23 autopsies Pearce fourxl
hronckopyummonia in S eases, usually in the form of small, discrete
noduUss, scattered alonfr the })aek or base of the lung. In 2 cases the
process was confluent, involvin<( tiu; greater [)ortion of one or more
lobules. In 5 of these cases both tiie strej)toeoccus and the staphylo-
coccus aureus were found. In I case the latter was found associated
with the pneumococcus; in 1 case the streptococcus was founfl alone.
A fierojihriiious fleurisy was noted in 1 case as the result of strepto-
coccus infection, and in another an em])yema witli atelectasis of the
lung. In the latter a small abscess cavity was found on the surface
of the lung.
Kidneys. — A voluminous and somewhat confusing literature has
accumulated upon the sul)ject of scarlatinal nephritis.
Klebs, in 1870, was one of the earliest writers to call attention to a
glomerulonephritis occurring during convalescence from scarlet fever.
He divided the kidney alterations into three groups: (1) a granular
desquamation of the epithelium in the febrile stage; (2) an interstitial
nephritis frequently seen late in the disease; the kidney in this condition
is large, lax, smooth on section and shows grayish-w'hite nodules; (3)
a glomerulonephritis during convalescence.
In 1883, Friedlander, from a careful study of the kidney in 229
autopsies, divided scarlatinal nephritis into three classes: (1) an early
catarrhal nephritis, occurring during the first week; (2) an interstitial
nephritis in which the kidney is large, white, and hemorrhagic; this
form occurs in severe cases with bad throats and other septic com-
plications; and (3) an acute glomerulonephritis which develops during
convalescence. The latter condition occurred in 42 cases and was
egarded by Friedlander as the most characteristic kidney 'esion of
scarlet fever. In this condition the interstitial tissue is practically
normal, the glomeruli being solely involved.
Councilman in 1897 characterized the condition of the kidney in
3 cases of scarlet fever as a pure interstitial nephritis. He states ihat
glomerular nephritis occurs chiefly in measles, acute endocarditis and
diphtheria, and acute non-suppurative interstitial nephritis in diph-
theria and scarlet fever. In the latter disease the kidney is large,
pale, and mottled. The principal lesion is an acute cellular infiltration
with a few phagocytic endothelial cells and leukocytes. The origin of
the plasma cells is presumed to be lymphoid cells which have undergone
conversion in the spleen, and which emigrate from the bloodvessels
and undergo mitotic change in the kidneys.
Pearce,^ in a study of 23 cases, found degenerative changes in all.
Of 8 specimens examined in the fresh state, 6 showed a more or
less marked fatty degeneration. Acute interstitial nephritis was the
most important lesion present. In 4 cases this process was extensive
and in 5 slight. In the former the cellular infiltration was most marked
in the cortex just beneath the capsule, around the glomeruli and around
' Loc. cit.
446 SCARLET FEVER
the bloodvessels in the intermediate zone. The cellular areas were
made chiefly of plasma cells with a few lymphoid cells and leukocytes.
The glomeruli were unaffected. These cases were fatal on the e ghth,
ninth, fourteenth, and fifteenth days respectively.
From the writings of various authors it is seen that a considerable
difference of Opinion exists as to the most characteristic kidney changes
in scarlet fever. Councilman expresses the view that differences in
local resistance doubtless influence the susceptibility of the various
structures. He believes that in all serious lesions of the kidneys the
changes in some cases may be principally in the glomeruli, and in others
in the interstitial connective tissue. The glomerular lesions may be
accompanied by degenerative alterations in the epithelium of the
tubules, which may or may not be secondary. Hyperplasia of the
connective tissue cannot be regarded as secondary to tubular changes.
Certain investigators, particularly Marie, Haskine, Guinon, and
Babes have found streptococci in nearly all forms of scarlatinal nephritis.
How far the inflammatory changes are due to such micro-organisms
and to what extent the scarlatinal toxin is responsible, time and future
research must determine.
CHAl'TKR VIII.
SCARLET FEVER. {Continued).
THE DIAGNOSIS OF SCARLET FEVER.
When scarlet fever exhibits itself in a prononnccd mid typifjil forin
the (lias[)ital three times vdthin a
year with the diagno,sis of scarlet fever, lie was admitted to the llos-
{)ital first on June li, 1902. He had vomiting, sore throat, slight fever,
and a generalized searlatiniform eruption. He desquamated y)rofusely.
The sealing lasted almost nine w(>eks, and the patient was diseliarged
on September 8, 1002.
The patient was readmitted on January 9, 1903. He had sore throat,
headache, slight fever, and a well-marked searlatiniform rash. Slight
desquamation occurred upon the face and trunk.
The patient was admitted for the third time on June 28, 1903. He
had had repeated vomiting, headache, sore throat, and some fever; on
admission there was a generalized, well pronounced searlatiniform
eruption, not punctated, however. The tongue was heavily coated, but
after this disappeared there w^as no enlargement of the papillfe. Desqua-
mation was well marked, being particularly copious on the hands and
feet. The latter were still peeling in large lamellae at the end of a
month.
Each of these attacks resembled scarlet fever sufficiently to cause
the resident physician to admit the patient.
We would call attention, however, to the fact that the fever and sore
throat on each occasion were very slight. There was no prostration
and the characteristic tongue was absent. We have no doubt that the
patient was suffering from a searlatiniform erythema, possibly due to
intestinal autointoxication.
Drug Rashes. — Quinine, antipyrin, opium, belladonna, chloral, and
mercury at times produce eruptions which may closely simulate that
of scarlet fever. The eruption resulting from quinine is the most
frequent and the most likely to be confounded with scarlet fever. x\s
a rule, in these eruptions the constitutional disturbance is dispro-
portionately slight, and severe sore throat, swelling of the glands,
strawberry tongue, and middle-ear disease are absent. The eruption
often fails to begin on the chest and pursue the normal progression
of the scarlatinal exanthem. The occurrence of desquamation has no
diagnostic value in these cases, as the drug rashes may be followed
by a variable amount of epidermal exfoliation.
Measles. — There is no difficulty in distinguishing between measles
and scarlet fever under ordinary circumstances. There are, however,
irregular cases of each disease in which the elimination of the other in
the diagnosis is by no means easy.
The rash in scarlet fever is now and then blotchy, especially upon
the extremities; in other cases, particularly of septic scarlatina, a profuse
rhinorrhoea may be present, even early in the course of the disease;
these symptoms, associated with an otherwise irregular s^Tnptom-
complex, may produce quite a resemblance to measles.
The eruption of measles may, as a result of coalescence of the macules,
454 SCARLET FEVER
closely simulate that of scarlet fever. In some epidemics the proportion
of confluent measles eruptions appears to be greater than in others.
A few years ago during the prevalence of a particularly severe form of
measles, we noted a frequent tendency of the exanthem, after the lapse
of twenty-four or forty-eight hours, to become confluent and present
the appearance of a diffuse scarlatiniform eruption. Usually, however,
there may be seen somewhere on the trunk or extremities sharp margin-
ation of the eruption with contiguous areas of pale, normal skin.
In measles the face is earlier and more copiously affected than in
scarlet fever; the eruption is dusky red in color, palpably raised above
the skin, and distinctly blotchy; it appears later than the eruption of
scarlet fever (about the fourth day) ; there is a prodromal stage, during
which time catarrhal symptoms affecting the eyes, nose, larynx, and
bronchial tubes are present, producing watery eyes, sneezing, running
nose, hoarseness, and frequent cough. The initial fever is not as high
as in scarlatina and the tendency to vomiting is less. Sore throat, great
glandular intumescence, strawberry tongue, lamellar desquamation,
and nephritis, commonly seen in scarlet fever, are absent in measles.
The presence of Koplik spots upon the buccal mucous membrane
would decide in favor of measles. The discovery of a marked leuko-
cytosis would, it is claimed, point strongly toward the scarlatiniform
nature of the disease.
At times a secondary roseolous or measles-like eruption appears later
in the course of scarlet fever. This is regarded by Thomas as a pseudo-
relapse, but it seems to us to be of the nature of a septic rash.
Smallpox. — Scarlet fever may be confounded with the prodromal
scarlatiniform rash that is occasionally seen during the initial stage of
smallpox. The absence of angina and the appearance of the variolous
papules will make the diagnosis clear.
During the later pustular stage of variola an intense scarlatiniform
eruption at times develops which may raise the question of a secondary
infection with scarlet fever. There may be high fever, prostration,
and subsequent desquamation. The absence of vomiting, sore throat, .
the strawberry tongue, and the development of the eruption about the
twelfth to the fifteenth day of smallpox will usually enable one to recog-
nize the character of the rash.
Influenza. — Influenza is sometimes accompanied by a scarlatiniform
eruption which may cause scarlet fever to be suspected. The presence
of severe muscular pains and catarrhal symptoms, and the absence of
the angina and the characteristic tongue, together with attention to
the character of the prevailing epidemic will usually suffice to distinguish
the two affections.
Rubella. — With the usual type of rubella scarlet fever scarcely comes
into differential confiict. It is with that form which tends to present a
diffuse eruption that errors may arise. (See article on Rubella.)
Diphtheria. — Ordinarily scarlet fever and diphtheria have but little
in common, and yet errors in diagnosis are not infrequent. Too often
physicians glance into the throat, see exudate present upon the tonsils,
THE DTACJNOSrS OF SCARLET FEVER 4.55
and perhaps iij)()ii tlie soft pnlatc, and straightway make the diagnosis
of (lipl)theria. Time and time again liave w(; received calls at the
Municipal Hospital for cases of diphtheria, only to discover on seeing
the patient the presence of a scarlatinal rash. l)ij)htheri;i is ordinarily
not accom])anied by an exanthem.
Vomiting is nnich more common as an invnsive sym{>tfjm of scarlet
fever than of diphtheria. The exudate in diphtheria is tough and thick,
of a grayish or grayish-yellow color, and quite firmly adherent to the
underlying mucous membrane. That of scarlet fever is yellowish, thin
and smeary, and more easily wiped off. In scarlet fever, moreover, the
tln-oat ordinarily shows more intense redness and oedema than in
diphtheria. The soft palate commonly presents a punctated, reddened
appearance.
Enlargement of the maxillary and submaxillary glands occurs in both
diseases. The temperature in diphtheria tends to subside in a few days;
in scarlet fever it commonly persists for a longer period. The straw-
berry tongue of scarlatina is absent in diphtheria.
Otitis media may occur in both diseases, but it is more common in
scarlet fever. Albuminuria is an early symptom in diphtheria and a
late symptom in scarlet fever. It is present in about one-half or more
of the cases of diphtheria and is commonly found on the third or fourth
day. A transient albuminuria may occur early in severe cases of scarla-
tina accompanied by high fever, but the true scarlatinal nephritis is ordi-
narily discovered about the end of the third week. The early albuminuria
of diphtheria is apt to be associated with the presence of tube casts.
While the finding of Klebs-LoefHer bacilli in the throat is of great
diagnostic importance, their presence does not exclude scarlet fever.
At the Municipal Hospital we have cultures made of all scarlet-fever
patients on admission to the hospital. The percentage of cases in which
diphtheria bacilli have been found varies from time to time. It has
been as low as 8 in 100 and as high as 30 in 100. It is by no means
always the bad throats that give positive cultures. In many of the
cases in which the Klebs-LoefHer bacilli are found there is no exudate
at all in the throat.
That diphtheria and scarlet fever may occur at the same time is
generally admitted. In our experience scarlet fever has more often
developed in the course of diphtheria than the reverse. Diphtheria
is more apt to appear after the acute symptoms of scarlatina have
subsided. Scarlet fever, on the other hand, not infrequently makes its
appearance early in the course of diphtheria.
To distinguish between the scarlatiniforin rash that occasionally
occurs in diphtheria and a true complicating scarlet fever is a most
difficult and, indeed, an often impossible task. Clinicians of experience
recognize this fact. Osier, for example, says: "Scarlet fever and diph-
theria may coexist, but in a case presenting widespread erythema and
extensive membranous angina, with Loeffler's bacillus, it would puzzle
Hippocrates to say whether the two diseases coexisted, or whether it
was only an intense scarlatinal rash in diphtheria."
456 SCARLET FEVER
It has been our custom to regard as a complicating scarlet fever any
well-pronounced scarlatiniform rash accompanied by distinct elevation
of temperature; if vomiting occur and the lingual papillae become
enlarged the diagnosis is much clearer. We have sent all such cases
to a mixed ward in which there have been undoubted cases of scarlet
fever, and it has been extremely rare for any children thus transferred
to contract scarlet fever. We have never seen an intense, well-pro-
nounced scarlatiniform rash in diphtheria that we felt could be regarded
as an erythema diphtheriticum.
Since the introduction of the use of diphtheria antitoxin the difficulties
of diagnosis have been increased, for a third possibility presents itself,
namely, a scarlatiniform antitoxin rash.
The occurrence of scarlatiniform eruptions in diphtheria wards is
always a source of anxiety. If the patient is allowed to remain, other
children may be exposed to scarlet fever; if, on the other hand, the
patient is transferred to a mixed ward, there is a risk of his contracting
scarlet fever. It is well to have nearby a number of small rooms in
which patients may be placed for a few days and watched. These cases
tax the diagnostic acumen of even the most experienced physicians.
Tonsillitis. — ^An inflammation and enlargement of the tonsils with
the development of exudate in the crypts is so often seen in scarlet
fever as to constitute a part of the symptom-complex of this disease.
It is recognized that scarlatina may occur without an exanthem. The
determination of the scarlatinal character of a tonsillitis occurring
in a person exposed to the infection of scarlet fever is a most difficult
matter. If the exposure has been intimate, the individual unprotected
by previous attack of scarlet fever, the characteristic tongue appearance
and the angina present, and otitis media or nephritis develop, the
existence of angina scarlatinosa would be highly probable. Follicular
tons llitis not infrequently develops in persons exposed to scarlatina
who have previously had the disease. Thomas says that all such cases
should be regarded with suspicion, but we would hesitate to regard
them all as scarlet fever. The symptoms are identical with follicular
tonsillitis occurring from other sources. We have known persons
unprotected by a previous attack of scarlet fever to contract, on exposure
to the disease, what appeared to be an ordinary foil cular tonsillitis;
although no eruption was discovered in these patients, they have at
times desquamated on the feet in a quite characteristic manner. Patients
with sore throats of this nature have also been known to communicate
scarlet fever to others. It is often impossible to determ ne with positive-
ness whether or not cases of follicular tonsillitis resulting from exposure
to scarlet fever are to be regarded as angina scarlatinosa.
Occasional y an erythema develops in the course of an ordinary
follicular tonsillitis. This eruption is often partial and may appear
first on any part of the body. The exclusion of the diagnosis of scarlatina
is only possible after a careful study of all of the symptoms, general
and local, and attention to the circumstances of exposure and epidemic
influence.
77//'; J'UOfJNOS/S OF SdAlffJ'/I' FI'lVFIi 457
THE PROGNOSIS OF SCARLET FEVER.
The most important factor bearing upon the prognosis of .scarlatina
is the character of the prevaiHng epi(l(;mio. Some outbreaks of scarlet
fever are of extreme mildness and others are frightfully severe. Syden-
ham never saw a severe cas:^ of the disease and, tlierefore, spoke of it
"with a sort of coutcmj)t wliich ho was fjir from having for measles or
smallpox." According to Trousseau, his illustrious master, liretonneau,
had not seen a fatal case of scarlet fever from 1799 to 1822; he was,
therefore, satisfied that "scarlet fever was the mildest of all the exan-
themata." Later experience with a severe form of the disease caused
him to change his opinion and regard the malady as equally mortal
with plague, typhus, and cholera.
The character of scarlet-fever epidemics, as regards benignancy or
severity, commonly persists for a period of years before a change in
type occurs. Graves^ has pointed out that a very fatal epidemic ravaged
Ireland in 1800 to 1804. Then the type changed, and from 1804 to 18,31
the affection was so wonderfully mild that scarcely any deaths occurred.
In 1831, however, a malignant epidemic broke out and in a few years
spread throughout Ireland, causing tremendous loss of life.
It is evident, therefore, that the mortality from scarlatina has an
extremely wide range. It may fall as low as .3 per cent., or reach the
frightful figure of 40 per cent. Johannsen states that in an epidemic
in certain localities in Norway the death rate actually reached 90 per
cent.; this murderous outbreak is absolutely without precedent.
Hirsch and Thomas hold that the average mortal ty of scarlet fever
is about 10 'per cent.; the more that the death rate exceeds this figure,
the greater is the severity of the epidemic. When the death rate remains
below 10 per cent., the epidemic may be looked upon as mild. Thomas,
in enumerating the most fatal epidemics of scarlet fever, says Hambursin
in Namur lost about 30 per cent.; Arrigoni about 40 per cent. ; Salzmann,
in Esslinger, from 1853 to 1857, about 36 per cent.; at Hornbach, in the
Palatinate, in 1868 to 1869, 34 per cent.
The severity of scarlet fever has been diminishing within recent years.
Johannsen says that among 84,580 reported cases in Norway there were
12,789 deaths, a mortality of 14.17 per cent. He regards the normal
mortality in Norway as 13 per cent.
Caiger^ states that during the past twenty-three years 81,350 cases
of scarlet fever have been treated in the hospitals of the ^Metropolitan
Asylums Board of London, with a combined mortality of 8 per cent.
Since 1874 the annual percentage has progressivelv fallen from 12.2
to 5.9.
1 Quoted by Trousseau, American edition, p. 137. - Loc. cit., p. 128.
458
SCARLET FEVER
Year.
Notifications.
Deaths
1890
. 15,330
876
1891
. 11,398
589
1892
. 27,095
1174
1893
. 36,901
1596
1894
' . . 18,440
962
SCAELET-FEVER MORTALITY IN LONDON HOSPITALS. (CaIGER.)
General Mortality. Hospital Mortality.
5.71 7.86
5.17 6.67
4.33 '7.28
4.32 6.11
5.21 5.92
The higher mortahty in the hospitals is said to be due to the larger
proportion of severe cases sent in.
The death rate in the Municipal Hospital has been as follows:
Scarlet-fever Mortality in the Municipal Hospital
OF Philadelphia.
Year.
Cases.
Deaths.
Percentage.
Year.
Cases.
Deaths.
Percent
1891 .
63
2
3.17
1898 .
380
45
11.84
1892 .
159
14
8:80
1899 .
604
57
9.43
1893 .
170
32
18.80
1900 .
646
53
8.20
1894 .
129
11
8.52
1901 .
. 1115
108
9.68
1895 .
163
11
6.73
1902 .
673
56
8.32
1896 .
253
18
7.11
—
1897 .
858
99
10.37
Total
. 5213
506
9.72
It is seen from these figures that the mortality rate is somewhat higher
in Philadelphia than in London.
The factors that influence the prognosis in individual cases are (1)
the age of the patient, (2) the virulency of the infection, and (3) the
character and severity of the complications.
Age. — Age affects the prognosis in a most striking manner. While
the general mortality of scarlet fever is from 10 to 12 per cent., in chil-
dren under five years of age, according to Holt, it is between 20 and
30 per cent.
In our own cases the general mortality among 5213 cases was 9.72
per cent.; in children under five years of age it was about double this
figure — 18.6 per cent.
The mort.ality for the different age periods of patients treated in the
Municipal Hospital is herewith subjoined:
Cases.
Deaths.
Percentage
Under one year of age .
40
13
32.5
One to five years . . . .
. 1670
305
18.32
Five to ten years ...
. 1766
106
6.0
Ten to fifteen years
. 476
19
3.99
Fifteen to twenty-five .
. 295
18
6.10
Twenty-five and upward
. 133
7
5.27
The above table shows the h'ghest mortality under five years of age,
and particularly under one year. In the first year of life about one-
third of our patients died.
After the age of five has been passed the mortality diminishes pro-
gressively. The death rate, in our own experience, reaches its minimum
in children between the ages of ten and fifteen years.
Virulency of Infection. — Virulency of infect on is indicated by great
severity of the invasive symptoms. The prognosis is bad when the tem-
perature is excessively high — 106° or 107° F.; when convulsions, stupor.
TIII<: TUf'JA TMMNT OF SCA IlLI'/r FKVKR 45'J
or coma develop; when the eruption is irregular or partial in distribution,
or when it is livid, suppressed, or beniorrliaf^ic. These are malignant
cases and tlie patient is, as a, rule, overwli(;liried early iu tlie course of
the disease.
During the first or second week the a[)pearance of severe anginose or
septic symptoms renders the diagnosis unfavorable.
Patients witli a sloughy throat with tendency to gangrene, great
lymphatic enlargement, purulent rhinitis, and otitis are apt to succumb
to the poison of the disease.
Influence of Complications. — The complications which are most apt
to cause death are nephritis, purulent otitis, meningitis, endocarditis,
pneumonia, etc. The symptoms of evil omen in nephritis have already
been referred to. It shou'd be remembered that cases of scarlatina
that begin in the most benign manner may develop a severe nephritis
with its attendant dangers. This complication comes on late, during
the third week, at a period when the patient and his family have per-
haps looked forward to complete convalescence.
A favorable course of the scarlet fever may be anticipated, under
ordinary circumstances, when the invasive symptoms are but moderately
developed, when the throat is but mildly involved, when the eruption
appears at the proper time, gradually reaches its maximum, and is
uniformly distributed; when the fever steadily declines with the fading
of the exanthem, and when complications are absent or of short duration.
In forecasting the result of an attack of scarlet fever, it is wise for the
physician not to give an unqualifiedly favorable prognosis, even in mild
cases; the liability to serious complications in this disease should cause
him to make some reservation in the expression of an opinion as to the
outcome of the illness.
THE TREATMENT OF SCARLET FEVER.
In the discussion of the treatment of scarlet fever, we shall take up
first the prophylactic or preventive measures, then the hygienic care of
the patient, and, finally, the direct treatment of the disease and its various
complications.
Prophylaxis. — Scarlet fever is an endemic disease in nearly all great
centres of population, and the health authorities of these common-
wealths require sanitary regulations for the control and prevention of
the disease.
As a prerequisite to the prosecution of this work compulsory notifica-
tion is essential. The health authorities must know when and where
scarlet fever exists in order to be able to check its farther extension.
It is the custom in some cities to placard domiciles in which scarlet
fever exists in order to warn persons who might be otherwise disposed
to enter the infected houses. While this plan has certain distinct advan-
tages it does not seem to have found favor among the general body of
physicians. Boards of Health should have the power of thus labeling
infected dwellings, but should exercise a discriminating judgment in
460 SCARLET FEVER
the employment thereof. When scarlet fever breaks out in a dwelling
which is also used as a store or which communicates with one, the
threatened use of the placard will often determine the tenants to send
the patient to an infectious disease hospital.
In the event of refusal, the public should be apprised by means of the
placard of the existence in the building of the disease in question.
There can be no doubt that many infectious diseases are spread through
the mingling of children in kindergartens and schools. Scarlet fever
almost invariably decreases during the summer vacation when the
schools are closed, and increases again when the sessions begin. Every
effort should therefore be made by the proper authorities to prevent
the infection from being transmitted in the schools.
The procedure in vogue in most large cities at the present time is as
follows: The head of the school is notified by the health authorities
that one of the pupils is sick with scarlet fever, and that he is not to be
permitted to return, save after certified examination by a medical
nspector or some other duly authorized person. Other members of
the same household that are in attendance at school should likewise be
debarred until the patient has been sent to a hospital and the premises
thoroughly disinfected, or until the patient has completely recovered
from his illness and proper domiciliary disinfection has been carried out.
A child who develops an attack of scarlet fever should be debarred
from school for a period of time not less than tivo months. Where nasal
or aural discharge or desquamation persists beyond this period the
enforced vacation must be still further extended. While such a rule
often works hardship it will be found to best conserve the public health
and welfare.
In large cities it is an excellent plan to have medical inspectors make
frequent examinations of the pupils in the public schools, with a view
to determining the existence of suspicious sore throats, late desqua-
mation, etc. Where such medical service cannot be commanded,
teachers should be instructed in the symptoms of scarlet fever, so that
cases presenting suspicious symptoms might be immediately sent home.
A careful and intelligent teacher may in this manner often discover the
disease in its incipiency and send the patient away before infection is
conveyed to others.
If these precautions be carried out it will not be found necessary
except, perhaps, in extensive epidemics to close public schools. The
proper ventilation and cleansing of schools, rooms, and buildings will
greatly lessen the danger of the transmission of contagious diseases.
Isolation. — The methods of isolation which are employed in checking
the spread of infectious diseases in general can be utilized with much
effectiveness in the prevention of scarlet fever. This is true (1) because
but a very brief period elapses before the appearance of the characteristic
eruption, thus making possible an early diagnosis, and (2) because the
infection is not apt to be transmitted during the first few days of the
disease. An opportunity is thus given to separate the patient from other
members of the family, who may in this manner be protected. In this
THF. TUICATMFjNT OF HCAlifJiT FEVER 461
respect scarlet fever differs essentially from measles, the conta^ium of
which is given off at a very early date; it is much more difficult to protect
persons who have been exposed to a case of measles than thf>se who
have ])een in contact with scarlatina during the (;;jrly flays. The con-
tagious principle of scarlatina is much less diffusihU' than that of
measles. This makes it possible to localize the infection more readily
in a portion of a house or a hospital.
In households in wliich an ell'ective isolation can be carried out, the
protection of other members of the family can be accomplished with
reasonable assurance. It must be recognized, however, under these
circumstances that eternal vigilance is the price of safety. It is a safer
plan to remove the well children to another place. The liability of
their contracting the disease from an early and brief exposure and
then carrying tlie infection with them is not very great. If there is
fear that this will take place they can be detained at home, carefully
separated from the patient for a week, which period will fully cover
the stage of incubation.
Where effective isolation cannot be carried out at home, and this is
the case in the large majority of households in a community, the patient
should be sent to a hospital, the whole or part of which is set apart
for the treatment of this disease. There can be no doubt that the
treatment of scarlet fever in special hospitals is one of the most important
means of preventing the spread of the disease. It is possible, with
hospital-treated patients, to continue the isolation until every vestige of
desquamation has disappeared, and until discharges from the nose and
ears have ceased. This may in some cases require detention in the
hospital for a period of twelve weeks or longer. In patients treated at
home, especially among the poor, who are not so apt to recognize the
responsibility of their actions, isolation for this period of time can
seldom be enforced.
A very large number of cases of scarlet fever are doubtless contracted
from patients who are prematurely permitted to associate with others.
This naturally brings up the important question: i^oii' long are scarlatina
patients to be isolated and quarantined f
This query is by no means easy of solution. Indeed, in no disease
is it so difficult to affirm that the danger of infection has passed. The
rule which is commonly followed is to continue the isolation until
desquamation has completely ceased and the patient is free from nasal
and aural discharges. In the average case this will cover a period of
six or seven weeks. In some cases it will be necessary to extend the
isolation beyond this period to eight, ten, twelve, or even fourteen weeks.
Despite the utmost precaution in this respect, second cases will at times
be infected at a late date.
All large scarlet-fever -hospitals receive what are known as return
cases. A certain small proportion, about 2 per cent, of the dis-
charged patients, will give rise to cases of scarlet fever in the same
household. The infection may be conveyed by patients who have been
in the hospital nine, ten, eleven weeks or longer; this occurs even though
462 SCARLET FEVER
desquamation is complete, and the patient antiseptically bathed and
clad in perfectly clean garments. The infection in these late cases is
probably derived from the secretions of the nose, throat, or ears. We
have already made mention of a fatal attack of scarlet fever contracted
by a mother from a child who was discharged from the Municipal
Hospital after a sojourn of nine weeks. This woman had been exposed
to her child at an early stage of the disease, at which time she escaped
infection. We have observed on a number of occasions that children
who are exposed to the infection at an early period of the disease may
escape only to contract the disease from a patient who is supposed to
be free of contagion.
The Contagiousness of Desquamating Epithelium. — The view has
generally been maintained that the infection in scarlet fever persists
as long as there is any desquamation. Within recent years the con-
tagiousness of the scales has been seriously questioned.
Millard,^ in a thoughtful article, challenges the view that scarlatinal
desquamation is infectious. The author obtained the opinions of a
considerable number of experts whose answers he has formulated as
follows: Sixteen gentlemen out of twenty-one state that (1) they can
adduce no evidence that desquamating epithelium is, per se, a source
of infection; (2) they consider that too much importance has been in
the past attached to desquamation as a source of infection; (3) their
experience does not support the popular view that desquamation after
scarlet fever is necessarily an indication that a patient is still infectious ;
(4) they believe that a patient may continue to desquamate for some
time after he has ceased to be infectious; and (5) they do not believe
that it is necessary, in order to prevent the spread of infection, that
patients who "otherwise are quite ready to leave the hospital should be
detained until every visible trace of desquamating epithelium has
disappeared.
In conclusion the writer briefly sums up the principal arguments
against the supposition that desquamation is infectious as follows:
"1. The absence of evidence supporting it. It is difficult to believe
but that if the old supposition were correct, strong evidence of it would
ere this have been forthcoming, as is now the case with discharges from
the nose and ears. 2. The fact that infectivity begins prior to the onset
of desquamation and frequently continues long after desquamation has
ceased. 3. The fact that scarlet-fever wards, although abounding in
desquamation epithelium, are not a danger to neighboring houses.
4. The fact that the proportion of 'return cases' does not appear to
be increased among patients sent out from hospital still desquamating.
On the other hand, the principal argument in favor of the view that
desquamation is infectious is the fact that patients still desquamating,
but otherwise apparently free from infection, have frequently been
known to convey the disease to others. The whole force of this argu-
ment disappears, however, when we consider that patients apparently
1 The Supposed Infectivity of the Desquamation in Scarlet Fever, Lancet, April 5, 1902.
Tni<: TfHe
carried out with tlioroughness. If perfunctory fumigation is relied upon
to destroy all infection, unfortunate consequences may follow. The
infection of scarlet fever has a remarkable tenacity and may remain
resident in articles for months or years. Numerous instances of this
are referred to in the chapter on Ktiology.
All articles of little or no value in the sick-room should be burned.
This is particularly true of those things with which the patient has
been in contact, such as body-linen, books and toys.
The apartments should be thoroughly fumigated or sprayed, prefer-
ably with formaldehyde solution; as a matter of extra precaution this
should be used in greater amounts than that ordinarily prescribed
for the given air space. (See chapter on Disinfection.)
The floors, woodwork, and furniture should be vigorously scrubbed
with a carbolic acid solution of about 1 part to 40. The walls, if
painted, should be washed with the same solution. If the walls are
covered with paper it is wisest to have them scraped and repapered.
Blankets, mattresses, upholstered furniture, clothing, etc., should be
disinfected by superheated steam under pressure. Many large cities
are now equipped with dis nfecting plants to wh'ch all such articles
may be sent. Where such is not the case the blankets and bed- linen
after being fumigated had better be boiled and the mattress destroyed
by burning.
It is a wise plan, whenever possible, to allow the sick-apartments to
remain unoccupied and exposed for some days or weeks to the purif\'ing
influence of sunlight and fresh air.
The above precautions may be troublesome and expensive, but it is
by careful attention to these matters that attacks of scarlet fever are
often prevented and human life and faculties thus preserved.
In the event of death from scarlet fever the body should be enveloped
in a sheet wet with a 1 : 1000 solution of bichloride of mercury. It
should be placed in a hermetically sealed casket and buried at as early
a date as possible. The interment should, of course, be private.
Care of Patient. Diet.^ — During the early days of scarlatina, when
the fever is high, milk constitutes the best and usually the most accept-
able diet. Cool milk is soothing to the throat and assuages the intense
thirst which is present in severe cases. ]Most writers insist upon an
exclusive milk diet throughout the entire febrile period, and many
counsel its continuance during the early convalescent stage. When the
patient is willing to take a sufficient quantity of milk to maintain his
body weight there can be no objection to an exclusive milk diet; but
30
466 SCARLET FEVER
some children and many youths and adults object to the monotony of
an exclusive milk diet. We have had an excellent opportunity of judging
of the effect of diet in scarlet fever. For many years the scarlatina
patients in the Municipal Hospital received an exclusive milk diet
during the febrile period. For the past eight months, during which
time over 500 patients were treated, the patients have had a more
liberal dietary. They were encouraged to drink plenty of milk, but
were permitted as soon as they cared to, to have bread and butter with
their meals and a simple pudding and stewed fruit once a day. We
found that patients desired nothing but the milk while the temperature
was high, but that when it became lower they were eager to obtain
bread and butter in addition. Our patients appeared to progress just
as well under the enlarged dietary. Urinary examinations were made
every other day and the results compared with those under the exclusive
milk diet.
Albuminuria was not more frequent in the former than in the latter
and the renal complications altogether were of a mild character. We
present these facts for what they are worth. It is a hardship for some
patients to be denied solid food for weeks, and they may as a result
receive an insufficient amount of nourishment. We have never seen
the above diet do any harm.
Caiger^ allows patients, during the febrile stage, milk with eggs beaten
up, broths, and calves-foot jelly. When the temperature falls he permits
eggs, custard, light puddings, and bread and butter. Ripe and succulent
fruit is given at any time throughout the illness. Caiger states that
there is no risk, as has been alleged, of inducing a nephritis by permitting
these articles of food to be taken.
Our present practice is to use an exclusive milk diet in infants and
very young children and in cases of nephritis, but to allow older children
and adults a little more latitude. The latter frequently request light
solid foods, and we believe that when there is an appetite for such
articles they do no harm.
Confinement to bed should be enforced during the febrile period, and,
during cold and inclement weather, in severe cases for a week or
more after the subsidence of the fever. Young and restless children
whose actions cannot be well controlled had better be kept in bed
from three to four weeks, or until the liability of nephritis has passed.
While it is generally believed that "catching cold" has been greatly
exaggerated as a factor in nephritis, Griffith states that chilling of the
surface certainly acts as a powerful accessory cause in the production
of complications.
The detention of the patient in his bed or room will be influenced
by the age of the individual, the season, and other factors which the
discretion of the physician must solve.
In view of the liability to kidney complications, it is necessary to
keep the skin, which is an important eliminatory organ, in a functionally
1 Loc. cit., p. 170.
77//'; rU/'JATMI'JNT OF HCAULI'/I' Fl-Vhlli 467
active state. All (clinicians are agreed as to the a(]visal)ility of cinployiiig
sponge baths; tepid water is preferably used and should be; apph(;d
twice daily. In addition to promoting gentle diaphoresis these baths
subserve the ends of comfort and cleanliness.
To lessen the tension of the skin and allay it(;hing the inunction of
some unguentous substance is desirable. We have for years employed
cacao-butter for this purpose and have found it cleanly and agreeable
alike to nurses and patients. When much itching is present a 1 per cent,
menthol or 2 per cent, carbolic ointment may be used.
Inunctions of salves containing oil of eucalyptus, ichthyol, certain
silver salts, and many other substances have from time to time been
lauded as possessing special therapeutic virtues.
Medical Treatment.^ — It must be frankly admitted that we possess
no medicament capable of directly influencing or abridging the course
of scarlet fever. Our therapeutic efforts must be directed toward
combating excessive development of the symptoms and toward prevent-
ing and modifying complications. The treatment is, therefore, purely
symptomatic in character.
In mild cases of scarlet fever special medication is often unnecessary,
the disease progressing to a favorable termination under the influence
of proper hygienic care and nursing.
During the febrile stage it is customary to administer a febrifuge
mixture. We have been in the habit of using a combination of the
liquor ammonite acetatis and sweet spirit of nitre, sw^eetened with a
little syrup.
Vomiting, when present, may be controlled by abstinence from food
and the administration of fractional doses of calomel. Constipation
may be corrected by the latter drug, or one of the mild vegetable
laxatives.
It is advisable to use some mild antiseptic in the throat, not only to
relieve the congestion and soreness, but to lessen secondary infection
and the habihty of extension of inflammation to the middle ear.
Fever. — There are many cases in which attention must be directed
to the control of high temperature and the accompanying nervous
phenomena. Scar.et fever is frequently characterized by a very high
initial pyrexia, which tends in a few days to defervesce. When the fever
is above 103° F., and particularly when there are severe nervous symptoms,
such as headache, delirium, stupor, or convulsions, antipyretic measures
should be employed. In the reduction of temperature preponderant
reliance is now placed upon hydrotherapy. Different clinicians have
individual preferences as to the mode of appl^-ing water ; the methods m
vogue are tepid sponge baths, cold sponge baths, wet or cold packs, and
warm, graduated, or cold tub baths. Ice-bags and Leiter's coils are
also employed.
The routine treatment of scarlet fever with cold tub baths, as in the
case of typhoid fever, has not met with general favor. They may be
employed in cases accompanied by great hyperpyrexia, provided there
is no pronounced cardiac depression. Cold baths are not borne well
468 SCARLET FEVER '
by infants or very young children, and should not be used in such
cases.
In cases of average severity with high fever, sponging with cold water,
with or without alcohol, will usually suffice to keep the temperature
within proper bounds. If this does not control the fever and nervous
symptoms, resort may be had to the cold pack, which has a more pro-
nounced antipyretic influence. In milder cases it may be all sufficient
to keep an ice-bag or cold coils applied to the head.
Warm tub baths of about the temperature of 95° F. are recommended
by many physicians. These will frequently reduce a high temperature,
and are more acceptable to the patient and the members of his family
than cold baths; or the graduated bath may be used, the temperature
gradually being lowered until the desired reduction in the fever is
accomplished.
The old superstition about baths being dangerous and causing
patients to "catch cold" has been dissipated, and a complete unanimity
of sentiment now exists among physicians as to the desirability of using
baths of one kind or another in scarlet fever.
Medicinal antipyretics are used to a very limited extent nowadays.
The general feeling is that they are dangerous in large doses and in-
effective in small amounts. Phenacetin in small doses (2 to 3 grains)
may be given as an adjunct to hydrotherapy in bad cases, or to relieve
headache and nervous symptoms in milder cases, Antipyrin and
acetanilid are not in favor, as they are apt to cause too much cardiac
depression.
Throat. — Where the throat shows but slight involvement mild anti-
septic fluids may be employed, either in the form of a spray or a gargle.
For this purpose a weak Dobell solution or a solution of boric acid
or chlorate of potash may be employed. Very young children cannot
use a gargle, and often vigorously object to efforts at swabbing or spray-
ing the throat. Where the physical resistance is so pronounced as to
exhaust the child the procedure is of doubtful advantage and had
better be discontinued. In the anginose variety of the disease it is
equally important to cleanse the nares and throat and to avoid an
exhausting resistance. A firm and skilful nurse is of great assistance
under such circumstances.
When the throat is severely involved and a streptococcus pseudo-
membrane is present, systematic and vigorous treatment is indicated.
Not only does the pharyngeal inflammation tend to spread to the nares
and middle ear, but a general infection is apt to result from strepto-
coccic absorption.
In these cases the throat should be frequently sprayed with peroxide
of hydrogen, plain or diluted, according to the age of the patient and
the degree of inflammation present in the fauces.
In septic cases with ulceration of some of the soft tissues, Caiger^
speaks in terms of high praise of a strongly acid solution of chlorate of
1 Loc. cit., p. 171.
77//'; THKATM/'JNT OF SdAh'LI'/J' h'EVI'lll 4G9
potash -containing a large amonnf of Free cliloiinc.' Tlio lliro;it .-md
nose are irrigated witli tliis fluid by means of a soft-rubber syringe
with a vulcanite nozzle, the head being held over a bnsiri wifli tlie
mouth kept open.
Caiger says: "No amount of gargling, spraying, or swabbing fan
compare with it (this method) in ])oint of cflicaey."
Forchheimer speaks highly of direct applications to flic throat by
means of a swab saturated with I^oeffler's iron-toluol solution. This
shonld be applied once or twice a day and held in contact with the
diseased parts for a little while to secure the best results. In cases of
extensive streptococcic exudate in the throat this writer counsels the
use of antistreptococcus serum, which, he believes, will occasionally
improve the local symptoms in a remarkable manner.
Purulent Rhinitis. — Purident rhinitis in scarlet fever is apt to accom-
pany severe throat involvement. The extension of the suppurative
inflammation to the nasal mucous membrane increases the 1 ability to
general sepsis and augments the gravity of the disease. A sanious, sero-
purulent discharge issues from the nostrils in great quantities. The
efforts of the nurse must be directed toward systematic and frequent
cleansing of the nasal cavities. But this must be done with great care
and gentleness. The forcible projection of liquids into the nose will
do harm, as will, hkewise, the use of strong and irritating antiseptics.
It has been our custom to have the nose gently irrigated with a warm
saline solution; this is done with a small glass piston-syringe with a
blunt end. In obstinate cases we have recently employed a 10 per cent,
solution of argyrol, one of the newer silver compounds. This remedy
has lessened the profuse discharge and has led to a healthier condition
of the parts.
Patients with gangrenous destruction of the soft palate or tonsils do
not, as a rule, recover. Apart from the stronger remedies referred to
in the treatment of membranous angina, one may, in this condition,
employ a warm solution of permanganate of potash, 1 : 2000. In
circumscribed gangrenous patches we have frequently applied the
tincture of iodine with good results.
Noma. — Noma is fortunately an uncommon complication of scarlet
fever. When the condition is still in its incipiency the pultaceous deposit
upon the mucous surface should be scraped away with a curette and the
base thoroughlv cauterized with fuming nitric acid. This had better
be done under the use of ether, which can be given in just sufficient
quantity to benumb the patient's sensibilities. If the cutaneous surface
becomes attacked, free excision will be found to be a not too radical
procedure.
Glands. — The glands at the angle of the jaw commonly attain the
greatest size and most frequently undergo suppuration. Glandular
1 According to Caiger the solution is prepared by pouring strong hydrochloric acid upon powdered
chlorate of potash in a large, stoppered bottle. The proportions advised are 5 minims of strong
acid to 9 grains of the salt, with suflScieut water to make an ounce. The solution is of a greenish
cplor, and has a strong chlorine odor.
470 SCARLET FEVER
abscess may be expected in nearly all cases of anginose scarlatina. In
the beginning an ice-bag should be applied about the neck. A special
bag manufactured for this purpose buttons around the neck and keeps
the ice in close apposition with the affected glands. A piece of flannel
should be interposed between the bag and the skin. A dried pig s
bladder filled with small pieces of ice will answer the purpose when an
ice-bag is not 'available.
If, despite the application of cold, the gland increases in size and
suppuration becomes inevitable, heat should be substituted. Flaxseed
poultices, rendered antiseptic by having incorporated in them a 1 : 4000
solution of corrosive sublimate, hasten the suppurative process. Upon
the first suspicion of pus formation an incision into the gland should
be made and free drainage established. It is better to lance prematur-ely
than to delay too long, for inflammation may spread to the periglandular
tissues. When cellular infiltration takes place free incisions should be
made, even though no pus focus can be demonstrated, for by this means
the deep -burrowing pus which forms later may be anticipated and the
most fatal of complications — Ludwig's angina — may be prevented.
The Ears. — Inasmuch as otitis media is an extremely common com-
plication of scarlet fever, it should be guarded against as much as
possible and the condition promptly met when it develops. The prophy-
lactic treatment relates to those measures which are designed to keep
the nasopharynx clean and free of infective secretions. While this
object is a laudable one, no treatment will, in bad cases, prevent the
development of otitis media. Indeed, it may be stated that the liability
to ear complications is directly proportionate to the severity of involve-
ment of the throat and nose.
Pain in the ear is best relieved by the application of heat; this may
be accomplished by syringing gently with water as hot as can be borne,
or, better still, by the use of external dry heat. The hot-water bag or
hot salt or bran bag may be placed against the ear. Dench suggests
heating a little salt in the tip of a kid-glove finger and thrusting the
same into the ear. The instillation of a few drops of a warm 4 per cent,
solution of cocaine is advised by some writers.
When the pain continues despite these measures, suppuration is
probable. If upon inspection of the tympanic membrane bulging is
seen, an incision should be made to evacuate the pus. It should be
remembered, however, that in very young children, in whom otitis
is commonest, the small size of the canal and the restlessness of the
patient make aural inspection and paracentesis extremely difficult and
unsatisfactory. Furthermore, spontaneous rupture is the rule in these
cases, and may be the first evidence of involvement of the ears.
After drainage is established it is necessary to keep the external
auditory meatus clean and free of pus. Various liquids are advised,
such as 1:5000 solution of bichloride of mercury, 1 in 4 solution of
peroxide of hydrogen, saturated solution of boric acid, etc. We have
found boiled water containing a little carbolic soapsuds very useful.
All solutions should be used warm and injected gently with a soft-rubber
Till'] tiii<:atmi<:nt of s(jaiuj<:t Fi'!V/toms
of measles during the epidemic of 1070-74, and his description of the
disease (barring a few terms, for instance the use of the word pustule)
com})ares not unfavorably with j)resent-day writings: "The measles
generally attack children. On the first day th(;y have chills and shivers,
and are hot and cold in turns. On the second day they have the fever
in full — disquietude, thirst, want of appetite, a white (but not a dry)
tongue, slight cough, heaviness of the head and eyes, and somnolence.
The nose and eyes run continually, and this is the surest sign of measles.
To this may be added sneezing, a swelling of the eyelids a little before
the eruption, vomiting, and diarrhoea with green stools. These appear
more especially during teething time. The symptoms increase until the
fourth day. Then, or sometimes on the fifth, there appear on the face
and forehead small red spots, very like the bites of fleas. These increase
in number and cluster together, so as to mark the face with large red
blotches. They are formed by small papulae, so slightly elevated above
the skin that their prominence can hardly be detected by the eye, but
can just be felt by passing the fingers lightly along the skin.
"The spots take hold of the face first, from which they spread to
the chest and belly, and afterward to the legs and ankles. On these
parts may be seen broad, red maculae, on but not above the level of
the skin. In measles the eruption does not so thoroughly allay the
other symptoms as in smallpox. There is, however, no vomiting after
its appearance; nevertheless there is slight cough instead, which, with
the fever and the difficulty of breathing, increases. There is also a
running from the eyes, somnolence, and want of appetite. On the sixth
day, or thereabouts, the forehead and face begin to grow rough as the
pustules (?) die off and as the skin breaks. Over the rest of the body
the blotches are both very broad and very red. About the eighth day
they disappear from the face and scarcely show on the rest of the body.
On the ninth there are none anywhere. On the face, however, and
on the extremities— sometimes over the trunk — they peel off in thin,
mealy, squamulae, at which time the fever, the difficulty of breathing,
and the cough are aggravated."
To Sydenham belongs the distinction of trenchantly separating small-
pox and measles. But scarlatina and measles were still confounded.
Twenty years later jNIorton regarded measles and scarlet fever as due
to the same miasm; he asserted that they bore the same relation to each
other as discrete and confluent smallpox. ]Many writers of this period
spoke of scarlatina under the designation of morhUli confJuenfes.
Reports of epidemics which were undoubtedly mealses were, according
to Fuchs, published bv Forestus (1563), Lange (1565), Ballonius
(1574-75), and Schenk (1600).
As far as any accurate knowledge is concerned, measles is a disease of
comparatively modern origin.
**^'
478 MEASLES
THE ETIOLOGY OF MEASLES.
Measles may be regarded as the inost contagious of the various
exanthematous affections. When it breaks out in a household or an
institution it is almost impossible to prevent its spread, so diffusible is
the contagious principle which causes it. This fact and the universal
susceptibility to the disease make ^measles the commonest malad^i.to
which human flesh is heir. But few persons go through life without
at some time or other passing through an attack of measles. When it is
escaped during childhood it is extremely apt to be contracted during
dult life; in this respect it differs markedly from scarlatina, against
which most adults acquire an immunity.
Whether or not measles can be successfully inoculated still remains
in doubt, despite the very considerable experimentation and literature
on the subject.
In 1758, Francis Home, of Edinburgh, attempted the inoculation of
measles at the suggestion of Monro. He saturated bits of muslin with
blood obtained by incising through the measle lesions. These were laid
open upon the excoriated arms of healthy persons. In this manner
he claims to have inoculated twelve children, in most cases with success,
although the disease appeared in a mild form. Pieces of muslin moist-
ened with the nasal secretion which were placed in the nostrils of healthy
children failed to produce the disease. Theussink,^ who attended
Home's clinics and saw these experiments, expresses doubt as to Home's
interpretation of the results. At Theussink's suggestion, his friend
Themmen later repeated these inoculations in 1816 with negative results.
In 1822 Speranza successfully inoculated measles, and claims to have
had the disease himself in this manner. In 1854, an Italian physician,
Bufalini, reported successful results both of his own and his countrymen,
Locatelli, Rossi, and Figueri; Horst and Percival are likewise credited
with positive inoculations.
In 1842 Katona^ performed 1122 inoculations in twenty-six townships
of the Borsoder Comitates; 93 per cent, of these were successful, the
attacks being of a mild character. An admixture of blood and the con-
tents of miliary vesicles taken at the height of the rash was rubbed into
excoriations made after the manner of vaccination. At the end of seven
days fever and the usual prodromal symptoms developed; the eruption
appeared two or three days later, about the ninth or tenth day after
the inoculation.
Mayr successfully inoculated measles in 1848 and in 1852. He placed
freshly secreted nasal mucus from a case of measles in the nostrils of
two children living at a distance from one another. At the end of eight
and nine days, respectively, catarrhal symptoms developed, followed in
a few days by fever and the eruption. In an article on measles^ published
1 Abhandlung iiberdie Maseru, translated from the Dutch by Dr. Doden, of Giittingen.
2 Nachricht von einer im Grossen erfolgreich vorgenommenen Impfung der Masern wiihrend einer
epidemischen Verbreitung derselben, Osterreich. med. Wochenschrift, 1842, No. 29, pp. 697-98.
3 Mayr's article on Measles in Hebra's Diseases of the Skin, 1866.
77//'; i<:ti()IJ)(!y of m/'JAsiJ'JS 470
in 1866, Mayr remarks: " Inoculations with l)Iood made by myself in
1848 and 1852 afforded iiepjative results." The use of d(;s(juainatin^
skin also failed to traiisnn't the disease, as had previously oeeurred in
the ex])eriineiits of Ahix.'uider Monro. The negative n.-sults in the
transmission of measles by the inoculation of blood, in the hands of
Thenimen, Albers, Mayr, and Thomson, should cause us to accept the
alleged successful results with some reservation. Only after there has
been confirmation by ])erfectly relial)le and careful observers, under
conditions that preclude the possibility of the natural transmission of
the disease, should measles be regarded as an inoculable affection.
The usual mode of contagion in measles is by direct exposure to a
person suffering from the disease. The contagium of measles differs
from that of scarlet fever in two respects — it is more diffusible anrl it is
less tenacious; the infection does not tend to any marked degree to cling
to objects or apartments, and transmission of the disease by fomites is,
therefore, distinctly unusual.
Richard^ claims that the contagium of measles cannot be carried by
fomites nor by a protected person. Bard^ states that the contagium of
measles does not remain viable in a locality from which patients have
removed. Comby^ says that the germ of measles has but little vitality .
outside of the body, and that every germ that emanates from a measles
patient is dead at the end of a few hours.
While we are not prepared to dogmatically state that measles cannot
be carried by infected objects or third persons, our experience is in
accord with that of most writers that such occurrences must be ver\'
rare. Von Kerchensteiner calls attention to the observation that
physicians' children do not as a class contract measles earlier in life
than other children. Considering the frequent neglect of precautionary
measures, this would not be the case if the disease were readily trans-
missible through infected garments.
Official reports of the extensive epidemic of measles in the Faroe /
Islands in 1846 (at which time over 6000 persons were attacked) gave
no instances of transmission of the disease by infected articles or by
third persons, and this point was carefully investigated by the physicians
who studied this epidemic.
Theussink states that he knew of a case where the infection was
conveyed by a letter sent through the post, and also an instance where
it was attributed to an engraving sent by mail. The negative evidence
of intermediate infection is so abundant that such cases must be sub-
stantiated beyond the perad venture of a doubt before they can be
unreservedly accepted.
When measles breaks out in a family circle it attacks all of the sus-
ceptible members thereof. Kindergartens and schools offer fertile
opportunity for the dissemination of diseases. Consequently measles,
as well as the other contagious diseases of children, is much more
1 Therapeutic Gazette, July 16, 18SS.
- Revue d'hygioue et de Police Sanitaire, May 20, 1S91.
3 Trait6 des mal. de I'enfauce.
480 MEASLES
common during the periods of the year that these institutions are in
session.
SusceptibiHty to measles is practically universal. All mankind,
almost without exception, will take the disease when exposed to it.
The temporary insusceptibility exhibited by very young infants will
be referred to later.
One of the most remarkable and instructive epidemics of measles
in history is that which visited the Faroe Islands_ija,-I846.^ These
islands had been free from measles since ITSl^ a period oFsixty-five
years. The disease was introduced by a Danish cabinetmaker who had
become infected in Copenhagen. On his arrival at Thorshavn, the chief
port of the islands, he communicated the disease to two friends. These
persons gave rise to an epidemic which in a short space of time attacked
over 6000 subjects out of a population of 7782. Persons of all ages were
stricken and almost every household was converted into a hospital.
The old inhabitants who had passed through an attack as children in
1781 alone escaped. Not one old person who was exposed to the
infection, and was unprotected by previous attack, failed to take the
disease.
That certain individuals may exhibit a temporary immunity against
measles is recognized by most writers. THomas says :^**T~oB'served,
during an epidemic among about 130 cases, 5 children, 2 of whom were
boys of two and three years, evince an immunity during this epidemic,
while 2, boys of eight and twelve years, and a girl of nine years had
evinced it as well during previous ones."
Hoff makes mention of 3 .men, acting as nurses in the epidemic of
1846 in the Faroe Islands, who remained exempt, but who contracted
the diseas ' when it recurred in the islands in 1875.
Spiess^ states that a number of children, varying in age from four to
seventeen years, after having been previously exposed to measles without
contracting it, fell ill in 2 cases after seven weeks, in 1 after two
months, in 4 after two and a half months, and in 1 after five months.
Moore^ reports the case of a boy who, passing through two epidemics
of measles with impunity, fell ill during a third and gave the disease to
a younger brother, who at the time of the first invasion was not born,
but who had successfully resisted the second one.
It is difficult to explain this temporarily absent susceptibility, but it
is quite analogous to that observed in suckling infants.
The presence of an acute disease is apt to temporarily diminish
susceptibility to measles, or, when the infection is received, to postpone
its outbreak until convalescence from the first disease. This is true of
most of the exanthematous affections. The susceptibility to measles
may even be temporarily abolished during the existence of another acute
malady. An instance of this has recently attracted our attention.
1 This remarkable epidemic was carefully studied and reported by Panum, who visited seventeen
of the twenty islands of the group during a period of four months. A later epidemic in 1875 was
assiduously investigated by E. M. HoflF; SundhedscoUegiets Aarsberetning for 1876.
* Quoted by Thomas, loc. cit. s Quoted by Thomas, loc. cit.
77//!,' KTIOLOCIV OF M/'JASLFS 481
A boy, aged five years, was believed to be su fieri ug from smallpox and
was sent into the wards of the Municipal IFospitaJ devoted to this dis-
ease. On making our rounds we discovered tliat the boy harl measles
at the height of Uw. eruj)tive stage aufl not small[)Ox; he was immedi-
ately transferred to other quarters. He had been in the ward about
fifteen hours; in this same ward were about fifteen children, from a few
months to twelve years of age, suffering from smallpox in its various
stages. Some of these children later succumbed to small})Ox; but not
one contracted measles.
Age. — Measles most commonly attacks indivichials l^etween the ages
of one and ten years. Jllliis age . incideucc is. determined by several
factors ail ahnosi universal vulnerability to the disease, a diminished,
"siiscepliltiliiy (hii-ing the (irst year of life, and. the imiiiunity conferred-
by one altack. There can be no doubt that infants under one year of
age and particularly those under six months will commonly escape
measles when exposed to the disease. This is ef|ually true of rubella,
and, in a measure, true also of scarlet fever. This immunity is not
absolute, but only relative. There are numerous records of infants of
tender age who have contracted measles, but under six rnontlis tliey
are very apt to resist the infection altogether.
Pfeilsticker^ reports an interesting epidemic of measles occurring in
Hagelloch, near Tubingen, in which 188 out of 197 children under
fourteen years of age, contracted the disease. Seven of the children
were under six months of age and all of this number remained xcell.
Of 10 infants between six months and one year, 9 contracted measles.
Tiiis-^kperience would tend toshow that-infants under six mjonths of
age ar e very nuKjli -more immune than those a few mouths older.
r]e~13arbillier," in an epidemic of measles in the Foundling Hospital
at Bordeaux, noted but 7 cases among 40 children under one year of
age. Mayr reports that of 10 newborn and suckling infants exposed
to the disease, but 1 contracted it.
The susceptibility, then, to measles is largely in abeyance during the
first six months of life; after this period it gradually increases so that
after the first year the temporary immunity has entirely vanished.
Measles may in extremely rare cases be contracted during intra-
uterine existence, and children may be born with fully developed erup-
tions. After careful search of the literature Thomas was able to find
but 6 properly authenticated instances of this occurrence. Numerous
authors refer to congenital measles, but the facts in many cases render
the diagnosis doubtful. Several authors cited by Thomas record cases
which bear the stamp of genuineness. Clarus reported to the ^Medical
Society of Leipzig that he had seen the eruption of measles quite plainly
on a foetus the mother of which had died during the exfoliative stage of
the disease. Hedrich speaks of a female child born on the fourth day
of an attack of measles in the mother that was covered with the measles
exanthem and had catarrhal symptoms, sneezing, coughing, and inflamed
1 Beitriige zur Pathologie der Masern, etc., Tubingen, 1863.
2 Quoted by Thomas, loc. cit.
31
482 MEASLES
eyelids. Vogel, Guersent, Hildanus, Lidelius, Michaelson, Seidle,
Ballantyne, and others have also reported cases which in all number
about 20. The diagnosis in such cases could be controlled, as Thomas
suggests, by noting the susceptibility or immunity of these children in
later years. He reports an attack of measles in a woman five months
pregnant, in which the susceptibility of the foetus was not affected, for
the child contracted measles at the age of nine years.
Von Jiirgensen says: "The poison must be able to pass through the
placenta. It is presumed that the child becomes infected very soon after
the disease organisms have attacked the mother, since the disease
presents the same stage of development in mother and child at the time
of the latter's birth."
Hoff, on the other hand, states that "without exception everybody
born in the year 1846 whose mother, according to her own statement and
as affirmed by comparison with the church records, contracted measles
during pregnancy, was attacked by the disease, if exposed to it, at the
time of the epidemic of 1875." Hoff states that this was true no matter
what month of pregnancy the mother happened to be in when she was
suffering from the measles. This experience throws a flood of light
upon the question of the placental transmission of measles. Hoff draws
therefrom the conclusion that "there is not the slightest ground for
believing the contagion to be carried to the foetus through the placental
circulation."
Adult life offers no such immunity against meiE!j(;cts fix; inf(M;f.ion
takes hold and an e})ideniic results. Thomas asserts that in large
communities epidemics mny be expected al)ont every two or four years.
In small towns and villii,ge. The eyes are
reddened and watery, sensitive to light, and often show puffiness of the
lids. The nose at first feels obstructed, but soon a discharge issues
therefrom, accompanied by repeated sneezing. Occasionally nose-bleed
occurs, but this is seldom severe. In pronounced cases the face may
present a pufl^y and swollen appearance. The involvement of the larynx
and trachea gives rise to hoarseness a^d to a dry, hjrd^ and-high-pitchfid
..,££aigh. At times the throat is sore, exhibiting'^upon inspection redness
and swelling of the tonsils, soft palate, and pharynx. The constitutional
symptoms consist of fever, headache, loss of appetite, drowsiness, and
irritability. Somnolence is often a prominent feature. Chills are rare,
1 Cited by Thomas, loc. cit. 2 Diseases of Infancy and Childhood, New York, 1899, p. 911.
3 Quoted by Thomas, loc. cit.
PLATE XLVIL
Fig. I.
'ig- 2.
Fig. 3.
Fig.
The Pathognomonic Sign of Measles (Koplik's Spots).
^^•^^ 1- The discrete measles spots on the buccal or labial mucous membrane, showing the isolated
rose-red spot, with the minute bluish-white centre, on the normally colored mucous membrane.
Fig. 2. — Shows the partially diffuse eruption on the mucous membrane of the cheeks and lips; patches
of pale i)ink interspersed among rose-red patches, the latter showing numerous pale bluish-white spots.
Fig. 3. The appearance of the buccal or labial mucous membrane when the measles spots completely
coalesce and give a diffuse redness, with the myriads of bluish-white specks. The exanthema on the skin
is at this time generally fully developed.
Fig. 4.— Aphthous stomatitis apt to be mistaken for measles spots. Mucous membrane normal in hue.
Minute yellow points are .surrounded by a red area. Always discrete.
Tlir<: SYM/'T()MAT()I/)(;V OF M/'JASfJ'JS
489
occiirriiifi;, ;i,('Cor(lin<^ (o Zi(Mr),s,S(;n and KniMcr, only five limes in ''>\\
cases studied by tlicin. 'I'lie bowfds arc iisnjdiy conslipjilcd, idtlioiif^li
occasionally a slight diarriura is ()l)serv('d.
3.^heje yer does not, ol)serv<; any set standard, hut ia subject to con-
._sideral)le variation. Ju some cases it rises rapidly fJuring tbe first
i3Vuiaty-fonr Iionrs, reaching by eveniiif,' 102° to lO.T F. On tlie morning
of the se<'()n
UJ
n
<
>
s
J
<
u.
I
X
'k
^
"-
"-
\
Y
J
/
ri
4
/*
"^
.«^~, .,.».«,...>■ : •»—
77//'; S)'MI"r()MAT()f/X;Y OF MFASLFS 497
Desquamation begins as tlu; rii.sli f.-ulcs iiwiiy inid is fir,-,( /irjfc*] upon
inili.'u sites of llie ci'dpiioii, ii;i,iiH'iy, (Ik; tuc(; uiid (he neck, llie scaling
is braiuiy ;ui(I fiirriirjiccous, and is often ,so fine as to require careful
"scrutiny (o obsnvc il. 'i'he skin seldom comes off in large flakes as it
does in scarlet icvcr. 'Vlw. junount of des()uair);itif)M varies in difl'erent
cases and is usually ])ro|)()rti()nate to tlie intensity of the antec^edent
eruption. In many [)atients no descjuamation will be seen at all. On
the trunk the perspiration which is common in measles obscures the
fine scales or enables them to cling to the body linen. The desquamation
is usually most observable on the face. S<"ding continues ordinaVily
from a few days to a week, but may rarely be j)rotracted for ten fJays
or iwo weeks.
Anomalous Cases of Measles. — All exanthematous diseases exhibit at
times variations from what might be regarded as the normal standard.
Anomalous cases of measles may develop individually during the course
of a normal epidemic, or there may be special aberrant features peculiar
to prevailing forms of the disease. The special predominance of the
papular element of the eruption is more common in certain epidemics.
Mayr says that the Nirlas or "Nirles of Alibert" was mostly probal^ly
a papular form of measles.
The chief deviations from the normal type are those forms that
exhibit unusual benignity or exaggerated severity.
Mild Measles. — In rare cases there may be an absence of one or several
of the important manifestations of the disease that go to make up the
characteristic symptom-complex, ^hus, measles inay exist ^^■ithout
fever, without catarrhal symptoms, or, indeed, without an eruption.
^'Measles Without Fever (Morbilli sine febre), Morbilli Apyretica. — Leulje
says: "Although there may be very little fever in mild cases, it is never
entirely absent." Nevertheless, von Jiirgensen^ reports two cases of
measles occurring in infants of four weeks and twenty-one months of
age, respectively, who had catarrhal symptoms and undoubted eruptions,
and who had been exposed to measles, who never had any elevation
beyond 99° F. Extremely mild and abortive cases of measles appear to
be more common in young infants, who, as has been stated, possess
only a very limited susceptibility to the disease.
Measles Without Catarrhal Symptoms (Morbilli sine catarrho). — The
absence of catarrhal symptoms is occasionally noted in infants during
the prevalence of measles of the ordinary type. In such cases there is
usually very little elevation of temperature and the eruption is not
intense. The genuineness of these attacks is established not only by
previous exposure to regular measles, but by the immunity conferred
against subsequent attacks. J.t.. 14. evident that when the fever and
catarrhal symptoms are insignificant the case must present considerable
resemblance to rubella. If a disease prevails epidemically, in which
these two groups of symptoms are uniformly in abeyance, the strong
probabilities are that the disease is rubella and not measles.
1 Loc. cit., p. 267.
32
498 MEASLES
Measles Without Eruption (Morbilli sine exanthemate, Morbilli sine
morbillis). — As is the case in sniallpox and scarlet fever, it is possible
^for measles to occur without the development of the exanthem.. Such
cases are, of course, excessively rare, but are recognized by careful and
conservative writers. Thomas says that the diagnosis is more often
made than is justified, but remarks that "this form of the disease may
be diagnosticated in persons previously unattacked, if in a single case,
during an epidemic of measles, the characteristic mucous membrane
synaptoms together with fever appear and become exactly as much
developed as in measles with an exanthem, so that we have ground for
assuming that this symptom alone is lacking from a normal course."
Cases may occur in which the attack of measles is typical up to the
eruptive stage, but at this point the anticipated exanthem fails to appear
and convalescence is established. Embden^ claims to have observed
20 patients among 461 cases of measles in Heidelberg, in whom the
eruption was absent. The cases were of a mild type, but some few
had severe complications.
Rush makes mention of persons who in 1789 presented the usual
manifestations of measles, fever, cough, etc., but no eruption except
in some cases a trifling efflorescence about the neck and breast. Webster^
claims to have seen similar cases in 1773 and 1783.
Well-authenticated cases of this kind are said to have been seen in
an epidemic in Paris in 1850. The usual premonitary symptoms of
measles appeared in a number of children; the regular course was
followed in a certain proportion, but in a number of others some present-
ing unequivocal spots of measles on the neck and chest, which rapidly
disappeared, the lungs became quickly involved.^
Rilliet* reports a case of severe measles without eruption in a twenty-
one-month-old child who contracted the disease twelve days after other
cases in the same family. There were fever, coughing, and sneezing,
but the eruption did not appear. On the fourth day a lobular pneu-
monia developed, the child succumbing on the eighth day. Some
authors accept the statement that desquamation may occur in measles
without eruption. We contend, as in the case of scarlet fever, that
desquamation does not occur without some antecedent structural change
in the skin, and that when desquamation occurs it signifies that a rash
has existed which was unobserved.
There are mild cases of measles in which all of the usual phenomena
are present, but in an extremely moderate, and sometimes imperfect,
degree. The maximum temperature in such cases does not exceed
102° F. and the fever lasts but four or five days. The eruption is faint,
poorly marked, of short duration, and often so indefinite as to require
other evidence to establish the diagnosis. The catarrhal symptoms are
also slight, but present more uniformity than the cutaneous manifesta-
1 Quoted by von Jiirgensen, loc. cit. " —
2 Quoted in editor's notes in Bulkley's American edition of Gregory's Lectures, 1851.
' London Medical Gazette, June, 1850, p. 572 ; cited by Bulkley, loc. cit.
* Barthez and Rilliet, p. 249 ; cited by von Jiirgensen.
77//'; HVMI'TOMATOIJXIY OF MI'lASLHH 4!)9
tions. This form is ;i,])(, l.o Ix^ iiii!itt,(;ii(lc(l Ity coniplications ;ui(l flic
prognosis is exlixniicly fav()rjil>l('.
Severe and Malignant Measles.- INJcuslcs of unusual severity may occur
in isolaicd inslaiiccs in ordinary c|)i(lf the
eruption, so that on the second or third day the rash became cjuite
scarlatinal in appearance.
In some cases characterized by great initial severity the system seems
to be overwhelmed by the poison of the disease. The temperature
soars to great height (105° to 107° F.), there is profound prostration , great
restlessness alternating with stupor, and the patient succuml)s })efore
the appearance of the rash. In these toxaemic cases the diagnosis may
be extremely difficult, and, unless elucidated by the history, quite
impossible.
Severity may also be manifested by the early development of pvbnonari/
complications. The first few days of the invasive stage may be quite
normal, but suddenly the lungs become attacked and a fatal result
rapidly ensues.
In the so-called typhoii form of measles the disease is ushered in
with high fever and great prostration. The skin is hot and dry; there
is great thirst and marked muscular relaxation. Nervous symptoms are
pronounced, the patient being either apathetic and somnolent or delirious.
The tongue is dry and furred, the lips glazed, and the teeth covered w^ith
sordes. The abdomen is tender and distended and the bowels often
loose. The eruption is poorly developed and bluish in appearance.
These cases are usually fatal, death taking place within a week or,
less commonly, convalescence may occur after a tedious and protracted
illness.
Such cases as the above were not rare during the Civil War. Camp
measles does not differ essentially from measles seen among civilians
save that as a result of privation and exposure the disease is apt to
assume a more severe form. IMeasles is one of the most formidable of
camp diseases, as is attested Ky^the morbiefore the heifjjht of the eruption is attained. The recession of
the rash may l)e temporary, tlie eruption later reappearing, or it may
be permanent. The lay community has a traditional dread of this
"striking in" of the eru})tion, fearing the involvement of one of the
internal organs. As a matter of fact the sudden fading of the exanthem
is not tlie cause, but the result of such condition. 'J^y^. plienonienon is
usually due to severe pulmonary involvement, leadii)g to canlijic fnihire
"a^nfr'conj^^^ crippling of the circulatory aftpafafi is. TIk- skin
necomes pale and the eruption fades either completely oy shows itself
as indistinct, bluish spots. With an improvement in the heart action
the spots naturally acquire more color and the eruption, so to speak,
returns. Thomas believes that rapid disappearance of the eruption
does not necessarily indicate the development of some complication.
He says: "I have never had an opportunity to convince myself of the
connection of a speedy fading of the spots with the sudden occurrence
of a complication. A simple rapidly progressing paleness of these can
certainly not be considered anomalous."
Postrubeolic Eruptions. — Reference has already been made to the
occurrence of a morbilliform rash, associated at times with renewed fever,
developing after convalescence from measles. In rare cases other
eruptions may make their appearance about this time. Roger^ has
seen cases, both of recurrent measles and also accidental erythematous
rashes after measles. He reports an instance of the latter in a young
woman twelve days after an attack of measles, and another in an infant,
two and one-half months old, thirty-eight days afterward.
Meyer-Hoffmeister^ saw a scarlatiniform erythema during con-
valescence from measles.
COMPLICATIONS AND SEQUEL .X OF MEASLES.
Larynx. — A moderate grade of catarrhal laryngitis is uniformly
present in measles, and is, therefore, scarcely to be regarded as a com-
plication. The laryngeal symptoms develop early in the invasive stage,
giving rise to hoarseness, frequent cough, arid occasionally spasmodic
dyspnpea* The cough is dry, loud and hollow in tone, and in the begin-
ning unproductive of expectoration. The paroxysms of coughing are
often violent and incessant, seriously interfering with sleep. I'pon the
appearance of the cutaneous eruption the cough becomes looser and
less frequent and is accompanied by expectoration. Holt states that
severe catarrhal laryngitis is present in about 10 per cent, of all cases
of measles.
Ulcerative Laryngitis. — Ulcerative laryngitis occurs in a certain pro-
portion of severe cases. In such instances the inflammation is so intense
1 Loc. cit., p. 875. 2 Quoted by Thomas, loc. cit., p. 90.
502 MEASLES
as to lead to necrosis of the mucous and submucous tissues. The vocal
cords are commonly involved in the destructive process. Barthez and
Rilliet found ulcerations and erosions in almost one-half of the cases
of measles that came to autopsy. Pseudomembranous deposits were
present in about one-fifth of the cases.
Gerhardt^ has seen these ulcerations by laryngoscopic examination
during life. He has found them particularly upon the posterior wall
of the larynx in cases that exhibit marked stenosis. They may be seen
at times early, but are more commonly observed during the eruptive
stage. The superficial ulcerations give rise to a rough, dry, frequently
repeated cough, accompanied by spasmodic attacks. There is pain upon
coughing, speaking, or swallowing, and often considerable dyspnoea.
The most dangerous form of laryngitis is that accompanied by the
formation of a pseudomembrane, the so-called membranous laryngitis.
The fatality of this complication is frightful. In the Hospice des Enfants
Assistes in Paris, Granlou^ found this complication 235 times among
1633 cases of measles; out of these 235 patients 218 died, a most appalling
mortality.
We have seen a number of these cases that had to be intubated; they
all succumbed to the disease. Holt has collected 35 cases of membranous
laryngitis out of 2837 cases of measles from miscellaneous sources; he
remarks that this complication is more frequent than this in institution
epidemics.
^^^^{Terpbranowg. Uryngitis JOjay resiult from the action of Jhestrepto;;;^
coccus, the diphtheria bacillus, and, perhaps, other organisms. ^Holt
states that when the membrane forms in the larynx at the height of , the
disease it is almost always, of, streptococcic origin; when it develops at*-
a later period it is usually due to the Klebs-Loeffler organism. ,,, The
.majority of cases appear to be due to pyogenic bacteria. The false
membrane is not always limited to the larynx, but may invade the fauces,
nose, and mouth. The laryngeal stenosis usually comes on gradually,
although more commonly the symptoms may be sudden in their appear-
ance.
The dyspnoea frequently becomes so alarming as to necessitate
intubation or tracheotomy. These procedures, however, give, as a rule,
but temporary relief, for a fatal bronchopneumonia is almost sure to
develop. «.^..«---
The diagnosis between true laryngeal diphtheria and membranous
laryngitis of streptococcus origin can only be indubitably settled by a
bacteriological examination; the former condition is apt to develop late
and the latter at the height of the disease. The prognosis appears to
be equally desperate in both conditions.
Lungs. — The trachea and larger bronchial tubes are so commonly
involved in the catarrhal process in measles that a moderate grade of
tracheitis and bronchitis may be regarded as belonging to the normal
symptomatology of the disease. It is only when the inflammatory
1 Lehrbuch der Kinderkrankheiteu, p. 63.
- La rougeole h rh6spice des enfants assist6s, Paris, 189a.
C.OMI'hldATIONH AND ^ICljU Ef.M 01'' Mf'JASL/'JS
503
disturbance is intense, ;ui(l downward extension takes ]:)lace that the
complication assunies a sei'ious Jisjx'c-I. Severe hroneliiiiJ eatarrfi usually
niMiiifests ilseU' just at or after tin; lieiirhi of iIk; eruptive statfe; if it )>e
sudieienlly widespread, llie fever, wliicli at this time falls, will eoutinue
to remain elevated. There is fre(|uent eouf^hin^, accompanied hy muco-
purulent exj)ect()ration.
Foreifi;!! writers still employ the term (•(lylllary hr one} litis; the tendency
in this country is to look upon the involvement of the minute bronchioles
as an essential part of a bronchopneumonia. The symptoms of capil-
lary bronchitis, therefore, are virtually those of catarrhal pneumonia.
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A
Measles. Pneumonia.
Boy, five years old. (Tuley.)
Bronchopneumonia. — Bronchopneumonia is the most common and
most fatal of all of the complications of measles. Other conditions fade
into insignificance when compared, to the slaughter tliat this complica-
tteiToccasions. Over a half-century ago Gregory wrote: "I am sure I
^peaK much within bounds when I say that nine-tenths of the deaths
by measles occur in consequence of pneumonia."
*^Bartels met with 68 cases of bronchopneumonia among 573 cases of
measles, or 11.9 per cent.; Ziemssen and Krabler report 50 attacks of
pneumonia among 311 cases of measles, or 16.1 per cent. The figures
of Embden give a much smaller incidence — 27 attacks in 461 cases, or
5.9 per cent. The frequency of this complication seems to vary con-
siderably in different epidemics. It is much more common in foundling
■^sylums, orphanages, and similar institutions. It is more apt to attack
feeBlelind poorly nourished children and those debilitated by previous
illness. This complication is particularly prone to attack children
504 MEASLES
under two years of age. Holt states that in two epidemics in the Nursery
and Child's Hospital, embracing about 300 cases, nearly all in children
under three years old, bronchopneumonia occurred in about 40 per cent,
of the cases. Of those who had pneumonia, 70 per cent. died. Henoch
says that a certain amount of pneumonia is seen in nearly all fatal
cases 01 measles.
Bronchopneumonia usually manifests itself when the eruption begins
to decline, although the onset may be delayed to a later period. The
posteruptive decline in the temperature fails to occur, the fever instead
remaining in the neighborhood of 103° F., with, perhaps, morning remis-
sions of a degree or so. The pulse is greatly increased in frequency,
and the respiration is shallow and hurried, and not infrequently labored
and difficult; it is a pitiful sight to see the little patient with dilating
nostrils and a livid countenance raise itself in the bed to relieve its
distressed breathing. The cough may be short and repeated or infrequent
and spasmodic. In unfavorable cases there is protracted fever, progress-
ive increase in the rapidity of respiration (60 to 80), cold extremities,
extreme weakness, and rapid-running pulse. Nourishment is refused
and, when taken, is often vomited. Great pallor develops and toward
the end a characteristic lividity is seen. A few hours before death the
temperature may rise to great height, 107° or 108° F. In favorable cases
the temperature at the end of ten days or two weeks declines gradually
to normal, the cough lessens, the respiration improves, the child becomes
brighter, desires more food, and takes an increasing interest in its
surroundings.
The symptoms that indicate the presence of a bronchopneumonia
are protracted fever^ cough, rapid pulse, hurried aiid labored breathing,
and prostration. Percussion will often discover some dulness over one
or both of the lower lobes posteriorly; the respiratory murmur is
diminished and bronchovesicular breathing is heard; in addition to
the coarse rales heard in the larger tubes, fine, moist rales are audible
over the small, consolidated areas.
Lobar Pneumonia. — Isobar or croupous pneumonia is a much less
frequent complication of measles than the catarrhal form, and is apt,
when it occurs, to develop in older patients. This form of pneumonia
is characterized by higher fever with fewer remissions, by its limitation
to one lung or lobe thereof, by the presence of pleuritic pains, a shorter
course terminated by crisis, and a lower mortality rate.
Pleurisy. — Pleurisy with effusion is an unusual complication of
measles. In some epidemics it may develop secondarily to a sevejgL^
pneumonia7 in' which case it is apt to eventuate in an empyema.- '^^
Fiirbringer^ calls attention to the occasional occurrence of a primary
pleurisy with effusion. He has observed a number of cases, most of
which ran an acute course and were probably purulent from the begin-
ning.
Pulmonary Tuberculosis. — Pulmonary tuberculosis may manifest itself
as a termination of a long-standing bronchopneumonia occurring after
* Eulenberg's Real-Encyclopedia, vol. xii., second edition, p. 559; quoted by von Jilrgensea.
COMPJACATIONH AND S/'JQf/l'Jf.A'J Oh' MHASLHH 505
measles. Tlie l)r()ncliial catarrli and llie l(;won-(l nisisfarioe of the
patient render the iniphintation of tuhfa-ciilosis n'.-ulily fxpHc^able. Jr]_
rases in wliicli a Ijifciit glaiuhilar tuherculosis, particularly of the
ihonicic lymph nodes, li;i,s existed, the "attack of measles stiniuTafeslHe
j)revioiis disense to noxious activity. Tn some cases tuberculosis rnay
""develop as a direct se((uel of measles, an irregular temperature persisting
after the incomplete convalescence from the latter disease. The tuber-
culous disease may take the form of an acute miliary tuberculosis.
Holt truly says: "An attack of measles in a child vv^ith tuberculous ante- ^
cedents should always be looked upon with a])prehension."
Barthez and Rilliet have observed gmrjreji/; of the Inn.r/s in four
instances, and Steiner and Neureutter have mcl wiih this complication
in two patients. This much to be dreaded condition may have its
origin in a severe bronchopneumonia.
Alimentary Tract.- — From what has already been said concerning the
measles exanthem it is evident that a mild inflammation of the buccal
and pharyngeal mucous membrane is uniformly observed. This comes
on in the invasive stage and tends to subside as the cutaneous eruption
increases in development.
The cheeks, gums, tongue, soft palate, tonsils, and pharyngeal wall
all participate in the catarrhal process. In feeble and debilitated
children this inflammation, especially under the influence of infection
with pyogenic and other bacteria, may lead to complications which
are not only subjectively distressing, but of serious import. Aphthous
stomatitis has been reported by a number of writers. The sores may
give rise to much pain and interfere with the desire of the child to take
nourishment. Ulcerative stomatitis not infrequently develops, particu-
larly in the buccogingival furrow. This is characterized by the form-
ation of small patches covered with grayish, necrotic epithelium. When
the dead epithelial covering is cast off there are disclosed to view ulcer-
ations of varying depth, with sharp and irregular edges; the base is
frequently covered with a pseudomembranous deposit. These losses
of tissue are not infrequently seen on the gums, and about the lips, par-
ticularly the oral commissures ; in the latter regions each movement of the
mouth causes pain and induces bleeding. In poorly nourished children
these ulcerations may last for a long time before complete healing
occurs.
A fortunately rare but most frightful complication of measles is that >
form of gangrene variously designated cancrum oris, gangrenous stom- ^
otitis, or noma. The fatal character of this complication makes the ^"^-^
condition of sufficient importance to warrant a description elsewhere.
To be sure, there are less serious forms of gangrenous stomatitis in
which the loss of tissue is circumscribed. We have not infrequently
seen necrosis of a portion of the gum and subjacent alveolar process
which, after the throwing off of the slough, has been followed by thorough
healing; in some of these cases a portion of the bone and the neighboring
teeth have come away.
In a certain proportion of cases membranous patches may be seen
506 MEASLES
on the tonsils and neighboring palatal mucous membrane. This
process may spread downward into the larynx and give rise to the
dreaded membranous laryngitis. The pseudomembrane may be of
streptococcic or staphylococcic origin like the exudate seen in scarlatina,
or it may be true diphtheria. In some cases tonsillitis is observed, in
which event there is enlargement and congestion of these structures and
pain upon swallowing.
The stomach is but rarely the seat of any serious complication.
Diarrhoea. — ^piarrhoea_is a common and not infrequently a serious
accompaniment of measles. It may exist in all grades, from a slight
catarrhal enteritis, lasting but a few days, to a severe enterocolitis
with fatal outcome. x4ls would naturally be expected, diarrhoea is more
jcommon in the summer months and especially in extremely hot summers.
This complication is also more frequently observed in tropical and sub-
tropical countries. Gregory says: "In India and other hot countries
thoracic complications are rare; diarrhoea and dysentery prove the
usual and most troublesome sequelae." It is not at all uncommon for a
mild diarrhoea to be present in the invasive and early eruptive stages.
There are frequent loose and watery movements, with or without pain,
which tend to subside as the eruptive stage advances. The severe
forms of enteritis and ileocolitis usually develop late during the decline
of the eruption. In some cases the large intestine is involved and
symptoms of dysentery manifest themselves; pain and tenesmus are
present and frequent; small, bloody stools containing mucus are passed.
Diarrhoea appears to be more common in some epidemics than in
others. Willischanin^ observed an epidemic of measles in a girls' school
in which 10 out of 50 of the patients had diarrhoea during convalescence.
It lasted from three to five days and was believed to be due to the
elimination of special toxins.
Intestinal inflammation is most frequently observed in infants and
young children, in whom it not infrequently leads to a fatal termination.
Cases are on record, however, in which adults have succumbed to
measles as a result of this complication.
Nervous System. — As is the case with most infectious diseases, measles
may be accompanied or followed by a great variety of disturbances due
to involvement of the brain, spinal cord, or the peripheral nerves. When
the fact is recognized that measles attacks almost the entire human
family, the relative infrequency of nervous complications may be
appreciated.
Mental Disorder. — Measles is, in rare instances, followed by insanity,
which usually takes either the form of mania or dementia. Christian^
reports a case of temporary mania and paralysis. Finkelstein^ saw 2
cases of mania after measles, and Bond^ observed a case developing on
the eighth day of the disease. Weber noted delusions of persecution in
one of his patients. In an epidemic of 108 cases occurring in an insti-
, 1 St. Petersburger med. Wochen., December 4, 1893 ; quoted by Williams, loc. cit.
2 Centralbl., 1874, p. 95. » Vratsch, 1898, No. 20.
■* Maryland Medical Journal, January 29, 1898.
COMPIJdATIONS AND S/<;(J(/ l'J/..^(;rt instances
of jraiifrreiie attackinf>; various portions of the eutaneons snrfa(;e.
l7npelir/o, boils, and abscesses are occasionally observed duririf^ con-
valescence from measles. They represent varying grades of infection
witii tlie common pyogenic organisms. Kczema occasionally makes its
initial ap})earance after an attack of measles and may persist for an
indefinite period. On the other hand, chronic eczemas have been
known to disappear after an attack, as in cases reported by Behrend
and others. Psoriasis has been observed to appear for the first time
after measles. Measles, of course, does not cause the ])soriasis, but
merely determines the date of its outbreak.
Disseminated tuberculosis of the skin may follow in the wake of
measles, as in the cases reported by Du Clastel,^ Haushalter,'' and
Adamson.''
Du Castel saw 3 cases and remarks that "it is not exceptional to see
a disseminated tuberculosis of the skin as a sequel to measles." This
usually attacks the face, legs, and especially the upper extremities. The
lesions appear soon after the decline of the measles eruption in the
form of small, deep-red nodules. Haushalter saw 2 cases of scrofulous
lichen, 1 of which later developed enlarged glands and tuVjerculous
gummata. Adamson's case was one of multiple warty lupus occurring
on the arms and legs. The patient subsequently developed a post-
pharyngeal abscess and later hip disease.
Roger'^ observed, in the spring of 1900, 4 cases of erythema nodosum
after attacks of measles. A girl, aged seventeen years, eleven days after
the termination of an attack of measles of moderate intensity, developed
fever, and twenty-four hours later a typical erythema nodosum of the
legs and subsequently the arms, accompanied by painful joints; the
condition lasted fifteen days.
The other 3 cases were analogous; they occurred in patients fifteen,
seventeen, and twenty-six years of age, respectively. Fever appeared
from nine to ten days after the termination of measles. The erythem-
atous nodes and the joint involvement persisted from seven to ten days.
Eyes. — Ocular complications are not rare in measles, a fact which
is easily explained by the severe catarrhal involvement of the conjunctiva
during the invasive and eruptive stages. The eyes are particularly apt
to suffer in scrofulous children. Corneal ulcerations mav occur, and,
in bad cases, lead to perforation and general panophthalmitis. It is not
rarejfor obstinate blepharitis, granular lids, or keratitis to persist a long
Time after convalescence from the original disease. Comby states that
proper Carre of the eyes gTeatly reduces the number of ocular complica-
tions, and in support thereof mentions the fact that he observed only
17 cases of conjunctivitis of moderate intensity among 71.5 cases of
measles.
1 Quoted by Thomas.
- Annal. de derm., etc., 1898, tome ix., Nos. 8 and 9, p. 729. •' Ibid., No. 5, p. 455.
•1 British Journal of Dermatology, 1899, p. 20.
s Loc. cit. p. 875.
510 MEASLES
Ears. — ^Inflaimnation of the middle ear is by ilo -^Hieaiis.,arLJ4iicommon
complication of measles, although it does not develop as frequently as
in scarlatina. The catarrhal inflammation of the nasal passages fre-
quently extends along the Eustachian tubes to the middle ear. Bezold^
carefully explored the ears in 16 fatal cases of measles, in all of which
he found inflammatory changes. The tympanic cavity contained either
a mucopurulent exudation or a material that was frankly puriform.
The streptococcus pyogenes was present in about 50 per cent, of the
cases; in the other half the staphylococcus aureus and albus were found.
The raucous membrane is red, swollen, and covered with a muco-
purulent or seropurulent exudate. Tobietz^ examined the ears of 22
cases of measles at autopsy and confirmed the above-mentioned find-
ings.
Both ofjl^ese writers are in accord as to the early development jqJE, the
aural catarrh. The ear troul)le is hot regarded as due to a secondary
"infection, but is rather the result of the localization in this region of
"the enanthe^3^ j^^^^ otitis may therefore develop in the early
eruptive period. In a case studied by Tobietz that died twenty-four
hours after the appearance of the eruption, otitis was already present.
This early otitis is comparatively mild and usually does not lead to
perforation of the tympanic membrane. The later-developing otitis
media usually results from infection from the nasopharynx, and is much
nibre prone to end in suppuration and perforation.
Severe purulent otitis media appears to be more common in some
epidemics of measles than in others. Downie'' states that children who
have adenoid vegetations and suffer from catarrh of the throat and nose
are more apt to develop middle-ear trouble. He furthermore claims that
the horizontal posture of the sick child favors Eustachian infection and
retention of the inflammatory products within the middle ear. Of 501
cases of tympanic involvement in children seen by Downie, the con-
dition was attributable to measles in 131 instances, or 26.1 per cent.
Curiously, only 63 cases (12.6 per cent.) were observed that developed
during an attack of scarlet fever.
It is not always easy to diagnose the onset of an otitis media, particu-
larly in young children who are unable to make verbal complaint. ^ The^
complication most commonly develops about the end of the second
week. Children are cross and fretful, frequently toss the head and
cry out with pain. The temperature is usually elevated and may rise
to great height. When an otherwise inexplicable rise of temperature
occurs about this, time, the "possibility of purulent otitis must be con-
-Jfdered. Inspection of the tympanic membrane is not an easy task in
young children. When this can be accomplished the membrane is seen
to be congested and lustreless, and when pus is present the tympanum
bulges into the meatus, the puriform secretion shining through the
lower tympanic segment.
In severe cases of middle-ear disease necrosis of the ossicles or of the
1 MiiQchener med. Wochenschrift, March, 1896. 2 Quoted by Comby, loc. cit.
8 British Medical Journal, 1894, vol. ii. p. 1163.
COMPLICATIONS AND HI'Kid KL/K OF M/'JASIJ'JS F)]]
surl-oundiiifij bony walls uiuy take place. Huikner' says: "An invasion
of the labyrinth by cocci causing necrosis has been repeatedly dernon-
strated of late. The lesion results in a very serious loss of functional
power." The suj)|)urative inflaniination may extend to the mastoid
cells or, in rare (•iis(\s, to the membranes of the brain. Ashby arifl
Wriglit have pointed out the fact thnt infection may take j>lace througli
the petromastoid suture, which in infancy is still ununited. Purulent
meningitis, abscess of the brain, or thrombosis of the lateral sinus might
thus (levelop. In general it may be stated that mi(Jdle-ear troul)le
complicating measles is^less serious than that whicli occurs in scarlet
fever.
" I\l;iny ciiscs of (Icaf-miiHsm are traceable to attacks of measles. Kerr,
Love, and Addison^ have collected statistics from ihstitutions in Great
Britain which show that of 1140 deaf-mutes, 138, or 9.8 ^per^ cent.,
attributed their lo.ss of hearingTo^-ttaCks of "measles. "O'f'lCTS accjufrerl
cases in American institutions, 52, or 3.1 per cent., were due to measles.
Among 1989 acquired cases on the continent of Europe, 84 cases, or
4.2 per cent., were ascribed to this disease.
In these cases the deafness results from destructive changes in the
internal ear which have resulted from extension of the inflannriatory
process from the middle ear.
The Heart. — Endocarditis, pericarditis, and myocarditis are rare
complications of measles. Inflammation and degeneration of the
cardiac muscle may occur in malignant cases, particularly when there
is hyperpyrexia. We recall a malignant family epidemic some years ago
which destroyed the lives of the three children of the household. The
first child sat up in bed during convalescence and dropped back dead.
The other two succumbed to a profound toxaemia.
Cases of endocarditis have been reported by Martineau, West, and
Kobler. Hutchinson^ records 4 cases in which mitral murmurs developed
during the course of measles, and Cheadle refers to 2 cases found in the
post-mortem records of Great Ormond Street Hospital. Gomby dis-
covered mitral insufficiency in a girl nine years old, after an attack of
measles. Although Sansom* states that the influence of measles in
predisposing to endocarditis has been much underrated, most writers
are of the opinion that this complication is a rarity.
Pericarditis, according to Autenrieth, is not infrequent. Cases have
been reported by Berndt, Majer, Espinouse, Braun, Siegel, Metten-
heimer, and Heyfelder.^ When pericarditis occurs it is apt to be asso-
ciated with a pleuropneumonia.
Kidneys. — Renal complications are rare in measles, their infrequenCy
coiitrasting sharply with their prominence in scarlatina. Nevertheless,
Baginsky says that his recent experience leads him to believe that they
would be discovered more often if carefully looked for.
1 Behandlung der bei Infectionskrankheiten Vorkommenden Ohraffectionen, loc. cit., p. 581.
- Deaf-mutism, a Clinical and Pathological Study, Glasgow, 1896 ; cited by Dawson Williams,
loc. cit.
3 Med.-Chir. Trans., 1891, vol. xxiv. * Quoted by Williams, loc. cit.
^ Mentioned by Thomas, loc. cit.
512 MEASLES
Febrile albuminiiria of brief duration is not uncommon in well-
pronounced attacks of measles, as in other infectious processes accom-
panied by fever. When the kidneys are seriously involved there may
be general anasarca, as in cases reported by Abeille, Denizet, and Comby
(2 cases). Ascites and anasarca may, however, occur without albumin-
uria, at times in association with chronic diarrhoea.
Cases of true nephritis have been placed on record by Geissler, Roser,
Frank, Rilliet, West, Kjellberg, Lehman, Bouchut, Malmsten, Spiess,
Hauner, Steiner, Neuretter, Zehnder, and Thomas, who cites these
various writers. Fatal cases with ursemic symptoms have been reported
by Miiller, Demme, Browning, and Zichy-Woinarski.^
Vulvitis.— ^ Among 715 cases of measles treated in isolation pavilions,
Comby observed vulvitis twenty-five times, an incidence which he
thinks was kept relatively infrequent through systematic antiseptic
irrigations. The inflammation of the vaginal orifice and vulva begins
early, as a rule, and may persist for some time. The parts are red,
swollen, covered with a mucopurulent discharge, and extremely tender.
Micturition is accomplished with considerable pain. In some cases
vulvar ulceration occurs and more rarely gangrene.
Glands. ^ — ^A moderate grade of adenopathy is a part of the normal
symptomatology of measles. In some cases the lymphatic glands
become greatly enlarged, particularly in the cervical region. In rare
cases suppuration may take place, as in cases mentioned by Gregory
and Rilliet.
In other cases the glandular enlargement may persist for a long time
and eventually terminate in glandular tuberculosis. This is particularly
true of the bronchial glands. Fichtbauer, Thore, Eiseman, Bufalini,
and Battersey^ have reported cases of inflammation of the parotid gland
accompanying measles, and Seidl, Schultze, and Kellner have seen the
parotids involved at a later period.
Purpura. — Hemorrhages developing late in the course of the disease
or during convalescence should not be interpreted as evidence of malig-
nant hemorrhagic measles, but as a secondary and superadded condition.
Nearly all of the exanthemata may at times be complicated at a late
stage by the development of hemorrhages into the skin and from the
various mucous membranes, including the kidneys and intestines.
Masarei^ saw eight patients convalescing from measles attacked with
fever, dropsy without albuminuria, and "scurvy, mostly in the form of
purpura;" all of the cases ended fatally. Gley* saw intense purpura
hemorrhagica, together with scorbutic appearances in the mouth, some
days after the disappearance of the measles rash.
Gangrene. — iVlthough gangrene is not a common complication of
measles, it appears to occur more often after this infection than any
other, excepting, of course, cutaneous gangrene in smallpox.
The necrosis is apt to take the form variously designated as cancrum
oris, gangrenous stomatitis, or noma. This formidable complication
1 Australian Medical Gazette, October 15, 1893.
2 Quoted by Thomas. ^ Quoted by Thomas, p. 104. * Quoted by Thomas.
COMPLICATION H AND HI':Q(J I<:L/I<: of Mf'JASLI'JS
01.3
commonly (lf;vel()])S during Uk; dcdinc of the (inipflon. If is r;ffr;n
associated With or"|'5TCred'prt-hynTTTi}ccr,ativ(; sfoiniiiifis. 'J'lic syjnpforn.s
that first attract attention arc salivation ;in(l a fetid breath. If the
mouth is inspected there will usually he found, })etween tlie commissure
of the mouth on the alVected side and the opein'ng r)f Steno's duct, a
vesicular elevation of a violaceous color; this becomes f^radually darker
and finally gives way to a blackish, pultaceous mass. The corresponding
portion of the cheek on the exterior is swollen and of a wax-like pallor.
Soon a bluish-red spot appears, which l)ecomes gangrenous and breaks
through. From tl)is point the necrosis now spreads in all directions.
The spreading border is surrounded by a dusky-red zone which is firm
and infiltrated. The immediate spreading edge shows a raising up of
the epidermis in the form of a vesicular ring. There may be an extension
Fatal cancrum oris after measles. The necrotic tissue has been removed, exposing to view the
alveolus and teeth.
of gangrene from one-quarter of an inch to an inch in twenty-four hours.
The gangrenous process m severe cases involves the entire cheek and
the greater part of the nose and hps. It has been known to attack the
ear, the eyelids, and a considerable portion of the neck. I'sually the
patient dies of exhaustion before such ravages are possible. In a small
proportion of cases the gangrene ceases, a line of demarcation is formed,
and the sphacelated tissues are gradually thrown off. In such instances
the deformity must subsequently be remedied by a plastic operation.
In the fatal cases there is great prostration, the child takes nourishment
with difficulty, and deatli takes place ordinarily in from one to two weeks.
A horrible odor emanates from the patient, which pervades the entire
room in whicli he lies.
There is a less serious form of gangrenous stomatitis in which the
33
514
MEASLES
Fig. S3
Cancrum oris complicating measles. Photograph taken two days after the cutaneous tissues
became involved.
Fig. 84
Same patient as Fig.
showing the spread of the gangrene. Photograph taken three (
after the previous picture.
COMPLICATION H AND HI':QUI<:L/K OF MFASLFS 515
necrotic process is limited to the iiiiieoiis inciriljraiif; and fjoriy tissues
of the mouth. Tliis (lommonly lias its orif^iu uhout, fhc ^ums and
alveolar process. After the loss of some of the teeth and a jjortion of
necrosed alveolus, the process may cease and recovery take place. In
some cases, however, this hony necrosis is merely j)art of the general
gangrenous process wliich attacks the cheeks.
The necrotic process may, in rare cases, attack the genitalia, particu-
larly of female children, giving rise to the condition known as noma
jiudendi. The course of the gangrene does not differ from that involving
the mouth.
Fig. 85
^^^^^^^
|P^^^
'%. '
P
-*•■'<►,■.,
ma^A
gjjIH
1
5
k.
..J. —
.^H
Same patient as Figs. S3 and 81. Pliotograpli taken alter deatti on the eighth day after the
beginning of the gangrene, and three days after Fig. 84.
Measles has preceded about one-half of the cases of cancrum oris
on record. In 106 cases of siangrene of the mouth, Tourde found 41
to follow or accompany attacks of measles. Caillout and Bouley, in
46 cases of gangrene of the mouth, noted measles as an antecedent dis-
ease in 40 instances. Mahieux saw measles produce gangrene of the
mouth in 3 out of 11 cases. Thus, in 163 cases of gangrene of the
mouth measles preceded in 84, or over 50 per cent.^
Rilliet and Barthez observed 11 children with measles attacked
with gangrene; the localization was as follows: gangrene of the mouth,
8 times; gangrene of the lungs, 4 times; gangrene of the pharynx, 3
times; gangrene of the larynx, once. The gangrene appeared in several
localities in some of the patients. INIoynier saw 6 cases of gangrene in
1 Mentioned by Moynier. Des accidents graves de la rougeole, etc., Metz, 1S60.
516 MEASLES
measles. In 4 cases the vulva was attacked, 2 dying. Gangrene was
noted five times attacking the skin, the following regions being selected :
abdomen, face (twice), arm, and buttock. A number of other cases
of gangrene of the mouth were observed. Pneumonia and diarrhoea
were frequent .complicating conditions.
Hildebrandt^ and Perthes^ from the literature have collected 133 cases
of cancrum oris in which the antecedent or accompanying disease is
mentioned. Noma accompanied or followed measles in 53 cases. The
diseases are as follows:^ measles, 53 times; typhoid fever, 26 times;
chronic diarrhoea, 21 times; scrofula, 19 times; smallpox, 9 times;
diphtheria and measles, twice; diphtheria and typhoid, once; diphtheria
of the genitalia, once; diphtheria and scarlet fever, once.
The affection is extremely rare in infancy and beyond the age of
puberty; it may be remarked that measles is also uncommon during
these periods. Von Bruns* collected 413 cases of noma, among which
only 6 cases occurred in infancy.
The cause of noma is but poorly understood. It has been variously
attributed to embolism, nerve involvement, the use of mercury, and
infection with some necrotizing micro-organism. The last-named
theory is doubtless correct, although the identity of this microbe does
not appear to have been determined.
Walsh^ made a careful bacteriological study of 8 cases of noma
occurring in a home for children in Philadelphia. It is an interesting
fact that these cases occurred during a period of two and one-half
years. The diphtheria bacillus was recovered by culture from each
case. Inoculation and tinctorial tests were employed to identify the
Klebs-Loeffler organism. Most of the cases followed measles, but
several occurred after diphtheria. Four of the cases began with ulcer-
ative stomatitis. A number of the cases of ulcerative stomatitis — 15 in
all — were cultured, but diphtheria organisms were not found. Walsh
states that "since noma is a species of moist gangrene, requiring probably
from analogy two different micro-organisms, one a saprophyte to produce
putrefaction, another a parasite to produce primary necrosis, it is
possible that in these cases where diphtheria bacilli are found they
may be the primary causative agents. When other pathogenic micro-
organisms capable of producing necroses are found, it is possible that
they may be the primary excitants."
The above investigation is of considerable interest, particularly in
view of the painstaking manner in which it was carried out. The result,
however, is scarcely in harmony with our clinical experience. W^e have
observed 4 cases of fatal cancrum oris within recent years; 3 occurred
with measles following scarlet fever, the other with measles alone. We
have never had a case of noma develop in the diphtheria wards, although
on a number of occasions measles has broken out there.
1 Dissertation, Berlin, 1873. 2 Verhandl. deutsch. Gesellsch. f. Chir., 28 Kongress.
3 Mentioned by Walsh. Diphtheria Bacilli in Noma. Proceedings of the Philadelphia Patho-
logical Society, June, 1901.
* Handbuch der prakt. Chir., Band i., Abth. 2. ^ Loc. cit.
(JOMf'fJC'ATIONS AND HKQd NIjA': OF ATh'ASfJ'JS .017
Noma is regarded l)y Matzenauer^ as a form of hospital gangrene, fjut
feebly contagious and requiring, as a rule, a severe preceding disease
to produ(;e a predisposition. He discredits tlie rliplitluiria bacillus as
an etiological factor, and believes the exciting organism is the same
anaerobic rod-sha])cd bacillus that is found in }iosf)itaI gangrene.
One fact is undoubted, that measles for some reason more strongly
predisposes to the development of noma than any other affection.
Babes and Zambilovici^ announce that they have discovered a very
small bacillus, cultures of which injected into the cheek of a rabbit
have given rise to gangrene similar to noma.
The mortality of noma is frightful, about 70 per cent, of the patients
succumbing to the disease.
Pregnancy.— Measles in 'pregnant women is uncommon, inasmuch as
most individuals pass through an attack of measles in childhood. As
is true of nearly all infectious diseases, the development of measles in
parturient women is apt to prematurely terminate the pregnancy.
Rosch has reported a case of abortion terminating fatally as a result
of measles.
Incidental Improvement in Chronic Diseases After Measles.^ —
Every infectious disease produces a certain systemic comraotionor change;
this may favor the development of diseases to which the patient may
be inclined. On the other hand, existing diseases, sometimes of long
duration, may disappear after such a systemic shaking-up. Thomas
has collected a number of interesting instances from which we freely
quote.
Behrend saw an eczema of the scalp of three years' duration, in a
woman of forty years of age, permanently cured after an attack of
measles. The curative influence of measles upon long-standing diseases
of the skin has also been attested by Rilliet, Taupin, Guersent, and
Rayer. Barthez and Rilliet saw chorea, epilepsy, and incontinence of
urine of several months' duration get well after measles.
According to Weisse, a girl who suffered from convulsions was
entirely cured. Guersent noticed, with the beginning of the fever of
measles, permanent relief from epileptiform seizures, of which the
patient had had several a day for a long time. Schmidt saw a six-
year-old girl, who had had daily convulsions that had so reduced her
strength that death was expected, completely recover after measles.
Feith and Schroder van der Kolk report the case of a woman who for
five years was confined to an asylum because of violent attacks of mania,
who, after measles, was cured and discharged from the institution.
Hildebrandt saw an obstinate disease of the joints, which had been
unsuccessfully treated for three years, promptly get well after con-
valescence from measles. Schmidt noted an almost magical recovery
in a five-year-old boy with contraction of the lower extremities of six
months' duration. Of course, such examples of the accidental curative
influence of an attack of an infectious disease are met with not only
I Arch. f. Derm. u. Syph., 1902, No. 60, p. 373. a Quoted by Koger, loc. cit, p. 402.
518 MEASLES
after measles, but also at times after other processes. Mention is made
elsewhere of a raving maniac, confined in an insane asylum, who was
completely cured after an attack of smallpox.
Coincidence of Measles with Other Infections. — Measles may be
complicated by- almost any of the known infectious diseases. In the
association of several infectious processes measles may be the primary
disease, or it may develop secondarily after some other infection. We
have, on a number of occasions, seen measles complicate diphtheria
and scarlet fever. We are inclined to believe that the prognosis is more
serious when measles is the secondary infection than when some other
disease is engrafted upon it. We have seen measles develop during
convalescence from smallpox and have also observed the reverse order.
In the vast majority of cases the one disease develops during the
decline of the other. We have never seen measles in its early eruptive
Fig. 86
Boy exhibiting eruption of measles wliich developed during convalescence from smallpox.
stage complicated by a second infectious disease. Measles and whooping-
cough seem to succeed each with more frequency than any other disease.
Among 166 cases of measles, Bernardy^ saw pertussis develop in 21
instances.
THE PATHOLOGY OF MEASLES.
Skin. — At autopsy the eruption of measles is not visibla .unless ,^ ^^^.^
^as been HfEinic extravasation into the skin.
The skin has been studied histologically by Neumann, Catrin, and
Unna. Neumann^ found as the chief changes a round-cell infiltration
, about the l)loodvessels, hair follicles, and sweat glands. Catrin^ likewise
observed a pronounced infiltration of leukocytes, but in addition, in the
nodular form of measles, a series of changes in the deep epidermal cells.
1 Annals of Gynecology and Pediatrics, July, 1894.
2 Histolog. Veranderungen der Haut. bei Masern u. Scharlach, Med. Jahrb., 1882, p. 159.
3 Les alterations de la peau dans la rougeole, Archiv. de med. exper., .1891, No. 2; quoted by
Unna.
77//'; I'ATIIOIJXIV O/'' Mf'JASfJ'JS 519
These consistcMl of a colloid (l(;^eneration of tin; perinuclear /one <)\' soiric
of the (l('ej)-lyin^ e|)i(,heli!il (lells. Around the areas of colloid cliarige
were dilated interepithelial spaces eontaininj^ coagulated fibrin and leuko-
cytes. In the centre of the papule the colloid masses run together and
undergo coagulation necrosis, tliis taking place in the fjrickle layer.
Catrin only found emigration of leid\ocytes from the pajnllary hlcjofl-
vessels at those places where the surface ej)ith('lium contained cf^lloid
cells. Unna regards the colloid change and necrosis of the epithelium
as the result of the direct influence of the poison of the disease upon
the epidermal structures.
Unna' states that in measles a spastic resistance in the cutaneous
vessels is added to the primary congestive hypenemia which develops
around the infection in the capillaries, and this explains the cyanotic
color, the papular swelling, and the urticarial oedema of the centre, as
well as the frequent escape of coloring matter of the blood. The rapidly
developing spastic oxlema always collects at the place of least resist-
ance, which, in children, is in the fatty tissue around the coil glands
and in the sheaths of the larger vessels, the cutaneous muscles and fol-
licles. The individual coils, the hair follicles, and the muscles seem to
swim free in widely dilated spaces.
Dilated lymph vessels and enormously distended lymph spaces are
seen m the lower and central parts of the cutis. Another characteristic
is the almost complete absence of a cellular exudate. Leukocytic
emigration is not more than in all simple stagnatory hyperpemias, less,
indeed, than in most. But a few leukocytes are found in the epithelium.
During the stage of scaling, the subbasal horny layer separates itself
from the basal and, with the central and upper horny layers, form the
scale. The lost epithelium is replaced, as usual, by mitotic proliferation.
The above description, Unna remarks, refers merely to the ordinary
flat or slightly papular eruption.
Mucous Membranes. — The mucous membrane of the nose, mouth,
pharynx, larynx, trachea, and bronchi is the seat of a catarrhal inflam-
mation. The epithelial cells undergo a colloid change and are often
swollen and detached. The lymph follicles and the surrounding struct-
ures are infiltrated with cells. Occasionally when the inflammation is
intense the follicles may break down and form ulcers. At times such
ulceration m the larynx may lead to involvement of the cartilage.
Slawyk,^ in a histological study of the oral mucous membrane, found the
epithelium thickened and in places undergoing fatty degeneration, giving
rise to the whitish dots described by Koplik.
Steiner^ observed in several cases, at autopsy, a blotchy redness of the
mucous membrane of the larynx and bronchi, and Wilson, Eisenmann.
Rayer, and Gerhardt saw a similar condition in the trachea and bronclii.
Heyfelder,^ one of the older writers, describes an eruption similar to
that on the skin in the duodenum, jejunum, and, at times, in the stomach
1 Histopathology of the Skin, translated by Dr. Norman Walker, 1900.
' Deutsch. med. Wochenschrift, April 28, 1898 ; quoted by Corlett.
* Quoted by Thomas, loc. cit., American edition, p. 72. * Quoted by Thomas.
520 MEASLES
and ileum; this has been noted also by several other observers. More
recently Steiner^ mentions a blotchy redness of the intestinal mucous
membrane occurring in children dying during the eruptive stage.
According to Worthington/ the lymphatic follicles and Peyer's patches
of the bowel may undergo destructive ulceration, leading even to perfora-
tion. Thomas says that Fuchs saw, upon the genital mucous membrane,
numerous red, somewhat puffy spots overspread with mucus. This
observation was likewise made by Henoch and Chomel.
Lymphatic Glands. — ^The lympha,tic glands are enlarged in measles,_
but to a less extent than in scarlet fever. When bronchopneumonia Ts
■present the tracheobronchial glands may be found distinctly swollen.
In a certain proportion of cases the glands show evidences of tuberculosis.
Loomis, Pizzini, and Kalbe^ found tubercle bacilli in apparently normal
tracheobronchial glands; the last-named observer noted the presence of
these bacilli in 8 per cent, of apparently healthy glands. It is suggested
that these lie dormant until an attack of measles or some other affection
involving these glands stimulates the tuberculous process to activity.
Lungs. — Bronchopneumonia is present in a large proportion of the
fatal cases. The process is not essentially different from that observed
in bronchopneumonia independent of measles save that there is a more
pronounced tendency in many cases to suppuration. It is not rare for
the pulmonary trouble to eventuate in tuberculosis, exhibiting usually
the form of a caseous pneumonia.
Cornil and Babes* have described a peripneumonia which occurs
early in the so-called suffocative cases, and which they regard as peculiar
to measles. It begins in the lymphatic tissue, involves the interlobular
and interalveolar structures, and leads to fibrinous exudation into the
air vesicles.
StiebeP speaks of a blotchy redness of the pleural membranes which
he observed in four autopsies. They were sharply contoured, red spots,
apparently situated just beneath the pleura on both sides.
Roger observed a purulent pleurisy during convalescence from
measles in a five-year-old child.
The sfleen is moderately swollen in measles, although this is more
often determined at autopsy than at the bedside.
Liver." — Freeman'' found focal necrosis of the liver in 4 out of 14
g^Utopsies on measles cases. The larger areas of necrosis are visible to
the naked eye and may be confounded with tubercle. Microscopically
there is a sharply circumscribed roundish area of necrosis in which the
cytoplasm fails to stain, and fragmentation of the nuclei is seen. The
condition is due to the local action of bacterial toxins.
Blood. — In uncomplicated cases of measles the condition of the
; blood is unaltered. Fibrin may be increased when the catarrhal symp-
toms are severe.
1 Quoted by Thomas. - Quoted by Dawson Williams.
8 Mentioned by Roger, loc. cit., p. 1004. * Quoted by Williams, loc. cit.
5 Quoted by Thomas, loc. cit.
6 Result of Work at the New York Foundling Asylum. Archives of Pediatrics, February, 1900,
and New York Medical Record, 1898, vol. liv.
TIIK BA(JTI<:h'l()l/)(!V Oh' M/'LASfJ-JS 521
The number oi red cdls is nof, strikingly reduced in mild or moderate
cases, and may at times be actually increase;*!. In 8 cases Felsentlial
counted from five to five and a half million eorjjuscles. I'lie h;/'mo-
globin is likewise slifijhtly or not at all reduced.
The v^hifc r.rlh not only are not increased in measles, but they are
often reduced below tlie iiormal. In 8 cases Rieder noted an average
of 7500 cells, the leukocytes being least numerous at the height of the
disease, and increasing as the fever disappeared. Cabot^ states that
during convalescence the lymphocytes and especially the large mono-
, nuclear forms are increased.
According to Coombe, uniform changes occur in the blood in the
incubation period. Coonibe^ ^^J^.} "In the incubation period of measles
tliere is a hyperleukocyfosis M'ithout other symptoms. Tliis is a constant
siii;n of the inc.ubation period. During the last two days of the period
of invasion or exanthem, and throughout the entire period of the
*e:tanthem:, there is a hypoleuJcocytosis."
'-■ These alterations are due to the change in the number of the poly-
morphonuclear neutrophiles. These observations were confirmed by
Platenga,^ Avho also found similar changes in rubella.
The eosinophile cells are usually decreased or normal in number.
Cabot found the differential counts normal; Felsenthal found the poly-
morphonuclear cells much increased and eosinophiles never over 1
per cent.
In cases in which the diagnosis between scarlet fever and measles
is obscure, a differential blood count should 1)6 of distinct value. On
the other hand, the examination of the blood is of no particular value
in differentiating measles from rubella (rotheln), inasmuch as the
cellular constituents are much the same in the two diseases.
THE BACTERIOLOGY OF MEASLES.
The extreme contagiousness of measles is proof of its microparasitic
origin; some reservation must, however, still be expressed as to the
etiological relationship of the organisms thus far described.
Braidwood in 1878 called attention to a bacillus which he found in
measles and which he regarded as the cause of the disease. Lombroso*
described cocci in the rete mucosum of the measles spots. Similar bodies
were found by von Leyden and Fiirbringer.
In 1892 Canon and Pielicke found in 14 cases of measles a bacillus
which they considered to be the specific causative agent. The discovery
was made possible by a special method of staining.'^ The organism was
variable in size, sometimes quite small and resembling a diplococcus,
i Clinical Examination of the Blood, fourth edition, New York, 1901.
» Archiv. de med. des enfants, 1903. ^ Archiv. de nied. des enfants, March, 1903.
* Lo Sperimen., 1884, x.
5 Stain for the bacillus of Cauou and Pielicke. Blood is thinly spread upon a clean cover-glass
and fixed by five to ten minutes' immersion in absolute alcohol. Then stain with the following
solution and incubate at 37° C. for from six to twenty-four hours : Concentrated aqueous solution of
methylene blue, 40 ; 0.25 per cent, solution of eosin in 70 per cent, alcohol, 20 ; distilled water, 40.
522 MEASLES
and other times as long as a red blood cell. It was present in the blood,
sputum, and secretions of the nose and eyes throughout the entire
disease, but disappeared when convalescence set in. The bacillus could
be grown on bouillon, but on no other media.
Czajkowski^ found a bacillus in the blood and mucous secretions of
50 cases of measles, which was apparently identical with that above
described. It grew, however, on various albuminous media, especially
blood serum and glycerin agar, but not on gelatin and plain agar.
Inoculations of mice produced a fatal septicsemia. Gregorieff, in an
examination of the blood in 13 cases, found the bacillus in each case,
and grew it in bouillon in 10 instances.
Josias^ failed to find this organism in a study of the blood and secre-
tions of 24 cases, and Barbier and Warschovsky also obtained negative
results, the latter examining 21 cases.
Arsamakor,^ in an examination of 665 cases of measles, found in the
blood and mucous secretions, grouped, rod-shaped bodies, 5 to 6 microns
in length, having bulbed extremities.
In 1900 Lesage* published the results of a study of 200 cases of
measles. He found a delicate micrococcus which grew best on gelose
(agar), took stains slowly, and was decolorized by Gram's method.
The cultures bore a resemblance to those of the pneumococcus. The
organism was found constantly in measles, but was absent in 25 cases
of scarlet fever and in 45 normal children. In 53 children who had
had measles previously it was found twice. Rabbits were inoculated
with blood and nasal secretions in many cases, and measles apparently
reproduced in nearly all.
Von Niessen^' examined the blood during the height of the measles
exanthem and found a bacillus which in some respects resembled that
of Canon and Pielicke. It produced, however, rose-colored colonies on
gelatin and grew well also on glycerin agar, bouillon, and potato. He
designated this organism "bacillus roseus."
In 1891 Doehle^ found in the blood of 8 cases of measles certain
bodies which he regarded as protozoa. In fresh blood they were observed
not only in the plasma, but also in the red blood corpuscles. After the
eruption appeared the bodies became visible almost exclusively in the
red cells. They were from a half to one micron in diameter and exhibited
an opaque nucleus with a surrounding clear zone. Later larger oval
bodies with two nuclei were seen.
More recently Weber^ has detected bodies in the blood which he
regards as protozoa. From the above divergent findings it is evident
that further research is necessary before any of the organisms described
can be accepted as the specific cause of measles.
1 Centralbl. f. Bakt. u. Parasit., 1895, Nos. 17 and 18.
s La medecine moderne, Paris, June 2, 1902.
3 Article abstracted in Revue de miSdecine, 1899, vol. xix. p. 561.
4 Bulletin de la Soci^tt^ des hOpitale de Paris, March 15-22, 1900.
6 Arch. f. Derm. u. Syph., 1902, vol. Ix. p. 429.
6 Centralbl. f. allgem. Path., etc., 1892, iii. p. 150.
7 Centralbl. f. Bakt. u. Parasit., 1897, vol. xxi. p. 286.
77//'; l)fA(JN()S/S (}/<• M/'JASfJ'JS f/Z'
THE DIAGNOSIS OF MEASLES.
It is a mii.ll<'r of f^rciU, iinporlfuicc, pjuliciihirly in iiishtutioiis for
cliiMnMi, tlia-1, t])v. stablislied. The existenee of an
epidemic of measles or knowled(i;(; of ('xpf)sure to th(^ disease will y;ijt
the physician on guard and often enable hiin to make a diagnosis, or
at least strongly suspect it, upon the first development of catarrhal
symptoms. The statement is erjually true of measles and smallpox,
that the diagnosis cannot be indubitably made before the appearance
of the eruption, although when all of the invasive symptoms are typi-
cally developed, when there has been exposure to the disease, and,
particularly when the characteristic buccal enanthem is present, the
diagnostic probability approaches almost to a certainty. _As in small-
pox. th^ v;^cci nal condition of the patient often constitutes information
o f impo rtant diagnostic value, so in measles does the history as to
p-e vioiTs'allacks . It.js generally agreed that second attacks of measle.s.
are of great rarity. In a doubtful case, an authentic history of a pre-
vious attack, of measles would constitute strong presumptive evidence
against the rubeolous nature of the disease under consideration.
While the diagnosis of measles is usually announced when the eruption
appears, it must not be thought that the rash is in itself all-sufficient
evidence.
The eruption of measles is merely its most conspicuous manifestation.
T^ P ,g!he,.:-.: ,--.«-u..:*,-.-,„,._. ,.^., , :,■-
The catarrhal symptoms affecting the eyes and respiratory passages,
which are so constant in measles, are, absent in smallpox, at least dur-
ing the prodromal stage. CJose^inspection of the mouth in smallppj^
may reveal the presence upon the soft palate of rounded, glistening,
pinhead-sized, reddish elevations, but these differ considerably from the
bluish-red spots on the buccal mucous membrane in measles.
The maculopapules of measles are soft and velvety to the touch, as
compared with the firm, shotty character of the smallpox papules.
Fig. 87
Smallpox on the second day of tlic erupLioii, prcscntiiiL
measles.
resemblance to the eruption ot
The sweep of an experienced hand over the skin will often suffice to
differentiate the two diseases. Where there is doubt, twenty--fouiJiauxs,'
^^ay will dispel all uncertainty, for by this time the eruption of measle s
will have become flatter and more diffuse, and the papules of smallpox
firmer and xnore distinctly elevated.
The prodromal morbilliform rash, the so-called roseola variolosa,
may be confounded with measles. This eruption occasionally develops
in mild cases on the second day of the invasive stage. The lesions are
non-elevated, irregular in distribution, of brief duration, and unaccom-
panied by catarrhal symptoms.
Typhus Fever.— During the epidemic prevalence of typhus a con-
founding of this disease with measles might take place when the eruption
77//'; l)fA(,'NOSlS OF MKAS/J'JS .027
is profuse. Pastau is (jiiofcd hy Tlioinas as saying' fliat. tlif exanflicrn
of typlnis is by no incjiiis rjircly papiihir or even li(!inorrhaf^i(; like that
of measles, arid a catarrhal afiectioti of the air passaf^es, especially of
the trachea, is one of its usual concomitant symptoms. The fever and
nervous symptoms are more pronounced in typhus and there is {^reat
enlargement of the sj)leen; the eruption is usually absent on the face,
and oculonasal catarrh is lacking. We recall a case of atypical measles
which was sent to the Municipal IIosj)ital as a ca.se of typhus by one
of the foremost physicians of this country.
Roseola Syphilitica. — The macular eruption of syphilis has on more
than one occasion been confounded with measles. The error of mis-
taking syj)hilis for measles may be made when the ))atient is an adult
and when the febrile symptoms are mild. On the other haufl, syphilis
with pyrexial elevation might be regarded as measles.
The eruption of syphilis is slower in development and the lesions are
much more uniform in size and distribution. The face is but slightly,
if at all, involved. Usually the initial lesion or the hardened remains
thereof can still be discovered. In addition otlier evidence of the
syphilitic infection maybe present, such as mucous patches, pronounced
inguinal adenopathy, etc.
Morbilliform Erythemata. — There are a number of conditions in
which rashes bearing a more or less close resemblance to that of measles
may occur. They may be divided into: (a) accidental rashes accom-
panying the exanthematous fevers, (6) drug eruptions, and (c) serum
eruptions.
Mention has already been made of the resemblance of the roseola
variolosa to measles. An analogous eruption, roseola vaccinosa, develops
occasionally about the tenth day of vaccination. The same features
which have been referred to as distinguishing the variolous roseola from
measles may be applied to the vaccinal rash. jNIorbilliform rashes may
in rare instances be observed also in the course of varicella, scarlet fever,
and other infectious diseases.
Drug Eruptions. — The drugs which most frequently give rise to
eruptions simulating measles are antipyrin, quinine, chloral, copaiba,
and cubebs.
The most common eruption resulting from the administration of
aritipyrifi is a morbilliform erythema. Of 52 instances of eruption from
the use of antipyrin collected by Spitz, 41 were of the measles type.
The eruption may be generally distributed over the trunk and extremi-
ties or it may be limited to certain regions thereof; an important distin-
guishing feature is that the face is usually exempted. Croker states
that these eruptions may be accompanied by oronasal catarrh. The
d ifficulty , in d iagnosia may be increased by the appearance of the anti-
pyrin eruption following catarrhal symptoms, such, for instance, as are
"eficountered in influenza, for which, the drug is administered. The con-
jtmctrvTtis, photophobia, hoarseness, cough, and buccal eruption are all
absent. Fever, when present, is slight and not characteristic of measles.
Furthermore, the normal progression of the measles exanthem from the
528
MEASLES
face and neck gradually downward will be found lacking. The eruption,
moreover, is apt to be non-elevated and exhibit irregularities as to dis-
tribution. If a large dose of antipyrin has been taken the drug can
be found in the urine by testing the same with the perchloride of iron.
Quinine. — Quinine gives rise not infrequently to erythematous erup-
tions. Of 60 quinine eruptions analyzed by Morrow, 38 were of the
erythematous variety. Most of these are of the scarlatiniform type,
but some resemble measles. The rash may develop after the admin-
istration of as small a quantity as a grain or even a fraction of a grain
of the drug. The idiosyncrasy appears to be most frequently observed
m women.
Fig. SS
A morbilliform eiythema somewliat resembling measles, probably due to intestinal
autointoxication.
The eruption may be generally distributed or limited to certain areas.
It sometimes appears first on the face, spreading thence downward
over the trunk and limbs. The lesions are bright or dull red macules
or papules, which may quite strongly resemble the measles exanthem.
Itching is apt to be a more prominent symptom than that accompanying
measles. Desquamation not infrequently follows. In some cases
febrile symptoms are present at the beginning; there may be a fever
of 101° or 102° F., with headache, nausea or vomiting, and weakness.
Catarrhal symptoms are absent.
Eruptions from the administration of chloral are less common than
those after antipyrin or quinine. Gee^ saw two cases in which there was
1 Quoted by Crocker, Diseases of the Skin, American edition, 1903, p. 483.
77//'; /'/>'()(,' NOSIS OF Mh'ASIJ'JS rj29
a dusky-red, papulnr eruption surrounded hy ;i more difl'use redness of
the face and neck, and pateliy or mottled-re(J sj^fjts on the extremities,
especially about the articulations.
The absence of the catarrhal and constitutional manifestations of
measles would enable one to exclude this infection.
Coj'AHiA and CiiiiKHS. — C!opaiba and cubebs may give rise to scarla-
tiniform or morbilliform rashes. The former (h-ug usually })roduces an
eruption consisting of rose-red colored, slightly raised patches, which
may be discrete or blotchy and generalized or limited. About the elbows
and knees there is a tendency toward confluen(;e of tjje patches. Itching
is apt to be a distressing symptom. The erui)tion may develop rapidly
after the administration of the drugs or only after some days have
elapsed. Most of the eruptions have occurred in persons who were
receiving treatment for urethritis. A peculiar and disagreeable balsamic
odor is often imparted to the skin when copaiba is taken.
All of the drug eruptions are apt to exhibit irregularities as to the
manner, rapidity, distribution, or duration of the eruption which will
arouse suspicion as to its nature; furthermore, the prodromal stage of
measles with its characteristic catarrhal symptoms is wanting.
Antitoxic Sera. — Antitoxic sera occasionally call forth eruptions
which are measles-like in character. Diphtheria antitoxin may now
and then give rise to a morbilliform erythema, although much more
commonly the eruption resembles urticaria or exudative erythema.
Antitoxin rashes may develop at any time from three days to three weeks
after its administration; most rashes, however, appear from eight to
fourteen days thereafter. There may be elevation of temperature
with joint pains and occasionally joint swellings accompanying the
eruption. The temperature may rise suddenly to 102° F. or thereabouts,
but it soon falls. Catarrhal symptoms are invariably absent.
The antistreptococcus serum and antitetanic serum may, on rare
occasions, also give rise to morbilliform eruptions.
THE PROGNOSIS OF MEASLES.
It appears to be a -difhcult matter to dispel from the minds of mothers
the idea that measles is a trivial disease. When it is stated, according
to the Twelfth Census Report, that measles in the United States, in the
year 1900, caused 12,866 deaths, more- than twice the number that
re?MiEed"lfom scarlatina, it is evident that this disease is not essentially
"beniOTTin its outcome. The above statement must not be construed to
mean that measles is more dangerous than scarlet fever, but that, attack-
ing as it does a much larger percentage of humanity, the aggregate loss
of life is greater.
The prognosis of measles in vigorous and well-nourished children
beyond the age of tw^o or three years is extremely favorable.
The factors that exert an important influence upon the prognosis
are the age of the patient, his previous health, and the nature of his
surroundings. Season and climate are thought to exercise some influence
upon the disease and its complications.
34
530
MEASLES
Age. — The age of the patient is the most important factor in estimating
the degree of danger attendant upon an attack of measles. During the
first six months of Kfe infants usually resist the infection of measles
altogether or take it in feeble form. "With this exception, children under
two years of age who contract measles have a dangerous disease to
contend with. Holt states that the average mortality from measles
during this period is not far from 20 per cent.
After the third year of life the danger rapidly diminishes, reaching
a minimum after the age of five has been passed.
The following figures of Tripe^ indicate the relation of age to mor-
tality.
Mortality of Measles in England from 1868 to 1872. — In 1000 fatal
cases the age of the patients was:
0-1 year .
. 200 cases.
5-15
years .
. 72 cases
1-2 years .
. 376 "
15-25
" .
. 3 "
2-3 " .
. 190 "
25-45
"
. 4 "
3-4 " .
. 101 "
45-60
" .
. 1 case.
4-5 " .
. 53 "
Over 65
" .
. "
It is thus seen that about three-quarters of the deaths occurred in
children under three years of age.
Dawson Williams states that in the forty years from 1848 to 1887 there
were in England and Wales 367,602 deaths attributed to measles, and
of this number 335,874 occurred in children under five years of age,
leaving only 31,728 to distribute among other ages.
The best opportunity of judging of measles susceptibility and fatality
at the various ages is afforded in studying an entire epidemic in a
locality. Dr. Theodore Thomson^ presents such a table of an epidemic
in an English town, from which the following data are abstracted :
Measles
Age. Population, attacks. Deaths. Mortality rate.
0-1 year
1-2 years
2-3 "
3-4 "
4-5 "
5-10 "
10 years and upward
At all ages .
This table indicates the lesser susceptibility of infants under one year
of age and also the lower death rate as compared with the next two
years.
During youth and early adult life the mortality from measles is low.
Patients who are advanced in years not infrequently succumb to the
disease. This is shown in Panum's^ report of the Faroe Islands epidemic
of 1845.
. 1155
166
16
6.9 per ct
974
233
46
23.6 "
. 1028
354
36
J7.5 "
. 1000
324
16
8.0 "
951
324
5
2.6 "
. 4530
560
6
0.7 "
. 25,968
39
0.0 "
. 35,606
1031
125
1.7 "
1 Quoted in Jahrbuch f. Kinder., vol. ix. p. 412.
» Loc. cit.,p. 287.
2 Quoted by Williams, loc. cit.
TIIM PROGNOSIS OF MEASLI'JS 531
Mortality Rate of Mrahmos in tiik Farok Ihi>ani)8 in 1845,
Age. Mortality rate. Ak';. Mortality rate.
Under 1 year . 30.0 per ct. 40-60 years . . 2.8 per ct.
1-10 years
10-20 "
20-80 "
80-40 "
0.6 " 60-60
0.4 " 60-70
0.75 " 70-80
2.1 " 80-100
4.5
7.8
Kll
26.1
These figures are unusual in that such a great mortality is shown in
infants under one year of age and such a remarkably small dfath rate
in those between one and three years. The increasing mortality in
patients past the age of forty is well illustrated. In an extremely mild
epidemic in the Faroe Islands in 1875, Hoff states that while only 8 out
of 1123 cases ended fatally, 5 of these were vigorous adults between the
age of twenty and thirty years. This must be regarded as an exceptional
circumstance.
Institutional Epidemics. — It will be found convenient to discuss here
the influence of institutional environment upon the mortality rate of
measles. It is a generally recognized fact that measles occurring among
children in homes, nurseries, asylums, hospitals, etc., is much more
fatal than when it develops among children in their private homes.
Indeed, measles is regarded as the scourge of children's institutions, for
it decimates the little patients like a plague. There are a number of
reasons for this. Such children usually come from poor stock and
therefore lack power of resistance. The children in foundling a.sylums,
nurseries, and hospitals are of a tender age, which in itself accounts for
a high mortality. They are usually frail and in poor health or already
perhaps suffering from an acute or a chronic disease. The atmosphere
is often vitiated and infected and the liability to such complications
as pneumonia and diphtheria is increased.
The mortality in such institutions as have been mentioned is often
frightful. Holt speaks of an epidemic in 1892 in the Nursery and
Child's Hospital in New York in which there were 143 cases with a death
rate of 35 per cent. An epidemic in the same institution in 1895 had
an almost identical mortality rate.
Comby gives the following statistics showing the death rate in some
of the Paris hospitals:
Hospice des Enfants Assistes.
Year. Cases.
1882 . . 280
1883 268
1884 328
1885 . . ~ 370
1886 .i29
Total in five years .... 1575 728 46.22
The death rate, therefore, during these five years was nearly 50 per
cent., a truly appalling figure.
In I'Hopital des Enfants Malades, for a period of seven years from
1882 to 1888, there were treated 2585 cases of measles, with a death rate
of 40.15 per cent.
Deaths.
Percentage
128
45.0
128
47.0
187
57.0
147
46.0
138
42.0
532 MEASLES
In I'Hopital Trousseau, from 1882 to 1886, there were 907 cases of
measles, with a mortaHty rate of 25.02 per cent. From 1890 to 1894
there were 2248 cases treated in special isolation pavilions, but the
mortality rate still remained high — 28 per cent.
It is difficult , to obtain accurate information as to the death rate of
measles in private practice, for while the deaths are recorded the number
of attacks is usually not known. The fact is well established, however,
that the fatality is very much less in this class of patients.
Sex does not influence the mortality from measles. Of 12,866 persons
who died of measles in the United States in 1900, 6231 were males and
6635 were females. The frequency of measles in pregnant women is
not sufficient to disturb the balance. Moreover, the infection of measles
superadded to pregnancy is not as serious as some of the other exan-
thematous diseases, notably scarlet fever and smallpox.
Previous Health of the Patient.^ — Measles as a primary disease is
very much less serious than when it becomes engrafted upon some
other acute or chronic affection. Secondary measles is an extremely
fatal disease; occurring in patients who are convalescing from diphtheria,
scarlet fever, whooping-cough, etc., the danger is greatly enhanced.
The mortality is also high when measles attacks children who are
badly nourished and who are scrofulous or anaemic. In those with
enlarged glands and a tendency to pulmonary tuberculosis an attack
of measles may be sufficient to stimulate this process into activity.
The unfavorable influence of hardship and privation is exemplified in
camp measles, which is nearly always characterized by a high death rate.
Character of Epidemic. — The mortality of measles depends much
upon the severity of the prevailing epidemic. At times the type of
measles is unusually mild and the death rate extremely low; some
epidemics, on the other hand, are characterized by special malignancy.
Fatal epidemics of measles may cause a high mortality, not only through
an excessive development of the regular symptoms of the disease, but
through the frequency of serious complications. Indeed, it is the
frequency or rarity of bronchopneumonia during an epidemic that
determines in a large measure its malignancy.
The average mortality of measles is from 4 to 6 per cent. The
deaths may in some epidemics not exceed 1 or 2 per cent., while in
others they may reach the murderous figures of 20 or 30 per cent.
In 1856, in Lippe, Hungary, a malignant epidemic prevailed, destroy-
ing the lives of 50 per cent, of those attacked. Measles again occurred
in this locality thirteen years later, with a mortality of 3 per cent.
Faber states that at Schorndorf in the epidemic of 1827-28 there were
2100 cases of measles, with a mortality of only 1.8 per cent. Among
other mild epidemics may be mentioned the following, quoted by Thomas :
According to Ranke the mortality in four epidemics in Munich varied
from 0.7 to 2,7 per cent. Kostlin reports a mortality in Stuttgart of
1,8 per cent, for the years 1852 to 1865,
Among severe epidemics (according to Thomas) may be mentioned
the fatal epidemic in the district of Zolkiew in 1840; Seidl mentions that
Cases.
JJealhH.
I'ercentagc.
582
139
27.7
45
13
28.8
125
40
32.0
457
1G8
36.7
TUIi l'J{()aNOS/S O/'' M/'JASLh'S 533
out of 1519 cases there were 196 deaths, a mortality of almost 13 per
cent. Accord irif^ to Schiiz measles f)revailed at Nagold with a mortality
of 10 per cent. Small (!f)idemics in certain localities have been accom-
{)anie(l by even hipjher mortality.
Colin^ gives the following figures:
Year. J.ocalities.
1861 . . . . . Ruelle
1864 Arras
1860 Val-de-Grace
1870 BicCtre
A mahgnant e})idemic raged in Sunderland, England, in 1885.
Harris^ states that of 1316 cases 384 died, giving a mortality of 20
per cent.
Measles often manifests unusual malignancy on reaching a virgin
soil, particularly among savage tribes. It is stated on the authority
of d'Alves that 30,000 Indians perished from mea.sles along the banks
of the Amazon River in 1749-50. In 1806, in Madaga.scar, 5000 persons
are said to have succumbed to the disease in a single month. Among
the Fiji Islanders measles has exhibited as high a death rate as 30 per
cent.; the disease has, as might be expected, inspired a wholesome
dread among the natives.
Season and Climate. — Inasmuch as the mortality of measles is greatly
influenced by the frequency of pneumonia, one would naturally suppose
that this complication would be more common and the death rate
consequently higher in the cold and inclement seasons of the year.
But such an assumption is not entirely borne out by facts. The figures
which are published by writers as to the influence of season on measles
mortality lack uniformity and preclude the possiblity of drawing there-
from satisfactory conclusions.
Deaths from Measles in England and Wales by Quarterly Periods.
Quarterly Periods.
1837.
1838.
1839.
1840
January, February, and March
2022
2074
2836
April, May, June
1512
3204
2641
July, August, September .
. 2362
1037
2767
1739
October, November, December
. 2392
1943
2892
2110
Total deaths ....
. 4754
6514
10,937
9326
Gregory, who publishes the above table, remarks that "season would
appear to have less influence on the mortality of measles than might
have been anticipated."
According to Karajan,' measles occurring in lower Austria in 1862,
during the presumably unfavorable cool months, was attended with a
mortality of only 2.29 per cent., whereas the disease prevailed in the
same district during the following summer with a mortality which
reached 6.29 per cent.
Passow* states that the fatal cases of measles in Berlin from 1863 to
1 Quoted by Comby. - Lancet, April 30, 1887, p. 970.
3 Quoted by Thomas, * Quoted by Thomas.
534 MEASLES
1867 were distributed as follows: winter, 41.4 per cent.; autumn, 33.4
per cent.; summer, 13.3 per cent.; spring, 11.9 per cent.
In the United States the most fatal season from measles would appear
to be the late winter and early spring months.
In the city of New York, during a period of fifteen years from 1830
to 1844, in which time 2104 deaths from measles occurred, the seasonal
mortality was as follows:
January, February, March 610 deaths.
April, May, June 574 "
July, August, September 536 "
October, November, December 384 "
It is thus seen that the highest mortality was in the first three months
of the year and the lowest in the last three.
The United States Census Report for the year 1900 shows that the
greatest number of deaths from measles occurred during the months
of February, March, April, and May.
Comparative Pboportion of Deaths in Each Month pee 1000 Deaths
IN the United States for the Year J 900.
January .
. 95.0
July .
. 48.5
February .
. 150.1
August
. 43.6
March
. 176.0
September .
. 34.7
April .
. 146.8
October
. 25.5
May .
. 130.3
November .
. 34.6
June .
. 66.4
December .
. 48.5
Climate doubtless has some influence upon the mortality of measles.
Gregory says that "in hot countries measles is not viewed with alarm,
evidently from the absence of thoracic complications." It occurs to us,
however, that the greater tendency to intestinal complications might
counterbalance the advantage. The mortality of measles varies in
different localities. It is, as would be expected, greater in large cities,
where there are greater numbers of overcrowded poor than in rural
districts. Even in large capitals a considerable discrepancy in the
mortality exists.
Thus the mortality from measles is much greater in London than in
Berlin; this is strikingly shown by the following figures:
Measles Deaths per 10,000 of Population.
Year.
Paris.
London.
Berlin.
Vienna
1880 to 1889 .
. 52
60
30
00
1890 " 1894 .
. 41
77
20
70
1895 ....
. 26
59
17
49
From a consideration of the above remarks it will be seen that many
factors influence the prognosis; chief among these, however, are the
age of the patient, his general health and environment, and the severity
of the epidemic. Those epidemics which furnish the largest number of
anomalous cases and the greatest percentage of serious complications
are most to be feared.
,B,,«*a***«'^«s?iBronchopneumonia causes nine .oiil^ ten deaths from measles. It
is the principal danger to which measles patients are liable. Holt states
THE TREAT Ml': NT OF Mf'JASLES 535
that of 51 fatal cases of measles 45 were due to bronchopneumonia,
4 succumbed to ileocolitis, and 2 to membranous laryngitis.
Among 36 deaths observed by Northrup,' in an epidemic in the New
York Foundling Hospital, bronchopneumonia was found post-mortem
in 31 cases.
Favorable Symptoms. — The symptoms of measles are favorable when
the initial temperature is moderate, not exceeding 103° F., and when it
remits in the pre-eruptive stage; when the temperature declines witli the
beginning fading of the eruption; when the eruption is discrete, well
developed, and of bright color; when it appears about the fourth day
and progresses gradually over the body; when the catarrhal symptoms
are of moderate intensity; when complications are absent.
Unfavorable Symptoms. — It is unfavorable for the initial temperature
to be very high (above 103° F.), or for it to persist high or increase be-
fore the eruption appears. It is ominous for the fever to remain high
after the rash fades, for this usually portends pulmonary complications.
It is unfavorable for the eruption to appear late, for it to be unusually
profuse or confluent or, on the other hand, sparse, pale, and livid. A
partial or poorly developed eruption with high fever is a bad sign.
Hemorrhagic eruptions are usually of evil portent, especially when
accompanied by hemorrhages from the mucous membranes. Sudden
and premature recession of the eruption indicates cardiac weakness.
Convulsions or other marked nervous symptoms, severe diarrhoea,
persistent hoarseness, with difficulty in breathing or continued high
temperature, indicate serious complications.
THE TREATMENT OF MEASLES.
In discussing the treatment of measles it must be remembered that
we are dealing with a disease which is far from trifling in its nature —
one whose aggregate annual mortality exceeds, at the present day, that
of any eruptive disease, not excluding smallpox. In 1889 there were
14,732 deaths from measles in England and Wales; in 1900 the mortality
from measles in the United States was 12,866. These figures are not
far from representing the average annual mortality in these countries.
We have no doubt that at least 100,000 persons, chiefly children,
perish throughout the world each year from measles.
The subject is, therefore, of sufficient importance to warrant a full
consideration of the prophylactic treatment of measles and its relation
to the community at large.
Prophylaxis — That the spread of measles can be greatly lessened by
proper sanitary measures has been shown by the results accomplished
by the Michigan State Board of Health.^ Public health measures may
be considered under the headings of (1) Notification, (2) Isolation,
and (3) Disinfection.
1 Medical News, 1897, vol. Ixxi. p. 817.
" Baker, Reports and leaflets on the Prevention and Restriction of the Infectious Diseases, etc., 1900.
536 MEASLES
Notification. — There is considerable difference of opinion as to the
benefits derived from making measles a notifiable disease. Bearing in
mind the fact that measles in many countries kills more children than
scarlet fever and diphtheria combined, there can be but one point
of view as to the desirability of checking its ravages. It is only through
a knowledge of the distribution and extent of measles that health
authorities are enabled to direct measures against its spread. How
effective such measures are offers latitude for discussion.
The chief difficulty arises from the early communicability of the
disease. As soon as a patient manifests the first symptom of measles,
those who have been exposed and are susceptible are almost sure to
contract the disease, and isolation, as far as these persons are concerned,
is too late. Infection may at times take place even before the patients
sicken, as is illustrated in the following cases mentioned by Dr. Fenton,
Medical Officer of Health for Coventry, England:^ "Thirteen children
attended a dancing class one afternoon, including 3 of my own
and 2 of a friend, who had just arrived in the district, and who
had been exposed to the infection of measles before arriving. These
2 children came to my house and spent the evening in my presence.
There was nothing to attract my attention to their condition, and,
indeed, so well were they that they had walked six miles in the morning,
had danced in the afternoon, and walked home about one mile at night.
Next day they both sickened and developed measles. Of the remaining
11 children 2 were presumably immune, having previously suffered
from measles, but the whole of the 9 developed measles during the
following fourteen days." This incident is evidence of the early con-
tagiousness of measles and the difficulties that are encountered in pre-
venting its dissemination. But much can be accomplished in prevent-
ing unnecessary exposure to the disease, and to this end notification is
eminently desirable, if not essential.
The education of the masses is a matter of paramount importance in
stamping out measles. Mothers must be taught that measles is a
serious disease — a disease that destroys many lives, and that exposure
to it must be avoided. Even among the intelligent middle classes there
is a tendency to regard escape from measles as futile, and mothers make
little effort to avoid an infection which is regarded after all as inevitable.
"The baby might as well take measles now as later" is the dangerous
and erroneous view often expressed.
Mothers should be made to realize the fact that measles kills more
children under two years of age than any other disease save possibly
whooping-cough, and that about 80 per cent, of all deaths from measles
are in children under five years of age. If children be safely guarded
through this period of their life without contracting measles an enormous
saving of life would result.
It is a good plan to send circulars of instruction to all households
which are in the neighborhood of an infected domicile.
1 Quoted by Dawsbn Williams.
THE TUKATMKNT OF MEASLES 587
Isolation. — When a child is stricken with measles in a househokl in
which there are other susceptible (children it should be promptly isolated.
The isolation should not be delayed until the dia^niosis is confirmed
by the ap])earance of the eruption, but uj)Om the first suspicion that the
disease mi^ht be measles.
In selecting an apartment for the patient such a room or, preferably,
a suite of rooms is to be chosen as can be most effectually separated
from the rest of the house. It will usually be found that the uppermost
rooms of the house are most suitable and available. In choosing the
apartment care should be given to the facilities for ventilation. Admir-
able ventilation is furnished by an open fireplace in which fire is kept
constantly burning, but such a convenience will usually be found
wanting. The most common method of securing the necessary change
of air is from a window sufficiently removed from the sick-bed to avoid
direct currents of air striking the patient. A rather safer method,
particularly in such a disease as measles, is to ventilate through the
adjoining room, as suggested by J. P. C. Griffith.^ The windows of this
room may be kept open and the fresh air permitted to enter the sick-
room through the communicating door, which is opened for this purpose
from time to time. As this room also forms the channel of communica-
tion with the remainder of the house, the opening of the windows will
tend to dilute or dissipate the infection.
All unnecessary articles of furniture, such as drapery, carpets, and
upholstery should be removed. The spaces around doors communicating
with parts of the house to be protected should be sealed by pasting
strips of wrapping paper over them. The contagium of measles is so
diffusible that unless this precaution is taken the infection will travel
beyond the sick-chamber. Over the door leading into the corridor
should be suspended a sheet which is kept moist with diluted Labar-
raque's solution, carbolic acid (5 per cent.), or a 1 : 1000 solution of
corrosive sublimate.
The woodwork and the floors of the apartment should be kept clean
by mopping with cloths saturated wdth antiseptic solutions. Owing to
the liability to pulmonary complications in measles, sweeping of the
sick-room should be assiduously avoided.
The nurse or attendant should not leave the sick-apartments save
after change of clothing and thorough ablution. If the mother wait
upon her child she should devote her time exclusively to the patient,
and not come in contact with susceptible members of the family. Such
garments should be worn by the nurse or mother as can be readily
washed.
All articles coming in contact with the patient, such as dishes, bed
and body linen, etc., should be disinfected in the adjoining room, where
solutions for this purpose should be kept on hand. A 5 per cent, solution
of carbolic acid will suffice for this purpose, although for the dishes
boiling water is to be preferred.
1 Hare's System of Practical Therapeutics, p. 132.
538 MEASLES
It is a difficult matter to state just how long measles patients should
be isolated. Unlike scarlet fever the disease is most contagious early,
and the period of infectiousness is short lived. Most pediatricians are
of the opinion that the period of isolation should be in all from two to
three weeks. In uncomplicated cases two weeks are probably sufficient
if desquamation has ceased. Whether or not the desquamation of
measles is infectious is an undetermined problem, with plenty of advo-
cates to champion each side of the question. It is proper to state that
certain physicians who have had unusual opportunities of judging, such
as Hoff, Peterson, and Comby,^ deny the infectiousness of the stage of
desquamation. The last-named observer says: "We know to-day that
measles ceases to be contagious after the eruption." In institutions
where so much depends on effective isolation, patients should be sepa-
rated for the full period.
Utility or Futility of Isolation. — There are many physicians
who deem isolation in private residences futile and, therefore, do not
advise it. It must be admitted that when measles appears in a child
to whom susceptible children have been freely exposed, isolation is too
late. If, however, patients are isolated upon the first suspicion of
measles, a certain small proportion of the exposed will probably escape,
particularly babies, whose susceptibility is slight and whom it is par-
ticularly important to protect. Where such young infants can be sent
to another household this course is eminently desirable, provided no
susceptible children be there resident. It is unjustifiable to send exposed
children to a home where unprotected persons reside, for these in turn
would be exposed upon the former falling ill.
It is, of course, recognized that the method of isolation above outlined
could not be carried out among the poor nor in families living in re-
stricted quarters. Moreover, there are many people who would refuse
to go to such inconvenience and expense, with the knowledge that the
benefits to be derived are doubtful. We feel that when measles breaks
out in a household in which unprotected persons, particularly children
under three years of age, live, the proper course to pursue is to isolate
the patient. Such a procedure would, in the long run, save lives.
When measles develops in an institution for children, the patient
should be immediately isolated. No new admissions should be per-
mitted save to quarters which are completely separated and protected
from the infected apartments. The exposed children should be kept
under close surveillance until the extreme limits of the period of incu-
bation have been passed.
Disinfection. — The germs of measles have comparatively little tenacity
to life outside of the human body. It is unusual for the disease to be
carried by infected articles or third persons. We do not subscribe,
however, to the positive statements made by some physicians that the
disease is never communicated in this manner. In hospitals and other
institutions for children wards should invariably be disinfected after
1 Loc, cit., p, 200,
THE TREATMENT OF MEASLES 539
measles has broken out; in private households tlionju^li cleansing and
subsequent airing nifiy tjike tlu; })la(;e of the more rigid measures of
disinfection eni[)loyc(i in otlutr infectious (h'seases.
General Management of the Disease. — Measles runs its course in a
definite period of time like other self-hmited affections, and tends in
uncomplicated cases to recovery. No know^n drug is able to abridge
or modify the course of the disease. The therapeutic indications,
therefore, are: (1) to mitigate or control excessively developed symptoms
and (2) to treat or, preferably, prevent complications.
The temperature of the sick-room should be maintained in the
neighborhood of 70° F., particularly during the cold months of the year.
It is important that the temperature l:)e kept uniform and not be allowed
to fall during the hours of the night. While it is desira})le to avoid
direct draughts upon the patient, it is equally essential to keep the
room well ventilated and the air pure. Owing to the irritating influence
of dry air and the increased liability to dissemination of dust in such
an atmosphere, it will be found advantageous to moisten the air by
one method or another. A pan of water may be heated over an alcohol
lamp or the old-fashioned kettle of steaming water may be brought
into the room. This use of steam is even more important when a
severe catarrhal laryngitis or bronchitis is present. Under such circum-
stances aromatic and sedative medicaments, such as the compound
tincture of benzoin may be volatilized by being placed upon the surface
of the steaming water.
The habit, fortunately obsolete for the most part now, of bundling
up measles patients with an excess of bed-clothes is to be deprecated.
Mothers should be instructed that the guide in this matter is the
comfort of the patient. Sydenham proved several centuries ago that
the "sweating regimen" was out of place with a feverish patient. In
changing the bed-linen of patients in the winter months it is advisable
to warm the sheets before they come in contact with the patient.
It will be found necessary to protect the eyes of measles patients
against too strong rays of light. It should be remembered, however,
that it is not necessary to make a room absolutely dark in order to
accomplish this purpose. Just sufficient light should be excluded to
make the patient comfortable. The complete shutting out of daylight
is not only depressing, but the air is robbed of the purifying and germ-
destroying influence of the sun's rays.
Patients with measles may be sponged daily with tepid water. The
old-time prejudice against the use of water in the eruptive fevers is still
harbored by some oversolicitous mothers, but is scouted by physicians
of experience.
In order to avoid complications which arise from the catarrhal
inflammation of the nose, mouth, and conjunctiva, it is well to employ
the following 'preventive measures as a routine. The mouth should be
washed several times a day with a solution of boric acid to which a
little glycerin and a few drops of oil of wintergreen may be added, or
instead some other mild antiseptic w^ash may be employed. By this
540 MEASLES
precautionary measure the liability to ulcerative stomatitis, a by no
means rare occurrence, is lessened. Williams regards the use of anti-
septic mouth washes as important, because "it has been shown that the
microbes associated with bronchopneumonia are present in the mouth
in more than half the cases of measles."
The nares should be irrigated every few hours with a decinormal
saline solution. Care should be taken that the syringe is gently manip-
ulated and the forcible projection of fluid into the nose avoided.
Comby prefers spraying of the nose, mouth, and throat with a steam-
atomizer. He state's that Siredey obtained excellent results by this
method at I'Hopital d' Aubervilliers ; before this treatment was used
50 cases of measles gave 23 complications (46 per cent.); since the
employment of the spray 53 cases have only furnished 7 complications
(13 per cent.). The genitalia, particularly in girls, should be kept
scrupulously clean owing to the vulnerability of these parts to gangrene
involvement. In addition to the use of soap and water a weak solution
of bichloride of mercury or a saturated solution of boric acid may be
employed.
Measles patients should always be confined to bed for the entire febrile
period of the disease; in severe cases the patient should not be allowed
to leave bed until a week or ten days after the termination of fever.
During the cold and rainy seasons this precaution should be carefully
observed. During the balmy days of late spring or summer one need
not adhere so rigidly to this rule. It is difficult to keep very young, rest-
less children constantly in their cribs; where care is exercised as to the
equability of the temperature in the room and to the clothing of the child,
it is permissible to gratify its desire to be taken up in one's arms. Season
and climate will influence the duration of the sojourn in-doors. Ordi-
narily the patient should not go out for ten days to two weeks after the
subsidence of fever; this period should be increased in cold, wintry
weather, and abbreviated during a warm and dry spell.
Diet. — For children, milk, preferably diluted with barley-water, is
the best diet. This not only constitutes the most assimilable and
nourishing food, but helps to assuage the thirst and acts on the kidneys.
When the temperature is high the milk may be taken cool and will be
found to be most acceptable to the patient. Where it is distasteful to
a child it may often be rendered more palatable by flavoring it with
a little extract of vanilla. As measles is a disease of short duration it is
not essential to force nourishment upon the patients as in more pro-
tracted affections, such as typhoid fever.
It will be found that when the temperature is high, children will want
nothing but cool milk; later there will be a desire for a more varied
dietary. As the fever declines there is no objection to the use of junket,
farina, milk-toast, broths, arrowroot, rice, custard, strained oatmeal,
soft-boiled eggs. It will be well to avoid those cereals which, by reason
of their husk, are apt to excite diarrhoea.
I For the relief of thirst, apart from the use of cool milk, the patient
may partake freely of water, provided it is not iced. In older children
77//'; TIINATMI'INT OF MJ'JASLKS o41
carbonated water is often gratefully received, or water acidulated with
lemon or orange juice.
There is no o})jection to the use of ice-creain, [>rovidcd it is taken in
moderation.
Medical Treatment in the Complicated Cases.-— Mild cases of
measles require but little medication ; the nursing is of greater importance.
It may be necessary to relieve constipation in the beginning. No irritant
purgatives should be employed, but rather such gentle remedies as
castor oil, elixir of cascara, or syrup of rhubarb, or a simple enema
may be given. Drastic drugs might lead to a catarrhal inflammation
of the intestines, to which measles patients are already predisposed.
More often the physician will be called upon to check excessive
bowel movements. If these are allowed to continue they soon ex-
haust tlie vitality of the patient. Usually the diarrhoea can be con-
trolled by a mixture containing paregoric and bismuth; if this does
not suffice the deodorized tincture of opium may be used instead of
paregoric.
Where the bronchial catarrh is slight no treatment is necessary.
When there is much cough it will be necessary to allay it by one of the
simple cough mixtures. The well-known "brown mixture" may be admin-
istered or a combination containing a little bromide of soda and ipecac-
uanha may be used. For severe and incessant cough one may be
obliged to resort to opium; it must be remembered that this drug must
be used with caution in young children. Five to twenty drops of
paregoric, according to the age of the child, may be given every few
hours.
The fever, when of moderate grade (102° F.), will require no treatment.
It is customary to prescribe some simple febrifuge containing a little
tincture of aconite, potassium citrate, and spirits of nitrous ether; this
preparation has a gentle diuretic and diaphoretic action. When the
temperature reaches 104° or 105° F., and particularly when it is accom-
panied by marked nervous symptoms, such as restlessness, delirium,
stupor, or convulsions, more active antipyretic treatment is demanded.
Of all measures for the reduction of temperature, hydrotherapy is to
be preferred. Cold tub baths are usually not well borne by young
children, and it is best to employ tepid or warm baths, except where
the fever cannot be thus controlled. Immersion in a bath of 85° F. to
90° F. will frequently bring down the temperature and quiet the disturbed
nervous system. These baths may be repeated as often as the occasion
demands. In those cases in which the temperature is not sufficiently
controlled by this means, recourse may be had to the use of cold sponge
baths or the use of the wet pack. The ice cap may be used as an adjunct
to any of these measures.
When the temperature is high and the extremities cold, the patient
may be immersed in a hot bath with or without the addition of mustard;
in such cases the ice-bag should be applied to the head. The cold bath
under such circumstances is badly borne, as the depression is too great
for an already weak heart.
542 MEASLES
The hot bath with mustard is also useful in those cases in which the
eruption is imperfectly developed or unusually slow in making its
appearance.
The reduction in the body temperature is accompanied by an amelio-
ration of the pronounced nervous symptoms which accompany hyper-
pyrexia. Where for any reason hydrotherapy cannot be employed, one
may resort to the use of some of the coal-tar antipyretics. Antipyrin
usually acts very well in children. It has been extensively employed
by many physicians with satisfactory results. Not only is there a
reduction in the temperature, but violent nervous manifestations, when
present, are promptly quieted. One to 3 grains repeated according
to indications will usually suffice. Comby has used this drug extensively
in measles, giving it in dosage of 7| to 15 grains. We would feel a
hesitancy about administering such a dose to a child, yet Comby states
that he has never seen any bad results therefrom; a reduction of temper-
ature of one or two degrees was obtained, which lasted from two to
four hours. Phenacetin may, if desired, be employed instead of anti-
pyrin. While these drugs usually act well, hydrotherapy is ordinarily
to be preferred.
Treatment of Complications. — Measles as an uncomplicated disease
nearly always ends in recovery; it is its complications which render it
frequently a grave and fatal affection. The preventive measures to be
pursued have already been discussed. The complicating disorders must
be treated much in the same manner as when they occur independently
of measles.
Nervous Symptoms. — The ushering in of an attack of measles with
convulsions is not of bad augury unless they persist; convulsions in
children take the place of the chill in adults. Where the seizure is brief
no special treatment is necessary; when it is prolonged or repeated
there is a possibility of a cerebral hemorrhage resulting therefrom and
measures thould be taken to check the convulsions. A few inhalations
of chloroform will frequently control the paroxysm, after which chloral
hydrate or antypyrin should be administered. An ice-bag to the head
will also be found to be of assistance.
Restlessness, stupor, or delirium can be controlled by the hydro-
therapeutic measures mentioned, for they almost always occur in
association with high temperature.
Skin. — The skin should be kept scrupulously clean throughout the
attack; this may be accomplished by sponge baths with alcohol and
water or mild antiseptic solutions.
Itching of the skin may be so intense as to necessitate measures for
relief. A lotion containing 1 drachm each of carbolic acid and glycerin
to the pint of water or an ointment of 10 grains each of carbolic acid
and camphor to the ounce of vaselin will control the pruritus. Not
infrequently impetigo vesicles and pustules develop about the nose,
mouth, or ears as a result of pyogenic infect'.on of the skin from purulent
discharges. An ammoniated mercury ointment, 10 grains to the ounce,
will effect the disappearance of these lesions.
Tm<: treatmi':nt of mj'JA,s/jarle ('120 cases), Edwards (16G
cases), Kingsley (21 cases), Atkinson, Griffith, and Hardaway.
At the ])resent day there is a unanimity of opinion concerning the
existence of rubella as a disease sui generis.
THE ETIOLOGY OF RUBELLA.
It is generally recognized that rubella, like the other exanthematous
diseases, is derived from and begets a like disorder. It confers pro-
tection only against rubella, and no immunity against it is granted by
an attack of measles or scarlet fever.
Many of the earlier vv^riters doubted and even denied the contagious-
ness of rubella, but there is at the present day a unanimity of opinion
concerning its transmissibility. As to the degree of contagiousness views
are somewhat divergent. Chadbourne and J. Lewis Smith regarded
it as feebly contagious; Thomas, Liveing, Tongue-Smith, Bourneville,
and others, as less contagious than measles; Jacobi, Dukes, Squire, and
Griffith look upon it as very contagious, and Edwards^ believes that
"rubella is one of the most contagious of all of the eruptive fevers."
Griffith states that in an institution of 100 children 37 took the disease
despite prompt and careful isolation. In another institution 26 per cent,
were attacked. Klaatsch believes that the degree of contagiousness
varies in different epidemics.
HatfiekP reports an asylum epidemic in which 110 inmates out of 196
contracted the disease.
From our experience at the Municipal Hospital we are inclined to
believe that a larger number of children escape rubella when this
infection is introduced into the wards than escape measles under similar
circumstances.
Rubella is essentially an epidemic disease and appears to be more
prevalent in the winter and spring seasons. The disease is about as
common as measles, with which affection it has doubtless often been
confounded. The infection of rubella seems to be more tenacious and
persistent than that of measles. It is, therefore, more apt to be carried
by fomites in the garments of third persons than is measles. Edwards
alleges that about 75 per cent, of his cases could be directly traced to
infection from the bunks of ships, and states that Emminghaus, Thomas,
Veale, and others considered such an origin proved. Corlett^ remarks
that rubella corresponds more with scarlet fever than with measles in
the persistence of the vitality of the contagium.
Opinions are at some variance in regard to the period of greatest
contagiousness. Thierfelder looked upon the stage of convalescence as
the time at which the disease was most transmissible. Squire con-
sidered all stages contagious, from the pre-eruptive period late into
1 Article on Rubella, Keating's Cyclopedia of Diseases of Children, Philadelphia, 1889, p. 6S7.
- Chicago Medical Examiner, August, 1881. s loq. cit.
550 RUBELLA
convalescence. Edwards coincides with this opinion. Griffith con-
cludes, from his observation in institution epidemics, that rubella is
certainly contagious at a very early date, for prompt isolation failed
to check the extension of the disease.
Age.— Rubella behaves much like measles as regards age incidence.
Infants under six months of age usually escape the infection, although
now and then the disease will be contracted. We have seen a six-month-
old infant live and remain well for months in a ward in which cases of
rubella were constantly appearing. Smith, Roth, Steiner, and Hardaway
have recorded attacks in early infancy, and Scholl reports a case occurring
in a child a few days after birth, the mother having suffered from the
disease two months previously. As in measles, those who escape the
disease in childhood may contract it in adult life; indeed, even in advancd
years, as is attested by Seitz, who reports a case in a woman seventy-
three years old.
Emminghaus saw only two adult attacks among 42 cases. Thomas
noted 3 among 77 cases; Kassowitz observed 5 in 64 cases and Thomas
but 1 in 100 cases. Edwards does not believe that adult life confers
any special immunity; he regards infrequent exposures to the disease,
and protection by an attack in childhood as the cause of the compara-
tive rarity among adults.
Thomas holds a rather different view. He says : "After the fortieth year
the susceptibility is nearly lost, and we may consider it as essentially
weakened at puberty, and as steadily diminishing subsequently." In
Forchheimer's^ experience more physicians have been attacked by
rubella than by all the other exanthematous diseases taken together.
He adds that, "with the exception of variola, possibly no disease of this
class so frequently affects adults."
THE SYMPTOMATOLOGY OF RUBELLA.
Period of Incubation. — Different observers have assigned incubative
periods to rubella varying from five days to three weeks. This variable
duration is regarded by Griffith as one of the diagnostic features of
the disease and in striking contrast with the fixed incubation period
of measles. To indicate the divergent observations of different clinicians
we present a table compiled by Forchheimer, to which we have made
additions :
1 Twentieth Century Practice of Medicine, article on Rubella, p. 180.
77//!,' SYMPTOMATOIJXJY ()!<' lilJ lihlLLA
551
Periods of Inctjra'i
'ION OF RUBKLLA.
Atkinson
. l-l to 21 days.
Hardawny .
2 weekKor longer.
Balfour.
2 weeks.
Hatfield
10 days.
Boudet .
. 12 to M days.
.laoobi .
H to 2] days.
Bourneville
S days.
Kas.sowitz .
2 to 3 wcekB.
Bricon .
. 8 to 10 days.
Klaat8(;li
2]4. ^1 3 weeks.
Bristowe
1 week.
Longstcl
18 days.
Cheadle
. 15 days.
Metteiiheirner
2 weeks or longer.
Clausen .
. 17 to 20 days.
Musser .
Just 6 days in lease
CottiiiK .
3 weeks.
I'icot
2 U> 3 weeks.
Culling vvortl
1 . . 2 weeks.
Pollock .
f. to 1 days.
Cuomo .
. 17 days; never less.
Juhel-r{enoy
15 days.
Duckworth
. Ifi days.
Robinson
G to 7 days.
Duke .
. 15 to 16 days.
Scholl .
5 to 21 days.
Earle .
. 17 to 21 days.
Steiner .
10 to 14 days.
Edwards
. 10 to 12 days.
J. L. Smith .
7 to 21 days.
Eichhorst
2 to 3 vVeeks.
Tongue-Smith .
14 days. •
Emminghau!
2 to 3 weeks.
Squire .
8 to 21 days.
Gerhardt
2 to 3 weeks.
Tbierfelder .
2 weeks or longer.
Glaister
4 to 5 days or longer.
Thomas
2y^ to 3 weeks.
Goodhart
2 weeks or longer.
Vacher .
13 days.
Griffith
. 5 to 11 days.
It is thus seen that the incubation may be either shorter or longer
than that of measles. Eleven writers have noted minimum periods of
five to eight days, and no less than thirty-two have seen the period
extend beyond fourteen days.
During the stage of incubation the patient is entirely free of any
disturbance of health except, perhaps, in extremely exceptional cases.
Period of Invasion. — In most cases of rubella this stage is either devoid
of symptoms or presents only mild manifestations which are readily
overlooked. It would appear that the more severe the attack is to be,
the more apt is it to be preceded by pronounced prodromal symptoms.
In the vast majority of our cases at the hospital the eruption was the
first sign to attract attention. In a severe attack in a trained nurse,
the symptoms of which will be fully detailed later, there was, however,
a distinct and protracted stage of invasion. This nurse was on night
duty in a ward in which rubella existed. On Wednesday, ^March 11,
1903, she was taken ill with headache and sudden vomiting; the emesis
was persistent, the patient vomiting four or five times each day and
retaining nothing. There were also feverishness, continued headache,
recurring chilliness, perspiration during sleep, restlessness, and weak-
ness. On March 16th, jour and a half days later, the eruption appeared.
No catarrhal symptoms whatever were present. This case must be
regarded as presenting exceptional initial manifestations.
While most writers refer to very mild and brief prodromes, some
rather severe invasive symptoms have been described. Edwards^ noted
in a severe epidemic in the Philadelphia Hospital the following s^inp-
toms: chilliness, languor, faintness, headache (more or less severe),
pain in the back and limbs, coryza, red and watery eyes, sore throat,
cough, occasionally a hoarse, husky voice, and a temperature from
I Loc. cit.
552 RUBELLA
100° to 103° F.; nausea and vomiting, delirium and convulsions, and
epistaxis were observed in three cases.
Other unusual prodromal symptoms have been recorded. Prioleau
reports 2 cases of hemorrhage from the eyes and ears; vomiting is
mentioned as a rare symptom by Smith, Murchison, McLeod, and
Emminghaus; convulsions by Smith, Lindwurm, Cuomo, and Alexander;
delirium by Hardaway and Cuomo. Nymann observed rigor in 19 out
of 119 cases; Earle, Kingsley, Thierf elder and Griffith mention a
slight redness preceding the eruption, and Cuomo (in 7 cases) and
Edwards (in 4 cases) a prodromal erythema.
Such symptoms as those detailed are exceptional, but nevertheless
of interest. The experience of most observers is that the prodromal
symptoms are absent or mild, consisting of drowsiness, anorexia,
"liquidy" eyes, sneezing, slight cough, etc.
Earle found that prodromal symptoms were more frequently present
in adults than in children.
As to the duration of the invasive period, opinions differ somewhat;
we would subscribe to the statement of Thomas, endorsed by Hardaway
and Griffith, that in the vast majority of cases the prodromal stage is
at most no longer than half a day. At the same time we recognize
that it may vary from a couple of hours to five days. Various writers
assign periods intermediate between these two extremes. It would
seem that long periods of invasion presage attacks of greater severity
than brief periods.
Period of Eruption. — A half -day or so after the onset of mild invasive
symptoms, or in many cases without any prodroma at all, the eruption
of rubella makes its appearance. The rash is commonly the first
symptom to attract attention, the other mild initiatory disturbances
then being recalled. Not infrequently a child awakens in the morning
with the eruption visible upon the face. In our cases at the Municipal
Hospital, all of which developed in scarlet-fever convalescents, the
rash was frequently discovered when the children were lined up for
inspection during our visits.
Most writers coincide in the view that the eruption appears first on
the face; other locations are, however, mentioned by some observers
as the initial site. Liveing and Morris state that it appears first on the
trunk; Murchison, Day, and Balfour speak of the breast and arms as
first attacked, Willcocks and Carpenter the face and margin of the
hair, and Thomas and Corlett the face and scalp. Patterson and
Copland assert that it comes out simultaneously on different parts of
the body.
In noting the eruption a short time after its appearance upon the face
we have seldom failed to find it to some extent on the trunk and arms.
In a severe case in a trained nurse (to which reference has already
been made) the eruption was carefully looked for by another nurse
occupying the same room and was observed to first appear at 3 a.m.
on the legs below the knees; it then spread upward and by 6 a.m. was
noticed on the wrists. At 3 p.m., the hour of our examination, it was
77//'; HYMI'TOMATOr/Xjy ()!<' Rf/Iif'JJ.A
553
present on the legs, arms, and trunk. 'I'lie face was flushet], but no
distinet eruption was seen in this rej^ion until tlie follf)\vin{( day.
It is evident that while the eruption of rubella normally appears first
on the face, thence extending downward, anomalous cases may occur
in which the origin is in other regions.
The exanthem spreads (juit(! ra})idly over the body in the course of
twenty-four to forty-eight hours. It is interesting to note, however,
that the maximum intensity of the rash is not siniultaneously noted on
the entire cutaneous surface. It is not unusual for the face, che.st, and
Fin. 80
Faint eruption of rubella upon the face in a mild attack.
arms to show the eruption at its height while the legs are yet unaffected.
When the lower extremities exhibit the exanthem in its greatest mtensity
it is fading upon the face and upper part of the body. In other words,
the rash often seems to pass over the cutaneous surface in a sort of
wave-like progression. The duration of the eruption at its height in
any given region is from a few hours to half a day. The more severe
the attack, the longer is the period of maximum intensity and the longer
the duration of the eruption.
This peculiar progression of the eruption is commented upon by
Thomas in the following words: "It happens with tolerable frequency
554 RUBELLA
that the maxima of its development occur at varying times upon different
portions of the body." Some writers, particularly Emminghaus, Roth,
Mettenheimer, and Hardaway, attach to this eruptive sequence great
importance,, regarding it as one of the safest diagnostic signs of rubella.
Griffith agrees with Thomas' statement as to the tolerable frequency of
this occurrence, but questions its diagnostic value, as he has nearly as
often observed that the rash persisted with equal intensity on the face
while it spread to the rest of the body, reaching its acme everywhere
upon the second day.
Character of the Eruption. — The eruption, in its most typical form,
consists of pinhead to lentil-seed sized, pale rose-tinted, slightly elevated,
moderately defined macules. -The lesions are usually rounded or oval,
but may be irregular. The elevation is scarcely sufficient to warrant
the use of the term papules, but is appreciable to the finger passed
over the surface of the skin. The macules are ordinarily discrete, with
considerable intervening pale skin, particularly at the onset of the
eruption and on the trunk. Later they are apt to become more closely
set and may coalesce, with the production of irregular patches resembling
measles or sheets of eruption of a scarlatiniform character.
Ordinarily, macular grouping, such as is seen in measles, is absent,
but we have now and then seen distinct linear and crescentic configu-
ration indistinguishable from that observed in measles. Rubella in its
purest form, however, shows smaller, more regular, and more discrete
lesions than those of measles, which are inclined to present an irregular,
blotchy appearance. The color of the macules of rubella has been
described as a pale rose-tint or rosy-red by most writers. Shuttleworth
refers to it as a brownish-red. The color doubtless varies to some
extent in different individuals, as does the tint in all eruptive diseases,
but it may be said in general that it is ordinarily not as vivid as the
eruption of scarlet fever, nor as dusky or bluish as the measles exanthem.
The discreteness of the slightly elevated macules gives the eruption
its distinctive appearance, the reddish spots standing out in striking
contrast with the pale integument. Confluence is, however, frequently
noted in certain areas, particularly on the face. On the second or
third day of the eruption it is not uncommon for the rash to become
paler in tint and to assume a more diffuse appearance.
Pressure or irritation of the skin seems to increase the intensity of
the eruption and to encourage confluence. Klaatsch and Griffith both
report cases in which the eruption was particularly well developed in
circular bands above the knees, where the garters had made pressure.
In scarlet fever, on the other hand, pressure, such as is produced by
garters, is apt to produce anaemic or pale bands in the areas thus affected.
Distribution of the Eruption. — The face almost invariably exhibits
an abundance of eruption, especially upon the forehead, cheeks, and
chin. The lesions may be so copious as to produce the appearance
of slight oedema. The eruption does not respect the circumoral region
as does the exanthem of scarlet fever. The scalp is profusely covered,
as is also the neck. The chest, abdomen, back, and arms show rather
Tim HYMI'TOMATOIJXIY OF lUJUHLLA
555
less eruption; the Inittocks and j)Ostorif)r aspect of the thighs, owing,
perhaps, to pressure, commonly exhi})it eruption in such j)rofusion as
to present confluent patches. The legs, as a rule, are the seat of the
least eruption, the lesions often being widely scattered. It has been
asserted by sonic writers that the palmar and |)lantar surfaces are
exempted, but this is not true, as lesions are not infrcfiuently found
in these regions in well-pronounced attacks. The above outline presents
the distribution of the eruption in normal cases; it is not rare for depart-
ures from this to take place.
Barthez and Rilliet have noted the fading of the (;ruption followed
by the reappearance of the same upon the same day or later. Griffith
also mentions a case in which it was invisible during one day and
returned.
Duration of the Rash. — The duration of the rash is influenced by
the intensity of the eruption and the character of the epidemic. The
ous periods a
Aitken .
ssigned by dmerent v
4 to 5 days (bad cases
i^riters are nei
Gerhardt
e tabulated:
. J^ to 1 day.
6 to 10).
Griffith .
. 2 to 3 days
Alexander .
. 14 days (one case).
Hatfield
4 days.
Alibert .
. 2 to 3 days.
Kingsley
2 to 4 days.
Balfour.
4 to 6 days.
Klaatsch
1 to 5 days.
Barthez .
2 to 3 days.
Liveing .
5 to 7 days.
Bourneville .
. 2 to 3 days.
Maton .
3 to 4 days
Bricon .
2 to 3 days.
Nymann
2 to 4 days
Carpenter .
1 to 4 days.
Picot .
3 to 4 days.
Claussen
3 days.
Rilliet .
. 2 to 3 days.
Copland
4 to 5 days.
J. G. Smith .
3 days.
Corlett .
2 to 4 days.
Thomas
. 2 to 3 days.
Edwards
2 to 15 days ;
average 5.
Trousseau .
1 to 2 days.
Emminghaus
2 to 4 days.
Willcocks
. 1 to 4 days
Porchheimer
. not exceedin
J 5 days.
It will be seen from the above figures that the duration of the eruption
offers considerable latitude. The long periods are doubtless isolated
instances. In about 100 cases which we have recently had the oppor-
tunity of observing, the rash did not persist beyond three days save in
the case of the nurse, in whom it lasted five days. In a great many of
the children the eruption was scarcely apparent after the first twenty-
four hours; the average duration was certainly not more than two days.
The brief duration is, perhaps, to be accounted for by the very mild
type of the epidemic. The average duration in over 200 of Edwards'
cases was five days; the type of the epidemic which he observed was,
however, distinctly more severe than ours.
The rash appears to persist longer in some regions than in others,
possibly the regions of greatest intensity. Edwards says that the face
and upper chest exhibit the most persistent eruption; our experience
coincides more with that of Griffith, who regards the face and buttocks
as the seats of the most protracted eruption.
Anomalous Features of the Eruption. — In rare instances miliary
vesicles have been noted upon the reddish macules. This has been
observed by Curtman, Cuomo, Thomas, Hardaway, and Copland.^
1 Mentioned by Griffith, loc. cit.
556 RUBELLA
Petechial spots have been recorded by Dunlop and Hkewise by
Cheadle; Erskine reports similar lesions on the uvula and soft palate.
A purpuric rash was also observed by Glaister.
Claussen makes mention of lesions which gave the impression of
small shot being buried in the skin. Griffith saw an unusual eruption
which also imparted a shotty feel to the finger.
Scarlatiniform Variety of Rubella. — Thus far reference has only been
made to normal rubella and to the form which bears more or less of a
resemblance to measles. There are other cases in which the exanthem
bears a strong resemblance to that of scarlet fever. Some writers of
prominence make no mention of this variety and express astonishment
at any suggestion of similarity between the rashes of rubella and
scarlatina. Thomas says: "According to my observations the exanthem
of rubeola (rubella) possesses a similarity to that of measles only, not
the slightest to that of a normal scarlet fever." Bristowe and Bourne-
ville and Bricon entertain similar views. These opinions may be
attributed to the fact that the scarlatiniform variety of rubella has not
come within the range of the personal experience of these physicians.
Mention could be made of a large number of writers who have
observed this variety. Hatfield speaks of an epidemic in which the
rash in many cases was indistinguishable from measles, and in other
cases strongly resembled scarlet fever. J. L. Smith refers to a case
which, had he been guided alone by the eruption, he would have regarded
as a mild scarlet fever. Griffith describes a case in which the eruption
was at first macular, yet on the second day it so closely resembled
scarlet fever that he was unable for several days to make a diagnosis.
The whole body was covered by a general scarlatinal blush and nowhere
could a single macule or papule be found. A short time afterward
the brother took rubella.
We have seen in the Municipal Hospital one or two cases of rubella
with scarlatiniform eruptions in children convalescent from scarlet fever.
Griffith,^ from a careful study of a large number of cases, comes to
the conclusion that there are two easily recognized types of variation
from the character of the eruption in a normal case:
1. "An eruption in which the spots are for the most part nearly or
fully the size of a split pea, more or less grouped, and, in fact, having
the greatest resemblance to measles.
2. "A rash which is confluent in patches or universally not elevated,
and which produces a uniform redness closely simulating that of scar-
latina. Very careful examination will often reveal a few papules amid
the general diffuse redness."
Desquamation. — Upon the subsidence of the eruption a delicate
brownish or yellowish staining may be noticed for a short time.
A slight branny or furfuraceous desquamation occasionally follows
the disappearance of the rash. The development of this scaling is
proportionate to the severity of the attack and the intensity of the
1 Loc. cit., p. 15.
Tlll'l KVMl'TOMATOfJXlY OF ItU I'.FLLA F)')!
eruption. Many writers, inclufiing Steiner, Thomas, Fleisclimann,
Brodie, McLeod, Wilson, Goodhart, Cuonno, Bourneville, and liricon
have not ol)served des(|naniutioii. Eflwards, on tlie other hand, in a
severe ej)ideniic discovered (Jescjiiamation in all of his cases. In quite
a number the scaling was well marked; in others it was limited to
certain regions, especially the nose. The buccal cavity, |)articularly
the throat proper, participated in the desquamative process. The
peeling was usually furfuraceous, beginning in the centre of the eruptive
patch and extending to the circumference. Larger scales were seen
on the hands and feet. The average duration of desquamation was
three days, but Edwards has seen it last twenty days. In our cases,
which it will be remembered were very mild, it was rare to .see any
desquamation.
Associated Symptoms of the Eruptive Stage. Fever. — The extent of
febrile reaction in rubella is largely dependent upon the severity of
the individual attack and the character of the prevailing epidemic.
The variant observations of different writers on this point is evidence
of the truth of the above assertion. There are some epidemics in which
there is but an insignificant rise of temperature, if, indeed, there be any
fever at all. Nymann failed to observe any appreciable rise of temper-
ature in 58 out of 119 cases. Emminghaus, Thomas, Vogel, Wunderlich,
Earle, Picot, and others have all seen afebrile cases.
On the other hand, in severe cases high fever may be present.
Edwards saw cases with temperature of 103° and 104° F. McLeod's
cases ranged from 100° to 105° F. Cheadle reports an epidemic in
which the initial temperature was 103° F., later reaching 104° and
105° F. Haig-Brown records a temperature of 105° F., and Davis
saw a temperautre of 106° F. in a boy with a livid rash, convulsions,
and rapidly running pulse.
The fever is, as a rule, proportionate to the extent and severity of
the eruptive and catarrhal symptoms.
There is no febrile course which occurs with any degree of constancy.
The evening temperature is, however, usually 1 or 2 degrees above
the morning. Most cases of rubella will exhibit slight fever varving
between 99° and 101° F. In most of our cases the temperature regis-
tered 99° or 100° F. In two patients it reached 102° F.
It 's not surprising that some of the older writers should have regarded
rubella as a hybrid of measles and scarlatina, for we commonly note
in this disease the catarrhal symptoms of the former and the angina of
the latter, but both in very mild form.
The catarrhal symptoms commonly affect the eyes, nose, throat, and
bronchial tubes. The eyes are commonly seen to be "watery" or
slightly injected. Our experience coincides with that of Griffith, who
observed this symptom in about one-half of his cases. It is uncommon
to find conjunctivitis and photophobia as pronounced as it is seen in
measles.
Sneezing. — Sneezing is a frequent symptom, although the paroxA'sms
may be but few and limited to the first day of the eruption. In none
558 RUBELLA
of our cases did we note any distinct discharge from the nose; neverthe-
less, coryza is recorded as occurring in a considerable proportion of
cases in some epidemics.
Cough. — Cough occurs in a variable proportion of cases, depending
upon the character of the prevailing epidemic. When it is present it is
usually slight and in no sense comparable with the severe cough of
measles. It was absent in the vast majority of our cases. Griffith says
a loose, bronchial cough was frequently present in his cases and occa-
sionally demanded treatment. In the severe epidemic observed by
Edwards cough was generally present, increasing in frequency and
severity and occasionally becoming laryngeal. In quite a large pro-
portion of these cases bronchitic rales, more or less diffused, were heard.
The cough lasted about as long as the eruption, so that it had entirely
disappeared about the fourth or fifth day.
Sore Throat. — Sore throat of a mild character is an extremely common
symptom of rubella. The angina is much milder than that observed
in scarlatina, and often does not lead to complaint on the part of the
patient. Without inspection it would, doubtless, be frequently over-
looked. The congestion is most pronounced upon the upper portions of
the anterior pillars. Occasionally a more serious involvement of the
throat is encountered, characterized by enlargement of the tonsils,
swelling of the pharyngeal mucous membrane, and painful swallow-
ing. Mild angina is regarded as a rather constant symptom by most
writers.
We have frequently seen upon the soft palate a number of pinhead-
sized, glistening, reddish elevations. Similar reddish spots have been
observed by Emminghaus, Nymann, Gerhardt, Picot, Parke, Dunlap,
Kassowitz, Cuomo, and Griffith. Forchheimer regards as a character-
istic exanthem "the small, discrete, dark-red, but not dusky papules"
which are seen early on the soft palate and which disappear in twelve
to fourteen hours.
We have carefully examined the buccal mucous membrane in a number
of cases and have frequently noted the presence of discrete, pinhead-
sized, deep-red spots, bearing a considerable resemblance to the macules
upon the cutaneous surface. We have never seen the central bluish-
white dots which Koplik describes as characteristic of measles.
Hoarseness. — Hoarseness, usually mild but occasionally severe, has
been mentioned by Thomas, Emminghaus, Griffith, Aitken, Cheadle,
Patterson, Edwards, and others. The catarrhal symptoms sometimes
subside after a duration of !a day or two, but more commonly disappear
with the eruption. Occasionally a certain amount of cough may con-
tinue for some days.
Tongue. — ^The tongue is usually covered with a thin, grayish coating,
the tip occasionally exhibiting some prominence of the papillae. While
a few writers (Balfour, Hemming, Tripe, Murchison, Burnie, and
Tompkins) claim to have seen the typical "strawberry" tongue in
rubella, this condition must be regarded as exceptional. In some cases
the tongue is clean and presents no deviation from the normal appear-
TILE SYMPTOMATOLOGY OF IKJIiKI.LA 550
ance. In severe cases Edwards states that tlie tongue may he dry and
brown.
Lymphatic Glands. — Enlargement of tlie lympliatic glands lias long
been regarded as a symptom of considerable diagnostic im|K)rtance.
Nearly all writers are agreed as to the constancy of tliis adenopathy.
It must be remembered, however, that a general glandular intumescence
occurs in scarlet fever and to a lesser extent in measles, and that lymph-
atic enlargement, therefore, does not specially differentiate rubella from
these diseases.
According to Griffith, J. F. Meigs regards the enlarged postauricular
gland as one of the most prominent diagnostic signs of rubella.
It is claimed by some writers (Squire, Thierfelder, Glover, Jalland,
Strover, Hardaway) that the glands increase in siz-e often before the
appearance of the rash. In other cases, however, the glanflular tume-
faction may not be noted until the second day after the appearance of
the eruption. The glands behind the ears and those lying posterior
to the sternocleidomastoid muscles are those most frequently enlarged,
although other glands, such as the inguinal and axillary, may participate
in the process. Kassowitz found lymphatic enlargement in but one-
third of his cases, and Eustace Smith observed it only in certain
epidemics.
Nausea. — Nausea and vomiting are rare symptoms in cases of the
average type. In severe cases, however, emesis may be severe and
persistent. In one of our cases the vomiting continued for several days
before the appearance of the eruption, the patient being unable to
retain any nourishment at all. Edwards states that in a severe epidemic
in the Philadelphia Hospital, vomiting occurred in a fair proportion
of the cases as the eruption was approaching the maximum. In five of
these cases it was almost uncontrollable. Griffith observed vomiting
on the first day of the eruption in a few severe cases.
The bowels are usually normal or constipated. In a nurse under our
care, suffering from a very mild attack of rubella, diarrhoea was present
on the first and second days of the eruption.
About 40 per cent, of Edwards' cases had gastrointestinal irritation;
this very unusual complication may be accounted for by the severity
of the epidemic. Among these cases were 10 of enteritis and 2 of entero-
colitis. Cuomo has also noted the presence of diarrhoea in severe cases.
Earle encountered 4 cases of intestinal irritation. Balfour found catarrh
of the colon a rather common symptom. The majority of writers make
no mention of any disturbance of the bowels.
Itching.— Itching varies both as to frequency and intensity, depending
much upon individual peculiarity. It is present in only a minority of
cases and is seldom severe.
Pulse and Respiration. — The pulse and respiration usually keep pace
with the elevation of temperature. The former may undergo acceler-
ation to 140 or 150 per minute. Edwards says several of his cases
presented well-marked symptoms of heart-failure, which yielded, how-
ever, to appropriate treatment.
560 RUBELLA
The following case of rubella in an adult patient under our care
presents many points of interest:
Miss R., trained nurse, aged twenty-seven years, had measles at the
age of eight and scarlatina at the age of six. Was on night duty in
convalescent scarlet-fever ward of the Municipal Hospital, in which
rubella appeared on March 3, 1903. Patient had been exposed to
measles in another building five weeks previously.
March 16, 1903. — On Wednesday, March 11th, the patient was taken
sick with headache and sudden vomiting. Since that time she has
vomited each day (or rather night, as the patient has continued on
night duty, not making known her illness.) Emesis occurred five or six
times each night. Patient claims to have retained absolutely nothing.
There has also been persistent headache, weakness, recurring chilliness,
perspiration during sleep, and restlessness. No catarrhal symptoms
whatsoever; neither coryza, cough, nor conjunctival redness.
Although patient had felt feverish for some days, her temperature
was first taken on March 15, 1903, in the evening, when it registered
102° F. This morning it is 100° F. Glands about the jaw and neck
are not enlarged.
The eruption was carefully watched for by another nurse who occupied
the same bed-room; it was observed at 3 a.m. on March 16, 1903,
making its appearance first on the legs below the knees, then spreading
upward. At 6 a.m. the rash was noticed on the wrists. At 3 p.m.
(the hour of our examination) the following notes were made: An
eruption of pinhead to lentil-seed sized, dusky red, slightly elevated
macules is seen, quite covering the legs and with even greater profusion
the arms. The macules form typical crescents on the arms and are also
arranged linearly. In other places they run together and present an
appearance quite indistinguishable from an intense measles exanthem.
The upper part of the chest shows a diffuse scarlatiniform redness.
On the back are a number of discrete macules which have just appeared.
The face shows no distinct eruption, but the cheeks are quite flushed.
The buccal mucous membrane exhibits faint reddish spots.
Ylth. The temperature last night was 101f°F. This a.m. it is
100° F. The patient is perspiring quite a little. The glands at the angles
of the jaw are now enlarged to the size of almonds and are distinctly
tender. There is also enlargement and tenderness of the cervical
glands. The eruption has become fainter and more confluent on the
legs and forearms and has extended to the hands, and also from the
legs upward to the thighs and buttocks. In the latter region the
exanthem is intense and of a morbilliform character. There is more
eruption on the back and chest, in which region it has the form of dis-
crete, lentil-seed sized, sharply defined macules. There is to-day some
macular eruption upon the face. The uvula and soft palate are slightly
injected.
l^th. The temperature this a.m. is lOOf ° F. The patient is perspir-
ing and complains of chilliness and pains in the back, arms, and legs.
The eruption is now faint on the arms and legs, but is still quite con-
COMPLICATfONS AND S/;ain this morning.
\Mh. Tlie temperature hist nin;ht was H)J;i°F. and this am. is
100|° F. Patient is feeling better. The eruption is still well marked on
the chest and back, where it shows many crescents. It is more })ro-
nounced on the face to-(hay than at any ])revious time.
20///. The cruptif)n is still present on the back and chest, but is
fading. There is still a little fever.
2lst. Temperature last night was 99 if ° F. This a.m. it is 99,!° F.
The patient is feeling much better; the appetite is returning. The
eruption has practically disappeared.
There were many anomalous features in this attack, among which
may be mentioned the long and severe prodromal symptoms, the origin
of the eruption on the legs, the complete absence of catarrhal symptoms,
and the distinctly morbilliform character of the eruption.
COMPLICATIONS AND SEQUEL -ffi OF RUBELLA.
Rubella and chickenpox rank together as exhibiting the lightest
incidence of complications of the various exanthematous diseases.
There is no special complication liable to develop during the course of
rubella, and in the vast majority of cases there are none.
Bronchitis and 'pneumonia have been mentioned by some writers.
Edwards saw three attacks of pneumonia among 166 cases and Griffith
observed two in 150 cases. Ryle and Edwards have each reported a
case of 'pleurisy. Reference to enteritis and enterocolitis has already
been made. Severe secondary sore throat has been reported by Tongue-
Smith, Emminghaus, and Eustace Smith.
Hatfield reports 2 cases of stomatitis and Edwards 4 cases. Earle
and Edwards make mention of aphthce, the latter noting it in 30 cases.
Rheumatis7n was seen once by Slagle and Edwards, and several times
by Earle. Endocarditis has likewise been observed.
Several cutaneous complications have been recorded. Alexander
records 5 cases of facial erysipelas; urticaria is mentioned by Slagle,
Earle, and Cullingworth; febrile a^dema and cedema of the legs have been
described. Miliaria, furunculosis, and pemphigus have been recorded
as rare complications.
Blepharitis, conjunctivitis, phlyctenular keratitis, and otorrhaa have
been met with. Mettenheimer speaks of chronic nasopharyngeal
catarrh, permanent swelling of the tonsils, and gingivitis. Painful
enlargement of the thyroid gland was observed by Slagle in 6 cases.
Albuminuria. — Hatfield found albumin in the urine twice and
Cuomo three times. Kingsley, Cheadle, Duckworth, and Reed each
record a case. We noted transient albuminuria in a case of rubella
sent into the scarlet-fever wards as a case of scarlatina; the patient
clearly had rubella and was discharged in ten days. In an attack of
rubella in a girl suffering from postscarlatinal nephritis, swelling of
the eyelids and legs followed the disappearance of the eruption.
36
562 RUBELLA
In a series of 166 cases seen by Edwards albuminuria was present
in about 30 per cent., but in the next 100 cases but 3 per cent, showed
albumin. In the first series 9 cases presented well-marked albuminous
urine, with dropsy. In none of the cases could tube casts be found.
Most of the complications above described excite interest rather
because of their rarity.
Association with Other Diseases. — We have observed 100 cases of
rubella occurring in children convalescent from scarlet fever. In none
of these cases did it occur earlier than the fourteenth day of the dis-
ease and usually considerably later. (About one-half of these children
had previously in their life had measles.) We have also seen rubella
in children convalescing from a mixed attack of scarlatina and diph-
theria.
In one little girl still scaling from scarlet fever, and showing the crusts
of a profuse chickenpox eruption, a well-marked eruption of rubella
appeared.
Relapse. — We have never observed a relapse in rubella, and from
the absence of reference to such instances on the part of most writers
it is evident that such occurrences are uncommon. Nevertheless,
competent observers have recorded instances of recurring outbreaks.
Emminghaus reports relapses in 3 cases and Earle in 2 cases. Edwards
noted it once on the fourth day and once on the twentieth. Griffith
noted a recurrence once at the end of eleven days and twice after a
period of three weeks. Kostlin, Lindwurm, Golson, and Kingsley have
also testified to the occurrence of relapses. The recurrent attack may
equal the original in the intensity of its symptoms or it may be milder.
There does not appear to be a single authentic case recorded of actual
second attack — i. e., due to a second infection and occurring after a
period of months or years. It may, therefore, be said that one attack
of rubella offers protection against subsequent infection.
THE DIAGNOSIS OF RUBELLA.
The diagnosis of an atypical case of rubella, particularly when occur-
ring sporadically, may be attended with the greatest difficulty. In its
classic form and especially during epidemic prevalence the diagnosis is
a very simple problem. There is no one symptom which in itself is
characteristic; the diagnosis must be made from a consideration of the
composite symptomatology.
Measles. — ^Measles is the disease which bears the closest resemblance
to rubella, and which has, doubtless, been most often confounded with
it. The differential diagnosis between these two diseases may be
prefaced by the remark that a morbilliform exanthematous affection
occurring as an epidemic among children who have had measles is in
all likelihood rubella.
A confusion between measles and rubella may arise when the former
disease presents itself in very mild form or when rubella appears, as it
sometimes does, with severe manifestations. The history as to the
77//'; l>fy\aNOS/S OF IWIihlLLA 563
previous occurrence in the patient, of measles or rubella is evidenee of
an important elinracter. It is nncommon for measles to attack an
individual twice and still rarer for rnlx-lla to act in this manner.
The incubation period of rub(^lla is from five days to three weeks.
Griffith regards the variable duration of this stage as comy)arefl with
the fixed incubation ])eriod (abotit ten or eleven days) of measles as a
feature of diagnostic im})ortance.
The prodromal stage is very brief, rarely lasting more than twenty-
four hours, or it may be absent altogether. Slight conjunctival redness,
sneezing, and sore throat maybe present. In measles there is a distinct
pre-emptive stage characterized by considerable fever and marked
catarrhal symptoms affecting the eyes, nose, larynx, and bronchial tubes.
The catarrhal symptoms are more pronounced in mild attacks of measles
than in severe attacks of rubella. Some redness of the throat is usually
present in rubella, whereas in measles sore throat may be a}>sent.
Pinkish pjnhead-sized elevations are at times observed upon the
soft palate in rubella. The buccal mucous membrane sometimes exhibits
reddish spots. The bluish-red spots surmounted by whitish dots
described by Koplik as characteristic of measles are not seen in rubella.
Fever m rubella usually ranges from 99° to 101° F., rarely exceeding
this. In measles fever is a prominent symptom, commonly registering
103° F. or more. It is much more protracted in measles than in rubella.
The eruption in rubella spreads more rapidly, fades on one part
while spreading to another, and is of brief duration (one to three days).
It consists of discrete, pale rose-red, slightly elevated, pinhead to pea-
sized macules. In measles the eruption spreads more slowly, reaches
a maximum intensity simultaneously all over the body, and lasts for
four or five days or longer, being followed by a staining of the skin.
The color is a deep red, at times being bluish. The macules are larger
than in rubella, irregularly grouped, often being disposed in crescents,
and presenting a distinctly blotchy appearance.
Glandular enlargement occurs in both diseases, but is more prominent
in rubella, intumescence and tenderness of the postauricular and post-
cervical glands being frequently present.
Measles is not infrequently complicated by pneumonia, an occurrence
which is extremely rare in rubella.
Children with rubella are often so little disturbed as to complain
about being put to bed. Measles is accompanied by an amount of
prostration and weakness which cause the patients to seek their beds.
The above differentiation w^ll suffice for ordinary cases. We occa-
sionally encounter, however, attacks of measles which present anomalous
features. The fever may be extremely slight, the eruption may be poorly
marked, or the catarrhal symptoms may be almost in abeyance. On
the other hand, severe cases of rubella are occasionally met with; con-
junctival redness, coryza, and cough may be developed to an unusual
degree, and the fever may be high. In other cases the eruption may be
deep red, the macules may be arranged in crescentic groups, the rash
persisting for five or six days. We have seen at least one case in which
564 RUBELLA
the eruption could not be distinguished from that of measles; in this
instance, however, catarrhal symptoms were absent. It is extremely
rare to find a case of rubella which in all respects answers to the descrip-
tion of a normal case of measles, and it is still rarer to find a series of
cases which fulfill this requirement.
Scarlet Fever. — It is quite possible to confound one form of the
eruption of rubella with that of scarlatina. Many writers have acknowl-
edged their inability to distinguish at times between the confluent
scarlatiniform type of rubella and the scarlet-fever exanthem. In these
cases other symptoms than the skin appearance must be relied upon
for the differential diagnosis.
The incubation period of scarlet fever is distinctly shorter than that
of rubella, lasting ordinarily from three to seven days. The invasive
symptoms are sudden and quite severe; vomiting occurs in the majority
of cases, followed by rapid rise of temperature, usually to 103° or 104° F.
There is marked sore throat, the tonsils, soft palate, and uvula being
particularly affected. The glands generally are enlarged, but more
especially at the angles of the jaw. The tongue is at first coated, later
exhibiting the characteristic red, papillated appearance.
The eruption appears first on the neck and upper chest; the face
usually shows the circumoral pallor. The eruption lasts ordinarily
five to six days. Desquamation occurring in flakes and most marked
on the hands and feet is quite uniform. Middle-ear disease and albumin-
uria are extremely common complications.
It will be seen that the symptomatology is quite different from that
observed in rubella. In the latter disease there is no vomiting, except
in rare cases; the temperature is seldom high; the eruption begins on
the face and is of short duration; the "strawberry tongue" is absent;
sore throat is usually mild; desquamation when present is branny;
complications are extremely rare. In addition the presence or absence
of an epidemic of rubella or scarlet fever will greatly aid in arriving
at a correct diagnosis.
Influenza. — Forchheimer states that in the epidemic of influenza in
1892 many cases were observed in which the differential diagnosis
between scarlatina, rubella, and influenza presented difficulties, at least
in the beginning.
There may be present in influenza an erythematous eruption, M^hich
may be localized or which may rapidly spread over the body. The
fever, prostration, severe gastrointestinal or respiratory symptoms and
the known prevalence of the disease will serve to distinguish it from
rubella.
THE PROGNOSIS OF RUBELLA.
The prognosis is absolutely favorable in the vast majority of cases.
Deaths have been so uncommon as to attract attention by their rarity;
they have invariably been due to complications usually affecting the
respiratory tract.
The mortality depends somewhat on the type of the epidemic and
77/ /i' TIIKATMENT OF JiUJJJ'J/J.A 505
the previous coiulition of health of the patients. Destitute airl yjoorly
noiivislied cliilth'cn are rnore apt to siifFcr from complications. IvJwarfls
had a mortiility of 4\ per cent. amonfiori
sparse.
The rash of typhoid is generally limited to the trunk, whereas the
typhus spots involve the trunk and extremities, even to the hands and
feet. The typhoid spots come out in separate crops and are more
papular and have a more defined border than typhus lesions. The
latter, moreover, tend to become petechial, when they no longer dis-
appear under pressure as do the typhoid rose spots.
Typhoid fever is more often accompanied by meteorism, gurgling in
the right iliac fossa, diarrhoea, and the peculiar pea-soup stools.
The mean duration of typhoid fever is three weeks and of typhus
two weeks. In addition to the above clinical symptoms, certain tests
are of importance. The agghitination reaction of Widal will aid in the
diagnosis of typhoid fever, but not during the early days. Eberth's
bacilli may be recovered from the spleen, or from the urine, stools,
blood, or rose spots. On autopsy Peyer's patches will be found to be
ulcerated in typhoid fever, but not in typhus.
Relapsing Fever. — The differentiation of typhus and relapsing fever
may be attended with great difficulty, particularly during the onset of
the disease. In both maladies the fever rises rapidly to great height.
Typhus, however, is accompanied by much more severe constitutional
commotion and by greater mental disturbance; in relapsing fever the
mind remains clear and the general condition remarkably good. Further-
more, there is entire absence of a cutaneous eruption. At the end of
five or seven days in relapsing fever the temperature subsides to normal,
where it remains for a similar period, then rising and ushering in the
relapse. Jaundice is observed in a large number of cases. Examination
of the blood will reveal the presence of the spirillum of Obermeier.
Malarial Fever. — In tropical countries and even elsewhere at times,
a malignant form of remittent fever is seen wdiich may in some respects
closely resemble typhus fever. The high fever is accompanied by great_
prostration and early disorder of the mental faculties. Later, manifes-
tations of the typhoid state may make their appearance. Where doubt
exists the examination of the blood will reveal the presence of the
hsematozoa of malaria and the diagnosis will thus be rendered clear.
Meningitis. — Both in idiopathic meningitis and in the epidemic
variety a similarity to typhus fever may be presented through the
predominance of the cerebral s3^mptoms. Cerebrospinal meningitis is,
moi'eover, accompanied by an eruption which may lead to error. It is
only, however, when the symptomatology is irregular that real diffi-
culties in the diagnosis are presented. In meningitis the headache is more
intense and of a sharp, boring character. Nausea and vomiting, which
are rare symptoms in typhus, are apt to be present. Rigidity of the
muscles of the neck and retraction of the head are of great diagnostic
importance in meningitis. Later various paralyses develop.
588 TYPHUS FEVER
Pneumonia. — In certain forms of pneumonia attended with typhoidal
manifestations and masked pulmonary symptoms, there may be a
resemblance to typhus fever. The rash will be absent and a careful
examination of the chest will discover the presence of consolidation of
the lung.
Delirium Tremens. — Typhus fever occurring in persons strongly
habituated to the use of intoxicating liquors may present symptoms
simulating mania a potu. Insomnia, delirium, and muscular tremblings
may be present in both conditions. The high fever, eruption, and course
of the disease will readily distinguish typhus fever.
In the eruptive stage typhus fever may be confounded with measles,
with hemorrhagic smallpox, and with severe forms of purpura.
Measles. — During the evolution of the eruption, the typhus exanthem,
particularly when it is profuse, with a tendency to coalescence, may
closely simulate that of measles. This is especially true in the case of
children, in whom it may occasionally appear upon the face. Roupell
believes that Sydenham was probably dealing with an epidemic of
typhus fever in 1674 when he described an anomalous and malignant
form of measles. Sydenham^ says: "The measles of 1674 deviated from
rule, did not preserve their type; the eruption came out irregularly, was
often confined to the neck and shoulders. The bran-like desquamation
did not result, peripneumonia more frequently took place, and in some
cases the fever would last fourteen days or more.
Typhus differs from measles in many particulars, and may usually
be readily differentiated. The prodromal stage of measles is char-
acterized by marked catarrhal symptoms giving rise to sneezing and
coughing; the fever rises gradually and not to such a height as in typhus;
the face is profusely covered with the rash, which spreads downward
over the trunk and extremities. In typhus the fever soon reaches its
maximum, and the febrile course is longer. The rash seldom occurs
on the face, the rose spots later exhibit petechial change, and the
sensorium is more prof oundly affected ; patients previously attacked by
measles are susceptible to the disease.
. Smallpox. — The symptoms of the initial stage of smallpox and typhus
fever present a striking similarity. In each disease we have chills,
sudden high fever, headache, general pains, and profound prostration.
Vomiting is much more frequent in variola than in typhus. The appear-
ance of the characteristic eruption on the third day after the onset of
the fever in variola will clear up the diagnosis. Between purpura
variolosa and hemorrhagic typhus fever a differentiation is often im-
possible. Both are characterized by hemorrhages into the skin and
from the various mucous membranes, associated with intense prostration
and death in a few days. The knowledge of the prevalence of one or
the other disease will aid in the diagnosis.
Purpura. — Severe cases of purpura hemorrhagica may likewise be
confounded with malignant typhus fever. The former, however, is
1 Opera, p. 232.
77//'; I'liOdNOHIH, 01'' 7'V/'II(J.H FJ'JVJ'JIi
589
seldom ushered in with intense fever and the prostration in the beginning
is not extreme. It is only under exceptional circumstances that a con-
fusion of the two diseases would take place.
THE PROGNOSIS OF TYPHUS FEVER.
The wide divergence in tlie mortality rates of epidemics of typhus
fever many years ago is doubtless due to the fact tliat typhoid fever,
relapsing fever, and typhus fever were often confounded and considered
one and the same disease.
The fatality of typhus is influenced by many factors, chief among
which are the age of the patient, his hygienic environment, the con-
dition of his health prior to the attack, and the severity of the prevailing
type of the disease. These and other influences will be considered
in detail.
Age. — The age of the patient influences the mortality to a considerable
extent. With the exception of very young children the disease is much less
fatal in childhood and youth than in age periods beyond these. Beyond
the age of twenty years the mortality progressively increases, reaching
its maximum in advanced old age. Below are appended three series
of age statistics. In the town of Greenock, according to Buchanan,
the death rate was as follows:
Age.
Mortality.
Under 10 years 5.0 per cent.
10 to
20 '
20 "
30 '
30 "
40 '
40 "
50 '
Over
50 '
8.6
15.6
21.5
42.0
66.6
The death rates of typhus fever in the London Fever Hospital, during
a period of two years and including 3506 cases, have been calculated by
Murchison as follows:
Age.
Admitted.
Died.
Per cent
Under 5 years 17
3
17.65
Between 5 and 10 years
1S3
14
7.65
10 " 15 "
363
18
4.95
15 " 20 "
. 546
26
4.76
20 " 25 "
495
47
9.05
25 " 30 "
348
52
15.15
30 " 35 "
323
55
17.02
35 " 40 "
270
89
32.96
40 " 45 "
292
87
29.79
45 " 50 "
212
83
39.15
50 " 55 " ■
150
78
52.00
55 " 60 "
100
51
51.00
60 " 65 "
88
49
55.68
65 " 70 "
42
28
66.66
70 " 75 "
24
17
70.83
75 " SO "
6
5
83.33
Over SO years .
2
2
100.00
Age unknown
50
11
22.00
3506
20.89
15 '
' 20 '
20 '
' 30 '
30 '
' 40 '
40 '
' 50 '
50 '
' 60 '
590 TYPHUS FEVER
Guttstadt^ gives the figures for 5545 cases admitted into Prussian
hospitals from 1878 to 1880 :
Age. Males. Females.
Under 10 years 2.2 per cent. 3.3 per cent.
Between 10 and 15 years 3.0 " 1.5 "
. 5.2 " 4.5 "
. 8.2 " 10.1 "
. 16.0 " 11.2
. 31.9 " 20.2
. 43.7 " 35.5
Over 60 years 57.1 " 45.2 "
It will be seen that while Guttstadt's tables exhibit lower mortality
rates than Murchison's, the same general influence of age is shown.
Curschmann believes that the increasing death rate after the age of
forty is due to the greater cardiac weakness at this period and to the
increased liability to hypostatic congestion of the lungs and other
pulmonary complications as a result thereof.
Sex. — Sex appears to exert but little influence upon mortality. Murchi-
son's figures give 19.67 per cent, of deaths in males and 18.20 per cent,
in females.
Hygienic Environment. — The social position and financial condition
of individuals influence to a large extent the character of their surround-
ings. Food, mode of life, and domiciliary environment, by modifying
the physical, mental, and moral tone of persons, influence to that extent
their general health and resistance to disease, and also their ability to
successfully cope with disease when stricken.
The mortality of typhus fever is particularly high among people
debilitated by famine and hardship. Physical exhaustion, such as occurs
in soldiers and among hard-worked nurses and physicians, doubtless
accounts for the comparatively high mortalities among these classes of
patients. The overcrowding and unhygienic conditions which often
prevail in barracks, prisons, and on board ships increase not only the
incidence of typhus, but also its mortality.
Murchison divided the patients admitted into the London Fever
Hospital into three classes, according to their social and financial
condition :
Admitted. Died. Per cent.
1. Pay patients " . . 94 15 14.89
2. Patients admitted free, but not classified as paupers. 2674 497 18.6
3. Paupers 738 204 27.6
It is seen from these figures that the niortality is higher according
to the poverty of the patients. Murchison believes, however, that the
larger death rate among the poorer patients is to be explained by the
more advanced age of these persons. He states that the current opinion
in Ireland is that the disease is accompanied by a higher mortality
among the rich than among the poor.
Intemperance and Previous Health of Patient. — It is no less true of
typhus fever than of smallpox and other infections that the disease is
' Quoted by Curschmann.
77//'; I'liOCNO^IH O/'' 7'VI'l/fJS Fl'JVJ'Jli 591
particularly fatal in alcoholics. Prolonged habits of intemperance
produce structural changes in tlie heart, bloodvessels, kidneys, liver,
and nervous system, and weaken the d(;ferisive resources of the body
when attacked by disease. In typhus fever, as in sniallj>ox, hemorrhagic
attacks are more common in drunkards than in other individuals.
The previous existence of chronic organic diseases or of acute diseases
unfavorably influences the prognosis in typhus fever, as would naturally
be expected. Debilitating illnesses which lower the resisting power of
the individual, or diseases in which the structural integrity of important
organs is affected, very considerably lessen the chances of recovery.
Unfavorable Symptoms. — Great intensity of any or all of the symp-
toms of typhus fever constitutes an unfavorable condition, yet the
comparatively brief course of the disease renders it possible for patients
exhibiting even the most alarming symptoms to recover.
High fever during the invasive stage and the remaining days of the
disease, if unattended by symptoms hereafter to be mentioned, need not
be regarded as of specially unfavorable significance. If, however, the
temperature continues very high during the second week, it indicates
an attack of great gravity.
More important than the temperature is the condition of the heart
and the bloodvessels. Lic^aga regards an early disproportion between
the pulse rate and the temperature as a sign of fatal omen. A pulse
rate of over 120 in the beginning of typhus fever should excite solicitude.
But the frequency of the pulse is not the only factor to be considered.
The rhythm, volume, and compressibility of the arterial pulsations and
the character of the cardiac sounds are of equal or greater importance.
Inaudibility of the first heart sound or irregularity, rapidity, or marked
compressibility of the pulse occurring early in the disease are bad
prognostic signs.
The condition of the nervous system offers valuable evidence. Early
wild delirium, persistent insomnia, progressively deepening stupor,
subsultus tendinum, carphologia, muscular twdtchings, and convulsions
are all of evil portent. The occurrence of profound coma or coma-vigil
renders the prognosis hopeless.
The presence of considerable albumin in the urine during the early
days of the disease indicates a grave infection. When blood and casts
are associated an alarming complication is present.
Pulmonary complications are commonly the cause of death, particu-
larly in persons advanced in years. Hypostatic congestion, severe and
widespread bronchitis, and pneumonia swell the mortality list. Cursch-
mann includes marked meteorism and "pinhole pupils" among the
specially unfavorable symptoms.
The profusion of the rash is of less prognostic import than its special
characters. The early appearance of petechise and an unusual degree
of hemorrhagic extravasation into the skin are grave signs. Pronounced
cyanosis of the skin, particularly of the face and extremities, indicates
cardiac weakness and is, therefore, an ominous manifestation.
Among the favorable symptoms are moderate intensity of the fever,
592 TYPHUS FEVER
ability to sleep, preservation of the faculties of the mind, moist tongue,
moderate frequency of the cardiac pulsations, and early subsidence of
the pyrexia.
Mortality Rate. — The death rate of typhus fever varies considerably
in different epidemics, but will be found usually to be in the nieghbor-
hood of 18 or 20 per cent. Murchison found that the mortality of 4787
cases of typhus fever treated in the London Fever Hospital between
1848 and 1862 amounted to 20.89 per cent. The same author collected
the immense number of 18,592 cases treated in London, Glasgow,
and other cities, and calculated the mortality as 18.78 per cent. Lebert
gives the general mortality in his experience as 15 per cent.; Buchanan,
10 per cent. ; and Curschmann, 23.4 per cent.
The mortality in hospitals is higher than in private practice. This
may be in part accounted for by the larger percentage of grave and
moribund cases received in hospitals.
In the most severe epidemics the mortality may reach 30, 40, or even
50 per cent. During military campaigns and in famine-stricken com-
munities the death rate is apt to be particularly high.
THE TREATMENT OF TYPHUS FEVER.
Prophylaxis. — In the prevention of such a disease as typhus fever
two lines of action are to be pursued. It is of paramount importance
to limit the infection, as far as possible, to the first afflicted patients.
This is to be accomplished through isolation of the sick and disinfection
of all articles which have come into contact with the patients. If these
measures could be carried out with precision and certainty, little else
would be necessary. But epidemics within recent years demonstrate
that even with the employment of modern methods it is impossible to
completely circumscribe the infection of the disease. It becomes
necessary, therefore, to remove all those causes in a community which
favor the development and dissemination of typhus. It has already
been pointed out that the congregation of large numbers of people in
closely crowded and poorly ventilated quarters is a potent contributory
cause in the spread of the disease. When the original infection is intro-
duced such conditions offer the most favorable opportunity for the
development of an epidemic. In countries in which typhus is prone
to appear, the health authorities should prevent the concentration of
men in barracks, prisons, lodging houses, tenement houses, and the like.
When this cannot be avoided free ventilation of these quarters must
be insisted upon.
It is likewise desirable to control, as far as possible, the movements
of beggars and vagrants in crowded slum districts; it is an oft -repeated
experience that these persons serve as carriers of contagion. Licdaga
quotes Monjares as stating that the removal from populous centres of
the crowds of beggars who swarmed the streets of San Luis Potosi
caused the disappearance of an epidemic of typhus fever which pre-
vailed in that town.
77//'; tiii<:.\tmi<:nt of tvi'Ikjh fkvich 593
As typhus often follows in the wake of fainijK- iiiifj warfare, the most
rigid precautionary measures should he em})loyed wlien these conditions
exist. Proper camp sanitation and care as to tlie feeding and housing
of troops are of great importance. This was exemplified in tlie Crimean
War in the relative freedom of the English soldiers as compared with
the French. The English army, owing to more stringent hygienic con-
trol, suffered much less from typhus fever than did the French troops.
Isolation. — As is true of all contagious diseases, the tyj)hus patient
must be separated from other persons during the entire periofl of his
illness. This can be most effectively accomplished by .sending him to
a hospital specially set apart for the purpose. No one at the present
day would hazard placing a typhus patient in the wards of a general
hospital.
Where the patient must be treated at his home, an airy room in the
upper part of the house should be selected.
Carpets, curtains, and all dispensable furniture should be removed
from the apartment. A communicat'ng room should be occupied by
the nurse and likewise utilized to disinfect all articles leaving the sick
apartment. Over the door communicating with the corridor should be
suspended a sheet wet with a 5 per cent, solution of carbolic acid or
a 1 : loop solution of bichloride of mercury. Whenever possible the
attendants and nurses should be chosen from those who have once
passed through an attack of the disease. One attack of typhus fever
protects against a second in the vast majority of cases. When an
immune nurse cannot be secured, the one employed had better not
sleep in the sick-room. Non-immune nurses should not be permitted
to go abroad among people, for fear of spreading the disease. Immunes
may be permitted this privilege only when every precaution as to personal
cleanliness and disinfection is taken. Intercommunication between the
patient and members of his family must be strictly prohibited.
Disinfection. — The destruction of the infection in all articles with
which the patient has come in contact is a measure of the highest impor-
tance. Mention has already been made of the frequent transmission of
typhus fever in the body linen of patients. To lessen the intensity of
the infection in these articles frequent bathing of typhus patients is
desirable. The baths, which may be sponge or plunge baths, subserve
the double purpose of reducing temperature and lessening the dissemi-
nation of the contagium of the disease.
The body and bed linen should be changed once or twice a day.
They should be received into an appropriate receptacle containing a
5 per cent, solution of carbolic acid or a 1 : 2000 solution of bichloride
of mercury.
The bodily excretions should be disinfected with chloride of lime
or one of the above-mentioned antiseptics. While there is no con-
vincing proof that the infection of typhus is resident in the dejecta,
the disinfection of the stools and urine is a wise and easily carried out
precaution. Eating utensils should be thoroughly boiled before being
permitted to leave the sick-apartments.
3S
594 TYPHUS FEVER
The physician in attendance upon typhus patients should protect
his clothing by wearing a long gown and a cap which covers as much
of his hair as possible. On leaving the patient he should carefully wash
his face. and hands and air himself thoroughly before seeing another
patient.
After the recovery of the typhus patient the apartments occupied
should be thoroughly fumigated with formaldehyde or sulphur and
subsequently aired for a number of days before occupancy. Walls
should be whitewashed, painted, or repapered according to desire.
Blankets and mattresses should be subjected to superheated steam or
hot air in the disinfecting plant provided by most large cities. When
such facilities are not available, blankets should be boiled and mattresses
burned and destroyed.
Wooden furniture should be washed with a solution of carbolic acid
or bichloride of mercury. The patients' clothing should be disinfected
by formaldehyde, steam, or hot air.
When death occurs the body should be enveloped in a sheet saturated
with a carbolic acid or corrosive sublimate solution. An hermetically
sealed casket should be used and interment should be private.
Ventilation. — Ventilation is a preventive measure which appears to
be of greater value in typhus than in other disease. That the free
admixture and circulation of fresh air in the sick-apartment or ward
lessens the danger of contagion is admitted by all writers. Lebert says
he found it an excellent plan, even during the severest cold of winter,
to keep the windows open part of the day and night; he adds that the
patients bear cold well during the continuance of fever, but are sensitive
to it later.
When epidemics occur in the summer months it is a good plan to
treat the patients in tents. The liability of attendants contracting the
disease under these conditions is distinctly lessened.
The temperature of the sick-apartments should be in the neighborhood
of 65° F. The floor is to be mopped with an antiseptic solution and
the atmosphere kept free from dust.
Nursing.' — The nursing of typhus fever is of great importance and
requires the services of a trained person. The body surface should be
frequently sponged with water containing a little alcohol or with a
weak carbolized solution. The teeth and oral cavity require careful
attention from the beginning; mild antiseptic mouth washes should be
employed. Diluted Dobell's solution, boric acid water, or a diluted
peroxide of hydrogen may be used. The cleansing of the mouth is of
particular importance when the patient is stuporous, as the mucous
membrane becomes dry and covered with mucus and blood crusts.
Careful attention is necessary to prevent the development of bed-
sores. Frequent ablutions of parts subjected to pressure and soiled
by excretions, and the use of pads or pneumatic cushions to relieve
pressure, will accomplish the object desired.
Diet. — The diet is the same as that prescribed in the other acute
exanthemata. During the intense febrile period the patient will desire
77//!,' Tkf'JATMI'JNT OF TV I'll US I'l'lVKIi. 695
nothinjTj hut li((ni(] iiotirislimont. Milk ;ukI hroflis iriay Ik- ^ivcn every
two or three hours. As soon as the j)atient cures for soft foods he may
be allowed to have soft-boiled eggs, gelatin, gruels, milk-toast, and like
foods. As the disease al)ates and the appetite incTeases, a gradual
return to the usual dietary may be begun. For tlie relief of thirst
lemonade and the carbonated waters may be given. The diet need
not be as rigid as in typhoid fever, in which disease the presence of
intestinal ulceration necessitates great caution.
Medical Treatment.— Although numerous remedies have been
advocated from time to time for their beneficial action upon typhus
fever, it must be admitted that we know of no drug which materially
affects the course of the disease. When the specific cause of typhus is
discovered a specific cure for the disease may be forthcoming. The
most approved treatment of typhus is that which is devoted to an alle-
viation of the symptoms and the maintenance of the patient's strength.
Fever. — The fever in typhus often reaches a great height and calls for
measures to reduce its intensity. Almost exclusive reliance is to be
placed upon hydrotherapy in one form or another. In the milder cases
it may suffice to employ tepid sponge baths several times a day. The
application of an ice-bag or Leiter's coil to the head is a useful supple-
mentary measure. When sponge baths are not sufficient to control
the pyrexia recourse may be had to the wet pack, the sheet being wrung
out of tepid or cold water according to the intensity of the fever. The
continuous tepid or warm bath will be found to control the temperature
in a most satisfactory manner; the patient may be kept for twenty-four
hours or longer in a bath the temperature of which is maintained between
93° and 98° F. When the graduated bath is employed the water is at
first warm, but is gradually lowered by the addition of cold water to
75° or 70° F.
The Brand method of cold bathing so extensively adopted in the
treatment of typhoid fever does not seem to have been systematically
tried in typhus fever, although its main features are referred to in
favorable terms by those experienced in the treatment of typhus. With
one or other of the above hydrotherapeutic measures it will be found
possible to control excessive fever. It should be remembered that the
reduction of fever by these measures is merely one of the objects desired.
Baths exert a tonic influence upon the respiratory and circulatory
centres and allay nervous excitability.
The coal-tar antipyretics should not be used except in very moderate
doses. Wlien given in large doses or over a long period of time they
may produce serious cardiac depression. Phenacetin, antipyrin, and
lactophenin are among the most eligible of these preparations.
Nervous Symptoms. — Headache is commonly so persistent and
distressing as to require remedies for relief. The light in the room
should be kept subdued in order to lessen retinal irritation. An ice-bag
should be applied to the head, and bromide of sodium, phenacetin, or
antipyrin administered. When these remedies fail to control the
cephalalgia it may be necessary to give opium.
596 TYPHUS FEVER
Insomnia.— Inability to sleep is a bitter complaint of typhus patients
during the early days of the disease. It is well to first try the bromide
of sodium in 20-grain doses, repeated once or twice during the night.
In other cases chloral appears to do well, but should not be used in
large doses for fear of depressing the heart. Ten grains may be admin-
istered in the evening, and followed later by a 15-grain dose if necessary.
Where sleep cannot be otherwise obtained it is proper to give a hypo-
dermic injection of morphine. The employment of a warm or tepid
bath at the sleeping hour will often materially aid in quieting nervous
excitement and inducing sleep.
Delirium. — The bromides, chloral, and opium may be employed to
quiet excessive cerebral activity. The best result in many cases is
obtained by an ice-bag to the head and a prolonged warm bath, or, when
the temperature is very high, a cold bath or pack.
Constipation. — In the constipation which usually exists early in the
disease calomel in fractional doses may be given or a mild saline may be
used. One of the disadvantages of employing opium in typhus is the
aggravation of the existing constipation. When there is much fever
a cold, high enema will serve a double purpose. Vomiting, when present,
may be controlled by pellets of ice, carbonated or lime water, and
temporary abstention from food. The late diarrhoea is best checked
by bismuth internally, and starch-water and laudanum enemata.
Meteorism may, when mild, be relieved by laxatives, and turpentine
internally and externally. Severe " gaseous distention occurring late is
a grave symptom, often defying all treatment.
Alcohol. — Alcohol is a remedy of great value in the treatment of
typhus, when it is used with discrimination. It should not be employed
as a routine, but rather to combat special symptoms. Many patients
will not require its use at all. Buchanan says that alcohol is needed in
two classes of patients — those who cannot take a sufficient quantity of
nourishment, and those habituated to the use of stimulants. He enumer-
ates the special indications as follows: Alcoholic stimulants are most
serviceable in (1) old people; (2) in cases of great prostration with low
delirium and coma; (3) where the pulse is very compressible and the
first heart sound feeble; also when the pulse is rapid or irregular; (4)
where the extremities are cold and the surface livid; (5) where there
is much congestion of the lungs; (6) where there is any erysipelatous
complication.
It may be given in the form of whiskey, brandy, or wine, or, as Cursch-
mann prefers, in Stokes' cognac mixture, the formula of which is as
follows :
Ji— Cognac opt.,
Aquse dest oa 15 ounces.
Vitelli ovi No. 1.
Syrupi 6 ounces.
Tablespoonful every two or three hoars.
When the pulse becomes compressible, rapid, or irregular, or when
the first heart sound is weak, it may be necessary to resort to other
cardiac stimulants in addition to alcohol. Strychnine, digitalis, stro-
77//'; tii[<:atmi<:nt of tyi'Iius fhyku r,u7
phanthus and cafl'eine may he employed with advantage. Nitroglycerin
and camphor dissolved in olive oil may he used hypf)deririieally to tide
over critical moments.
Pulmonary and renal (•oTri|)hc;Uions are to he treated in the same
manner as when these conditions arise indej)endently.
In conclusion a v^^ord of caution should be uttered concerning the
necessity for constant vigilance on the part of the nurses and attendants
to prevent suicidal or lioniici(hd attempts during maniacal excitement.
CHAPTER XI L
DIPHTHERIA.
Definition. — Diphtheria is an acute infectious disease characterized
by the production of a fibrinous exudate or false membrane on certain
parts of the mucous surface of the body. The regions by far most
commonly involved are the tonsils, the pillars of the fauces, the soft
palate, the uvula, the pharynx, and the nares. Not infrequently the
disease extends into the larynx; or it may begin there primarily and
remain limited to this locality. Except at the onset, or when there is
laryngeal involvement, febrile reaction is not a prominent symptom.
The disease is caused by a specific micro-organism and begins as a
local affection, but becomes systemic as the result of absorption of
toxins elaborated by the specific bacilli and, perhaps, certain associated
bacteria. In severe cases the toxaemia may be extreme. After the
general symptoms have disappeared, paralysis is liable to follow. This
may be limited to a few muscles, or there may be complete ataxia.
History. — Of the various diseases belonging to the infectious group,
which have prevailed from time to time in epidemic form, diphtheria
is believed to be one of the oldest. Some writers have sought to prove
that it was known at the time of Hippocrates, and described under the
name of Malum vEgyptiacum. While in the absence of suflBcient
literature on the subject this cannot be determined definitely, yet it is
true that Aretseus, a Greek physician of Cappadocia, who lived in the
latter part of the first and the beginning of the second century, portrayed
the critical features of this malady in language which warrants the
belief that the disease he described was diphtheria. He speaks of a
thick, white, moist material which forms over the tonsils and spreads
over other parts of the mouth; of ulcers which appear on the tonsils,
and which may be superficial and benignant, or extensive, putrid, and
malignant, according as the case is mild or severe. In malignant cases
the foetor from the mouth is loathsome. Fluids are sometimes regurgi-
tated through the nose in the effort of swallowing, the voice is husky,
and when the disease extends into the air passages death speedily results
from suffocation. He mentions that the disease is most common among
children. Aretseus believes that this malady originated in Egypt, Syria,
and especially in Coele, Syria; hence the name of Malum ^gyptiacum.
It was also known by the name of Egyptian and Syrian Ulcerations.
During the fourth century a disease presenting the same symptoms
prevailed in epidemic form in Rome, and was described by Macrobius.
From this time forward for several centuries there seems to be a paucity
of literature upon the subject; this may possibly mean that there was
a long lapse of epidemic prevalence of the disease.
DII'll'I'III'llilA 509
In the sixtecntli, sevciitctuitli, and (M^litcciitli (•(•rlfllri(^s (;[)i'leirii(.'.s of
a disease presentui<:j tin; (isscntial cliaracterislics of dijjiitlieria arc said
to have prevailed frequently, and often with great virulence in many
parts of Europe, particularly in Holland, Spain, Italy, France, and
Germany. The affection apj)eared also in England, and was described
by Fothergill, Iluxham, and others. In Sy)ain the flisease was known
by the name of fregar when confined to the fauces or the cavity of the
mouth, but when it appeared in the laryn.x and caused suffocation it
was called garotillo. In the different countries in which the disease
appeared it was described by tlie physicians under various names,
such as, besides those already mentioned, cynanche maligna, cynanche
contagiosa, angina mahgna, angina gangrjcnosa, ulcerative sore throat,
malignant sore throat, morbus suffocans vel strangulatorius, epidemic
croup, etc.
It is not known exactly when this malady made its appearance in
America. In 1771, Samuel Bard, of New York, published a brochure
entitled, '^An Enquiry into the Nature, Cause, and Cure of the Angina
Sujfocativa, or Sore Throat Distemper, as it is commonly called by the
inhabitants of this City and Colony." In this article a clinical descrip-
tion is given of a disease comparable in its essential features to diph-
theria. It prevailed chiefly among children under ten years, and was
evidently infectious. Bard says the disease began as a sore throat,
which, upon examination, showed that the tonsils were swollen and
inflamed, and presented a few white specks which, in some cases,
increased so as to cover the entire surface of the tonsils "with one
general slough." The swelling was sometimes so great as to interfere
with deglutition. In other cases there was difficulty of breathing, which
was often of so great a degree as to threaten immediate suffocation.
In his brochure Bard speaks of an article previously written by
Douglass, of Boston, describing a new epidemic of an acute throat
affection which was seen in that city, and which was quite similar in
its clinical manifestations to the disease which later appeared in New
York City.
It must be said that these clinical descriptions by the earlier writers
were not very exact, and that doubtless several diseases were not infre-
quently included in the same category. It is safe to assume that some
of the anginose affections other than diphtheria, especially scarlatina,
were not always differentiated. Indeed, Bard speaks of "inflamed and
watery eyes, a bloated and livid countenance, with a few red eruptions
here and there upon the face," as being among the earlier sATiiptoms in
many of the cases that came under his observation. Likewise, Douglass
characterized the disease he described as "An Eruptive Miliary Fever,
with Angina Ulcusculosia."
In regard to the history of diphtheria in America, literature shows
that the peculiar form of sore throat described by Douglass was seen
about 1735 in certain inland towns in New England, and gradually
spread westward, reaching the locality of the Hudson River two years
later. The disease prevailed more particularly in towns to which people
600 DIPHTHERIA
resorted for trade, and was spread by means of commercial intercourse
and travel. In New York an epidemic was noted by Father Middleton
in 1752. After Bard's description of the disease in 1771 very little
seems to have been said about its presence in New York until 1826.
From 1855 to 1858 it prevailed in some parts of the State, especially in
Albany, with great malignancy.
In 1856 Dr. J. V. Fourgeand published a monograph on a terrible
ep demic of sore throat which occurred in San Francisco and other
towns of California.
An epidemic of a similar affection occurred in Philadelphia as early
as 1809. Again in 1831 another epidemic prevailed. The records of
the Health Office of Philadelphia, however, do not show that any
deaths occurred in this city from "diphtheria" until 1860, during
which year the number reached 307. From the preceding historical
facts it is quite evident that diphtheria was not a newly imported disease
in Philadelphia in 1860, but that it previously prevailed under other
names.
The earliest accurate observations on the clinical manifestations of
diphtheria were made by Bretonneau, of Tours, in 1821, when he
presented his first celebrated paper on the subject to the French Academic
de M^decine. This paper, it is said, was not published until 1826.
The name he suggested for the disease was Le Di'phtherite, or Diphther-
itis. He gave it this name because of its essential characteristic, namely,
the formation of a false membrane. Subsequently the name diphtheria
was proposed by Trousseau. This title, as Flint suggests, has the
negative merit of not involving any hypothesis as to the pathology of
the affection. Bretonneau, however, believed that the membranous
exudate itself constituted the pathological criterion for the disease ; that
an inflammation without an exudation is not a diphtheritis, neither is
an inflammation with an exudation when it is not infectious. In other
words, he not only regarded the exudate as an essential part of the
disease, but also as constituting the only source of the infection. He
believed the contagium spread, not through the atmosphere, but by
inoculation, as it were, resulting from particles of the exudate, either
in a fluid or dust-like state, coming in immediate contact with the moist
mucous membrane.
Bretonneau's observations, which were quite extensive, led him to
conclude that membranous croup and diphtheria were identical affec-
tions ; the only difference being that in croup the disease process extended
into the larynx and trachea. He at first fell into the error of regarding
diphtheria as wholly a local disease, but later frankly admitted that
systemic poisoning was an essential pathological condition. Angina
gangrsenosa, he declared, is in no way related to this affection.
Trousseau with his acute power of clinical observation directed
attention to the difference between diphtheria and some of the throat
affections, especially scarlatina, with which it was often confounded,
and also pointed out the danger of this disease from its liability to extend
into the air passages. The fact that death not infrequently resulted
i>ii'iri'iii<:itiA 00]
at an early period of the diseast; from an adynamic conrlition wa.s
observed by him and e,s])ecially commented upon, lie is credited with
rendering vahiable assistance to Bretonneau in establishing the operation
of tracheotomy for tli(> r(;lief of membranons croup; even th(; inriications
given by liim for its adoption woidd still s(!rve as a useful guide for u.s
at the present day.
Recognizing that the disease was primarily local, Jiouchut recom-
mended the removal of hypertrophied tonsils when covered with an
exudate, with the object of preventing the membrane from extending
downward into the larynx and trachea. He was the first to practise
"tubage" of the larynx for relief of the stenosis caused by membranous
croup.
This procedure, however, was condemned and fell into disuse for
nearly a quarter of a century, when, in 1880, it was revived and brought
to a high state of perfection by O'Dwyer, of New York. Intubation is
now almost universally regarded as an indispensable auxiliary in the
treatment of membranous croup.
After Bretonneau's publication appeared diphtheria was recognized
and described by the physicians of every civilized country, and there
soon developed a wealth of literature upon the subject. Many excellent
works were published by French, German, and English waiters. There
w^ere, however, some conflicting notions regarding the nature of the
disease. Some maintained that it began as a general systemic infection,
entirely independent of any previously existing local affection. In other
words, the exudate was regarded as a local expression of a constitutional
disease, manifesting itself by preference upon the mucous membrane
of the fauces, just as the rash of scarlet fever does upon the skin. This
view was opposed by most of the ablest writers, and in the light of our
present knowledge is regarded as untenable.
The question about which there was perhaps the greatest difference of
opinion was whether diphtheria and membranous croup were identical
affections, or whether they constituted two distinct morbid processes.
It may truly be said that physicians of the present day are not yet
entirely agreed on this question. Bretonneau, Wagner, and many others
contended that no clinical or pathological distinction between these
diseases could be made, while Virchow threw the w^eight of his authority
on the opposite side of the question. This distinguished pathologist
sought to establish an anatomopathological distinction. He believed he
had succeeded in showing that in the croupous form of inflammation
the exudation is deposited upon the surface of a sound mucosa, while
in diphtheritic inflammation the exudation takes place into the very
substance of the mucosa as well as upon its surface, and that this mem-
brane undergoes interstitial necrosis from want of nourishment caused
by compression of the bloodvessels. This attempt to distinguish between
membranous croup and diphtheria has been unsuccessful, and the
leading clinicians and pathologists now admit their specific identity.
The consideration of diphtheria has assumed a new phase since
bacteriology has become so important a hand-maiden to the clinician.
602 DIPHTHERIA
The study of micro-organisms in their relation to this disease dates
back over a period of many years, even more than a quarter of a century.
In 1868, Oertel, together with Buhl and Hueter, discovered bacteria
in the false membrane, the blood, and in certain tissues of patients,
which he believed sustained a causal relation to the disease. He
described these organisms as presenting various forms, such as spherical,
rod-like, and corkscrew-shaped. They were also demonstrated by
von Recklinghausen, Nassiloff, Waldeyer, Klebs, Eberth, Heiberg, and
others. While these investigators were evidently working along the
right lines, and may have seen the specific bacillus, yet they failed to
differentiate it from its associates.
The credit of discovering the true bacillus of diphtheria belongs to
Klebs, of Zurich. It is generally stated that this discovery was made
in 1883, but Lennox Browne makes the following statement in reference
thereto: "Professors Hamilton and Sternberg have drawn attention to
its discovery by the same observer (Klebs), and to publication of the
fact at a congress held at Wiesbaden so far back as the year 1875.
The circumstance appears to have attracted but little attention, notwith-
standing that on examination of the original reference it is found that
Klebs had announced at this date that he had not only detected the
bacillus, but that he had also made an effort to cultivate it, and, as far
as one can judge, successfully. To Klebs, therefore, the credit of having
discovered this organism is undoubtedly due. But since he never
definitely announced that he had been able to obtain pure cultures of it,
it must be said that he failed in establishing its causal relationship to
the disease."
This relationship was later established in 1884 by LoeflQer, who
succeeded not only in obtaining pure cultures of the bacillus, but also
in proving its specific character by communicating diphtheria to guinea-
pigs and birds by inoculating them with this organism. Hence, through
the combined labor of these two investigators, in discovering and
establishing the specificity of this micro-organism, it is known by the
name of Klebs-Loeffler bacillus. This discovery has had the effect of
settling the long and often animated controversy as to whether diph-
theria is primarily a constitutional or local affection in favor of the
latter, and has placed the study of the disease on a scientific basis.
THE ETIOLOGY OF DIPHTHERIA.
In considering the causation of diphtheria in the light of our present
knowledge it might be thought sufficient to give simply a description
of the Klebs-Loeffler bacilli and the associated bacteria, with an explana-
tion of their causative relation to the local and systemic manifesta-
tions of the disease. This is the course pursued by many writers of
the present day. But while it is impossible to convey a correct knowl-
edge of the etiology of diphtheria without carefully describing its bac-
teriology, yet for a comprehensive understanding of the subject it is
necessary also to consider the predisposing causes as well as the means
77//'; I'VriOIJXIY f>F DII'IITIIHIilA 603
by which the disease may l)e disseminated, and tfie (■onditions favrjrable
for its spread.
The disease is (lontagious. While sporadic cases may be met with, yet
when it once obtains a foothold in a community it is j>artionlarly prone
to assume an epidemic character. The evidence of its infectiousness
is very conchisive. When diphtheria appears in a family it frequently
attacks many members in succession. The fact that some meml^ers of
the family often escape is no evidence that it is not contagious, for this
not infrequently hap})ens with scarlet fever, the contagiousness of which
no one doubts. In regard to such instances it may be said that ever so
little positive evidence outweighs any number of negative facts. Further
evidence of its contagious nature is found in the fact that physicians and
nurses in attendance upon cases very frequently contract the disease.
In the Municipal Hospital of Philadelphia most of the resident 7>hysicians
who have worked in the diphtheria wards have suffered from the disease
in variable degrees of severity. In one instance the attack was so severe
that death resulted at an early stage. The majority of the nurses have
shown symptoms more or less marked soon after beginning work
in the wards. It is not unusual for physicians and nurses who have
been in attendance upon cases in private practice to be admitted to the
hospital suffering from the disease.
Not infrequently diphtheria has been communicated by direct contact
with detached pieces of exudate or the secretions from the throat and
nose of patients. We have known nurses to show symptoms of the
disease within forty-eight hours after having had coughed into their
faces some of the infectious material from the throats of patients. We
have likewise known infection to result from kissing. ]\Iore than one
physician has fallen a victim to diphtheria through his zealous efforts
to save the life of a patient by clearing out an obstructed tube after
tracheotomy by suction, or by trying to inflate the lungs after the oper-
ation by blowing his own breath into them through a tube. Oertel says:
"In this way Otto Weber, Seehusen, Valleux, Blache, Cillite, fell
sacrifices to their professional devotion. Dr. Wiessbauer, of Munich, lost
his child, who had a short t'me previous to its death unfortunately gotten
hold of a cannula and put it in its mouth, the cannula having just been
removed from a patient sick with diphtheria." Still further evidence
that the disease is infectious is found in the fact that it has been com-
mvmicated to some of the lower animals experimentally by inoculation.
It is well known that diphtheria, like all contagious diseases, some-
times occurs sporadically, at other times endemically, and then again
epidemically. In attempting to explain these circumstances one must
take into consideration not alone the causa causans, or the specific germ
of the malady, but also the causa efjiciens, or that which determines the
occurrence of widespread epidemics. In studying the latter it is neces-
sary to enquire into the sanitary surroundings of each particular locality
where the disease prevails, and into all conditions which may influence
individual receptivity to the infection, such as climate, domestic environ-
ment, age, sex, rainfall, season, etc.
604 DIPHTHERIA
Geographical Distribution. — No country can be said to be absolutely
exempt from diphtheria, although it prevails to a much greater extent
in some places than in others. The disease has invaded both hemi-
spheres, and it has occurred in the northern and southern portions of
each. Altitude seems to exert but little influence over its spread, as it
has been found in both high and low-lying countries. According to
statistics of the United States, however, it has caused the greatest
proportion of deaths in the Southern Central Appalachian region, the
Central Appalachian reigon, and the region of the Western plains;
while the proportion of deaths was least in the South Atlantic coast
region and the Gulf coast region.
The disease occurs in the higher degrees of latitude ; but of all localities
it is most common in the temperate zone and that part of the frigid zone
immediately adjacent thereto, and least common in the tropics. The
records of India show that it is rare in the tropical climate of that
country; nor does it thrive anywhere in the tropical parts of Asia.
It is also rare in Central and South America.
Conditions of the Soil.' — Some writers have ascribed to the soil a
certain influence over the propagation of the disease. It was a common
impression among the older writers, and, indeed, some of the more
modern still hold to the opinion, that low, damp soil, such as is found
in marshy regions with bad drainage, especially near rivers which
frequently overflow their banks and where there is a good deal of
vegetable matter undergoing decomposition, favors the development of
diphtheria; while, on the other hand, a high, dry soil, or a soil composed
largely of dry sand has been regarded as unfavorable to the spread
of the disease. At least, some observers claim that it appears less
frequently and is less likely to be disseminated in localities characterized
by the latter geological conditions.
While it is recognized that for the production and propagation of
diphtheria the presence of the specific micro-organism must be regarded
as a sine qua non, yet it is not improbable that these organisms may
thrive under certain conditions and perish under others. Whether soil
in any of its forms exerts any such influence one way or the other is
uncertain. At times it does appear as though such an influence was
especially marked, yet statistics show that the disease has occurred
and even prevailed in epidemic form in districts where the local con-
ditions were regarded as unfavorable for its spread.
According to Lennox Browne, epidemics of diphtheria in England
"have been very catholic in their distribution from both the geographical
and the geological aspect." But an interesting table compiled by him
seems to justify the belief that the disease has a decided preference
for a clayey soil. This table bears out the opinion of Dr. Thorne Thorne,
whom he quotes as saying that "where a surface soil is, by reason of its
physical constitution and topographical relations, such as to facilitate
the retention of moisture and of organic refuse, and where a site of this
character is, in addition, exposed to the influence of cold and wet winds,
there you have conditions which tend to the fostering and fatality of
77//'; F/riOLOdY OF DII'irrilFiilA OOo
diphtheria, and also go to determine the specific (juality of local sore
throat." The marked predilection of the disease for wet, clayey soils ha,s
been commented upon by many writers, some of whom have yjointed out
that diphtheria is not only more common but more fatal in localities
with wet and retentive soils than in those with dry and pervious grounrl
conditions.
Evidence could be cited tending to show that the disease is fostered
by decomposing heaps of manure and vegetable refuse, such as are
found about stables where sheep, cattle, and other animals are kept.
Outbreaks of diphtheria have been reported where this condition
existed in close proximity to dwelling-houses. The drainage from
decomposing animal and vegetable matter imparts to the soil a .serious
contamination. The digging up of old drains, especially those connected
with dwelling-houses, has been followed more than once by an outbreak
of diphtheria. Surely the upturning of soil thus polluted is a fertile
source of diphtheroid sore throats, or pseudodiphtheria, if not of the
true disease itself. At any rate it cannot be denied that the emanations
from such a source act as a predisposing cause to precipitate an attack
when the diphtherial entity is present.
Rainfall. — The question as to whether the annual amount of rainfall
exerts any influence over the prevalence of diphtheria or its mortality
has not been positively determined. Statistics have been cited to prove
both the positive and negative sides of the question, and are, therefore,
conflicting. After fully considering the evidence at hand we are inclined
to believe with most writers that rainfall is not a very important factor
in determining the diffusion of the disease.
Season.^ — Diphtheria is undoubtedly much more prevalent during
the cold-weather months than during the summer. This is shown very
clearly by the statistics of all countries where the disease prevails, and
is made especially clear in the last census report on vital statistics of
the United States. While the returns of deaths in this report are, for
obvious reasons, incomplete, yet they are sufficiently complete for
comparative purposes. Of course, the number of cases of diphtheria
is not given, but the number of deaths by months may be regarded as
a fair index of the prevalence of the disease for the same periods.
The following table shows for the United States the deaths by months
from diphtheria in the census year 1900:
Months. Deaths. Months. Deaths.
January 1816 July 827
February 1496 August 89S
March 1411 September .... 1303
April 115S October 1739
May 1081 November .... 1912
June 795 December .... 1904
This table indicates that diphtheria (including croup) is most prev-
alent in the United States during the nine months beginning with
September and ending with May, and least prevalent during the summer
months of June, July, and August. The three months showing the
greatest number of deaths are November, December, and Januarv.
606
DIPHTHERIA
By dividing the year into quarters, representing the four seasons, we
find the number of deaths for each season to be as follows: spring,
3648; summer, 2510; autumn, 4954; winter, 5246. The winter months,
and especially the autumn and winter months, show by far the greatest
proportion of deaths.
The following table shows the admissions by months of diphtheria
patients into the Municipal Hospital of Philadelphia during the last
decade :
Year.
Jan.
Feb.
Mar.
April
May
June
July
Aug.
Sept.
Oct.
Nov.
Dec.
1893 ....
36
24
21
■J
16
24
7
13
5
21
26
17
1891
15
2ii
33
. 20
28
25
38
33
39
70
81
64
1895
65
65
66
46
56
54
68
61
38
48
66
73
1896
(i2
54
67
48
74
60
44
45
66
86
122
141
1897
107
97
76
87
61
105
109
112
87
145
149
150
1898
137
78
71
84
88
73
76
84
121
146
146
125
1899
117
72
81
83
109
103
94
139
110
123
178
164
1900
143
126
119
95
102
102
92
94
:08
133
141
112
1901
101
87
98
97
80
76
47
53
66
62
53
69
1902
89
58
59
45
51
55
36
611
25
36
52
46
45
Total
872
681
691
612
665
677
659
676
886
1008
960
This table also shows that the disease was most prevalent during
the months of November, December, and January, and least prevalent
during the three summer months. Considering the table as a whole,
the total number of cases in each of the four seasons is as follows:
spring, 1968; summer, 1937; autumn, 2560; winter, 3513.
It will be noticed here that the autumn and winter months furnished
by far the largest number of cases. This is in accordance with the
observation of many writers. Newsholme says: "Diphtheria is most
prevalent in autumn and in the early winter months, when the opti-
mum temperature and the optimum degree of humidity of the soil are
rapidly disappearing or have departed. It is also most prevalent after
the wet weather, occurring in or immediately following exceptionally dry
years. Both these conditions tend to raise the ground water and to
drive out any pathogenic micro-organisms from the soil."
The greater prevalence of diphtheria during the cold -weather months
can be rationally explained, we believe, by the well-known observations
that the fauces and upper air passages are then much more liable to
attacks of catarrhal inflammation, thus affording an increased suscepti-
bility to the disease, and that the sanitary surroundings in schools and
dwelling-houses at this time of the year are apt to be at their worst.
Domestic Environment.— Under this head might be included the
unsanitary conditions of domestic life, such as result from the crowding
together of a large number of people into tenement houses, narrow
streets, courts, and alleys, where, besides the crowding, the drainage
is bad, and the air almost necessarily impregnated with animal emana-
tions and all kinds of foul odors. Surroundings of this nature are sure
to prejudice health and exert a definite influence in determining an
outbreak of diphtheria and favoring its spread. It is a matter of common
Till': F/riOLOCV of UWIITIII'IKIA {]()-
observation in all i;u-n;e cities when; this fiisc^ase is eiifleniic that the
inhabitants of such localities sufler to the f^reatest extent. While j^ersons
who live under more favorable circumstances are not spared, yet the
transmission of the infection is particularly favored by poverty and
uncleanliness.
Not alone do overcrowded conditions of rlwcllin^-houses favor the
propaf];ation of diphtheria, but in all congested institutions, especially
those for the care of children, in factories, schools, barracks, and, in
short, wherever there is a large aggregation of persons living under
unhygienic environments, there the disease is wont to break out and
assume an epidemic form. But, as already stated, more favorable
modes of living do not ensure safety against the ravages of the malady.
Oertel very truly says: "Robust children who enjoy the best of care
and nourishment are seized and carried off by the disease, although the
number of such cases does not reach that attained in other classes, in
which poverty and uncleanliness favor the spreading of the pestilence."
Even the rich and cultivated dwellings, under the most modern sanitarj-
improvements of ventilation, plumbing, drainage, and the like, have
furnished a fair quota of victims to this fell destroyer of human life.
This shows that the specific organism of diphtheria is no respecter of
persons; nevertheless, certain environments or conditions of life exert
a very potent influence over the spread of the disease.
Dissemination of the Infection. — The infection of diphtheria is
commonly communicated through direct exposure to a person suffering
from the disease. The dust from a sick-room, contaminated with
particles of dried secretions from the throat and nose of a patient, may
serve to convey the infection for a short distance through the agency
of the atmosphere. The well members of a family in which the disease
exists often unwittingly carry the contagium to others. It is frequently
disseminated, especially where no attention is given to disinfection, by
means of infected articles, such as clothing, bedding, towels, handker-
chiefs, carpets, drapery, upholstery, books, toys, and the like. It must
be admitted that physicians and nurses are sometimes the agencies of
transmitting the infection. Even pet animals may play a part in this
baneful work.
Doubtless the disease is often spread by exceedingly mild cases — so
mild, indeed, that the symptoms are not correctly interpreted. Of
course no restrictions are placed on the movements of persons thus
mildly afflicted. Adults continue at their daily vocation, and children
go to school as usual. Such cases are constantly met with, especially
in large cities where diphtheria is endemic. It is well known that some
cases of chronic rhinitis are really of a diphtheritic nature, inasmuch as
the Klebs-Loeffler bacilli are sometimes found in this disease. "When
this condition exists, it is frequently not recognized, and therefore no
restrictions are enforced, nor even any precautionary measures advised.
Really, it is a question whether the mild and unrecognized cases of
diphtheria are not much more often responsible for the spread of the
disease than the severe cases, for the latter are usually surrounded with
(308 DIPHTHERIA
the proper sanitary measures, such as isolation, disinfection, and the
like. Yet it should not be overlooked that after recovery from a
well-marked attack patients not infrequently leave their homes and
associate with the public before their throats are free from the bacilli.
Experience shows that these organisms sometimes remain in the nose and
throat in a virulent form for five or six weeks, and at times much longer,
after the clinical symptoms have disappeared. Then again, it is not
impossible for the disease to be spread by well persons in whose throats
the bacilli are present. It has been estimated, by an able observer, that
these organisms may be found in the throats of about 2 per cent, of all
well persons.
Milk has been charged with spreading diphtheria. In order that it
should play this role the infection must be introduced through outside
contamination. Once introduced, bacilli will find in milk a good
culture medium in which to grow and multiply. In the reports of the
majority of epidemics which were believed to have been caused by the
milk supply, it is stated that either diphtheria prevailed at the dairies
or the milk cans were washed with contaminated water. In some
instances it is said the cows showed on their teats and udders inflam-
matory conditions.
After carefully studying a number of reports on epidemics alleged
to have originated from infected milk, we feel obliged to say that the
contention is supported only by very strong presumption that the milk
was at fault. There is no evidence that amounts to absolute proof.
So far as we know the Klebs-Loeffler bacilli have never been found in
any of the suspected milk. A few years ago the Board of Health of
Philadelphia collected samples of milk from sixty-two houses in which
diphtheria prevailed and subjected them to careful bacteriological
examination, but the result in every instance was negative. In this
connection it might be well to add, on the authority of I^ennox Browne,
"that the bacillus when grown in milk loses many of its chief character-
istics, or, perhaps, it would be more correct to say it assumes others
peculiar to its culture medium. It probably undergoes degenerative
changes with rapidity; possibly these are due to the presence of lactic
acid."
Schools are commonly regarded as an important factor in the spread
of diphtheria. It is a matter of observation in large cities where the
disease is constantly present that the number of cases increases soon
after the opening of the schools in autumn, and that the number is
smallest during the summer vacation. The rules created and enforced
by health authorities, excluding from school all children suffering from
sore throats, and all those from families in which diphtheria exists,
have done much to limit the spread of the disease. But in spite of this
wise sanitary measure it not infrequently happens that children attend
school while suffering from mild and unrecognized forms of diphtheria,
or, at least, in whose throats virulent bacilli are present. Outbreaks of
the disease in certain districts may often be explained in this way.
On the contrary, efforts have been made to show that congregation in
Till': hyrioLoav of hii'irriii'iniA (;0J>
schools is not a common cause of cj)i(Jemics. In supjxjrt, of this negative
view it has been pointed out that the mortality from diphtheria is by
far the greatest among children imder five years, who have not yet
arrived at the school age. Jt has been stated also that there frequently
is a great increase of its prevalence in sf;hools irnmefliatcly after a
holiday recess. The latter statement is undoubtedly true of boarding
schools and kindred institutions; but when diphtheria breaks out in
such a school it is aj)t to cause not only a local epidemic, but so great
alarm among the pupils as to occasion a stampede, and thus the disease
is often widely disseminated. When the infection is introdijced into a
family it is not surprising that the younger children — those who have
not yet attained to the school age — should be the principal sufferers.
Therefore, the fact that the greatest mortality is found to be among
children under five years does not invalidate the view that schools
operate as an important factor in spreading diphtheria.
While writing these lines a late issue of American Medicine comes to
hand containing this paragraph: "Diphtheria of a somewhat malignant
type is reported to be raging in Milton, Mass. The disease first appeared
among the pupils of one of the public schools, and afterward spread to
such an extent that the school was ordered to be closed. At this time
there were 28 cases in the immediate neighborhood."
Like all infectious diseases, diphtheria is most rapidly disseminated
in countries and localities where there is the freest personal inter-
communication. Hence, it is by far more common in urban than in
rural communities. After having illustrated this fact in diagrammatic
form, Newsholme says: "The whole of Michigan, which has a large
proportion of rural population, has much less diphtheria than the
neighboring city of Chicago; the whole of INIassachusetts has less
diphtheria than Boston or New York; the whole of England less than
London; the whole of Japan less than its great towns; the whole of
South Australia less than Adelaide."
Constitutional Predisposition.— The presence of catarrhal affections
of the mucous membrane of the nose and throat seems to increase the
liability to diphtherial infection. Children who suffer from adenoid
growths in the pharynx, with chronic inflammation of the nasopharyngeal
region, and from enlargement of the tonsils are regarded as being
particularly susceptible to the infection. When these conditions exist
together they usually cause what is known as mouth-breathing, by
which act the air, instead of being warmed and filtered by passing
through the nares, goes direct to the fauces cold and irritating, and,
perhaps, laden with germs. Lennox Browne writes: "My personal
experience leads me to say that diphtheria hardly ever, if ever, occurs
in a child under seven years of age who is not the subject of one or
other of these forms of glandular overgrowth. It appears needless to
enforce their tendency to abrogate the hygienic function of the nose as
the first avenue of respiration and to induce the marked deficiency in
vitality and resisting power to contagion which are to be found in all
such children."
39
610 DIPHTHERIA
Everyone knows that the first evidence of diphtheria is commonly
seen on the tonsils. It would, therefore, appear that these glandular
organs were the most vulnerable part of the body for attack by the
Klebs-Loeffler bacilli. The peculiar anatomical structure of the tonsils,
having on their exposed surface deep crypts or lacunte into which the
organisms may lodge and multiply, affords a very probable explanation
why they are so often the seat of the disease process. When these
glands are inflamed and swollen the lacunae become deeper and the
mucous covering so delicate that they have been not inaptly compared
by Virchow to open wounds. Hence, it is easy to see how this condition
may increase susceptibility to diphtheria.
Certain other diseases with anginose manifestations also furnish a
marked predisposition to diphtheria. Of these we would mention
particularly scarlet fever and measles. The frequency with which the
Klebs-Loeffler bacilli are found in the throats of scarlet-fever patients
is really astonishing; according to our experience at the Municipal
Hospital they are present in 10 per cent, to 33 per cent, of all cases.
Indeed, they are often found when the clinical conditions would not
suggest the existence of diphtheria. These two diseases, however, not
infrequently coexist, the symptoms peculiar to each appearing at the
same time. But symptoms of diphtheria may develop during the course
of scarlet fever or during conva'escence.
As might be expected from what has already been said, the catarrhal
affection of the fauces and upper air passage incident to measles renders
the individual very responsive to the action of the diphtheria bacillus.
Membranous croup associated with measles is by no means an infre-
quent occurrence, and, moreover, is exceedingly fatal. When measles
prevails in Philadelphia we have numerous applications for the admis-
sion to the Municipal Hospital of cases complicated with membranous
laryngitis. Many of them belong to the true type of diphtheria, but
others, it must be admitted, are probably caused by other bacteria, as-
the diphtheria organism is not always found.
The predisposition to diphtheria varies greatly in different persons,
and often quite independently of any known abnormal condition of the
throat. Children are much more susceptible than adults. The pre-
disposition is undoubtedly much more strongly marked in some families
than in others. This may be explained on the supposition that in the
more susceptible families there is an inherited tendency to the develop-
ment of some form of chronic catarrh of the mucous membrane of the
throat, thus favoring the operations of the bacilli. Some writers believe
that infection through a healthy mucous membrane, if not impossible,
is very unlikely.
Recurrent Attacks. — In most infectious diseases one attack usually
confers immunity against subsequent attacks. This is particularly true
of measles, scarlet fever, and smallpox. But with regard to diphtheria
this announcement cannot be made with equal stress, as recurrent attacks
are by no means rare. We have frequently seen patients suffer from
a second attack before leaving the hospital. Also children have been
77//'; I'JTfOLOaV OF DII'IITIIFUIA ()]]
admitted to the hospital a second time, and, in two or thn^e instances,
a third time sufl'ering from diphthc^ria, after intervals of a few weeks
to three or four years.
Age. — The (h'])htli(M-ial infection finds in childrfui the most favorahlf
soil for its reception and propagjition. Th(; disease is exceedingly
common amonj^ children up to the age of ten years, but those from
one to five years are most susceptible. Some writers state that diph-
theria attacks but seldom infants under a year old, and that in the
first half-year of life there is complete immunity to the disease. It has
fallen to our lot to see a large number of infants suffer and perish from
this scourge, and many of them were under the age of six months.
We believe, however, the infection is not so readily received at this
early age. Adults not infrecpiently acquire the disease; but their chance
of escaping it or of recovering when attacked is much greater than is
the case with children.
It is a recognized fact that in all epidemics of diphtheria as well as
in endemics children are the first to suffer from the disease. They also
furnish the principal part of the mortality. This will be considered
more fully under the head of prognosis. It is worthy of notice that the
laryngeal form of diphtheria is limited almost entirely to children.
The following table shows the diphtheria patients admitted to the
Municipal Hospital of Philadelphia during the last decade classified
into age groups:
Under 25 years and
Year. 1 year. 1-5 yrs. 5-10 yrs. 10-15 yrs. 15-25 yrs. upward. Total.
1893
1894
1895
1896
1897
1898
1899
1900
1901
1902
217
16 218 120 31 52 28 465
26 327 187 46 56 65 706
33 404 276 71 49 36 869
34 560 437 126 89 49 1295
42 652 447 93 47 48 1229
38 659 462 102 62 50 1373
40 595 473 117 90 52 1367
30 374 287 106 56 36 889
38 305 159 40 33 26 601
Total 299 4076 2901 750 570 418 9011
This table bears out the statement that children from one to five
years of age are most susceptible to diphtheria; and also shows that
the susceptibility diminishes very considerably after the age of ten
years. We would direct attention to the table as showing the large
number of infants that have come under our care. As parents are
naturally loath to send children of this tender age to a hospital it is
not improbable that the table shows a smaller proportion of patients
under the age of one year than if the entire number in the city were
considered.
Sex. — It scarcely seems probable that sex should exert any influence
over susceptibility to diphtheria. It has been stated, however, by some
observers that up to the age of four years there is no difference in suscept-
ibility, but subsequent to this age males suffer more frequently than
females.
612 DIPHTHERIA
The last census report of the United States shows that for the
census year the deaths were quite equally distributed between the
two sexes — 14,878 were males and 14,081 were females. This very
extensive statistical evidence warrants the conclusion that predisposition
to the disease is not influenced by sex, and that where any disparity is
found it is accidental rather than otherwise.
The following table shows the number of patients admitted to the
Municipal Hospital each year during the last decade divided as to sex:
Year. Males. Females. Total.
1893 .94 123 217
1894 214 251 465
1895 315 391 706
1896 ........... 424 445 869
1897 636 659 1295
1898 562 667 1229
1899 641 732 1373
1900 669 698 1367
1901 416 473 889
1902 285 316 601
Total 4256 4764 9011
It is worthy of remark that of the diphtheria admissions to the
Municipal Hospital, Philadelphia, the females have exceeded the males.
The table shows that this was the case every year during the last
decade.
Race. — It cannot be said that race plays any prominent part among
the predisponent causes of diphtheria. The opinion expressed by some
observers that the Jews are especially liable to the disease cannot be
accepted in the absence of positive proof. It is true in some of the
large cities of this country the Russian Jews furnish a large contingent
of the cases admitted to hospitals for infectious diseases, but this may
be explained by the unsanitary environments of these people. The
colored race has been thought to possess a considerable degree of
immunity, but we have found no material difference between the death
rates of the white and colored patients.
THE BACTERIOLOGY OF DIPHTHERIA.
In 1883 Klebs first observed and reported the constant presence of
a bacillus in the false membranes in diphtheria patients.
The following year Loeffler^ isolated these organisms in pure culture
and demonstrated their pathogenic power by reproducing the disease
by inoculation of the mucous membranes of animals.
Roux and Yersin^ studied the effects of the diphtheria toxin elaborated
by the bacilli, an investigation which led up to the development of
serotherapy.
By 1891 the requisite postulates of Koch concerning the specificity
of the germ had been fulfilled as regards the diphtheria bacillus. Its
1 Mittheil. aus dem Kaiser. Gesundheitsamte, 1884, Bd. xi.
'•i Ann. de I'Institut Pasteur, 1888-1889.
PLATE LVII.
K.O
b. Colonic
^ iif i)^eu(ii)ili|)hll)oria b.ifilli. X KiO. ^•. ('(ilinii-x oi diphi Ikm ia i);ii-illi.
240.
;. Di|.hilieriabi.-i!i;. ^< 1000.
r..
;'. PseiKlodiphiherialjacilli. KKK). r/. SiiciiK,
1000.
/i. Streptococci.
)iplitheria Bacilli and Streptococ
TlIK liACTI'UaOLOdV OF Dl I'llTII I'llilA (;].'}
constant presence, its isolation in pure culture, the nrproductifni of flic
disease in animals by inoculations of pure cultures, the presence of tlic
bacilli in the orif,niial and in the experimentally induced disease, dernfjii-
strated the bacillus of Klebs and r.oefllcr to b(; the cause f)f dij)li-
theria.
Morphology. — The diphtheria bacillus is a straight or slightly curved,
rod-shaped organism with rounded ends; the diameter is ordinarily
from 0.5 to 0.8 microns and the length from 2 to 3 or more microns.
It is subject to the greatest variation of form; this is true to suc-h an
extent that polymorphism is an important characteristic;.
Abbott^ says that spindle and club shapes are extremely common,
and that not rarely many of the rods stain irregularly; in some of them
very deeply stained round or oval points can be detected. He adds:
"When cultures are examined microscopically it is especially char-
acteristic to find irregular, bizarre forms, such as rods with one or both
ends swollen, and very frequently roc^s broken at irregular intervals
into short, sharply defined segments, either round, oval, or with straight
sides." The form and size of the bacillus vary gready according to
the culture medium used; it is smallest and most regular on glycerin
agar; on Loeffler's blood serum one sees, "instead of the very short
spindle, lancet, club-shaped, always segmented and regular staining
forms as seen upon glycerin agar, long sometimes, extremely slender,
sometimes thicker, irregular-staining threads that are usually clubbed
and frequently pointed at their extremities."
In 1900 Wesbrook read before the Association of American Physicians
a carefully prepared article on the various morphological types of diph-
theria bacilli. He divided them into three groups — the granular (those
with deeply staining granules), the barred (those with transverse bands),
and the soHd or evenly staining forms. Further subdivisions of these
groups were discussed.
The granular type of bacillus is the one most commonly seen in the
beginning of the disease; later these give way wholly or in part to the
barred or solid forms; soHd types may sometimes be replaced by the
granular when convalescence is established and just before the throat
begins to clear. Wesbrook's findings have been more recently con-
firmed by Gorham.
The relation of the sohd forms to true diphtheria bacilli is still
unsettled. They are said to be sometimes encountered as variants in
pure cultures of diphtheria organisms. Certain of the sohd forms have
characteristic i which seem to distinguish them from the diphtheria
bacillus and to class them with the pseudodiphtheria organisms. For
instance, some of the solid forms fail to produce acid in dextrose bouillon,
a property which is possessed by the true diphtheria bacilli."
Staining Properties. — ^llie diphtheria bacillus stains well with the
ordinary aniline dyes and with the Gram stain. The best results are,
1 Principles of Bacteriology, fifth edition.
2 Statements made in a report on " Diphtheria Bacilli in Well Persons" by a Committee of the
Massachusetts Association of Boards of Health, Boston, 1902.
614 DIPHTHERIA
however, obtained with Loeffler's alkahne solution of methylene blue,
which brings out the granules well. This solution is made up of
Concentrated alcoholic solution of methylene blue .... 30 c.c.
Caustic potash in 1 : 10,000 solution 100 "
Neisser Staiii. — The stain suggested by Neisser in 1897 is said by
Abbott to enable one to overcome in a very large part the difficulty
occasionally experienced in differentiating the diphtheria bacillus from
other throat organisms which may simulate it. The method is described
by Abbott as follows : The culture to be tested should be grown upon
Loeffler's blood-serum mixture solidified at 100° C. ; it should develop
at a temperature not lower than 34° C. and not higher than 36° C,
and it should be not younger than nine and not older than twenty-four
hours. A cover-glass preparation made from such culture is stained
for from one to three seconds in the following solution:
Methylene blue (Grubler's) 1 gram.
Alcohol (96 per cent.) 20 c.c.
When dissolved, mix with
Acetic acid 50 c.c.
Distilled water 950 "
After thoroughly rinsing in water the preparation is then stained
for from three to five seconds in vesuvin (Bismarck brown), 2 grams
dissolved in a litre of boiling distilled water, filtered and allowed to cool.
It is again rinsed in water and examined as a water-mount or dried
and mounted in balsam.
When so treated the bacilli appear as faintly stained brown rods in
which from one to three brown granules are always to be observed.
The dark granules are at one or both poles of the cell, are more or less
oval, and usually seem to bulge a little beyond the contour of the bacillus
in which they are located. In the vast majority of cases it seems safe
to regard all bacilli that do not stain in this manner as distinct from
bacillus diphtherise (Abbott). ^
Biological Characters. — The diphtheria bacillus is aerobic, non-
motile and liquefying, and does not form spores. It grows freely in
the presence of oxygen, but is also a facultative anaerobic (Sternberg).
The diphtheria bacillus is destroyed by exposure to a temperature of
58° C. (136° F.) for ten minutes. In the dried state it may maintain' its
vitality for a long period. Park found active bacilli on dried membrane
after seventeen weeks, and Roux and Yersin living but non-virulent
bacilli after five months. Bacilli were found by Abel to persist for
five months on children's toys kept in the dark. When the organisms
are preserved in sealed tubes and protected from light and heat they
may remain virulent for years.
Growth on Loeffler's Blood Serum.^ — This is the best medium for the
growth of the diphtheria organism and the one which is ordinarily
employed for the culture test. It is a mixture of three parts of blood
serum with one part of bouillon, containing 1 per cent, of peptone,
Till': liACTF/illOLOCY OF hi I'II'I'IIIuH A 015
1 per cent, of grape-sugar, aixl 0.5 \n's cent, of .sodluni diloiiilf,-; the
mixture is sterilized and solidified at a low tcniper.'itiire (Stfrnlx-rgj.
I'he di[)litheria organism grows so mucli more {>njmptly upon tliis
mixture than other mouth and throat bacteria that at the end fjf twenty-
four liours the (H[)htheria colonies may be readily recogniyx-d while the
other colonies are still inconspicuous.
Growth on Glycerin Agar. — The development u[)on this medium
is nuich more delicate and less luxuriant than U|>f)n bUjrjd serum.
The colonies apj)ear at first on the surface as Hat, almost transparent,
dry, non-glistening, non-elevated round points. When slightly inagnified
they are seen to be granular with an irregular central marking. The
colonies are always dry in appearance; the deep colonies are coarsely
granular (Abbott). Bacilli taken directly from the throat develop
poorly, or not at all, on agar, but subcultures may grow very well.
Growth on Gelatin. — The colonies on gelatin do not present tlieir
characteristic appearance in less than three days. If slightly magnified
the colonies show a denser centre than periphery; the border is notched.
The colonies are granular, particularly the deep ones (Abbott).
Growth on Bouillon. — According to Abbott, the growth on bouillon
produces fine clumps which fall to the bottom of the tube or become
deposited on its sides without causing diffuse clouding. Sometimes
the clumps cannot be discerned by the naked eye. The reaction of
the bouillon is at first acid and later alkaline. According to Schabad
the maximum acidity occurs most often on the second day, although
sometimes it may be on the third and rarely on the fourth or later.
Many observers regard the acid formation a feature of importance
in distinguishing between the diphtheria and pseudodiphtheria organism ;
the value of this test, however, is not yet definitely determined.
Growth in Milk. — Sternberg states that milk is a favorable medium
for the growth of the diphtheria bacillus and adds that, as it grows at
a comparatively low temperature (20° C), this fluid may become a
medium for conveying the bacillus from an infected source to throats
of previously healthy children. The appearance of the milk remains
if j. unchanged.
^'' Growth on Potato. — Welch and Abbott state that the diphtheria
bacillus grows on ordinary steamed potato without any preliminary
treatment, but that the growth is usually entirely invisible or is indicated
by a dry, thin, glaze after several days. At the end of twenty-four
hours, at a temperature of 35° C, microscopic scrapings of the potato
reveal a decided increase of the bacilli.
Pathogenesis. — According to Park the diphtheria bacillus is patho-
genic for guinea-pigs, rabbits, chickens, pigeons, small birds, and cats;
to a less extent it is pathogenic for horses, cattle, dogs, and goats, but
not for rats and mice. The rat and the mouse exhibit a remarkable
insusceptibility; a dose of 2 c.c. of a bouillon culture will kill a rabbit,
but not a mouse.
The inoculation of such animals as cats and rabbits by rubbing a
pure culture of the diphtheria bacillus upon the mucous surface of the
QIQ DIPHTHERIA
opened trachea produces a disease which is essentially the same as
that seen in man. The animal usually dies in from two to four days,
not from a general invasion by the diphtheria organism, but as a result
of the absorption of the soluble toxins formed at the seat of infection.
The wound at autopsy is covered with a grayish, adherent, necrotic,
distinctly diphtheritic layer. The surrounding subcutaneous tissues are
oedematous and the lymphatic glands at the angles of the jaw are
swollen and reddened. The mucous membrane of the trachea at the
site of inoculation is covered with a firm, grayish-white, loosely attached
pseudomembrane identical in all respects with that seen in human
diphtheria. The membrane and the oedematous fluid about the wound
show the presence both by smears and by culture of the diphtheria
bacillus (Abbott).
In animals that did not die too quickly Roux and Yersin have noted
the development of paralysis of the posterior extremities.
It is a well-established fact that the diphtheria bacillus under ordinary
circumstances remains in the vicinity of the site of inoculation. When
it is found in the blood or visceral organs its presence is probably
accidental. The widespread changes in important organs in diphtheria
must therefore be ascribed to a diffusible circulating poison produced
by the diphtheria organism in its original nidus. That such is the case
was proved by Roux and Yersin in 1888, when they demonstrated the
presence of a poison in diphtheria cultures which were filtered through
porous porcelain. It was found that old cultures and particularly those
of alkaline reaction, had a much greater toxic potency than recent
cultures of acid reaction. Injection of filtered cultures into susceptible
animals produced local redema, congestion and hemorrhage of the
internal organs, effusion into the pleural cavity, etc. It is thus seen
that practically all of the symptoms produced by the injection of pure
cultures of bacilli may be obtained by injection of the filtered cultures
save the production of a false membrane. Sternberg remarks that this
deadly toxin appears to be an albuminoid substance (a toxalbumin), but
its exact chemical composition has not yet been determined.
Virulence and Avirulence of Diphtheria Bacilli.^"V\hen virulent
bacilli are grown in bouillon, soluble toxins are developed which produce
certain noxious effects upon guinea-pigs. Even where the l>acilli are
removed by filtration the injection produces death of the animal.
Practically all bacilli derived from clinical cases of diphtheria produce
toxins with these properties. Conversely, it would seem that bacilli
that produce no toxins in bouillon will not produce them in the human
subject. Wesbrook and Gorham rather dissent from the view generally
accepted, and believe that animal inoculation of cultures is no definite
test of virulence of the bacilli in the human species.
Formerly the non-virulent bacilli were classed by some writers in
a group apart from the genuine diphtheria organism. It is now pretty
generally recognized that true diphtheria bacilli may possess varying
grades of virulence. Those occurring in the throats of convalescent
patients and those found in the throats of healthy persons have fre-
77//'; liACTI'lh-IOIJXlY 01'' Dl I'll'I'll Klil A (; | 7
quently a very low i^ritdc of vii-iilcncc. 'I'lic less vinilcni, lorins rominonly
increase in niiinhcrs ;is |)r()^n-css lovvunl the rcfovery of (li[)litijeria
advances.
The Distribution of Diphtheria Bacilli in the Body. — Abbott says:
"In a certiiiii luniihcr of cases (li[)litlihtheria bacilli in their throats. In the
eastern part of the United States it is 1.3!) per cent.
"This would mean in Boston, if the smaller figure be u.sed, abont
the enl^e of tlie ('])i^1otli,s, the cartilafjje of Wrisher^, and the like. It
very frecjuently covcu's c()inj)let<;ly not only the tonsils, hut tlie anterior
and posterior pihars, the pliaryngeal wall, the uvula, an(J the entire
soft palate. In severe cases it is not uncommon to see the exudate on
the vault of the mouth piled up so high as to form a thick spongy mass,
seriously interfering with deglutition. At the time of writing tliese lines
we have in the l)os[)ital three or four patients in whose throats this
extensive form of exudate is seen. The clinical history of f>ne of these
patients is as follows:
K. R., aged seven years, white, female, admitted December 7th, on
ninth day of the disease. On the first and second days in the hospital the
temperature was 100° F., on the third day it fell to y7;i°F. The pul.se
ranged from 104 to 112 per minute during the first and second days, and
on the third day fell to 82. The culture was positive. On admission
the exudate covered completely and thickly both tonsils, the anterior
pillars, the pharyngeal wall, the uvula, and the greater part of the soft
palate. On the latter it was piled up in a thick, spongy mass. Deglu-
tition was difficult. The face was swollen, pale, and glossy. The breath
was very fetid. Both nares contained large plugs of exudate, and were
constantly oozing blood. The cervical glands on both sides of the neck
were very much swollen. Immediately after admission the patient
received 4500 units of antitoxin; twelve hours later another dose of
3000 units was given, and again a third dose of 4500 units, making in
all 12,000 units. Death resulted on December 9th, from toxaemia
and exhaustion.
We have seen the exudate even more copious than in the case just
cited. Cases have come under our observation in v^^hich not only the
entire fauces, including the soft palate, were covered, but even the hard
palate and the greater part of the buccal cavity also. Sometimes it
appears on the gums, but more often invades the edges of the tongue.
It is frequently seen in the pharyngeal vault, and may extend into the
Eustachian tubes. The nares and the larynx are so often involved that
the behavior of the disease in these cavities will subsequently receive
special notice.
The exudate is usually of a yellowish-white or cream color, but it
may present a dark-gray appearance. Its color is liable to be changed
by the ingestion of certain drugs, or by remedial agents employed
locally. It sometimes is rendered darker by having coagulated blood
incorporated with it. But in perfectly typical cases it does not look
unlike moist chamois skin. Indeed, when large fragments or casts are
exfoliated and floated in water they have a strong resemblance to this
material.
The exudate may be thick, or thin and filmy. When very thick it
may be seen, even at quite an early state, lying rather loosely on the
mucous membrane, or partly detached at its margin, especially when
located on the soft palate. If forcibly removed it is liable to be repro-
duced in the course of a few hours, although in many cases it exfoliates
quickly and does not reform. Instead of presenting the appearance of
624 ' DIPHTHERIA
a distinct membrane lying upon the mucous surface, the exudate some-
times forms into and becomes a part of the mucous membrane itself.
In this case there is a grayish discoloration which disappears slowly, and
often by the process of necrosis, rather than by exfoliation of the mem-
brane. Of course, this process is followed by an ulcerating surface
which heals by granulation.
The involved parts of the fauces, especially the uvula, become oedem-
atous and swell considerably. After the exudate has disappeared from
the uvula, the latter is apt to present an ulcerated appearance, and,
through loss of tissue, is not infrequently left smaller than normal. In
all severe cases in which there is oedema and swelling of the fauces
there is not only difficult and painful deglutition, but the respiration
and articulation are also affected
In the act of swallowing it is not uncommon to see milk regurgitated
through the nares. As the case progresses the voice becomes distinctly
nasal, and is apt to continue so for some weeks.
At first the exudate is free from odor; but when the disease is severe
a distinct odor is noticed in the course of two or three days. Indeed,
the breath of the patient is often so peculiarly offensive that an experi-
enced clinician might be led to suspect the nature of the affection
before an examination of the throat has been made. In septic cases,
when decomposition of the secretions and the exudate goes on rapidly,
the odor is in the highest degree offensive, and is well calculated to
excite suspicion that extensive necrotic changes of the tissues may be
taking place. The tissue change, however, is not always as great as
the odor would indicate. A copious mass of exudate is often thrown
off very quickly by the process of exfoliation, leaving the parts only
slightly ulcerated. In such cases the odor will promptly disappear,
especially with the use of cleansing or antiseptic lotions. With this
apparent improvement one should not be too hasty in pronouncing the
patient out of danger, for the probabilities are that the most critical
period of the disease is yet to be encountered. Where the mucous lining
of the fauces is at all destroyed, leaving the absorbents exposed, the
toxin of the specific micro-organisms is permitted to enter the circu-
lation, and the subsequent danger from toxaemia is far greater than
the primary local disease.
While there is usually some swelling and tenderness of the cervical
and submaxillary glands at an earlier stage of the diphtherial process,
coincidently with intense involvement of the fauces, these glands,
together with the surrounding areolar tissue, become indurated and
infiltrated, giving rise often to extensive tumefaction. The face, besides
being pale and sallow, presents also a swollen and glossy appearance.
As the exudate and septic secretions disappear from the throat, the
tumefaction of the neck subsides. Occasionally, however, the cervical
glands take on suppurative action, but not so frequently as in scarlet
fever.
Nose. — Next to the fauces the nose is the most common site of the
diphtheritic process. The disease not infrequently attacks the nares
77//'; HVMI'TOMATOl.OdY Oh' 1)1 1'llTII hlUI A 025
primarily, but most often the exudate ext(>n(ls I'rojii (lif (liro;it io flic
nasal cavities l)y way of the posterior aspect of the uvula. When this
occurs the posterior wall of the pharynx is also liable to be involved
through contiguity of structure. At first there is but little discharge
from the nares, as in the l)eginning of an a(;ute catarrh, but it soon
increases and becomes Hoccnilent. When the disease has fully develofx-d,
the discharge is often profuse and sometimes fetid.
Before the diphtherial process has continued very long, evidence of
copious exudation may be seen by inspecting the nares. In many cases
the membrane is very thick and dense, and o(;cludes the nasal cavities
completely. There is then but little discharge from the external orifices;
but the voice becomes distinctly nasal, and the patient is obliged to
breathe through the mouth.
When the fauces are at the same time severely involved, the respira-
tion becomes considerably hampered, and there is also difficult deglu-
tition, with marked restlessness and insomnia.
The amount of exudate that is sometimes expelled from the nares
is enormous. The membrane is often thrown off in perfect casts, and
on inspecting these one is apt to feel surprised that so much material
could have been contained within the nasal cavities. When the exudate
begins to separate, or has been either partly or wholly cast off, the
discharge usually returns, and is often sanguinopurulent in character.
There is no form of diphtheria more dangerous than that of the nares.
The injury sustained by the capillary bloodvessels prepares the way
for rapid absorption of the toxins, the effects of which are apt to become
painfully visible in a short time. Not only is systemic poisoning seen,
but the more common sequelae of diphtheria most often follow the nasal
form of the disease.
Epistaxis is of frequent occurrence even in mild cases; but when
the diphtheritic involvement is intense the hemorrhage from the nose
is liable to occur repeatedly, as the disease progresses, and may prove
to be a very troublesome symptom. In some cases there is a constant
oozing of blood, while in others the hemorrhage is sometimes so free
as to be the immediate cause of death.
In the severest form of nasal diphtheria the nose is slightly reddened
externally, and moderately swollen or oedematous. The face also is
oedematous, remarkably pale, and has a peculiar glistening appearance.
The pulse is usually feeble, the circulation bad, vomiting often occurs,
and not infrequently there is marked drowsiness. Indeed, the symptoms,
taken together, are such as would indicate profound systemic poisoning.
Many patients in this condition die at a comparatively early stage of
the disease.
In the more favorable cases the exudate is thrown oft' en masse in
the form of casts, and the constitutional symptoms do not become so
pronounced. But one should not feel too sanguine of recovery in any
case, for danger of the development of toxaemia is never absent. Even
when this serious condition does not arise, and the general symptoms
seem most favorable, still there is a strong liability that the aftection
40
626 DIPHTHERIA
may be followed by paralysis, either partial or general. Postdiphtheritic
paralysis is more common after the nasal form of the disease than after
any other variety.
Nasal diphtheria sometimes assumes the form of chronic rhinitis.
In such cases there is usually a discharge from the nares and often
excoriation of the skin about the nose. But the affection may persist
for months, with little or no nasal discharge. Persons thus afflicted
often unwittingly spread diphtheria. It is important that such cases
should be recognized and treated, and even isolation should be advised
until a cure is effected and the specific organisms have disappeared. It
is only by the aid of bacteriology that this form of diphtheria can be
definitely determined.
Middle Ear. — From the pharyngeal vault the exudate sometimes
spreads by way of the Eustachian tube to the middle ear, causing an
acute median otitis. This is often unattended by pain; hence the con-
dition may not be recognized until suppuration takes place and the
tympanum has ruptured. The purulent discharge which flows from
the meatus will show the presence of the bacilli of diphtheria associated
with certain other organisms, such as streptococci and staphylococci.
There is usually some rise of temperature, often assuming a septic
character.
The otorrhoea frequently persists a long time, but is seldom followed
by permanent deafness. Temporary deafness, however, may be seen
as the result of a paretic condition of the muscles of the Eustachian
tube and of the tympanum. Only in rare instances are the changes
in the intratympanic cavity so great as to cause permanent deafness.
This is not so likely to happen in diphtheria as in scarlet fever.
Eyes. — Diphtheritic involvement of the conjunctiva is not very fre-
quently seen. It occurs sometimes, but the wonder is that it is not more
common in children, since they so often convey the infectious discharges
from the nares to their eyes by means of their hands. Physicians and
nurses who work among diphtheria patients are frequently subjected to
the risk of infection by having the secretions from the throats of such
patients coughed into their eyes. While we have sometimes seen a mild
conjunctivitis occur from this accident we have never known it to
assume a diphtheritic character, though such a result is not impossible.
It has been suggested by some writers that the diphtheritic inflam-
mation may extend to the conjunctiva by way of the tear duct, but
this we believe is of rare occurrence. As an unhealthy mucous mem-
brane is more prone to diphtherial infection, it is therefore probable that
an acute or chronic inflammation of the eyes furnishes a predisposition
to eye involvement when diphtheria occurs in a child thus afflicted.
When the conjunctiva becomes involved the membrane usually
spreads rapidly from one eyelid to the other, and the bulbar conjunctiva
is almost always greatly chemosed. The exudate is first seen as flocculi,
but it rapidly forms into a thick membrane, so thick, indeed, as to press
hard upon the cornea, causing it to become hazy and often undergo
a destructive necrosis. When the cornea of the eye becomes weakened
77//'; SYMPTOM ATOIJXIV OF 1)1 1'llTII HKI A
(■,27
or perforated by lliis pnH-css (lie iris i)rolapses. J)uring tli<- foursc of
the disease (lie eyelids swell and stiU'en, so that it is ainiost iinjjfjssihie
to ins])e('t the vyc, itself. From wliat has heeii said it is evident that
loss of vision is iniininent.
Fortunately the affection is not always so destructive In thr mildci-
cases recovery may take place without impairment of vision. I>iif \vl,atier)t
to live for hours, sometimes even a day or tw(i, with no peree[)tible
pulse at the wrist. It is remarkable to note that consciousness in this
condition is usmdly retained to the last.
Septic Diphtheria. — In diphtheria there are always associated with
the specific micro-organisms streptococci and staphylococci in {^reat
abundance, and the latter often give rise to a concurrent septic infection
which constitutes an important factor in the course of the disease.
It is sometimes difficult to determine to what extent this secondary
infection is responsible for results, as distinguished from those of the
primary infection. Doubtless in many cases of diphtheria streptococcus
infection is the principal cause of death.
Septic infection is most liable to occur in patients with intense nasal
involvement, and in whose fauces the exudate assumes a dirty-gray
or brownish appearance. Instead of becoming detached and peeling
off en masse, the exudate breaks down into a semisolid or gnmious
mass. In such cases the decomposing and liquefying membrane gives
rise to an offensive discharge from the nares and mouth, and a fetid
breath. This discharge, ichorous in character, causes reddening and
excoriation at the orifices of the nose and corners of the mouth, and
the denuded surfaces are often converted into ulcers v/hich quickly take
on a dirty-gray coating. Sometimes there is considerable ulcerative
action seen in the fauces and nares, but, strange to say, this process is
commonly limited to the mucous membrane. It is only in rare cases
that the subepithelial tissue is lost to a greater exteht than would result
from a small ulcer here and there. These ulcers are apt to remain
covered for a long time with a yellowish coating.
The disorganization of the mucous membrane of the affected parts
is commonly attended with capillary hemorrhages, more or less marked.
As might be supposed, the color of the false membrane is changed by
its becoming infiltrated with blood. When the hemorrhages are copious,
and the blood is poured out between the mucous membrane and the
exudate, the latter is quite sure to be separated to a considerable extent.
It is, therefore, not unusual to find in such cases a good deal of loose
exudate in the throat, and in the nose also, undergoing rapid decom-
position.
As the result of septic infection, the lymph glands of the neck become
inflamed and swollen. The periglandular connective tissue may also
inflame and swell to a certain degree. In some cases the swelling is
so great that the neck is raised to an even line with the face. The skin
becomes tense, smooth and shining, and may either feel doughy to the
touch or as dense as a board. Suppuration may or may not result.
Attention has already been called to the fact that in septic cases a
rash is apt to appear on the skin. The rash may at first be erythematous
or slightly macular, but as the disease progresses it often assumes a
petechial character.
In this form of diphtheria the temperature runs comparatively high — •
630
DIPHTHERIA
ranging from 102° to 104° F. There is usually considerable variation
between the morning and evening records. The pulse is rapid and
feeble, and the extremities are often cool. Suppuration of the middle
ear is liable to occur, and pneumonia sometimes develops.
Children, restless at first, become apathetic later on, which condition
increases until death supervenes. Death, however, is not the inevitable
result, for the milder cases frequently recover.
Fever. — Except at the onset of diphtheria, fever is not a prominent
symptom. The disease almost always begins with fever, more or less
intense. In the milder cases the temperature of the body may not rise
Fjg. 93
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B. G., ordinary type of diphtheria, occurring in a child five years of age, showing a high initial
temperature with a rapid decline.
much above the normal, but in the severer cases, during the first day
or two of the disease, it usually ranges from 101° to 102° F.; but after
the full appearance of the exudate— that is, after the second or third day
— the temperature commonly drops to normal, and sometimes below.
Our experience accords with that of Lennox Browne, who says: "Of
1000 cases which came under observation, on an average, on the third
day of the diphtherial attack, the temperature in 80 per cent, was 101°;
while in 50 per cent, the average temperature during its course was
below 99°."
As already stated, the average temperature in the septic form of
TlIK ^YMI'TOMATOIJJdY OK 1)1 1'llTllEIilA
iuW
diphtlieriii is always (:onif)aratively \\\li:}\, wliilf in \\\c fox;rrr)if; cases it
falls to normal and ev(m lower.
In acute adenitis, which often occurs as a cojnplieatioji in di|)htheria,
the temperature ranges high, sometimes to the extent of i(J'1^ to MWy" V.
[f suppuration takes place and the pus is liberated the hyperpyrexia
at once subsides. In every case of continued liigh temperature one
should suspect the existence of some complication. 'V\\v degree f>f fev(;r,
under such a circumstance, is usually not did'crent from that which is
characteristic of the associated disease.
What has been said of the temperature in ordinary diphtheria does
not apply with equal force to the laryngeal form of the disease. In this
class of cases, instead of falling after the first two or three days of ill-
ness, it frequently continues high, especially when intubation is required
Fig. 94
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.luno July
M., aged five and one-half years ; septic type of diphtheria in a patient with copious exudate
in the throat ; swollen cervical glands, later suppurating. Recovery.
for relief of the stenosis, and while the tube is in the larynx. In the
majority of such cases the temperature continues at 101° to 102° F.
for a number of days. If bronchopneumonia develops, which is not
an infrequent comphcation, the temperature will continue high for an
uncertain length of time.
Circulatory Symptoms. ^ — In all well-marked cases of diphtheria the
pulse is frequent. Its rapidity, indeed, may be out of proportion to
the temperature. In severe cases, especially in children, the pulse
ranges between 120 and 160 per minute, and, as the disease progresses,
becomes irregular and weak. The apex beat of the heart is often
diminished in intensity and the first sound becomes indistinct. Atten-
tion has already been called to the fact that the action of the heart
is greatly influenced by the profound asthenia resulting from toxaemia.
632
DIPHTHERIA
An abnormally slow pulse is of grave import, and will be referred to
again when considering the question of prognosis.
Fig.
95
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C. S,, case of laryngeal diplitheria of average severity admitted to the Municipal Hospital on
the third day of the disease, showing decline of temperature after removal of the intubation tube.
Recovery.
The Urine. — In the milder cases no marked change is found in the
urine, either in the quantity voided or its constituents. In severe cases
it contains an excess of urea, and sometimes epithelial cells and casts.
Hsematuria is much less common than in scarlet fever. Albumin in
77//'; ^YMr'rOMATOIJXIY Oh' l>ll'IITIII':iaA {Y.\:\
small (|tiiiiil,i(i('S is found ii) a- hir^c. profxtrlion of cases. It is said io
be present in nhoul one-third of all cases; hut t[)is estirnate is, according
to our experience, much too low. Some writers believe that albumin
is more often found since antitoxin has come into use. Suppression of
urine and ura'mic symptoms are rare. This subject will be n;ferred to
afijain when considering; the complications of diphtheria.
Nervous Symptoms. — In the acute stage of ch'phtheria nervous
symptoms are not a prominent feature of the disease. Convulsions
sometimes occur as an initial symptom in (children of nervous tempera-
ment. In fatal cases convulsive movements are not infrequent in the
death stru<2;,7
usually well marked from the hcfrinriin^. 'Vhv, tcmperaturf- runs up
quickly to 102° or l():i'^ F., there is loss of appetite, the tliroat is painful,
and the child is restless and unable to sleep long at a time, (^,'hilly
sensations may be experienced, and oc(;asionally convulsions occur.
When an early examination of the throat is made the mucous mem-
brane will be found to l)e of a vivid-red color, with moderate swelling
of the parts. The uvula soon becomes (x.'dematous, elongated, and
swollen. This inflammatory action does not continue long, perhaps
only a few hours, until the exudate appears. In its earliest manifestation
it presents the form of grayish or yellowish-white spots of pinhead size.
These form into groups which (juickly coalesce, and thus develop into
large patches. In most cases the exudation is first seen on the tonsils
and rapidly spread to other parts of the fauces. Frequently, in twenty-
four to forty-eight hours it covers not only the tonsils, but the anterior
pillars, the uvula, and a large part of the soft palate. With this increase
of exudation the temperature, strange to say, often falls one or two
degrees. The lymphatic glands of the neck, near the angle of the jaw,
are almost always swollen.
In favorable cases the local symptoms reach their maximum develop-
ment in forty-eight hours, and after remaining stationary for a day or
two begin to subside. The exudation sometimes exfoliates in large
masses, and at other times melts away little by little. When it becomes
detached and peels off it may disappear entirely in from six to eight
days, sometimes sooner; but when it melts away gradually, a longer
time is required. The mucous membrane of the parts involved is left
reddened, and shows superficial ulcerations. Often the uvula suffers
the greatest loss of substance from the ulcerative action, as it is honey-
combed, shrivelled, and tapers down to a small point. The ulcers
usually heal rapidly. Simultaneously with the decrease of exudate the
pulse becomes less frequent, and, in favorable cases, maintains fair
volume and regularity. The swelling of the glands of the neck subsides,
the appetite improves, and the patient is fairly on the road of con-
valescence. But even when recovery seems most probable, the physician
in giving a prognosis should express himself with some reservation,
for dangerous symptoms may yet follow, such as indicate toxaemia,
heart-failure, or paralysis.
In very severe cases all symptoms are, of course, greatly intensified,
and complications are much more liable to ensue. The exudation is
usually copious, covering thickly the entire fauces, and is often seen
extending forward on the vault of the mouth beyond the junction of the
soft and hard palates, on which location it is apt to be especially thick.
It frequently travels backward to the pharyngeal wall, the postnasal
space, and into the nares. It may even extend downward into the
larynx and trachea.
As already mentioned, the local and constitutional symptoms do not
progress pari passii. On the contrary, while the exudation is increasing
the fever may diminish to such an extent that the body temperature
is but little above the normal. The pulse rate, however, does not
638 DIPHTHERIA
always decrease proportionately, but may even grow more rapid.
The appetite often improves, swallowing appears to be less painful, and
not infrequently the general condition and strength of the patient seem
improved, while the danger is in nowise diminished. The physician
should be careful not to be misled by this apparent improvement while
the disease is still progressing.
When diphtheria assumes the se'ptic form, the secretion and exudation
of the throat and nares undergo rapid decomposition, and, unless these
parts are frequently cleansed with antiseptic washes, there is emitted
with the breath a peculiar odor which is in the highest degree offensive.
This odor is often so foul as to suggest the existence of gangrenous
destruction of the tissues, and yet the disorganization of the parts rarely
amounts to more than a superficial ulceration. Coincidently with this
condition, the cervical and submaxillary glands, usually somewhat
swollen from the beginning, greatly increase in size by inflammatory
action, which also involves the adjacent cellular tissue. While abscesses
frequently form, yet it is surprising how rapidly this swelling will often
subside without abscess formation as soon as the throat symptoms show
signs of improvement.
In septic cases the fever, instead of diminishing in two or three days,
as in the other varieties of diphtheria, continues, or may even increase,
until the throat and nose symptoms improve and the swelling of the
neck subsides. Recovery may take place from this form of the disease,
but the majority of patients die. Death often occurs at an early stage,
as early as the fifth to the seventh day, from extensive systemic poison-
ing due to a mixed infection. Sometimes the poisoning is more gradual,
in which case the exudate disappears, the glandular swelling subsides,
and the temperature falls, but instead of improving the patient remains
apathetic, loses weight, becomes anaemic, grows weaker and weaker,
and gradually passes away. A not uncommon cause of death is pneu-
monia of septic origin.
The presence of epithelial and hyaline casts in the urine, together
with a large amount of albumin, points to a rapidly developing systemic
poisoning, and may often prove to be an early monitor of danger.
When recovery takes place from the septic form of diphtheria con-
valescence is usually very slow, often, indeed, extending through many
weeks. The symptoms of septicaemia become less and less marked,
and prostration gradually gives way to general improvement. But in
the fourth or fifth week of the disease, even after an apparent recovery,
some late complication, more especially general paralysis, is extremely
liable to set in. This is true not only of the septic form, but of all well-
marked cases of diphtheria. The vast majority of patients recover
from the paralysis, but it is sure to prolong the period of convalescence
for weeks or even months.
In the malignant type of diphtheria the earliest symptoms give
marked evidence of systemic poisoning. By the time the false membrane
has formed, which is usually in twenty-four to forty-eight hours, the
whole organism is profoundly affected. The membrane covers thickly
PLATE LVIII.
Malignant Diphtheria.
Showing purpuric discoloration of the face, ecehynnoses of the eyelids,
petechia upon the chest, s-welling of the tongue and the glands of the neck.
Death ensued.
77//'; COUIiHI'], DUIiATION, AND Th'JlM IN ATIOS Oh' hi I'll'l II l:i{l A {]'.\\)
the entire fiuices, often involving \hv iiares tilso; tli(; hreatli is fefifl, the
saliva dribbles from the mouth, blood oozes from the nose, and pnrj)ijrir
or petechial spots appear upon the skin; the f^lands of the neek ;irid the
periglandular tissue are greatly swollen; th(; face is bloated, pale, and
waxy in color; the tera})erature is either slight ly elevaterl or subnormal;
the pulse may be rapid and feeble or slow and irregular, and the intel-
lect, clear at first, soon becomes clouded. Death in these cases may
occur in forty-eight hours, and is rarely delayed longer than three or
four days.
The course and duration of membra nous croup vary in different
cases, according to the extent of the disease. In mild cases the symp-
toms often disappear in a few days under ordinary treatment, withf)ut
operative interference. When the larynx is involved to the extent of
causing stenosis, death is sure to result speedily if relief be not afforderl
If the exudation is limited to the larynx the obstruction to respiration
is almost always overcome by intubation, and in the course of six or
eight days the patient may be considered comparatively free from
danger, at least so far as the primary trouble is concerned. But when
the exudation extends into the trachea, intubation may give relief at
first, though death is liable to occur a few" hours later. Death commonly
results when the disease extends into the bronchi and bronchioles. It
occurs through insufficient decarbonization of the blood, due to the
mechanical obstruction caused by the false membrane and retained
secretions in these parts.
In cases which linger longer the fatal result may be brought on by
collapse of certain parts of the lungs to which the air does not have
access, or by the development of capillary bronchitis or broncho-
pneumonia. Many patients develop the latter affection when they are
believed to be well on the way to convalescence. This, indeed, is one
of the principal causes of fatal termination in laryngotracheal diph-
theria.
When membranous croup is likely to terminate in recovery, improve-
ment begins with a decrease in the fever and an abatement of the
laryngeal symptoms. The false membrane usually disappears in from
four to eight days. vSomethiies it is coughed up in cylindrical or irregular
casts, but more often it disappears gradually, probably by being liquefied
and expectorated; it is quite impossible to believe that it ever undergoes
absorption. When throwai oft' in casts it is liable to reform, and when
such new formations take place the disease is apt to terminate fatally.
In patients that recover, hoarseness or aphonia, and often some difficulty
in swallowing, continue for a longer or shorter tune after the intubation
tube has been removed. This change in the voice, according to Oertel,
is to be ascribed to a flaccid condition of the vocal cords and atony of
the laryngeal muscles.
640 DIPHTHERIA
RECURRENCE OF DIPHTHERIA.
Many authors believe that a second attack of diphtheria seldom
occurs in the same individual within a short space of time. While this
may be accepted as the rule, yet it must be admitted that there are
many exceptions. It is certainly true that a person who has survived
the disease does not have conferred upon him for any considerable
length of time that immunity which is so characteristic of scarlet fever,
measles, and smallpox.
We have quite often readmitted children to the hospital with recurrent
diphtheria within a few months from the previous attack; and in two
or three instances, at least, children have returned with a third attack.
Quite often also have we seen patients suffer from a relapse of the
disease before leaving the hospital. In such instances, after the sub-
sidence of all constitutional symptoms and the complete disappearance
of the membrane, the patient, during convalescence, is seized with a
sore throat, the temperature rises, the glands of the neck become swollen
and sensitive, and the exudation recurs in the throat, or nares, or both.
The relapse is not, as a rule, so severe as the primary attack, but
there are some exceptions. We have more than once seen death result
from a recurrence of the disease.
COMPLICATIONS AND SEQUELS OF DIPHTHERIA.
Heart.^ — The poison elaborated by the bacilli of diphtheria is espe-
cially prone to affect the heart. In all severe cases heart-failure is
extremely liable to occur. Symptoms of this condition may appear
before the pseudomembrane has entirely separated, but in most cases
they are not apparent, or, at least, do not become prominent, until the
characteristic feature of the local affection has, to a great extent, dis-
appeared. In other words, signs of cardiac failure are rarely seen
until the diphtherial process has made considerable progress. They
do not often appear before the end of the first week, but during the four
or five succeeding weeks the patient is in constant danger of heart-
failure.
It is believed by some authors that the heart is affected to a greater
or less degree in all cases of diphtheria. Jacobi^ says: "There is no
case ever so mild apparently that will not affect the heart's function
at once to a certain extent. From mild cases to the gravest there are
gradual transitions." In a large proportion of the severe cases which
survive long enough the myocardium shows (post-mortem) certain
anatomical changes, the most common of which is fatty degeneration.
Undoubtedly, heart-failure not infrequently results from paralysis
of the cardiac nerves, and quite independently, too, of any anatomical
change in the heart muscle. Lennox Browne credits Vincent, of Paris,
and P. Meyer with having found "widespread parenchymatous changes
1 Twentieth Century Practice of Medicine.
COMPrJdATlONS AND SI'JQUKLAi: OF 1)1 1'llTII h'Jil A fJ41
in the cardiac plexus in two cases of y)afierits dyin^' of }ieart-failure
during convalescence from dij)hlheria, in which the heart muscle was
unaffected." He says: "The changes were exactly similar to those
found in the peri})heral nerves in orflinary j)ostfli[)}itherific j)ara]ysis."
The symftomn of heart-failure do not dilVcr from those of toxamia.
Vomiting is often an early sign. The patient is pale and sallow, some-
times livid and cyanotic; the pulse at first may be rapid and feeble,
but soon becomes slow, irregular, and intermittent, or dicrotic. The
pulse rate is frequently as slow as 40 to 50 per minute. The first sound
of the heart grows less distinct. The circulation is sluggish, and the
extremities are cold, but the mind remains clear. In severe cases,
as the end approaches, the pulse becomes absolutely lost at the wrist,
and death results gradually from asthenia, or it may result suddenly
from heart-failure. Undoubtedly death sometimes occurs from paraly-
sis of the cardiac plexus. Recovery but seldom takes place after the
symptoms of heart-failure once assume a threatening character.
Lungs. — In faucial diphtheria the lungs do not very often become
affected. Bronchitis occasionally occurs, as does also bronchopneumonia.
But in the laryngotracheal form of the disease these complications are
extremely common. Indeed, bronchitis, more or less marked, is not
very often absent in membranous croup. As the inflammation extends
downward from the laryngotracheal surface to the bronchi, the inflamed
mucous membrane is apt to become involved in the diphtherial process.
But quite apart from this, bronchopneumonia, catarrhal in character,
is of frequent occurrence, and constitutes one of the principal sources
of danger. It most often sets in before the acute stage of membranous
croup has passed, but it may occur at any period following this stage,
even during convalescence. J. Lewis Smith says: "In 121 cases of
bronchopneumonia complicating diphtheria, observed by Sannp, the
pneumonia commenced in 2 on the first day of diphtheria, and in 71
between the second and sixth days inclusive."
When it develops at a later stage, or during convalescence, it s in
most cases preceded by a mild bronchitis that has never entirely dis-
appeared.
The existence of a bronchopneumonia is revealed by physical exam-
ination. Both lungs may be found involved, although the disease is
usually better marked in one than in the other. The physical signs
may show that the inflammation is limited to the lower lobes, but more
frequently disseminated areas of inflammation are found throughout
one or both lungs.
As already stated, bronchopneumonia is one of the chief sources of
danger in diphtheritic croup. The mucopurulent material secreted in
the bronchial tubes may be so abundant as to clog the tubes and prevent
proper decarbonization of the blood. As the inflammation extends
to the smaller tubes, these often become clogged in the same way so
as to prevent the entrance of air to the alveoli, which gradually collapse.
Autopsies often reveal areas of atelectasis disseminated throughout the
lungs. Even where the tubes remain pervious it is almost impossible
41
G42 DIPHTHERIA
for the child to expectorate the mucopus on account of its viscidity.
Hence, the minuter tubes are usually found (post-mortem) to be filled
with a thick, viscid material, containing also not infrequently floating
particles of pseudomembrane.
Bronchopneumonia is always attended by an elevation of temperature.
The disease may either run an acute course, terminating in recovery
or death in six to eight days, or assume a subacute form and continue
to progress for two, three, or more weeks. In some of these persistent
cases recovery finally takes place, but more often death results from
exhaustion. Bronchopneumonia is the chief cause of death after
tracheotomy.
Lobar 'pneumonia is not a very frequent complication. It has been
known to occur during the stage of convalescence. Areas of con-
solidation in the lungs are not infrequently seen, but they are almost
always associated with inflammation of the bronchi.
Pleurisy does not very often occur as a complication. According to
J. Lewis Smith, "Peter found the lesions of pleurisy 9 times in 121
autopsies in diphtheria, and Sannd observed them in 20 cases." The
latter is quoted as saying that pleurisy always accompanies some other
phlegmasia. In our experience in the hospital we have not seen more
than two or three frank cases of pleurisy attended with pleuritic effusion.
Lymphatic Glands. — Enlargement of the cervical and submaxillary
glands is of common occurrence in diphtheria. It may be either slight
or excessive. In septic cases this complication is usually most marked.
As already stated, the inflamed glands sometimes break down into
abscesses.
Kidneys. — Renal complication occurs earlier in diphtheria than in
scarlet fever. Albuminuria is frequently seen as early as the third or
fourth day, sometimes even on the second, while the quantity of urine
is not diminished, but may be increased. It is believed that the elimi-
nation of the toxin with the urine irritates the kidneys, and thus tends
to affect their function or even damage their parenchymatous structure.
In cases showing albuminuria the kidneys may be found to be normal,
or they may exhibit various degrees of parenchymatous inflammation.
While acute nephritis is not so common as in scarlet fever, yet it does
occur. This is evident from the fact that hyaline and granular casts
are sometimes found. Red blood cells are rarely present. The urine
in such cases is diminished, sometimes scanty, and the skin becomes
pallid. Qildema is less pronounced, and ursemic symptoms are much
less frequent than in postscarlatinal nephritis. Still patients die now
and then from uraemia. According to Jacobi, "When albumose is
found, together with considerable albumin, Berlin believes the prog-
nosis to be rather favorable. Still, in most of the cases at the clinic at
Strassburg in which he made his observations, the renal complications
were only trifling."
Park^ says that in most severe cases of diphtheria the kidneys are in
1 Loomis-Thompson, American System of Practical Medicine.
COMPLldATIONH AND SI<:QI/ l':/..'l'J OF hi I'll'I'll I'.UIA 643
a state of more or less acute iiepliril is; tliat tliey an; usually hypenemic
and enlarged; that the surface of the kidney is smooth, and frecjuently
the seat of small hemorrhages, and that, microscopically, the signs of
marked parenchyniatf)us changes are evident up to complete necrosis
of the epithelium lining of the tubules. "In severe cases the urinr'
contains abundant albumin, degenerated kidney epithelium, leukocytes
and hyaline casts, and, in the most severe, coarse and fine granular
casts. Blood cells are infrequent."
Lennox Brow^ne believes that there is a decided tendency to renal
complications in all cases intoxicated with the diphtherial poison. In
a series of 1000 cases of diphtheria tabulated by him he found, however,
that the mortality due to nephritis and its results was only 2.7 per cent.
This is a much larger rate than was observed in all the Metropolitan
Asylums' Board Hospitals in 1893, when, he says, out of a total of
2848 cases of diphtheria treated, with 865 deaths, only 8 cases of neph-
ritis were reported. But while actual nephritis does not occur with
great frequency, yet, as already stated, the parenchymatous structure
of the kidneys is very commonly damaged to an extent that interferes
with their proper function. Lennox Browne says albumin in some
quantity is to be found in the urine in fully one-half of the cases of true
diphtheria. Some other observers state that it is present even in a
much larger proportion of cases, and believe, with Lennox Browne,
that it is more frequently seen since the serum treatment has been
employed. When it is present to the extent of more than one-eighth
of the volume of urine, the amount of urine secreted is apt to be dimin-
ished, and ursemic symptoms may appear.
As to the frequency of albuminuria in diphtheria, J. Lewis Smith
says: "Bouchut and Empis found it in two-thirds of their cases, Germain
S^e in one-half of his, and Sann^ in 224 cases out of 410. In New
York City, where diphtheria has been many years naturalized or endemic,
I made, in the years 1875 and 1876, daily examinations of the urine
in 62 consecutive cases, and found it present in 24, while 38 were recorded
exempt. But the proportion of cases as stated in my statistics is probably
below the truth, for the albuminuria is sometimes transient and it often
occurs as a mere trace and is liable to be overlooked. Its duration is
frequently not more than from one to three days, and in the majority
of instances it does not continue longer than ten days; but we are all
familiar with cases in which it continues fifteen or twenty days, or
even months."
As the amount of albumin in the urine varies in different patients,
so also does the day of the disease on which it makes its appearance
vary. In referring to Sanne's observations on this point J. Lewis Smith
says: "In 224 cases albuminuria was detected on the first day of diph-
theria in 3, on the second day in 10, on the third in 30, on the fourth
day in 30, on the fifth day in 32. From the sixth day to the eleventh
the number on each day in whom albuminuria was present for the
first time varied from 10 to 33. After the eleventh day there were only
9 new cases, and after the fifteenth day only 1 new case. Hence, from
644 DIPHTHERIA
these statistics we infer that there is Httle danger that albuminuria will
occur after the second week, if the patient has exhibited no symptoms
of it previously."
In exa.minations of the urine made under our direction of 149 diph-
theria patients in the Municipal Hospital, albumin was found to be
present in 85 per cent, of the cases. The cases were not selected, but
taken consecutively as they were admitted to the hospital in two differ-
ent periods of time. The observations, therefore, include both mild and
severe cases of diphtheria. The first series of examinations comprised
samples of urine from 37 patients, and the second from 112 patients. Of
the former, 73 per cent, of the cases showed albumin, and a few showed
tube casts also. The urine was not examined in all cases as frequently
as we desired, for the reason that most of the patients were young
children from whom it was often impossible to obtain specimens. But
in no case were there less than two examinations, and in some as many
as twelve. In most of the patients that recovered the urine became
normal during convalescence, but a few still showed a trace of albumin
when discharged from the hospital.
Of the second series of examinations pertaining to the urine of the
112 patients, albumin was found in 90 per cent.; 20 per cent, of these
cases showed albumin in large quantity, and 70 per cent, in a less
amount — not more than a trace being found in some.
In 24 patients showing a large amount of albumin the urine was
examined microscopically, and tube casts, hyaline and granular, were
found in 2 of this number. We should add that 1 of these patients
had nine months previously suffered from scarlet fever, and we had
no knowledge of the condition of the urine since then.
Strange to say, in a few of the fatal cases in which the kidneys were
examined post-mortem there was macroscopic evidence of parenchy-
matous changes, although examination of the urine had failed to show
tube casts of any description.
Scarlet Fever. — Scarlet fever is not an uncommon complication in
diphtheria; or, more properly speaking, one of these diseases is often
found associated with the other. We venture to say that anyone who
has had experience in a hospital for contagious diseases will bear out
this statement. Being familiar with the experience of, at least, two or
three such hospitals, we know how frequently scarlatinal rashes are
found in the diphtheria wards, and, on the other hand, how often
diphtheria appears in the scarlet-fever wards. For the past two years
we have been in the habit of examining (bacteriologically) the throats
of all scarlet-fever patients as soon as they are admitted to the hospital.
In dividing these examinations into series of 100 cases each, the
Klebs-Loeffler bacillus has been reported present by The Bacteriological
Division of the Bureau of Health, Philadelphia, in from 10 to 33 per
cent, of the patients. Some showed well-marked clinical evidence of
diphtherial complication, while in others, it must be said, such evidence
was not apparent. It is not uncommon to admit to the hospital patients
in whom these diseases coexist in a well-pronounced form.
COMPLICATION H AND S/'JtjU l':/..K OF 1)1 1'll'lll lUilA f;4rj
Lennox Browiic (jiiolcis Dr. \\r\\v.v. Low as sayiiif^ that "rJuritij^ flie
prevalence of diphtheria in Hastings the two diseases in certain instances
were concurrent, and in a number of persons who, on account of their
suffering from scarlet fever, were sent to the borough sanatorium for
isolation and treatment, were attacked by well-marked diphtheria
during their convalescence," giving also several examj)l(;s "of irn[)or(a-
tion of diphtheria into families by members returning home from the
sanatorium after recovery from scarlatina, the patients in each instance
not having been known to suffer from diphtheria during stay in the
hospital."
In many cases of diphtheria with concurrent scarlet fever it is impos-
sible to explain the source of the double infection. In hospitals for
contagious diseases it is sometimes felt that one disease is engrafted
upon the other through exposure to the second infection; but in private
families these diseases not infrequently coexist without any known
or explicable cause. One of the writers has just witnessed an instance
of this kind in which two children of a family of three took scarlet fever;
subsequently an infant of eleven months, who had not been out of the
house for some time, fell ill with the disease and in two or three days
developed also symptoms of severe diphtheria. Copious exudate
appeared in the fauces and nares, and death cpiickly ensued from
systemic poisoning.
Measles. — The relation of measles to diphtheria is a matter that
has not received as much notice by writers as its importance deserves.
Ryland referred to it in his Jacksonian Essay in 1837, and Dr. West
in 1843. A few other observers have called attention to the fact that
in times of concurrent epidemics of diphtheria and measles, subjects
of the latter disease frequently suffer also from the former. In reporting
on an outbreak of diphtheria in 1894 at Barnham Broom, England,
Mr. T. W. Thompson says: "I find from my notes that with one or two
exceptions, all the children, who later suffered from diphtheria, had
about this time suffered from measles, which in some cases had been
attended with considerable soreness and external swelling of the throat.
The frequency with which diphtheria is found to coexist with or quickly
follow in the wake of measles is such as to suggest a relationship between
the two phenomena; though the relationship may be of an indirect
kind only, the measles increasing susceptibility to diphtheria, mainly,
in all likelihood, by the damage inflicted on the mucous membrane of
the throat." There is no doubt that the catarrhal inflammation of the
upper air passages incident to measles affords a fertile soil for the
propagation of diphtheria bacilli.
The occurrence of measles with diphtheria should be regarded with
great apprehension. The diphtheria is liable to assume the laryngo-
tracheal form, and the development of bronchopneumonia is to be
feared. In the year 1900 measles of an unusually severe t^'pe broke
out in the diphtheria wards of the INIunicipal Hospital, and in all 68
cases came under our observation. Of these 34 died, making the
death rate 50 per cent. Of the 68 cases, 34 developed membranous
646 DIPHTHERIA
croup, and of these 29 died — a death rate of 85.29 per cent. Broncho-
pneumonia was the principal cause of death, though some sank and
died in a state of adynamia.
Paralysis. — Paralysis might be regarded with much propriety as a
symptom of diphtheria, but as it is not seen until the acute stage is
passed, and more often during convalescence, we have preferred to
consider it as a complication or sequela. Very little seems to have
been known of diphtherial paralysis prior to the latter part of the
sixteenth century. Nicholas Lepois called attention to it in 1580, and
Miguel Heredia in 1690. According to J. Lewis Smith, Ghisi, of
Italy, in describing an epidemic which occurred in 1747-48, when his
own son had paralysis in a severe form following diphtheria, says:
"I left to nature to cure the strange consequences, . . . which
had been remarked in many who had already recovered, and which had
continued for about a month after recovery from the sore throat and
abscess. During this period this child spoke through the nose, and
food, particularly that which was least solid, returned through the nares
in place of passing down the gullet." About the same time (in 1748)
Chomel, of France, described two cases of paralysis following what he
called gangrenous sore throat. In 1771, Dr. Samuel Bard, of New
York, described the symptoms seen in a little girl of two and a half
years who had recovered from "Sore Throat Distemper," as follows:
"Whenever she attempted to drink she was seized with a fit of coughing;
yet she was able to swallow solid food without any difficulty. She
improved, but in the second month she could scarcely walk or raise
her voice above a whisper."
For the next fifty years and more but little is said of diphtheritic
paralysis. This sequel must either have been overlooked, or regarded
as a coincidence, or else diphtheria at that time was of so mild a type
that paralysis did not often result. It appears that Bretonneau had not
yet observed this sequela at the time of his first publication on diphtheria
in 1826. It is said by J. Lewis Smith^ that Bretonneau "did not recollect
that he had seen a case of diphtheritic paralysis prior to 1843. Although
a close observer of diphtheria, the paralysis had not been observed by
him, or at least had not attracted his attention, until it occurred in the
person of his townsman. Dr. Turpin, in 1843." From this time on,
until his second publication appeared, in 1855, he saw a sufficient
number of cases to convince him that this sequela occurs not infrequently,
and called attention to it in his paper of the latter date. Since then
nearly every writer on diphtheria has described this peculiar form of
paralysis, and its frequent occurrence is an accepted fact.
Paralysis does not often follow mild tonsillar diphtheria. But when
the soft palate and especially the nares are involved, partial or complete
paralysis, not only of the muscles of the parts covered with exudate, but
also of the entire muscular system is liable to occur. , General paralysis
does not appear immediately after the local evidence of diphtheria has
1 Keating, Cyclopedia of the Diseases of Cliildren.
aOMI'LICATION^ AND SFJjlII'.L.K Ol' I >l I'll! II HUI A 047
disappeared, hut (level()]),s grii(liiiilly and slowly. The parfs earliest
affected are the soft j)alate and fh(; j)haryiix, wliile the upper and lower
extremities show tliis syni[)toin later. From tlie slow development of
the affection it seems probable that at first only a few fasciculi are inca-
pacitated, and that gradually more and more of these become involved
until the affected muscles are no longer under the control of the will.
Paralysis is sometimes ol)served in the muscles of the eyes, the trunk,
the bladder, the rectum, and the diai>hragm. In most cases the paralysis
is incomplete, but in rare instances it progresses to such an extent that
the entire muscular system becomes incapacitated.
The cause and pathology of the paralyses are not fully understood.
It seems probable that the condition is due to a toxic neuritis involving
the peripheral nerves, causing an interruption of the nerve supply to
the muscles involved. It is said that the neuritic change may extend
the entire length of the nerves, from their periphery to their origin,
not only of the spinal but also of the cranial nerves.
It may be that some of the fasciculi of the enervated muscles undergo
fatty degeneration, as this change has been seen in the myocardium.
Anatomical changes have been found in the spinal cord, apparently
resulting from myelitis. S. G. Henschrn has reported a case of acute
disseminated sclerosis of the cord with neuritis. Some writers believe
that changes of this nature contribute an important part in the pro-
duction of the paralysis. ,
Hemiplegia is but rarely seen in diphtheria. Only 2 cases have
come under our observation. One case has been reported by J. W.
Brannan. This writer is quoted by Jacobi as saying: "There are 35
cases in all recorded in medical literature of postdiphtheritic paralysis
of cerebral origin. Six cases have come to autopsy; in 1 of these
a hemorrhage was found in the internal portion of the lenticular nucleus,
with destruction of the neighboring part of the internal capsule. In
the other 5 cases there was embolism of the Sylvian artery. . . .
In the total 35 cases there was complete recovery in 4, death in 7; and
in all the others there was permanent paralysis of greater or less
extent."
In studying the causes of diphtheritic paralysis Trousseau felt that
the explanation of this symptom is beyond our comprehension and
will probably never be known. Realizing the insufficiency of any one
theory to explain all cases, Jacobi, in his renowned treatise on diph-
theria, says: "It may be positively asserted that diphtheritic paralysis
does not in every case depend on one and the same cause."
The frequency with which paralysis follows diphtheria depends upon
the character of the epidemics. It occurs, of course, much more fre-
quently in severe attacks than in mild attacks of the disease. According
to Lennox Browne, in 2S48 cases of diphtheria treated at the various
Metropolitan Asylums' Board Hospitals of London, in 1SP3, it was
noted in just 14 per cent. This proportion, he says, agrees in the main
with that deduced from his own table of 1000 cases of diphtheria.
While we have no data at hand of our own experience on this point,
g48 DIPHTHERIA
we believe that at least 14 per cent, of our patients developed paralysis
more or less marked.
Since paralysis develops very gradually and slowly, it is not always
easy to determine at which stage of diphtheria it begins. The difficulty
is increased from the fact that most of the patients are young children
in whom the affection is usually not discovered until the more char-
acteristic symptoms have appeared. However, it has been found from
careful observation that paralysis of certain muscles, the palatal, for
example, may occur in the acute stage, or, at least, immediately after
the disappearance of the pseudomembrane. But the later manifesta-
tions, as seen in muscles remote from the fauces, especially in those of
the extremities, diaphragm, etc., are more serious, and usually do not
appear in a pronour^ced form until after an interval of more than four
weeks from the commencement of the diphtherial attack. We cannot
better illustrate our experience with this affection than by quoting
J. I^ewis Smith's account of two cases reported by Holt: "A child, aged
two years, had diphtheria in August, and a second attack in the middle
of October. She convalesced slowly, and in her convalescence had no
paralytic symptoms, except a nasal voice, until December 1st, when
multiple paralysis suddenly developed. A brother of this patient also
had diphtheria in October, moderately severe, and early in convalescence -
paralysis of the muscles of the palate began, followed by that of the
other muscles; but it was not until the middle of December that the
lower extremities were paralyzed." J. Lewis Smith very properly adds:
''These cases are examples of the usual mode of commencement and
extension of the paralysis."
While this sequela is not so often seen after the mildest attacks of
diphtheria, at least not to any marked degree, yet instances have been
recorded in which paralysis has occurred in persons who, presumably,
were infected with the diphtherial poisons without having exhibited
any of the ordinary symptoms of the disease. According to the author
just quoted. Dr. Boissarie^ has related cases of this kind which are
remarkable, if not indeed unique. He says an officer of the police
force, after ailing for two or three days, had a nasal voice, and, in
attempting to drink, the liquids returned through the nose. The
velum palati was found insensible and motionless, but the fauces were
otherwise apparently normal. "In the hospitals alongside the barracks
in which the above case occurred, a young man without fever, redness,
or swelling of the fauces, had also a nasal voice, and return of liquid
food through the nose. The porter of the hospital was similarly affected,
and the doctor stated that certain other patients in like manner pre-
sented symptoms of paralysis, without the history of an antecedent
diphtheria. Dr. Reynaud, called in consultation, expressed the opinion
that the paralysis had a diphtheria origin; and this opinion was strength-
ened by the occurrence immediately afterward of an epidemic of diph-
theria in the place where these cases occurred." J. Lewis Smith follows
1 Gazette hebdomadaire, 1881.
COMI'LI(!AT]()NH, AND SI<:Q(/I<:LA'J ()!<' 1)1 1'llTII KIU A VyW)
the account of these unicjue cases witfi the pertinent reniark that it is
probable an antecedent diphtheria had occurred of so mild a form as
to have escaped notice.
The paralysis, as a rule, affects princijjally tlie motor nerves, althou^li
the sensory nerves are not infrequently involved also. Anaesthesia of
some parts, particularly the fauces, has h)een observed, and tingling
and numbness are sometimes felt in the extremities. The sense of
taste has been known to be affected. Paralysis of the sensory nerves
may be quite local, and is not seen until a somewhat later period than
the motor paralysis.
As the sympton)s and course of diphtheritic paralysis vary according
to its location and muscles involved, it seems most convenient to speak
of the clinical manifestations of its various forms separately.
Paralysis of the palate is often seen at an early stage of the disease.
It may be observed as soon as the exudate has disappeared, or as early
as the tenth day of the diphtherial attack. The first evidence is mani-
fested by a nasal tone of the voice. This results from dropping of the soft
palate, causing the air to escape through the nose in the act of speaking.
There may be slight difficulty in swallowing, enough to make it necessary
for the patient to drink cautiously. Later, in the third or fourth week,
or after convalescence has actually set in, the deglutition may become
more difficult, so that fluids, instead of being easily swallowed, regur-
gitate in large part through the nares, while some run down the
larynx, causing cough and sopietimes pneumonia. As already mentioned ,
anesthesia is associated with this form of paralysis and adds to the
difficulty of swallowing. In infants starvation may occur through their
inability to suckle. Even in older children, and in adults also, when
general paralysis of an extreme form develops, deglutition often becomes
impossible, and death from starvation may result if feeding through an
oesophageal tube be not resorted to.
When paralysis of the palate has continued for a week or two, faulty
accommodation of the ocular movements may be seen. Most frequently
the paralysis of the ciliary muscles is bilateral. The most common
variety of axis deviation met with is convergent strabismus, resulting
from paralysis of the external recti muscles. Diplopia is not of infrequent
occurrence.
Slight facial paralysis occasionally occurs. It has been noted as
appearing soon after the acute stage. We have seen but very few
such cases, and in these the affection was unilateral.
Paralysis of the cardiac and respiratory neri'^es may appear any time
after the first week of the illness. The exudate may have disappeared,
more food is taken, the patient appears to be gradually improving,
and the members of the family are cheerful at the prospect of a speedy
recovery, when suddenly the scene changes. The heart action becomes
weak, the pulse feeble, slow and irregular, sometimes rapid, the respira-
tions superficial, and the patient becomes pale, often slightly cyanotic.
Severe precordial or epigastric pain is often complained of in cases of
sudden heart-failure. In the more favorable cases improvement may
650 DIPHTHERIA
follow active stimulation, and the patient may eventually recover. But
too often the improvement is only temporary, for the heart-failure is
liable to return after a few hours, or a day or two at the most, causing
sudden and, to the inexperienced physician, unexpected death. There
is no other disease in which symptoms of heart-failure occur so suddenly
and unexpectedly, and there is perhaps no other disease in which
physicians are so often deceived in the matter of prognosis.
Involvement of the respiratory nerves leads to paralysis of the dia-
phragm and sometimes pulmonary collapse.
General paralysis does not make its appearance until a very late
stage of diphtheria. It is not often seen earlier than the fourth week,
and may occur later than the sixth week. In most cases it appears
between the fourth and sixth week. In almost every instance it is
preceded by well-marked palatal paralysis, sometimes by loss of function
of the muscles of the eye, especially those presiding over motion and
accommodation. As a rule, the loss of power is first noticed in the
lower extremities. This may increase until the limbs, especially the
lower limbs, are rendered entirely useless for weeks.
The comparative immunity of the fingers in many cases may be
mentioned as a peculiarity. Parsesthesia or anaesthesia, however, is
frequently noticed in the fingers, palms of the hands, and feet. The
degree of paralysis is not the same in all muscles ; in some it is complete,
while in others it is only partial. When there is complete loss of power
in the lower extremities it is not unusual to find that the patient has
considerable use of the upper extremities. The muscles of the trunk
are often partially paralyzed, but only rarely is there loss of sensation.
In general paralysis the diaphragm is often affected, but rarely to the
extent of seriously interfering with respiration. Its involvement is more
apparent in the act of coughing. In this act, instead of the sudden
expiratory explosion, the cough is slow and straining, and apparently
attended with some effort on the part of the patient. But paralysis of
the muscles of the pharynx, preventing complete closure of the glottis,
may have more to do in causing this peculiar symptom than paralysis of
the diaphragm.
As J. Lewis Smith very truly says, even where the paralysis seems
to be general there are groups of muscles which entirely escape. He,
therefore, prefers the term multiple paralysis to that of general paralysis
to designate this form of the disease. .
Of the internal and visceral muscles liable to become involved,
paralysis of the diaphragm or of the heart is of the most serious import,
as it may be responsible for sudden death.
The bladder is sometimes involved, but rarely to any marked degree.
We have never found it necessary to catheterize a patient to relieve
this viscus, nor have we ever observed any loss of power in the sphincter
muscles. Paralysis of the muscles of the lower bowel and rectum is said
to occur at times, giving rise to constipation, but not affecting the
sphincters.
The ensemble of symptoms of general or multiple paralysis is very
COMPLICATIONH AND HI<:Q(J l<:i.A<: Oh' h/ f'lIT// l:UfA (;ol
graphically described by Dr. C. W. Fallis in the Medical Summary,
January, ]}itheria, Ifolt refers
to some important investigations made upon this point by the New
York Healtli l^epartment/ He says: "As the result of observations
upon 450 cases which were followed, the cf)nchision was reached that
the disease was so slightly contagious (if at all), and usually so njild,
that strict isolation and subsequent disinfection wen; unnecessary. Of
113 cases occurring in 100 families, in only 14 was there a history of
exposure to a similar case, and in only 9 was there another case in the
same family. In many of the latter a common origin appeared more
probable than that one case was derived from another.
"At the present time the general opinion of the profession .seems to
be that these cases are to a slight degree communicable, to be compared
in this respect to ordinary catarrhal colds or possibly to pneumonia.
They are probably more contagious in the presence of the poison of
scarlet fever or measles."
For the purpose of testing the communicability of p.seudodiphtheria,
Park^ made some very interesting experiments by inoculating human
throats with streptococci. He describes the experiments as follows:
" A very thick culture was made on agar plates from a severe follicular
tonsillitis in a young child, so that there was obtained a luxuriant
growth of streptococci growing both in long and short chains, and also
of other micrococci. A large amount of these mingled bacteria were,
with the permission of the patient, plastered on a swab and then rubbed
gently on the right tonsil and into its crypts. He felt a peculiar sensation
in the tonsil for some twelve hours; this then passed away, and was
probably simply the result of the mechanical irritation.
" The next morning the tonsil appeared healthy except for a small
patch in a crypt; from this, and from the throat, cultures w^ere made.
The plates gave very numerous colonies of streptococci, w^hile cultures
made from the same regions the day previous to the experiment gave
very few streptococci.
" A second trial was made in a similar w^ay from a culture of strepto-
coccus pyogenes, eighteen hours old, from a case of extensive pseudo-
membrane and tonsillar abscess. The results were also entirely negative,
except for the increase of streptococci in the throat for some days.
With the same streptococcus the tonsils of two other adults were daubed,
and with similar negative results.
"These trials having shown that in three throats the application of
streptococci from cultures made from virulent cases of tonsillitis pro-
duced no effect, a different experunent was tried. On two separate
occasions a sterile swab was rubbed on the tonsils in a case of severe
tonsillitis, and then immediately rubbed on a healthy tonsil. In neither
case was' there any inflammation excited. On the third day after the
last experiment a sudden fall in the temperature occurred, and after
exposure a follicular tonsillitis developed, such as frequently has followed
previous similar exposures."
1 Diseases of Infaucy and Childhood.
- Loomis-Thompson, American System of Practical Medicine.
654
DIPHTHERIA
These experiments seem to warrant the conclusion, as Park says,
" that the pyogenic cocci are not sufficient, as a rule, to excite an inflam-
mation in the throat." Or, in other words, that the presence of strepto-
cocci in the throat are probably harmless so long as the mucous mem-
brane is normal, or intact.
In primary cases the disease makes its appearance like an ordinary
sore throat. There may be vomiting, slight rigors, headache, general
pains, painful deglutition, and fever. The constitutional symptoms
are usually well marked at the beginning. During the second or third
day of the disease the temperature may rise to 103° to 104° F., but it
quickly falls and the other symptoms also subside. On inspecting the
Fig. 97
A case of pseiKlodiphilifi'ia iu lui adult negro; the exudate covered pmuoiis of the hps, tougue,
buccal mucous membrane, and fauces. Diphtheria bacilli were absent, but streptococci and staphy-
lococci were present.
throat the mucous membrane is found reddened and the tonsils swollen.
Very soon an exudation appears upon the tonsils, and sometimes upon
other parts of the fauces and the buccal mucous membrane also. The
exudate is grayish in color, shreddy or pultaceous, and seems to lie upon
the surface, as it may be readily removed with a cotton swab. It does
not remain long, usually disappearing in three or four days. The in-
flammation of the throat is often more marked than in genuine diph-
theria, and swelling of the lymphatic glands in the neck may be seen,
though this is not excessive in mild cases.
In many cases of pseudodiphtheria in which the disease is secondary
to another affection the symptoms are as mild as those just described.
COMPLICATIONS AND SICQil HL/K OF 1)1 1'llTII Klfl A (\r,r,
But frequently the local iri,'uiif(\stati()ii.s are as severe as in the worst
forms of pharyngeal (iiphtlK^ria, and the constitutional syni[)torns as
well marked as in the septic form of that disease. Indeed, the clinical
description given of scarlatina anginosa by some of the older writers
is not essentially different from that of sej)tic diphtheria, at least so
far as the greater part of the local and constitutional symptoms are
concerned.
In scarlet fever the streptococcic process is liaV)le to set in at an
early stage of the disease. In severe cases the process may reach its
maximum in the latter part of the first week, and continue for two
weeks or longer. The disease almost always involves the nose as well
as the fauces, and very frequently extends to the middle ear, giving rise
to a suppurative otitis media, which may permanently affect the hearing.
The local process in the throat is often more destructive to the tissues
than is the case in true diphtheria. Deep sloughing of tlie tonsils and
soft palate is sometimes seen. The lymphatic glands of the neck and
the periglandular connective tissue frequently inflame and break down
into abscesses. This process also may be attended by considerable loss
of tissue, and occasionally is followed by serious hemorrhage.
When pseudodiphtheria occurs secondary to measles the throat
involvement is mild as compared with scarlet fever, but the strepto-
coccic process much more frequently extends to the larynx, giving rise
to a dangerous form of membranous croup. When this condition
develops there is not only danger from stenosis, but also from broncho-
pneumonia. Sometimes the larynx is involved when there is no sign
of exudate in the fauces. Holt believes that this is very infrequent
unless the disease is true diphtheria; but w^e have seen a number of
such cases in which the Klebs-Loeffler bacillus was absent.
In secondary cases the temperature, as a rule, ranges higher than
in the primary. The pulse rate is more rapid and feeble, and the
constitutional symptoms as a whole are severe. When the primary
disease is scarlet fever, there is usually restlessness, delirium, great
prostration, and albuminuria. Death is liable to result from septic
poisoning. If, however, the patient withstands the toxic effects of the
streptococcus organisms, the throat symptoms improve, the constitutional
disturbance subsides, and recovery takes place as from true diphtheria.
But none of the secondary affections peculiar to the latter disease, such
as heart-failure and multiple paralysis, are liable to follow.
From a clinical point of view it is often difficult to distinguish between
pseudo- and true diphtheria. We believe that in the majority of cases
the experienced physician will make a correct diagnosis at the bedside,
yet frequently one most skilled in the art of diagnosis will find it
impossible to say, in a given case, that the pseudomembranous affection
of the throat is not true diphtheria. In such cases, the assistance
afforded by bacteriology is of great importance. Holt very truly remarks :
" The bacteriologists have taught us to be cautious in pronouncing too
positively upon even the mild cases, as it has been clearly shown that
some of them may be caused by the most virulent of diphtheria bacilli."
656 DIPHTHERIA
Even in the secondary cases one should not be too ready to exclude
true diphtheria in making the diagnosis, for it is well known, as has
been already pointed out, that this disease often co-exists with scarlet
fever, and not infrequently follows in the wake of measles, particularly
when it is prevailing in the neighborhood. The clinical features dis-
tinguishing pseudo- from true diphtheria will be considered later.
Except in rare instances of laryngeal involvement, primary pseudo-
diphtheria is not a serious malady. Some mortality, however, seems
to attend the disease, as death rates varying from nil to 5.5 per cent,
have been reported by different observers. According to Holt, of 117
primary cases observed by Park in the Willard Parker Hospital, New
York, "the mortality was 3.5 per cent.," while ''of 127 cases of true
diphtheria seen in the same institution at the same time, the mortality
was 34.5 per cent." Out of 34 primary cases of pseudodiphtheria,
which, in a limited time, came under the observation of Baginsky
(in hospital), the mortality was 5.5 per cent., against 38.2 per cent,
from true diphtheria. Holt says : " From the same hospital, Philip has
published a report upon 376 cases; 332 of these were true diphtheria,
with a mortality of 37 per cent.; 31 were cases of primary pseudo-
diphtheria, with no mortality." He also calls attention to the fact that
" The Bulletin of the New York Health Department contains a report
upon 324 cases of pseudodiphtheria in children, with a mortality of
9, or 2.8 per cent.; 4 of the fatal cases complicated scarlet fever; of the
primary cases, the mortality was but 1.5 per cent." He adds, "These
were not hospital cases."
During the past ten years we have observed in the Municipal Hospital,
Philadelphia, 172 cases of pseudodiphtheria, with no deaths. All of
these cases were sent in as true diphtheria. There was present on the
tonsils, rarely on other parts, a rather loose, filmy exudate, which
disappeared in two or three days after admission. Streptococci and
other pyogenic organisms were present, but the Klebs-Loeffler bacillus
was absent. We have not included in this number the cases of acute
follicular tonsillitis which were also sent to the hospital with the mis-
taken diagnosis of diphtheria.
The mortality among the secondary cases of pseudodiphtheria is often
very high. It is highest when the disease occurs secondary to scarlet
fever or measles. Holt is inclined to believe that under such conditions
it is from 20 to 40 per cent., and that in institutions for young children
it not infrequently reaches 70 or 80 per cent., especially when these
diseases prevail epidemically. He says that under the latter conditions
" the cases complicating measles give, as a rule, a higher mortality than
those complicating scarlet fever." This statement accords with our
own experience.
As pseudodiphtheria is rarely communicated from one person to
another the enforcement of stringent preventive measures, such as
quarantine and disinfection, does not seem to be necessary. It is,
however, advisable to exclude healthy children from the sick-chamber.
In regard to the secondary cases, especially when the primary disease
(JOMrLICATIONH AND SI'X^I ! HL.K Oh' hi I'll ■III i: HI A (;r,7
was scarlet fever or measles, the c()iii[)li(,'ate(J cases slioiihJ rner, IJaurngarten,
Haginsky, Middcldor])f and Gokhiian, Neunian, and others have
made interesting studies of the diphtheria membrane.
Councilman, Mallory, and Pearce distinguish, microscopically, two
distinct varieties of the membrane corresponding to the differences
observed macroscopically. The dense, firm, elastic membrane which
can be stripped off in large flakes is composed of a reticular structure
with beams of uniform size. The reticulum contains masses consisting
of leukocytes and epithelial cells which have undergone hyaline degen-
eration.
The other variety of membrane, which macroscopically is characterized
by greater friability, is composed of fibrin. The fibrin forms a reticulum
just as does the hyaline material, but varies greatly in the size of the
fibres and the spaces. The spaces may contain numerous leukocytes,
either well preserved or broken down.
The fibrinous membrane is often continuous over the entire surface
of the tonsil and extends into every crypt. The hyaline membrane
never extends into the crypts, though occasionally small masses of
hyaline reticulum are found in them.
The changes in the tissues observed by the above investigators are
summarized as follows: The first step in the membrane formation is
degeneration and necrosis of the epithelium, often preceded by active
proliferation of the nuclei of the cells by direct division. The cells may
either break up into detritus or become changed into refractive hyaline
masses. An inflammatory exudation rich in fibrin factors comes from
the tissues below, and fibrin is formed when this comes in contact with
the necrotic epithelium. The fibrin in part is formed into a reticulum
around exudation cells and degenerated epithelium ; in part it combines
with the hyaline degenerated cells to form a hyaline membrane. The
latter is most often formed on those surfaces which are covered with
epithelium having several layers of cells. The fibrinous membrane is
formed both in the surface and in the tissues. The membrane is never
formed primarily on an intact epithelial surface, but it may extend
over it. There is nothing specific in the membrane formation in diph-
theria, as typical hyaline and fibrinous membranes may be found in
ovarian cysts in which bacteria play no part; but it is accompanied by
degenerative and exudative changes in the tissue beneath.
The connective tissue and bloodvessels undergo a hyaline fibroid
degeneration. Necrosis may extend deeply into the tissues, but there
is little tendency to ulceration or abscess formation. The degeneration
in the mucous glands, particularly of the glandular epithelium, is so
pronounced as to be almost specific. The extent of the necrosis in the
primary lesions is greater than is found in the action of any other
bacteria.
G60 DIPHTHERIA
Diphtheria bacilli were never found growing in the hving tissue or
in connection with those degenerative changes in the epitheUum seen
in the beginning. They were found in the necrotic tissue and in the
exudation, usually only in the latter. The bacillus shows an affinity
for solid structures and is found rather on the reticulum than in the
spaces between. The beginning of the lesions is probably due to the
toxic action of the bacilli possibly growing in the fluids of the mouth
or throat. When necrosis is once produced the necrotic tissue forms
a suitable culture medium. The membrane and necrotic tissue are
often invaded by pyogenic cocci and by fungi.
Heart. — The pronounced clinical evidence of involvement of the
cardiac muscle has led to extensive investigations of the underlying
pathological changes in the heart. This subject has received careful
study on the part of many pathologists.
Hayem was the first to call attention to the granular and fatty degen-
eration of the heart muscle and to changes in the vessels and interstitial
tissue. Rosenbach noted a granular and waxy degeneration of the
muscles and a cell exudation into the interstitial tissue.
In 2 cases of suddenly fatal diphtheria Birch-Hirschfeld found
evidences of acute interstitial myocarditis. Martin regards the myo-
cardial change to be secondary and a result of acute endarteritis of the
coronary arteries.
One of the most important studies of the heart in diphtheria has been
contributed by Romberg/ who made careful examinations in 8 cases.
He found that the cardiac muscle was not uniformly affected, but that
some portions might be normal and other areas show extensive changes.
Small foci of leukocytic infiltration were found around the smaller
coronary arteries, but the most important lesion was the degeneration
of the cardiac muscle. The degenerated fibres had a peculiar vacuola-
tion in the centre and were without nuclei. The nuclei undergo hyper-
trophy with an accompanying vesicular condition. The inner and outer
portions of the myocardium showed most degeneration.
Focal interstitial changes, most common beneath the pericardium,
were present in all cases. In 5 of Romberg's cases pericarditis was
present, and in 3 there was endocarditis.
Hesse^ made a study of the heart in 29 cases of diphtheria. The
parenchymatous changes were not marked under three days, and were
more pronounced on the left side. In 25 out of 29 cases interstitial
myocarditis was present, and in 4 it was marked. It was noticeable
in the first week, but was more pronounced later. The interstitial
changes were more frequent in the left ventricle. The leukocytic
infiltration was believed to be due to an increased penetrability of the
vessel walls which were acted on by the toxin.
Papkow, who examined a number of hearts of patients who died on
the third or fourth day, found extensive fragmentation of the muscle
1 Ueber die ErKrankung des Herz mnskels bei typhus abdom. Scharlach und Diphtherie, Deutsche
Archiv f. kiln. Med., 1891, Bd. xlviii.
- Beitrage zur path. Anatomie des Diphtherie Herzens, Jahrbuch f. Kinderheilk., 1893, Bd. xxxvi.
Till': I'ATIIOI/XJY OF DII'irrilKKIA OGl
fibres, with white and red cells between th(^ fni^rneiits. 'I'lie fragmenta-
tion was eansed by the swelling juid destrneti(;n of the eenient snl>stanres.
Tliis is an early change, while tin; waxy degenerafion and infersfifial
infiltration occur later.
Welch and Flexner found fatty defi;eneration and necrosis of the
muscle fibres, l^'^lexner later described swelling and deeper staining of
the nuclei, with final disaj)})earance.
Conncihnan, Mallory, and Pearce have made an extended series of
careful examinations of the cardiac muscle in 00 cases of dij)htheria.
The results of this valuable study are herewith presented : Fatty degen-
eration of the muscular fil)res, varying in extent, was found in 30 of
the GO cases; there were prol)ably more than this numl)er, as only -^0
hearts were examined in the fresh state, and of this number 29 showed
fatty change.
This degeneration varies in extent, at times affecting the myocardinm
generally, and at times in foci. The fatty change accompanies and
appears to precede more advanced forms of degeneration which lead
to complete destruction of the muscle.
The sarcous elements become swollen, broken, and converted into
hyaline masses. Vacuolation, fragmentation, and fracture of the degen-
erated fibres are often seen. Simple fatty degeneration is found in
severe cases of short duration, and the more extensive degenerations in
protracted cases. The degenerations are due to the bacterial toxin,
and account for the impairment of the heart function.
Two kinds of interstitial lesions are found. In the one there are
focal collections of plasma and lymphoid cells, which may be accom-
panied by an independent myocardial degeneration, analogous to acute
interstitial nephritis. In the other the interstitial change is secondary
to the muscle degeneration. This form may lead to excessive connective-
tissue formation and a fibrous myocarditis.
Thrombosis is not infrequently seen as a result of prmiary necrosis
of the endocardium. The only bloodvessel change of interest is pro-
liferation of the intima, which is also observed in other organs.
Lungs. — Pulmonary complications are present in a very large pro-
portion of fatal cases of diphtheria and commonly determine the lethal
outcome.
The lesion found is a bronchopneumonia of varying extent. Holt^
says that in infants and young children bronchopneumonia is found at
autopsy in at least three-quarters of the cases. Councilman, ^Mallory,
and Pearce found bronchopneumonia in 131 out of 220 post-mortem
examinations; 98 of these were in cases of diphtheria only, and 33 were
in diphtheria complicated with scarlet fever or measles. The lung
complication was much more frequently observed in patients in whom
the larynx, trachea, and the bronchi were the seat of membrane. It
is believed that the most important factor in the production of these
pneumonias is the aspiration into the lungs of micro-organisms, chiefly
micrococci.
1 Loc. cit.
662 DIPHTHERIA
Of the 131 cases of bronchopneumonia, the areas were discrete in
76 and confluent in 55. In the majority of cases the posterior portion
of the lung was affected, and especially the lower lobes. The bronchi
were affected in the majority of cases. The mucous membrane of the
large tubes was reddened and covered with exudation; drops of pus
could usually be forced from the small bronchi by pressing the cut
surface of the lung.
In 43 cases there was a fibrinous exudation in the bronchi, forming
in the larger ones a distinct membrane and completely filling the
smaller.
Councilman, Mallory, and Pearce conclude that there is no organ in
which lesions accompanying diphtheritic infection are so generally found
or so serious as in the lung. In very many cases they are so extensive
that death may be considered as due rather to the condition of the
lungs than to the throat affection. The essential lesion is broncho-
pneumonia; true acute lobar pneumonia was never found. The cases
resembling lobar pneumonia were found on close examination to be
cases of extensive confluent bronchopneumonia. The character of the
exudation varies; it may be fibrinous, hemorrhagic, serous, or almost
entirely cellular; rarely it may be hyaline. Atelectasis is commonly
present in varying extent, and the same is true of emphysema.
The cellular exudate is in part made up of leukocytes and in part
derived from proliferation of the lining of the membrane. I^ymphoid and
plasma cells are also found. In some cases there is organization of the
exudation and connective-tissue formation within the air spaces. The
lining epithelium of the air vesicles shows proliferation. Necrosis, in
some cases leading to abscess, is not an uncommon feature.
Large objects considered to be marrow cells which in many cases have
undergone degeneration are frequently found in the capillaries; it is
possible that these have been frequently mistaken for hyaline thrombi.
Thrombi are occasionally found in the large vessels, but not in the
capillaries. The lymphatics are commonly dilated and contain coagu-
lated albumin, fibrin, or cells. They are often found packed with
lymphoid and plasma cells, and large cells similar to those seen in the
air spaces. (This summary is based upon a microscopic study of the
lungs in 133 cases.)
Bacteriology of Complicating Bronchopneumonia. — Considerable dif-
ference of opinion has existed as to the comparative influence of the
diphtheria bacillli and other organisms in the causation of pneumonia
complicating diphtheria.
Thaon, in 1885, was the first to study the relation of the diphtheria
organism to secondary bronchopneumonia. He showed microscopically
in the lung tissues the relation of the bacilli to the inflammatory process.
The diphtheria bacillus was not found alone, but in association with
various cocci.
Loeffler, iri his study of the bacteriology of diphtheria in 1884, reported
the presence of the diphtheria bacillus in the lung, but regarded it as
a post-mortem invasion.
THE PATUOUMjIY OF Dl I'llTII I'UilA {](])>,
Various observers since this time liav(; [)iiblis}if'(| t[i(; results of their
study of tliis siihjeet. Tliese reports (ixhihit extretrxily fhver^erit firnJings.
For instarice, Wriht}ifria
liave l)een studied i)y Branlt, Fiirhrinf^er, l^'i.s(;hl, Cjcrtel, iiernard and
Felsenthal, Reiehe, Katzenstein, and others. The alterations iriflueed by
experimental diphtheria have been specially described l;y Flexner.
Councilman, Mallory, and Pearce examined the kidneys micro-
scopically in 171 cases. The ages of the patients varierl from two
months to thirty years, and averaged three and three-quarter years.
It v^as found possible to divide the kidneys into five classes according
to the microscopic findings: 1. Those in which degeneration of the
epithelium was the chief or the only lesion. 2. Those in which acute
interstitial changes consisting of cell accumulations in the vessels and
interstitial tissue were present. 3. Those in which the chief lesions were
found in the glomeruli. 4. Those in which hemorrhages into the
tubules were present. 5. Those in which chronic interstitial lesions
were present as shown by atrophied glomeruli and increase in the
connective tissue.
1. Degenerative Changes. — Degenerative changes of varying grades
were found in 112 of the 171 cases examined. Many kidneys, almost
or quite normal in appearance, showed under the microscope a con-
siderable degree of degeneration. The degeneration was slight in 26
cases, moderate in 38, marked in 37, and extreme in 9 cases. The
most extreme degree was found in severe cases dying shortly after entry
into the hospital.
Fatty degeneration, as determined by examination of frozen sections,
was only slight in degree; it occurred in 44 out of 58 cases examined in
this manner.
Some degree of hyaUne degeneration w^as found in almost all the cases,
affecting prominently the proximal convoluted tubules. Casts w^ere
present in practically all of the cases, especially when the hyaline
degeneration was pronounced.
The most constant change seen in the glomeruli consisted of a small
amount of granular coagulum between the tuft and the wall.
In 40 cases of simple degeneration the urinary record is available.
Albumin was found in 33 of the cases. There was, with some excep-
tions, a general agreement between the presence of albumin and the
degree of degeneration.
There appeared to be no relation between the character of the degen-
eration and general infection with various bacteria. In the 110 cases a
general infection with diphtheria bacilli was noted in 20 cases, with the
streptococcus in 29 cases, with the staphylococcus aureus in 4 cases, and
with the pneumococcus in 3 cases. In the 9 cases of severe degeneration
general infection was noted but once, and that with the streptococcus.
2. Acute Interstitial Changes. — iVcute interstitial nephritis, evidenced
by infiltration of the interstitial tissue with cells of the plasma t^•pe,
was present in 43 of the cases. The kidneys were but slightly, if at all,
enlarged, save in the most marked cases, when considerable swelling
was present. The interstitial infiltration was general in all parts of
the kidney, but was more intense in foci; most of the cells were plasma
668 DIPHTHERIA
cells with typical nucleus and protoplasm. Lymphoid cells and, in
severe cases, large phagocytic cells were also present. The amount of
epithelial degeneration varied in different cases.
The infiltrating cells were usually limited to the interstitial tissue;
the changes we.re accompanied by alterations in the vessels, the cell
infiltration at times almost obscuring them. The degeneration found
in foci of intense infiltration appears to depend on malnutrition resulting
from blocking of the vessels by the cells.
In all of the interstitial cases the duration of the disease was more
prolonged than in the cases of simple degeneration. The average
duration of the illness was twenty-one and one-half days. The inter-
stitial process apparently takes some time for its development, and
the cases dying early do not, as a rule, show the process at its maximum.
Mixed infections with scarlet fever and measles are more apt to cause
interstitial changes than simple degeneration. The urine was tested
for albumin in 15 cases, in 14 of which it was found present.
3. Glomerular Changes.^ — This variety of the disease was found in
11 cases, in all of which the glomerular changes were the predominating
ones. Lesions of the glomeruli were uncommon in the cases of simple
degeneration and in those showing interstitial involvement.
The first evidence of change in the glomeruli is increase in the number
of cells. The endothelial lining of the vessels undergoes proliferation
and occludes the vessel. Later a hyaline degeneration of the cells and
the vessel walls takes place.
Glomerular nephritis was present in subjects averaging a greater age
than the degeneration and interstitial cases. The average duration of
the disease at the time of autopsy was also greater.
4. Hemorrhage. — Slight hemorrhages in the kidney were seen in 3
cases, but true hemorrhagic nephritis was noted in but 1. The red
blood cells were found chiefly in the tubules and the interstitial tissue.
The rarity of hemorrhagic cases was considered surprising.
5. Chronic Cases. — In 4 cases chronic changes were present, as
evidenced by atrophy of the tubules and increase in connective tissue.
In these cases death occurred at entirely too early a date to attribute
the changes to diphtheria; the lesions were evidently due to some ante-
cedent disease.
Councilman, Mallory, and Pearce conclude that lesions of the kidney,
varying from simple degeneration to the more serious conditions of acute
nephritis, are found in all fatal cases of diphtheria; there is, however,
no type of lesion peculiar to the disease.
Lymph Nodes. — The changes in the lymph glands have been studied
by Bizzozero, Oertel, Bullock and Schmorl, Barbacci, Bezancon and
Labbe, Flexner, and Councilman, Mallory, and Pearce. The most
constant changes observed by these investigators have been a marked
cellular infiltration and the presence of necrosis. Bullock and Schmorl
found diphtheria bacilli in the nodes in 11 out of 14 cases.
Councilman, Mallory, and Pearce examined the lymph nodes in 109
cases. They were constantly the seat of pathological changes.
Tim PATIIOLOCV 01'' DII'II'IIIFJUA GOD
Tlie nodes iiiosl. involved are tliose neuresl, l,o the seat of exudate -
the tonsils aixl the cervical {glands. The distant nodes are very rarely
aH'ected.
The lesions are most prononnced in severe cases, in vviiich a fatal
termination occnrs early. Two varieties of lesions are descril)ed :
1. The ordinary lesions, which may follow an injnry of almost any
sort and wliicli consist in congestion, hemorrhage, and diffuse and
circumscribed necrosis. Numerous new cells are found which are
derived partly from the lymphoid cells, and partly from proliferation of
the endothelial cells of the sinuses and reticulum. The swelling of the
nodes is due chiefly to congestion, hemorrhage, and dilatation of the
sinuses; the lymphoid cells do not increase perceptibly in number.
2. Lesions which are distinctive of diphtheria, but which may be
found in other infectious diseases in children. Foci are formed which
are similar in appearance to miliary tubercles; these are the result of
a combination of processes^proliferation, })hagocytosis, and degen-
eration. Large epithelioid cells are formed from proliferation of the
endothelial cells of the reticuhim and vessels. These devour lymphoid
cells, and they themselves ultimately undergo necrosis. Bacteria seem
to exert no direct influence in the production of these lesions, and were
not found in the nodes.
The lesions are believed to be due to the absorption of the toxic
products of the diphtheria bacilli and other organisms.
The lesions found in the tonsils differed somewhat from those seen
in other lymphoid structures. They were constantly present, and in
most cases more pronounced than in the glands.
Thymus. — Flexner studied the changes in the thymus gland in
experimentally induced diphtheria in animals. He called attention to
the frecjuency with which the degenerated cells occurred in the neigh-
borhood of the Hassel bodies. The changes in general were similar
to those observed in the lymph nodes.
Councilman, Mallory, and Pearce examined the thynuis in 20 cases.
The principal change found was degeneration of the lymphoid cells.
The degenerated cells were usually seen in large cells with vesicular
nuclei; the changes were most marked in the vicinity of the Hassel
bodies. There was dilatation of the lymphatics and hyaline degen-
eration of the walls of the vessels. No bacteria were found in the
sections.
Skeletal Muscles. — Councilman, jMallory, and Pearce state that where
fatty degenerations of the heart and the nervous system are present, a
similar change will be found in the skeletal muscles. In one case in
which the nerve fibres of the central nervous system and of the per-
ipheral nerves showed marked fatty degeneration, the muscles of the
tongue, of the ulnar side of the forearm, the sartorius muscle, and the
biceps of the thigh exhibited a similar degeneration.
In another case where fatty degeneration of the heart and nervous
system was pronounced the muscles of the tongue, the diaphragm, and
the tibialis anticus were likewise degenerated.
670 DIPHTHERIA
Pancreas, Adrenals, Thyroid Gland, Salivary Glands, Testicles,
Pituitary Body. — No gross changes were observed in these glands by
Councilman, Mallory, and Pearce; neither did a careful microscopic
examination reveal the presence of pathological changes.
In one case the submaxillary gland showed superficial necrosis and
purulent infiltration due to extensive inflammation from the throat.
Welch, Flexner, and Wright commonly observed congestion, hemor-
rhage, and focal necrosis in the adrenal glands in experimental diph-
theria, but such changes apparently do not occur in this disease in the
human subject.
Nervous System. — Councilman, Mallory, and Pearce refer to a study
of certain nerve structures made in 28 of their cases by Thomas and
Steensland. The cases were selected either on account of the presence
of cardiac symptoms, paralysis, or the severity of the disease. Various
cranial and other nerves were submitted to careful microscopic study.
In all of them some grade of fatty degeneration was noted. The degen-
eration seems almost invariably to begin in the myelin sheath. The
change in the axis cylinder consists chiefly of an irregular swelling
which often causes it to present a beaded appearance.
The cerebrum was examined five times, the cerebellum twice, the
pons three times, the medulla four times, and the cord seven times.
In all of these examinations a varying degree of fatty degeneration was
present in the white substance. The same change was noted in the
anterior and posterior nerve roots.
In general it may be said that a slight to a marked diffuse fatty degen-
eration, involving the central nerve fibres and their peripheral exten-
sions, occurs in certain cases of diphtheria.
Bone-marrow. — Councilman, Mallory, and Pearce examined the
bone-marrow in 48 cases of diphtheria. Of this number all but 3 were
children. In all of the cases the marrow was hyperplastic, although in
the 3 adults the hyperplasia was less pronounced. In the latter the
marrow was reddish with areas of yellow fat.
In the children the marrow varied in appearance, but was usually
red, of firm consistency, and removable in solid pieces.
Very little connective tissue was found in the marrow, and that was
along the arteries. The veins were numerous and the walls like those
of capillaries; it is through these thin walls that the marrow cells appear
to enter the blood.
The changes in the marrow in diphtheria are not distinctive of the
disease, as they are also found in other infectious diseases.
Blood. — According to Baginsky there is an increased coagulability
of the blood in diphtheria due to the action of the toxin on the blood
stream through weakness of the heart, and also as a result of the lowered
blood pressure and changes in the lining of the bloodvessels. This, it
is claimed, may lead to the formation of thrombi in the heart or blood-
vessels. In severe septic cases a thinning or dissolution of the blood
occurs, which may cause hemorrhages in various tissues.
The specific gravity is said by Grawitz to be raised at the height of
77//'; I'ATIIOIAJdY ()/<' bll'IITllHUIA f;71
the disease, both in (h'phtheria, in man, and in exyx'rirnenf;)! (li])lith('ria
in animals.
Red Cells. -Diii'i 11 <^f the first f(^w (hiys of the disease the red eorjjuscles
are about normal in number, according to the investigations of Morse,
Ewing, Engel, and Billings. From the fifth to the fifteenth days, liillings
observed an average loss of 510,000 cells per cubic millimetre. The loss
ranged from 470,000 on the third day to 2,040,000 on the sixth. These
were in cases not treated by antitoxin. Of 2?> severe and carefully
counted cases treated with antitoxin, 3 alone exhibited a reduction in
the erythrocytes, the loss being less than 400,000 cells per cubic centi-
metre.
Cabot remarks that "antitoxin largely prevents the ana'mia which
usually develops in the first five to ten days." Healthy persons receiving
antitoxin, according to a study of 15 cases by Billings, show a moderate
loss of red cells in about one-half of the cases; the greatest diminution
observed was 930,000 per cubic millimetre.
Haemoglobin .^ — A reduction in the hajmoglobin occurs coincidently
with the diminution in the number of red cells, but restoration of the
former takes place more slowly than the latter. Billings states that in
cases treated without antitoxin an average loss of 10 per cent, was
noted; whereas, when antitoxin was administered the reduction of the
haemoglobin was less marked.
Leukocytes. — Gabritschewsky, in 1894, was the first to point out the
more or less constant hyperleukocytosis in diphtheria. He demon-
strated by animal experimentation that the increase in the white cells
was due to the action of the diphtheria toxin.
Morse found a leukocytosis in 26 out of 30 cases, Ewing in 49 out of
53, and Billings in 34 out of 36 cases. The grade of the leukocytosis is
in a general way proportionate to the severity of the disease. Morse
observed very high counts in the fatal septic cases.
Cabot says that when leukocytosis is absent the cases are either very
mild or very severe, conditions analogous to those noted in pneumonia
and septicsemia. The counts range from normal to 48,000 (Morse),
or to 38,000 (Billings). Bouchut counted over 75,000 white cells per
cubic millimetre in some of his cases, and Felsenthal found 148,229
in one case.
The white cells ordinarily increase as the disease progresses, and
decrease as convalescence sets in.
According to Ewing, the leukocyte count is not influenced by the
use of the antitoxin serum, except during the first twenty-four hours
after its injection. Within thirty minutes the leukocytes are said to be
considerably diminished.
Engel states that antitoxin in the beginning causes a slight increase
in the percentage of lymphocytes; in some cases the increase is pro-
nounced. In one case after injection they rose from 24 to 65 per cent.
Engel also emphasizes the bad prognostic import of the presence of
a considerable number of myelocytes.
It is generally conceded that an examination of the blood in diph-
672 DIPHTHERIA
theria lends little or no aid in diagnosis. The absence of leukocytosis
and the presence of a considerable number of myelocytes would seem
to be of ill augury.
THE DIAGNOSIS OF DIPHTHERIA.
As diphtheria is a communicable disease with a decided predilection
for young children, among whom it is also most fatal, it is important
that an early diagnosis should be made, both with regard to prevention
and treatment. Without a history of previous exposure to the infection
it is confessedly difficult to recognize the disease in its very earliest
manifestations; for there is no throat affection more varied in its clinical
aspect and more deceptive in its initial stage than diphtheria. But,
fortunately, the disease is not long in revealing its true nature. In the
majority of cases the diagnosis is not difficult after the affection has
continued for twenty-four hours, since by this time the characteristic
exudation may be seen on the tonsils or some part of the fauces. When
thus clearly marked the nature of the throat disease is at once apparent
on the first examination.
But all cases are not so readily diagnosticated, even by experienced
physicians. Neglecting to inspect the throat of a child, who is feverish
and indisposed, may sometimes be a reason for failure in making an
early diagnosis. While sore throat is one of the earliest symptoms of
diphtheria, yet it is a fact that many children, even those old enough
to make known their sensations, do not complain of the throat until
the disease has made considerable progress.
On his first visit to a child, on account of whose illness he has been
summoned, the physician should be careful to examine the fauces,
especially when diphtheria is prevailing in the neighborhood. In this
way the disease may be discovered early and its spread to other members
of the family prevented.
In well-marked cases it is usually not difficult to make the diagnosis.
In doubtful cases it may be helpful to know whether the patient has
been recently exposed to the infection of diphtheria, scarlet fever, or
some other infectious disease. If exposure to diphtheria is known to
have occurred, the mildest form of sore throat should be regarded with
suspicion and carefully watched for further development. But, in a
section of the country where diphtheria is not prevailing, it is probable
that a sore throat presenting some of the characteristics of the disease
will turn out to be something else.
It sometimes happens that an early diagnosis is not made because
the exudation is concealed in the crypts of the tonsils, or in some other
depressions of the faucial surface. When thus located it may be brought
into view by pushing the tongue depressor far back on the tongue and
causing the child to retch slightly; or these surfaces may be exposed
to view by having an assistant make firm pressure on the neck near the
angle of the jaw while an examination of the throat is being made.
In some cases it is impossible to make a positive diagnosis, clinically,
77/ A' DIAdNOShH OF 1)1 1'lll'll Fill A 073
until the disease h;is been under ()[)servati()M for two or three days.
Tiiis is more (!Sj)eeially triu; in some; forms of nasal diphtlieria, without
involvement of the fauces to a greater ext(;nt than the oeeurrenee f)f
a general hypenemia. The uneven surface of the cavities of the nose
favors concealment of the disease until it has made some progress. It
may then be discovered either by insjx'cting the nares at their external
orifices, or by an examination with a nasal speeuhnn. In nasal flij;h-
theria there is apt to be a mucopurulent diseharg(; from the nose,
and when there are seen in this discharge small, white specks, exudate
is probably present, although it may not yet be visible. It usually,
however, makes its appearance before the disease terminates.
There are no prodromata that are peculiar to (iij)htheria. The
general malaise, followed by headache, nausea and vomiting, so
commonly seen, are the forerunners of many other affections also.
Even the sore throat, pain in swallowing, tenderness of the glands near
the angle of the jaw, and swelling of the neck are all present in the
ordinary forms of tonsillitis. The distinguishing feature of diphtheria
is the peculiar exudation that appears upon the mucous membrane,
particularly in the fauces. A knowledge of the fact that this exudation
takes place not only into the epithelium, but also into the subepithelial
tissue, is helpful only to a limited extent in solving the problem of
diagnosis. Indeed, in many severe cases the diphtheritic process does
not penetrate deeply into the mucous membrane, as it peels off quickly
and leaves only small areas of superficial ulceration. On the other hand,
an exudation of streptococcic origin is sometimes very adherent, and
its disappearance may be followed by marked ulceration of the mucous
membrane. But in most streptococcic affections of the throat, certainly
in the milder varieties, the disease is limited to the tonsils, and the
greater part of the exudation may be removed with a cotton swab.
In considering the diagnostic feature of the diphtherial membrane
it is necessary to recall some of its characteristics already described.
It is deposited not only on the tonsils, but frequently also on the pillars
of the fauces, the soft palate, the pharyngeal wall, in the nares, and in
the larynx. One of the peculiarities of the meml)rane is that it is liable
to start on some of the small prominences of the fauces, such as the
uvula, epiglottis, and the like. As already mentioned, it is also liable
to form in some of the small recesses, such as the lacunfe of the tonsils
and the ventricles of the larynx. The formation of membrane on the
uvula, especially on its posterior surface, is believed by some writers
to be almost pathognomonic. When seen on the sides of the uvula it
is quite sure to be present on its posterior surface also. Frequently
the entire uvula is invested with membrane, which is often shed as a
complete cast, resembling, as Trousseau has said, the finger of a glove.
When the diphtherial exudation is examined carefully it is found to
be distinctly membranous. It is of a yellowish-white color, and when
exfoliated in large pieces or casts and allowed to float in water it bears
a strong resemblance to pieces of chamois skin. Lennox Browne's
description of the exudation is worth repeating. He says it "begins
43
674 DIPHTHERIA
almost invariably as a thin, bluish-white deposit, something like a
shaving from the boiled white of an egg of the duck, goose, or plover.
As the deposit increases in thickness, it gradually becomes more white
and opaque, resembling the boiled albumen of a fowl's egg, or it may
then partake of a very pale lemon tint. Then it becomes of a yellowish
or greenish gray, brown, and sometimes almost black, as the necrotic
process advances, or as blood is extra vasated. Only in the comparatively
uncommon case of a lacunar diphtheria do we see the exudation com-
mencing as discrete spots of deposit, which may be of a yellow color
at the very first onset, and, even when coalesced, may never exhibit
the pearly or opalescent appearance which characterizes the more
ordinary form on its first manifestation." He adds, "The membrane
is sometimes plastered, as if put on with a palette knife, or laid on with
a trowel." This latter comparison applies with much aptness to what
is seen when the entire fauces and soft palate are covered with the
exudation.
Adenitis, or more or less enlargement and tenderness of the
lymphatic glands of the neck, is a symptom rarely absent. Its im-
portance depends to some extent on the region in which the glands
are involved, and the degree of inflammation and swelling. In mild
tonsillar diphtheria the cervical glands alone are swollen, but, as a rule,
only very slightly. In the more severe cases, including the complex
or septic form of the disease, the whole chain of cervical glands is
converted into one large mass. The inflammatory enlargement includes
also the periglandular cellular tissue. In such cases not only the
cervical, but the submaxillary and sometimes the parotid glands are
affected.
Catarrhal Croup. — ^There is frequently some difficulty in distinguish-
ing between membranous croup in its early stage, and catarrhal, spas-
modic, or non-specific croup. But if a few of the principal points of
difference be borne in mind the difficulty should not be very great.
For instance, in membranous croup the symptoms are progressive,
being as well marked in the day-time as in the night. The hoarseness
gradually increases, so that the child in a short time can speak only
in a whisper. The breathing becomes more and more obstructed as
the exudation increases; the temperature reaches 100° to 103° F., and the
child constantly grows more restless and cyanotic. There is marked
recession of the ensiform process of the sternum, and of the lower ribs.
These symptoms are not relieved by the relaxing influence of an emetic.
Moreover, the characteristic exudation may be present in the fauces.
On the other hand, in catarrhal or spasmodic croup the symptoms are
usually intermittent, being due to a paroxysmal spasm of the glottis,
resulting from subacute laryngitis. In the vast majority of instances
the affection occurs at night-time, and more often in the early part of
the night. During the day the symptoms, if present at all, are usually
much more moderate. The duration of the paroxysm varies from a
few minutes to several hours. The voice, though hoarse, is very rarely
quite extinct or whispering, and scarcely ever more than temporarily so.
77//'; DIAdNOHIH OF 1)1 1'llTII l<:UIA 075
This is a diagnostic point of niucb value in (Jistinguisliing Ijetwccn tlip
two forms of crouj). In sj)asnio(Jic croup an cnictic generally gives
relief, but does not in membranous erouj). The fauees are free from
exudate.
Pseudodiphtheria. We have already remarked that a membranous
sore throat, in whi(;h the streptococcus is the principal if not the sole
orgaiu'sni present, sometimes occurs, and we have pointed out some of
the characteristics of this ad'ection in comjjarison with those of true
diphtheria. We repeat that, as a rule, in true diphtiieiia the exudate
is so intimately connected with the mucous membrane that it cannot
be removed without injuring the parts, while in pseuflodiphtheria it
lies upon the surface and may be quite readily removcf]. It must be
admitted, however, that there are many exceptions to this rule. The
physician, therefore, will often find it impossible to make a positive
diagnosis without a culture and a microscopic examination.
Follicular Tonsillitis. — There is perhaps no throat affection more
often mistaken for diphtheria than follicular tonsillitis. It is a very
common disease, being more frequently seen in some families than in
others. It sometimes spreads as though it were contagious. It begins
with sore throat, fever, and tenderness in the neck below the angle of
the jaw. There is often a good deal of constitutional disturbance, such
as high temperature, headache, and chilliness, with sometimes pain in
the back and extremities. The fauces at first are hypersemic, but the
tonsils soon become enlarged and dotted over with rounded masses
of whitish material of pinhead size. These dots frequently coalesce,
forming quite large patches, particularly in the crypts of the tonsils.
The dots or patches consist of a peculiar secretion having incorporated
with it epithelial cells. It differs from the diphtherial exudate in that
it is readily detached by a swab. The cheesy dots that form on the
tonsils will, when crushed between the thumb and finger, emit a fetid
odor. The disease is of short duration, and is not followed by sequel [e.
The diagnosis is easily made, except in some cases of the mildest form
of diphtheria when dift'erentiation may be difficult. In acute quinsy
the jaws are stiff, and there is often considerable difficulty in opening
the mouth sufficiently wide for a satisfactory inspection of the fauces.
Where any doubt is felt as to the nature of the affection it may be
readily dispelled by a bacteriological examination.
Herpetic Pharyngitis. — There is usually no great diflaculty in recog-
nizing an herpetic pharyngitis, but, like follicular tonsillitis, it is occa-
sionally mistaken for mild diphtheria. If seen in the early stage, before
the minute vesicles have disappeared, the diagnosis is easily made;
but the ulcers that remain often show a whitish covering, which has
often been mistaken for diphtherial exudate. As the ulcers are very
small, the whitish concretions are usually seen in the form of dots.
It is only when these concretions unite and form a patch that any
difficulty is experienced in the diagnosis. It has been said that the
presence of an herpetic eruption on some other part of the body would
afford presumptive evidence that the throat affection was of the same
676 V DIPHTHERIA
nature, but we have often seen herpes labiaHs in children suffering
from diphtheria. Fortunately, in these diseases the clinician does not
have to base his diagnosis upon symptoms alone; he can invoke the
aid of bacteriology.
Gangrenous Pharyngitis. — In our experience gangrenous pharyngitis
is rare in diphtheria. We do not recall having seen a single case. The
affection, however, is not uncommon in scarlet fever. The ulcerative
action and loss of tissue are much more extensive than that which is
seen in diphtheria. The necrotic tissue resulting from the gangrenous
process has often been mistaken for diphtherial exudate. The pseudo-
membrane in this variety of sore throat is, from the beginning, of a
dark-gray or brownish color, and is exceedingly offensive. On the other
hand, the pseudomembrane of diphtheria is white or yellowish-white
in the commencement, and continues so to the end unless it becomes
stained with blood. The foetor in the latter disease is mild in comparison
with the former. The diagnosis is not difficult if the case comes under
observation at the beginning.
Stomatitis.' — In diffuse inflammation of the mucous membrane of
the mouth the small ulcers that commonly appear show a whitish
covering. This condition not infrequently increases to the extent that
many of these ulcers coalesce, forming patches consisting of a whitish,
curd-like matter; and the affection often extends gradually to the roof
of the mouth, the inside of the cheeks, and may even reach the pharynx.
The exudation is usually thin, and sometimes covers evenly a large
part of the mucous membrane of the mouth, but more commonly it is
seen in irregularly scattered patches and points. When the disease
assumes this appearance it is occasionally confounded with diphtheria.
In making a diagnosis it is important to note that the exudation is thin
and filmy; it never becomes membranous. On parts where it is thicker
it is curdy or cheesy.
We have known gangrenous stomatitis and even syphilitic sore throat
to have been mistaken for diphtheria. In view of the general character-
istics of these affections the diagnosis is not difficult.
The presence of albumin in the urine in diphtheria deserves some
notice as a diagnostic sign. We have found it in quite a large pro-
portion of our cases in which the urine was examined. Its presence
would be of still greater diagnostic importance were it not true that it is
occasionally found in some other varieties of inflammation of the throat.
Since the advent of bacteriology as a science the clinician has at his
command a most useful means of determining the diagnosis of diph-
theria in all doubtful cases. While every well-informed physician
should be familiar with the clinical evidences of the disease, yet as the
clinical disguises of this throat affection are so varied it is fortunate
that the doubtful points of diagnosis can be solved by bacteriology.
Therefore, any consideration of the subject of diagnosis in diphtheria
would be regarded as incomplete at the present day without some
reference to the means employed to determine the presence of the
Klebs-Loeffler bacilli in the pseudomembrane.
77//'; i)iA(JN()Sis OF nii'ii'i'iiKin \ 677
The Bacteriological Diagnosis of Diphtheria.
In a patient presenting .suspicious cliuicjil evidences of diplillicria,
the diagnosis may Ix^ firmly estahlislied by determining the [jresence
or al)sence of the di})hth(;ria hacilH in the false inenihrane. 'i'his may
be accomplished by examination of (a) smears, and (b) cultures.
Smears. — In a large ])ercentage of cases a satisfncfory result may
be obtained from an inunediate microscopic examinafion of the exudate
present. A cover-glass is smeared with material taken from the throat
by means of a swab. The cover-glass preparation is allowed to flrv,
is then passed several times through a flame to fix the albumin, and is
finally stained witli Loeffler's solution of methylene blue. By this means
the presence or absence of bacilli may often be determined in a few
minutes.
The rapidity with which the examination can be made makes it a
procedure of great value, particularly where an immediate diagno.sis is
a matter of great importance. We have examined a considerable
number of smears at the Municipal Hospital, and in these casts we
were enabled in the vast majority of cases to predict the subsefpient
cultural findings.
The procedure just mentioned, however, has only a relative value
and should not be depended upon to the exclusion of the culture. The
bacilli found in smears are ordinarily much less typical than those
grown upon culture media, and the chances of contamination are
greater. Abbott^ says: "There are other organisms present in the
mouth cavity, particularly in the mouths of persons having decayed
teeth, the morphology of which is so like that of the bacillus of diph-
theria that they might easily be mistaken for that organism, if subjected
only to the usual method of microscopic examination." He adds,
however, that where there is suspicious clinical evidence the direct
examination of smears will serve to confirm or negative the diagnosis
in the vast majority of cases.
Cultures. — Cultures are ordinarily made with a swab, although a
platinum loop may be employed for the purpose. The swab consists
of absorbent cotton wrapped around the end of a piece of heavy w'uq.
The swab, enclosed ordinarily in a plugged test-tube, is sterilized by heat.
In taking the culture the tongue should be depressed by means of
a spoon or depressor, and the swab firmly rubbed over the surface of
the membrane. When no membrane is present, the swab should be
brought in contact with the tonsils, faucial pillars, and pharyngeal
wall. When laryngeal symptoms alone are present, the swab should
be introduced as far down as possible. The moistened cotton is then
rubbed lightly over the surface of a tube of Loeffler's blood serum, care
being taken to carefully replace the cotton plug. The swab containing
the remains of the infected material should be returned to its own tube
and subsequently destroyed or disinfected.
1 The Principles of Bacteriology, 5th ed., 1899, p. 361.
678 DIPHTHERIA
Great care should be taken not to make the culture directly after
antiseptic applications have been applied to the throat. It is well, in
such cases, to wait a half-hour or an hour before culturing. The
inoculated tubes are incubated at a temperature of from 99° to 100° F.
(37° C.) for twelve to fourteen hours, at the end of which time the
colonies may be examined.
The gross appearances of the culture are more characteristic at the
end of twenty-four hours. The diphtheria bacillus grows so much more
rapidly than other mouth organisms upon the surface of Loeffler's blood
serum that they are often the only conspicuous colonies present. The
colonies are large, round, grayish-white or cream-colored, elevated
with irregular periphery, which is less dense in the centre.
Examination of Cultures.— A drop of sterile water is placed upon a
clean cover-glass and rubbed up with a couple of colonies which have
been detached from the culture media with a platinum loop. The
preparation is allowed to dry in the air and is then passed several times
through the flame of a Bunsen burner or alcohol lamp. It is then
covered with Loeffler's alkaline solution of methylene blue for ten
minutes, after which it is rinsed, dried, and mounted in balsam.
The specimen is examined with a one-twelfth-inch oil-immersion lens.
Diphtheria bacilli may be found in pure culture, or micrococci of different
varieties may also be present.
In order to test the virulence of diphtheria bacilli a guinea-pig is
subcutaneously injected with a small quantity of a pure culture in
bouillon. Death results in from twenty-four hours to five days, usually
within seventy-two hours.
There is intense oedema with congestion and hemorrhage at the
site of injection. The changes in the other tissues, according to Abbott,
are as follows: Swollen and reddened lymphatic glands, increased
serous fluid in the peritoneum, pleura, and pericardium; enlarged and
hemorrhagic adrenal bodies; occasionally slightly, swollen spleen; and
sometimes fatty degeneration in the liver, kidney, and myocardium.
The bacilli are always to be found at the site of inoculation, most
abundantly in the grayish-white, fibrinopurulent exudate.
THE PROGNOSIS OF DIPHTHERIA.
The forecast of diphtheria cannot be made with any degree of
certainty. The disease itself, to say nothing of the complications that
are liable to occur, is so treacherous that it is almost impossible to
predict a favorable ending of any attack however mild the earlier
symptoms may be. Not infrequently cases that appear to be mild in
the beginning and give the best promise of recovery suddenly change
into a severe form through extension of the diphtheritic process into
the larynx, or the development of some dangerous secondary affection.
On the other hand, cases that begin with marked severity, giving rise
to gloomy forebodings, often take a favorable change and speedily
end in ^recovery.
Tim PiiocNOHJH OF j)ii'iiriii<:iiiA 071)
So variable are the elements of prognosis in diphtheria that tliey
cannot be considered from any single standpoint. C)ne mnst take
into consideration the prostrating efl'ects of the toxins of the disease;
the history, enviromnent, and age of tlu; f)atient; the complications
affecting vital parts during the course of the attack, and the nature of
the secjuehe. Likewise, the character of the prevailing epidemic must
be taken into account. In some epidemics a large proportion of the
cases are mild, and the death rate is low. In other epidemics, or in sr>me
localities, the disease assumes a more severe form, and, in spite of the
best treatment, the proportion that perish is much larger. A death rate
as high as 60 per cent, has been reported; while in very rnihl epidemics
it has been as low as 5 to 10 per cent.
It is a question whether social status and domestic surroundiricjs have
as much to do in determining the character of the disease as is generally
supposed. It is true, however, that when diphtheria breaks out in an
institution for children, especially foundlings, it is apt to be attended
with great fatality. In our experience the patients sent to the hospital
from careless and indigent families are not more liable to suffer from
severe diphtheria than those which come from better and more sanitary
homes. Nor do we find that delicate children perish in a larger pro-
portion than the robust. In speaking of the influence exerted by social
status, Lennox Browne says it has appeared to him "that when diph-
theria attacks members of the upper classes it is often more malignant,
and runs a more qiiickly fatal course than among the indigent; the
disease finding, as it w^ere, a more receptive soil in the case of these
delicately nurtured than in those whose systems are in a manner accus-
tomed to insanitary influences. On the other hand, and for obvious
reasons, recovery from the sequelae, when once the acuteness of the
attack has passed off, is more expeditious and complete in the well-
to-do."
There can be no doubt, however, that when diphtheria is at all severe,
unsanitary surroundings would contribute toward an unfavorable prog-
nosis. The less adequate the facilities for caring for the patient and
the poorer the service, the greater are the probabilities that the disease
will spread and increase in virulence. Where no attention is paid to
ventilation of the sick-room, the vitiated condition of the atmosphere
tends to lower the resisting power of the patient, and thus diminishes
the chances of recovery.
Idiosyncrasy, or any family susceptibility to diphtheria that may be
known to exist, should be taken into consideration as affording important
prognostic data. Every practitioner knows how fatal the disease is in
some families. It is worthy of notice that when diphtheria breaks out
in a family, or in a neighborhood, children are almost always the first to be
attacked, showing that in them the susceptibility to the disease is most
marked.
Age. — There is not only an age disposition to diphtheria, but there
is also an age mortality, and this must be taken into account in a forecast
of the disease. The vast majority of all deaths from this affection
680
DIPHTHERIA
occurs among children under five years of age, and the mortahty rate
at this age period is vastly higher than in any other quinquennial period
of life. This statement is confirmed by the statistics of all large hos-
pitals for the treatment of diphtheria patients.
The following table shows the mortality, according to age, in the
Asylums' Board Hospitals, London, 1892-93:^
Percentage.
Age.
Under one year
f 1892
^1893
One to two years
fl892
1 1893
Two to three years
J 1892
11893
Three to four years
f 1892
11893
(1892
Four to five years < ^ggg
rl892
Five to ten years i ,gg„
f 1892
Ten to fifteen years -j j^ggg
f 1892
Over fifteen years ■! .g^g
Admitted.
Died.
. 49
31
. 40
37
89
68
. 108
66
. 166
106
274
172
. 163
90
. 219
131
382
221
. 195
96
. 296
149
491
245
. 240
106
. 339
143
579
249
. 631
163
. 880
233
1511
396
. 209
15
. 298
30
507
45
. 414
16
. 610
36
76.4
62.7
26.2
5.0
Of 1000 consecutive cases of diphtheria observed by Lennox Browne
the age mortality was as follows:
Age.
Under 1 year 11
1 to 2 years
2 '
3 "
3 '
4 "
4 '
5 "
5 '
6 "
6 '
7 "
7 '
8 "
8 '
9 "
9 '
10 "
10 '
11 "
U '
12 "
12 '
13 "
13 '
14 "
14 '
15 "
Over
15 "
f cases.
Deaths.
Percentages
11
5
45.45
71
45
63.38
85
34
40.00
117
54
46.15
118
43
36.44
108
34
31.48
84
24
28.57
57
9
15.78
31
11
35.48
38
5
13.15
29
8
27.58
20
16
22
2
9.00
15
2
13.33
178
7
3.93
1000
1 Lennox Browne, Diphtheria and its Associates.
Till': I'UOdjMOSI.S ()!<' DII'li'l'IIICidA
G81
Classified a(;c()nHii(^ to (juinqucnnial a^c [xtIcxIs, \\\c cusvh in the
above tabU^ show as follows:
Age. No. of rji,Ki,'H.
Under 5 yearH WZ
5 to 10 " 31K
10 " 15 " 102
Over 15 " 178
1000
/)«fUllH.
PcrceiitaKCH
IHl
45.0
83
26.1
Vl
11.7
7
■.•,'.)Z
283
2».3
In the following table of statisties, including over 9000 oases of
diphtheria, which were treated in the Municipal Hospital, Philadelphia,
during a period of ten years, from 1893 to 1902, iiichisive, the nuujljer
of patients and the mortality rate within certain age [xriods are shown:
Under 1 year.
1 to 5 years.
5 to 10 years.
10 to 15 years.
15 to 25 years.
25 years and
upward.
•6
•6.
^
. "^
.
-c
T3
. "O
Year.
■oii
"O
o
^±
o
'^?.
•o
o
■C -i
■a
o
■C ^
•d
o
■6s
13
o
■<^
0)
s <;^
o
^■n
a>
t-.
-t^.n
a>
"i^
a;
<.t:
0)
u*
H
;;
Ph
U
Q
Ph
■a
«
Oh
ti
O
Q^
"
ft
P.
b
«
s:,
1893
3
2
66.66
82
35
42. 68
53
17
32.07
18
3
16.66
36
3 8.33
25
2
8.00
1894
16
i)
56. 25
218
98
44.95
120
36
30.00
31
6
19.35
52
3 5.77
28
2
7.14
1895
25
10
40. 00
327
122
87.3
187
43
22.9
46
7
15.2
56
4 7.1
65
4
6.1
1896
S3
IS
54.54
404
12S
31.68
27 (i
35
12.68
71
5
7.04
49
1 2.04
36
3
8.33
1897
34
16
47.05
560
199i 35.53
437
65
14.87
126
14
11.11
89
3 3.37
49
3
6.12
1898
42
20
47.61
552
200; 36.23
447
66
14.76
93
8
8.60
47
3 6.38
48
1899
38
24
63. 15 659
181 27.46
462
59
12.79
102
7
6.81
62
2
3.22
50
2
4.00
1900
40
21
52.50, 595
192 32.27
473
71
15.01
117
7
5.9S
90
4
4.44
52
3
5.76
1901
30
15
50. m
374; Il9i 31.81
287
28
9.75
]06| 5
4.71
56
6
10.71
36 1
2.77
1902
38
12
31.57
3061 97
1
1
31.08
159
2901
25
445
15. 72
40 1
2.5
33
2
6.06
26
1
299
147
49.16
4076
1371
33.63
15.33
750 63
8.4
570
31
5.43
1
415! 20
1
4.81
Sex. — We see no reason why sex should exert any influence on the
mortality rate, and yet according to our observation, as well as that of
some other writers, the death rate among the males is almost constantly
in excess of that of the females.
The following table shows the mortality, according to sex, of all cases
of diphtheria treated in the Asvlums' Board Hospitals, London, from
1888 to 1894, inclusive:^
Sex. Admitted.
Males 5,245
Females 6,353
11,598
Died.
Per cent
1677
31.97
1839
28.94
3516
30.31
The following table shows the mortality, according to sex, of 1000
consecutive cases of diphtheria observed by Lennox Browne:
Sex. Admitted. Died.
Males . . . 533 162
Females 467 121
1000 283
1 Lennox Browue. Loc. eit.
682
DIPHTHERIA
The following table shows the mortality, according to sex, of all
cases of diphtheria treated in the Municipal Hospital, Philadelphia,
from 1893 to 1902, inclusive:
Males
Females.
Year.
Admitted.
Died.
Per cent.
Admitted.
Died.
Per cent.
1893 .
. 94
29
30.85
123
33
26.82
1894 .
. 214
81
37.85
251
73
29.08
1895 .
. 315
83
26.4
391
107
27.3
1896 .
. 424
100
23.58
445
90
20.22
1897 .
. 636
147
23.11
659
153
23.21
1898 .
. 562
152
27.04
667
145
21.73
1899 .
. 641
139
21.68
732
136
18.57
1900 .
. 669
151
22.56
698
147
21.06
1901 .
. 416
94
22.59
473
80
16.91
1902 .
. 285
64
22.45
316
73
23. 10
4256
1040
24.43
4755
21.8
Race. — Race seems to exert no influence over the death rate from
diphtheria. At least this is true in regard to the white and colored
patients. Some observers believe that the blacks are more liable to perish
from the disease than the whites, but this is not in accordance with
our experience, as the following table shows:
White.
Black.
Year. Admitted.
Died.
Per cent.
Admitted.
Died.
Per cent
1893
208
60
28.84
9
2
22.22
1894
434
144
33.18
31
10
32.26
1895
660
178
26.9
46
12
26.00
1896
838
183
21.83
31
7
22.58
1897
1217
281
23.08
78
19
24.35
1898
1177
289
24.55
52
8
15.35
1899
1304
262
20.09
69
13
18.84
1900
1309
286
21.84
58
12
20.68
1901
843
163
19.33
46
11
23.91
1902
567
129
22.75
34
8
23.52
8557
1975
23,08
102
While it is impossible to predict at the onset of diphtheria the ending
of any case, yet it may be said that when the inflammation of the fauces
is mild and the pseudomembrane not extensive, with but moderate
swelling of the lymphatic glands of the neck, the termination is usually
favorable. When the exudation is limited to the tonsils the danger is
not great; the vast majority of such cases recover without any untoward
after-effects. On the other hand, if the inflamed surface be extensive,
the pseudomembrane copious, the exhalations ofl^ensive, and the neigh-
boring lymphatic glands and the adjacent tissue very much swollen,
the patient's condition becomes perilous. It may be safely asserted
that the danger is increasingly grave in proportion to the extent of
surface involved and the copiousness of the exudation. The parts
implicated in the diphtheritic process must also be taken into account
in forming a prognosis. In Lennox Browne's analysis of 1000 cases of
the disease, the mortality, according to the site of the exudate, was
found to be as follows:
DuathH.
Per cent.
81
12,1<5
1
25.00
1
50.00
51
45.53
106
64.24
30
61.22
2
33.83
11
01.06
TTJE PROGNOSIS OF 1)1 1'llTII I'llil A 083
Site of iiioinhraiic. (/'aBCH.
FauceH (alone) 666
Larynx " 4
Naros " 2
Fauces and larynx 112
" " narea 165
" larynx, and naros 49
Membrane involviiiB the buccal cavity and IIijh 6
Membrane involvhifi; the hard palate . . 12
If the fauces alone are involved the patient has a fair chance of
surviving the attack. Ikit v\'here the exudate forms in a thick mass
on the hard and soft palates the danger becomes imminent. Some-
times, however, the membrane peels off quickly, leaving the parts quite
free from ulceration, and recovery speedily follows, although paralysis,
more or less marked, of the palatine muscles, is rarely absent. The
chief source of danger in such cases is from the absorption of the tcjxins,
giving rise to toxajmia and heart-failure.
When the nares are involved the prognosis should always be guarded.
Very many if not the majority of the milder cases of nasal diphtheria
recover, and also some of the severe ones. But it is not often that the
disease is limited to the nares. If the nasal cavities show distinct plugs
of exudate in conjunction with marked faucial involvement, as is usually
the case, the child's condition should be viewed with grave apprehension.
The foregoing table shows that the mortality from faucial and nasal
diphtheria was as high as 64.24 per cent.
In the severe cases of diphtheria nasal involvement is commonly
present. As the capillary bloodvessels are very superficial in the cavities
of the nose, the slightest congestion or ulceration of the mucous mem-
brane of this part is liable to give rise to troublesome hemorrhage.
This of itself is .sometimes a source of danger. But the greatest danger
is from systemic poisoning, which is extremely liable to occur, since
the lymphatics, which are very numerous in the submucous connective
tissue of the nostrils, take up the toxins and convey them to every part
of the system. This condition always involves great danger of death
by asthenia, due to toxpemia and heart -failure. If recovery takes place,
more or less paralysis, local or general, is quite sure to develop during
convalescence.
The occurrence of middle-ear disease as the result of diphtheria is
deemed of sufficient importance to warrant prognostic consideration.
It is believed that the diphtheritic process not infrequently extends
from the postnasal space through the Eustachian tube to the middle
ear. The aural involvement may impair the hearing, but only in rare
instances does it result in deafness. likewise, in severe nasal diph-
theria the infection may be conveyed through the cribriform plate to
the brain, causing meningitis. In analyzing liis 1000 cases of diphtheria,
Lennox Browne says: "It may also here be mentioned that, in one case
of nasal diphtheria, death ensued from meningitis, and no aural coni-
plication was to be found. This circumstance offers a not improbable
explanation of the gravity of nasal diphtheria. For, not only do the
684 DIPHTHEHIA
turbinals constitute an extensive and readily absorbent surface, but
there is a liability to direct cerebral infection through the cribriform
plate, as has been observed in regard to cerebrospinal meningitis in
which the specific organisms have been found in the anterior meninges."
On the first , or second day of diphtheria there is but little to be
learned from the subjective syiaptoms that is of prognostic value. A
little later, in the graver forms of the disease, one may often see in the
facial expression of the patient something indicating the serious nature
of the malady that presents itself for treatment. This appearance has
been characterized as a "peculiar facial cachexia." The face is pale
and sallow, often puffy, bloated, or slightly oedematous; the skin is
smooth and shiny, a mucopurulent discharge issues from the nostrils,
the facial outline is somewhat changed by the swelling of the neck,
the eyes are clear and bright, but the expression is often that of indolence
and apathy. When the attack is likely to prove fatal the face becomes
livid or of a dusky, pallid hue ; in case of nasal involvement blood may
either ooze or flow freely from the nares, and, in malignant cases,
petechiae or ecchymoses may appear, not only on the face, but also on
other parts of the cutaneous surface. Altogether the facial expression
is that of profound blood poisoning, and death may be expected at
any moment.
Only in the mildest forms of toxaemia is recovery possible. When
the patient suddenly becomes extremely pale, vomits everything that
is swallowed, and the first sound of the heart is found to be diminished
in intensity or absent, and the pulse becomes feeble, slow, and irregular,
or disappears entirely at the wrist, the fatal end is not far off. Often
the little patient will utter a shriek, as if suffering from pain, and place
his hand over the precordial region just as he is about to expire. In
these cases death results from asthenia or heart-failure, due to profound
systemic intoxication. W^hen diphtheria terminates in this manner, it
is usually in the second week of the illness.
Temperature. — The prognostic significance of the temperature has
been, v/e think, overrated by most writers. With Lennox Browne we
feel that "One is so accustomed to read and hear of the fever of diph-
theria that we almost hesitate to declare our conviction — formed on
personal observation and confirmed by others whose experience is
much greater — that as regards fever there is little to speak of as com-
pared with the acuteness of the constitutional disturbance characteristic
of the disease."
If the temperature continues high after the first few days of the
illness it is most probably due to the development of some complication.
In the worst cases of diphtheria the temperature soon falls to near the
normal point, and, as the disease progresses, often becomes subnormal.
With the other symptoms of toxaemia present, the occurrence of algidity
should be regarded as a fatal omen, as it indicates the approach of
death by asthenia. In septic cases the temperature may continue high,
or it may fluctuate as in most other septic conditions, l^'his can readily
be explained by the inflammation of the lymphatic glands of the neck
Tiii<: ru.()(;N()Sis or i>ii'irriii:in.\ 085
which always accompanies this form of tlic fliscasc. 'J'hc })rognosis in
this variety of (h'phtlieria should \m'. exceedingly quarried.
Pulse.-- By carefully studying the pulse from time t(; time one may
sometimes acfjuire information of considerabht prognostic value. So
long as the j)ulse is not too rapid, remains regular and of normal volume,
the case is j)rol)al)ly progressing favorahly. I^ut when it hecfjines very
rapid and fe(>l)le, or slow and irregular, our gravest apprehensions should
be aroused. The ])ulse rate as well as its volume is influeneed nif)re l)y
the absorbed toxins than by the pyrexia.
A ra])id j)ulse within certain limits is not necessarily unfavorable so
long as it remains regular. But if it constantly grows more and more
rapid, and becomes irregular in its rhythm and force, the prognosis is
proportionately bad. If, with a frequent and compressible, or a slow
and intermittent pulse, there is also subnormal temperature, a pale,
puffy, apathetic, and cachectic face, the prognosis becomes most grave.
In speaking of the prognostic value of the pulse in diphtheria, Sir
William Jenner says: "An extremely rapid and feeble pulse is of grave
import; a very infrequent pulse is of fatal significance."
This disturbance of the circulatory system means that the heart's
function is affected by the action of the toxin on the carrliac nerves,
and possibly also that the myocardium is undergoing some change
through the influence of the poison. When the heart's action becomes
slow and weak there is danger of clots forming in the ventricles or in
the large bloodvessels connecting with the heart.
One of the special dangers to be feared in diphtheria is iuAolvement
of the larynx, giving rise to membranous croup. The disease may
occur primarily in the larynx, but more often it begins in the fauces
and extends into the larynx. The patient cannot be considered free
from danger of the pseudomembrane extending into this part so long
as the disease continues, but the liability of such an occurrence pro-
gressively diminishes after the first week.
The danger in membranous croup is twofold: first, from laryngeal
obstruction, causing suffocation and death; and, secondly, from bron-
chitis or bronchopneumonia. Much may be done toward overcoming
the first source of danger by operative measures, but even then the
diphtheritic inflammation too often extends downward into the trachea,
bronchi, and bronchioles, and not infrequently into the alveoli of the
lungs, giving rise to bronchopneumonia. We believe that about one-
half of the deaths we have seen in membranous croup resulted from
the latter complication.
The prognosis may be favorably influenced to a considerable extent
by promptitude in employing such measures as intubation or trache-
otomy for relief of the laryngeal stenosis. If, after either of these pro-
cedures, the child continues to breathe easily and noiselessly, sleeps
quietly, takes nourishment well, runs a temperature of not more than
one or two degrees above normal, and has a good color, the chances
of recovery are favorable. On the other hand, if the respirations are
uneasy and noisy, the temperature continues high, a troublesome cough
686 DIPHTHERIA
with rales throughout the lungs appear, and the color of the patient
shows that the blood is not properly decarbonized, the chances of
recovery are slim.
Membranous croup is much less liable to be attended by toxaemia or
followed by general paralysis than are most other forms of diphtheria.
But these affections may occur in cases of membranous croup as the result
of involvement of the fauces or nares synchronously with the larynx.
Renal Complication.^ — Renal complication is not often of much
prognostic importance. The slight amount of albumin that is fre-
quently present in the urine is of no great significance, provided that
granular and hyaline casts are absent. But when these, together with
a large amount of albumin, are found, and the amount of urine excreted
is greatly diminished, the outlook is not encouraging. If suppression
of the urine occurs, death from convulsions and coma, as the result of
ursemic poisoning, would soon follow if relief were not promptly afforded.
In our experience such a termination in diphtheria is rare.
The prognosis of diphtheria should be greatly qualified when it
occurs coincidently with or as a sequel to some other infectious disease,
like scarlet fever or measles. In patients suffering from the latter disease
diphtheria seems especially liable to assume the form of membranous
croup, probably because of the catarrhal affection of the larynx usually
present in measles. In the year 1900, measles of a malignant type
broke out in the diphtheria wards of the Municipal Hospital, Phil-
adelphia, and the mortality assumed unduly grave proportions. Of
68 cases of diphtheria complicated with measles, 34 died, a death rate
of 50 per cent. Indeed, any independent affection, however mild
ordinarily, supervening on an attack of diphtheria may become inordi-
nately severe in consequence of the changed condition of the blood
and nervous system of the patient.
Diphtheritic Paralysis.— The danger from diphtheritic paralysis
depends very much on the parts involved. So long as the vital organs
of the body remain unaffected the prognosis is not unfavorable. Par-
alysis of the soft palate, however inconvenient it may be to the patient,
is not fatal. Likewise, in the average case of multiple paralysis recovery
may be expected. Even in the more extreme cases, if the heart's function
and the respirations are not affected, the chances of recovery are fair,
provided the patient receives proper attention during the critical period.
When deglutition is impossible, life may be preserved by feeding the
child through an oesophageal tube. Cardiac paralysis, which is most to
be feared, often develops suddenly and gives rise to dangerous symptoms
of heart-failure. It is liable to occur either early or late in the disease.
We have already mentioned the fact that multiple paralysis does not
make its appearance until the fourth to the sixth week of the illness.
This complication, as well as some others to which attention has been
called, tends to keep the patient's life in danger for a long time. Even
when a well-marked case of diphtheria is progressing favorably, it is
not too much to say that the danger period is not passed until at least
six weeks have elapsed since the beginning of the attack.
CIT APTER XI 1 r.
DIPHTHERIA (Continued).
THE TREATMENT OF DIPHTHERIA.
Since antitoxin has achieved for itself so much credit as an immun-
izing agent against diphtheria, it would seem that it deserves first place
among the prophylactic measures to be considered. So important,
indeed, is the question of serum treatment, not only with reference to
its power of preventing but also of curing the disease, that we have
concluded to devote a special chapter to the subject. We find it most
convenient, however, to consider the question of treatment of diphtheria
in the following order: first, the hygienic or preventive treatment;
second, the medicinal treatment; third, the specific or serum treatment.
Preventive Treatment. — As soon as the nature of the disease is known
the patient should be separated as far as possible from the other members
of the household. This is important even when the attack is ever so
mild, as severe cases may result from mild ones. If the patient is to
be treated at home the other children, if there be any, should receive
an immunizing dose of antitoxin and should be immediately sent
out of the house. If this is not feasible, they should be excluded
from the sick-chamber and assigned to bed-rooms in the most distant
part of the dwelling. Their hygienic conditon should be looked after;
at least they should be properly fed, regularly bathed, and provided
with plenty of fresh air day and night. Their throats and nostrils
should be examined every day, and as soon as anything abnormal is
discovered the child should be immediately separated from the others
and given suitable treatment.
One of the uppermost rooms in the house should be selected for
the patient. It should be light and properly heated, and pronded with
facilities for obtaining ventilation without incurring the risk from
draughts. An open fire-place, with at least a little fire burning, is a
very desirable aid toward maintaining the purity of the air in the room.
The most suitable temperature is 70° to 72° F. All unnecessary hang-
ings, furniture, and the like, that are liable to retain the contagium,
should be removed from the chamber. In the winter months, when the
heated air of the room is usually dry, it may be moistened by steam,
which, if deemed advisable, may be slightly impregnated with eucalx-ptol,
or some other fragrant essential oil. This is more especially advisable
when the patient manifests croupy s}^Ilptoms.
If more than one member of the family be ill with the disease, care
should be taken not to overcrowd the patients. Each patient should
688 DIPHTHERIA
be allowed at least 2000 cubic feet of air space, with an additional
allowance for the nurse. The nurse should be instructed to keep the
patients as quiet as possible; at least, so far as active bodily movements
are concerned. When the heart is found to be weak, she should feed
the patient by means of a feeding cup, and not allow him to rise or get
out of bed under any circumstance whatever.
During the illness of the patient the privileges of the well members
of the household should be restricted. They should be advised not to
attend church nor public assemblages of any kind. The children, if
there be any, should at once be required to leave school, and should not
be readmitted until the family physician or some qualified sanitary
officer certifies that the sickness has ended, and that the house has been
thoroughly cleansed and disinfected. The isolation of the patient
should continue until the diphtheritic exudate has disappeared, and the
affected mucous membrane has become entirely normal. When possible,
cultures should be made to determine the absence of the specific bacilli;
if two successively negative cultures be obtained it may be considered
safe to allow the patient to associate with the other members of the
family, provided he has had an antiseptic bath and is dressed in clean
clothing.
As the infecting principle of the disease clings to articles which have
been used by the patient, or which have been in the same apartment,
all such articles as are worthless should at once be burned. Only such
books, toys, and the like, as may be burned at the termination of the
illness should be allowed in the sick-chamber. All articles for the
laundry should be steeped for some time in a disinfecting solution, such
as two fluidounces of chloride of zinc, or four fluidounces of strong
carbolic acid, to a gallon of water, and afterward boiled for half an hour.
For the disinfection of woollen goods formalin may be used, but for
efficiency there is nothing that ecjuals superheated steam. All utensils
used by the patient in eating or drinldng should be purified each time
by means of boiling water. The secretions from the patient's mouth
and nose should be disinfected by receiving them into a strong solution
of chloride of lime, or a mercuric chloride solution (1 : 1000), or some
other equally powerful gerrn-destroying agent. Small pieces of worn
cotton goods, or cheesecloth, may be used to receive such secretions,
and should be destroyed at once by fire.
T'he nurse or any other attendant should wear clothing made of such
material as can be readily boiled and laundered. Before associating
with well persons she should take an antiseptic bath, washing her hair
at the same time, and change her entire clothing. The physician also,
should exercise care lest he himself may be the means of conveying the
infection to others. He should not remain in the sick-chamber longer
than is necessary to make a proper examination of the patient. Before
leaving the house he should take the precaution to wash his face, hair,
and hands; the latter should be held for a few moments in some anti-
septic solution, as inercuric chloride, 1 : 1000. He should delay visiting
another patient until he has spent some time in the open air, or, what
77//'; tr,i<:atmI':nt of dii'ii'iiiI'IHIA 680
is better, chaiif^ed his clothing. It is (icsirahle for liini to w^-ar in the
room a long rubber coat or Wuv.n gown, which shoiiM b<- kept hanging
in i\\v o[)('n air (hiring th(; interval of In's visits.
As the body of a patient who has died of diphtheria is slill eajKiljle
of transmitting the contagium, certain j)reeaiitions in regard to it are
necessary. An effort should be made to disinf(;ct th(! body by thf)roughly
washing it with some powerful disinfecting solution. Ther(! is jx-rhaps
nothing more relial)le than chloride of lime. Six ounces of tin's d their action on animals, and afterward on
man. For the latter purjxjse Ix; emj^loyed a mixture containing irc^n,
toluol, and creolin or rnetacresol. Finding, however, that this solution
produced a marked smarting sensation in the throats of children, he
added to it menthol.
"A cotton tampon steeped in this solution is apy^lied to the affected
parts twice in succession for ten seconds, and this treatment is r(!peated
every three hours, until all the local symptoms have disappeared, which
ordinarily occurs within four or five days. While the affection is still
local, it may be arrested in its course by this solution; bacteriological
examination will show that all the bacilli in the membranes are killed.
Loeffler reports that in 96 cases treated in this manner, three-fourths
of which were shown by bacteriological examination to be true diph-
theria, not a single death occurred."
Ijoeffler recommends two solutions, the formulae of which are as
follows :
Loeffler's Solution (1).
'!^ — Menthol 10 grams.
Solve in toluol ad 36 c.c.
Alcohol, abs 60 c.c.
Liq. ferri sesquichlorid 4 c.c— Nf .
Loeffler's Solution (2).
Jk— Menthol 10 grams.
Solve in toluol ad 36 c.c.
Alcohol, abs 02 c.c.
Creolin 2 c.c— M.
Either of these solutions may be applied with a cotton swab to the
diphtheritic patches every three or four hours in the manner mentioned
above. It may be well to clear the throat of mucus by mopping it with
cotton before making the application. It is advised that the applications
be made a little more frequently in bad cases.
We have not used these solutions extensively, but have given them
a fair trial without obtaining results anything like as favorable as those
seen by Loeffler.
Jacobi says: "Wlien the diphtheritic pseudomembrane is within
reach, it should be either destroyed or disinfected. For that purpose
one or two drops of a 50 per cent, solution of carbolic acid in glycerin
may be applied once (not more than twice) a day, or of the tincture of
iodine, or of a solution of 1 part of the bichloride of mercury in 100 or
500 parts of water, several times a day." But he calls attention to the
fact that only a small part of the pharjnax is accessible to such treatment,
and that it is possible to apply it to only a small class of patients. He
condemns in forcible language the indiscriminate use of strong appli-
694 DIPHTHERIA
cations to the throats of children. He says: "Smaller children will
object, will defend themselves, will struggle. It takes many an anxious
moment to force open the mouth; meanwhile, the patient is struggling,
perspiring, screaming, and exhausting his strength. One may succeed
in forcing open the jaws, then there begins the practice of making
applications, of swabbing, of scratching off the pseudomembrane, of
cauterizing, of burning. The struggling child will prevent the limitation
of the application to the diseased surface. One cannot help injuring
the neighboring epithelium, and thus the morbid process will spread.
Instead of doing good, we have done harm; for, indeed, no local appli-
cation can do so much good as the struggles of the frightened children
do mischief. I have seen them die while defending themselves against
the attempted violence, leaving doctor and nurse victorious and alive
on the battle-field." Jacobi believes that a very good local effect may
be produced by the swallowing of medicines which are at the same
time disinfectants, digestible, and easy to take; that they should be
given in small doses and frequently repeated. Of this class of medicines
he mentions tincture of the chloride of iron, lime-water, solutions of
boric acid, bichloride of mercury, or benzoate of sodium.
Solvents. — For the destruction and removal of the pseudomem-
brane, certain agents known as solvents have been employed from time
to time. Among the unirritating solvents may be mentioned alkalies,
pepsin, trypsin, and papayotin. The agent that has been most largely
used is, perhaps, lime-water, or steam from slaking lime. Its solvent
action, if it has any, is due to its alkalinity, which, as J. Lewis Smith
says, may be increased by adding sodium bicarbonate to it. From
observing its effects in a considerable number of cases, this author
recommends with confidence the following formula:
P — 01. eucalypti 5 ij.
Sodii benzoat. S j.
Sodii bicarbonat . 3 ij.
Glycerinse ' . . S ij.
Aqusecalcis Oj.— M.
Sig. — To be used witb tbe hand atomizer from three to five minutes every
half-hour, or with the steam atomizer almost constantly.
The writer says: "This alkaline spray not only exerts a solvent action
on the pseudomembrane, but also renders the mucopus thinner, less
viscid, and, therefore, so changes its character by diminishing its viscidity
that it is more easily expectorated."
As trypsin is an active solvent in an alkaline medium, J. I^ewis Smith
suggests that it may be added with advantage to the alkaline mixture
just described. Indeed, this writer is inclined to believe that such a
combination forms the best solvent mixture known. The pseudo-
membrane has been seen to dissolve and disappear quickly under the
use of the following formula:
]^— Trypsin gr. xxx.
Sodii bicarb gr. x.
Aquse destillat g j. — M.
Sig,— To be applied frequently with the hand atomizer or a cotton swab.
Tlll<: TIINATMI'INT Oh' 1)1 1'llTII hllU A P,05
Pepsin has hccu used as a .solvent, with varyini^ n-sults. It was
recommended in di[)hth(M-ia solely on tlieoretif;al ^roniifls, and has
proved to 1)0 of douhtful utility.
Some writers sp(!ak favorably of pajmyotin. in s(;lution as a solvent
of pseudomem})rane. Among these may he mentioned Ko.ssbach,
J. K. l^auduy (Jr.), and Jaeohi. 'l^'he drug is said to he readily soluhle
in 20 parts of water, and it is claimed hy Kosshach that if a few minims
be placed on the tongue every five minutes tlu; membrane will dissolve
in two or three hours. Jacobi has u.sed it with fair results, applying
the solution with a swab or the atomizer. He says he employed the
drug many years ago in greater concentration to dissolve, after trache-
otomy, the diphtheritic meml)rane in the trachea below the tracheal
tube.
As already intimated, Lennox Browne gives lactic acid first place
among the local applications. He believes its efficiency is due in a
measure to the fact that an acid medium is inimical to the V)acillus, Vjut
that its greatest merit is its power to disintegrate or digest false mem-
brane. He makes this strong statement: "Truth to say, we have been
so well satisfied with lactic acid that we have been loath to try any other
local remedy. We have not found it injurious to contiguous healthy
tissue — that is to say, wherever the epithelial layer is entire. Its action
appears to be limited almost solely to unhealthy tissue, promoting its
disintegration by a process analogous to that of digestion; there is, it
is true, some circumferential inflammation, but as this is only of the
degree of healthy reaction and leads to the outpouring of scavenging
leukocytes, it is to be regarded as a desirable result."
This author advises that the lactic acid be applied pure, or rather of
(British) pharmacopoeial strength, by the physician at least once or
twice a day, and that the drug, moderately diluted, be applied by the
nurse every three or four hours until the membrane has disappeared.
The following formula is recommended:
]^— Lactic acid (P. B.) 1 part.
Distilled water 3 parts. — M.
Sig.— To be applied by the nurse or attendant every three or four hours with
a cotton swab or the hand atomizer.
Our experience with the so-called solvents in diphtheria has led us to
believe that they are not to be depended upon. They may act very
well in the test-tube, but their digestive and solvent action is too feeble
to be of much practical value during the short time that it is possible
for them to remain in contact with the pseudomembrane in the throat.
^Vhile the antiseptic mouth washes, gargles, and sprays are useful to
a limited extent, yet their action is too feeble and intermittent to be of
any great practical value. We have already expressed our disapproba-
tion of caustic applications, and we agree with those who believe that
nothing is to be expected from mere astringents, ^^^len we consider
that the purpose or design of local treatment is the prevention of
extension of the pseudomembrane, promotion of its separation, destruc-
tion of the bacilli, and the prevention of toxic absorption, we must
696 DIPHTHERIA
admit that of the various remedies recommended, some of which even
vaunted as specifics, no one has stood the test of experience.
We would not be understood as discouraging local applications in
diphtheria; on the contrary, we believe that when used with good
judgment they may be of great service. We have but little confidence,
however, in their power to accomplish to any marked degree the purposes
mentioned above, although as cleansing agents they are very useful.
Any unirritating antiseptic solution may be employed, but, after all,
quite as much may be accomplished with a warm normal salt solution.
It should be the aim of the physician to keep the parts involved as clean
as possible without taxing too much the strength of the patient. This
may be best accomplished by irrigation, either with a syringe similar
to the one devised by Lennox Browne, or with the ordinary fountain
syringe. Swabs should not be used, except by the physician or trained
nurse, and then only with great care.
At the very beginning of diphtheria, or even when the disease is
simply suspected, the throat should be sprayed every hour, at least
for a few hours in succession, with a mild and unirritating antiseptic
solution, such as a 1 per cent, boric acid solution, diluted Dobell's
solution, hydrogen peroxide with equal parts of water, or a solution of
1 : 4000 or 6000 of bichloride of mercury. Twenty-four hours will
probably determine whether it is possible to prevent or limit the develop-
ment of the exudation. If not successful, and the disease goes on to its
fullest development, the same applications may be continued every hour
or two for the purpose of cleansing the throat. As already mentioned,
a warm normal salt solution will accomplish the same end. We now
employ it almost exclusively. Park, consulting physician to the Willard
Parker Hospital, New York, prefers, in older children and adults, irri-
gation with a warm solution of salt every hour or two, and also every
three to six hours to irrigate with some antiseptic solution, especially
1 : 1000 of bichloride of mercury. The irrigation of the throat, he
believes, is best carried out with the fountain syringe. In the Mu-
nicipal Hospital of Philadelphia we were in the habit of spraying the
throat every two hours with peroxide of hydrogen. So long as the
fauces are covered with exudate this drug may be used without dilu-
tion, but when the exudate has thinned out very considerably, leaving
the mucous membrane excoriated and irritable, the peroxide should
be diluted with one or two or more parts of water. When the exudate
has almost entirely disappeared, and the throat remains irritable, the
following application is often useful:
Jfc — Menthol gr. x.
Oil of sweet almonds fS j.— M.
Sig. — Apply in form of spray.
An operative procedure consisting of removing the tonsils at an early
stage of diphtheria has been recommended. Lennox Browne and his
colleague, Mr. Percy Yakins, and also a few other writers, claim to
have seen good results follow the operation.
riii<: TUi<:ATMh:NT of Dii'irriihiiaA 697
The ol)jec'ti()ns to this treatment are that the exufhite is liable to
reform on the cut surface and the adjacent parts; that the injury inflicted
affords a fertile soil for the propagation of the bacilli, and that the
exposed lymphatics will [XTmit of ready absorption f>f the tfjxins. 'J'he
procedure has not met with much favor, and w(; would strtjiigly advise
afjjainst it.
Nasal Diphtheria. -As diphtheria of the nose and nasopharynx is
most dangerous, immediate and persistent local treatmctnt should be
adopted with the object of preventing, as far as possible, absor})tion of
the noxious products. The treatment consists in frc^fiuent cleansing
and disinfecting the nasal cavities. The remedies usually employed
do not differ materially from those recommended in faucial diphtheria.
The decomposing material and foul discharge should be washed away
as fast as they form. In order to do this, it is necessary to irrigate the
nose very frequently — often every hour, or every two hours, day and
night. In severe cases with a profuse fetid discharge the nares should
be kept clean, no matter how much the child resists. The little patient
may be restrained without suffering any harm by rolling him up in a
sheet. If much exhausted, the child should not be raised from the
recumbent position during the cleansing process. Only bland solutions
should be employed, such as boric acid (5 to 10 grains to the ounce
of w^ater), chloride of sodium (teaspoonful to a pint of w'ater), or some
other equally mild antiseptic solution. The nose wash should always
be used lukewarm, and the more thorough the washing the better it
is for the patient. Instillations wdth a small medicine dropper, so often
used by physicians, are not sufficient. Nor will the atomizer convey
a sufficient amount of liquid into the nasal cavities to accomplish the
purpose aimed at. A small (not too small) blunt-pointed syringe will
answer the purpose much better. If carefully used, there is perhaps
no better irrigator than the fountain syringe. It should be held just
high enough for the solution to flow without undue pressure, and thus
obviate any possibility of injury to the middle ear. If the nose inclines
to bleed, the irrigation should be very slow and gentle. But if the epis-
taxis be free and quite uncontrollable, as sometimes happens, the
irrigation will have to be dispensed with. It may then become necessary
to direct attention to the hemorrhage. Alum, tannic acid, Monsel's
solution, and the like, may be used. We have frequently found it
necessary to plug the nares. I/Cnnox Browne says the hemorrhage may
generally be arrested by syringing the nostrils with the following anti-
septic solution at a temperature not less than 100° F. :
9i — Chlorate of potassium >2 oz.
Bicarbonate of sodium 5^ oz.
Borax J^ oz.
White sugar (in powder) 1 oz. — M.
Sig.— A teaspoonful dissolved in five or ten ounces of water at 100° F. and use with nasal syringe.
For the local treatment of nasal diphtheria many physicians prefer
some of the more active antiseptic and disinfecting solutions, such as
peroxide of hydrogen, permanganate of potassium, carbolic acid.
698 DIPHTHERIA
bichloride of mercury, and so forth. Peroxide of hydrogen is quite
useful if it be properly diluted. It is very irritating to the mucous
membrane of the nose, and will cause pain if not diluted with 8 or 10
parts of water. Carbolic acid has been used in solution varying from
1:1000 to 10:1000 parts of water. Care should be taken lest too
much of this drug be swallowed. Permanganate of potassium has been
highly recommended. It has been applied to the fetid nares with a
cotton swab, in the strength of 1 : 250 of water, once or twice a day.
For irrigation it may be used several times a day in a solution of 1 : 2000
to 1:4000.
For washing out the nares, as well as the fauces, bichloride of mercury
in solution has many advocates. Its well-known power as a germ
destroyer has led to its use. It would doubtless be more freely employed
were it not for the danger incurred through its poisonous qualities. As
young children always swallow some of the liquid that is injected into
the nares, most physicians hesitate to use a solution which is so
highly poisonous. The same objection holds good against its employ-
ment for irrigating the fauces. Among those who recommend this
drug for washing out the nares may be mentioned Jacobi. He advises
that 1 part of bichloride of mercury })e mixed with 10 parts of chloride
of sodium or chloride of ammonium, and that from 2000 to 10,000 parts
of water be added to form a solution, which should be used freely. He
says if moderate quantities of this weak solution of mercuric bichloride be
swallowed while being injected no harm is done. For correcting the
fetid odor from the nares, he recommends, besides some of the solutions
already mentioned, creolin in a 1 per cent, solution.
After some experience with most of the nasal washes mentioned above,
we have, for the last few years, settled down to the use of the warm
normal salt solution almost exclusively. We find that it answers the
purpose quite as well as any of the antiseptic washes, and that it has
the advantage over some others of being perfectly safe and unirritating.
We may add that we have used with benefit peroxide of hydrogen well
diluted with lime-water.
Aural Diphtheria. — But little treatment can be applied to the com-
paratively rare form of acute median otitis of diphtheritic character
other than what is suitable for that affection when it occurs ordinarily.
As pain is not often complained of, the condition is usually not realized
until a purulent discharge issues from the external m^eatus. Nearly
all that can be done then is to syringe the ear with a warm solution
of boric acid or some other mild antiseptic wash. At the same time
the nose may be irrigated with a similar solution. It is advisable that
Pollitzer infiation be also employed with the hope of clearing the Eus-
tachian tubes.
The insufflation of dry powders into the ear is not considered advis-
able, as they are likely to form dry crusts which may prevent the escape
of the purulent material. Extension of the suppurative action to the
mastoid cells rarely occurs; but when it does occur surgical treatment
applicable to that condition should be resorted to.
TTTK TRI<:ATMKNT OF I)! I'llTII KIU A
699
Ocular Diphtheria. — For diplilliciific involvcnicnt nf the; conjunctiva,
fortunately rare, the (^ye should he irri^'ated frefjuently- say every hour
— with a boric acid solution (ten grains to the ounce of water), or
some other equally mild antiseptic sohition. 'J'his will be found difficult
when the eyelids are very much swollen; but an effort must l)e made
to keep the pus from accuniulatincr under the lids. Ice applications,
Fl«. 98
Position of child during irrigation of tliroat and nose. (After Park.l
in the form of iced cloths, are always indicated at first; but later it may
be better to use %varm applications. A strong solution of nitrate of
silver may be applied to the pseudomembrane on the palpebral con-
junctiva if care be taken to neutrahze the silver salt immediately with
a solution of chloride of sodium^
According to Lennox Browne,^^Hermann, of Breslau, has employed
very efficaciously hourly pencillings of the affected eyelids with a 5 per
700 DIPHTHERIA
cent, solution of benzoate of sodium, and declares that since he began
to use this treatment no patient under his care with this form of diph-
theria has lost an eye.
Paralysis of the muscles of the eye occurring as a sequel to diphtheria
calls for no special treatment. It will almost always disappear entirely
in the course of two or three months.
Constitutional Treatment. — As diphtheria begins as a local disease
very little internal treatment is required at the onset. Constitutional
disturbance, however, occurs early, partly as a result of the local disease,
but more especially from absorption of the toxic products of the diph-
theria bacilli and the associated organisms. The prostrating effects of
this poison are well known. The indications for internal remedies may
be stated as follows : To aid the system in the elimination of the poison ;
to reinforce the debilitated vasomotor system; to improve the quality
of the blood; to combat the poisonous effects of the toxins; to sustain
the vital powers; and, lastly, to conduct to a favorable termination the
secondary affections that may arise.
At the outset of the disease it is well to administer a gentle purge.
For this purpose there is perhaps nothing preferable to calomel. Liquor
ammonii acetatis (U. S. P.) is useful, as it tends to increase the secretions
of the skin and kidneys. Water may be allowed ad libitum. Small
pieces of ice held in the mouth will often have a soothing effect on the
inflamed and painful fauces. Should the temperature of the patient
be high, no attempt should be made to reduce it by the internal admin-
istration of antipyretic drugs, especially the coal-tar products, as they
ai'e too depressing. It is better to trust to tepid bathing. Bathing has
the additional advantage of keeping the function of the skin active.
At this early stage there is no article of diet equal to milk. There is,
however, no objection to beef-tea and broth.
As soon as the diphtherial character of the disease is recognized iron
should be administered. For the past fifty years this drug has had the
confidence of physicians in this country, as well as those in most of the
European countries, and by many it is regarded as our sheet-anchor
in the constitutional treatment of diphtheria.
The preparation of iron that has achieved the greatest reputation in
this disease is the tinctura ferri chloridi. It is believed to have both a
local and general effect. It should be administered frequently and in
positive doses. A child of one year may take as much as a fluidrachm
in twenty-four hours, and a child of three to five years from two to
three fluidrachms in the same period of time. It should be admin-
istered every hour or two. Some WTiters advise that it be given every
fifteen, twenty, or thirty minutes. It should always be given diluted
with a little water, so that the dose is about a teaspoonful. The addition
of glycerin makes the drug more palatable. One part of glycerin to
three parts of water makes a very good vehicle. If there is too much
dilution no local effect can be expected from the drug. As a rule, it is
well borne by the stomach; but there are exceptional cases in which
it is not tolerated at all.
77//'; Tfi/'JATM/'JN'/' Oh' 1)1 1'llTII HlilA 701
Jacohi, aftor iisin^ tlii.s pre[)aratif)ii of iron for many years, cxprrssps
great confidence in it. He feels sure he has seen many bacJ cases recover
through its use. But he has met with some cases in which its action
was not so satisfactory. lie says: "Still, I have often been so .situatr-f]
that 1 had to give it up in pecidiar cases. 'I'hey were those in which
the main symj)toms were of so intense a sepsis that tlu; iron and other
rational methods of treatment were not powerful enough to prevent
the rapid progress of the disease. Children with nasopharyngeal diph-
theria, large glandular swelling, feeble heart, and fref]uent pulse,
thorough sepsis, and irritable stomach })esides, those in whom large
doses of stimulants, general and cardiac, may pcjssibly bring any relief,
are better oft" without the iron. When the circumstances are such as to
leave the choice between iron and alcohol, it is best to omit the iron
and rely on alcoholic stimulants mostly. The quantities required are
so large that the absorbent powers of the digestive tract are no longer
sufficient for both."
J. Lewis Smith regards the ferruginous preparations as holding an
important place in the treatment of diphtheria, and says the one which
has stood the test of experience is the tincture of the chloride of iron.
He believes it should be given in large and frequent doses, as five drops
hourly to a child of three years. He thinks it probable that those Avho
have not observed its good effects have treated unusually bad cases
or have given the medicine in small and inadequate doses. The best
vehicle, he says, is glycerin and water.
Some writers maintain that an effort should be made to saturate the
system as soon as possible with this drug, and, with this object in \iew,
recommend that it be given in as large and frequently repeated doses
as the stomach will tolerate. Ferguson, according to the author last
mentioned, believes that this preparation of iron when freely admin-
istered partially arrests the blood change in diphtheria, and he recom-
mends for a child of ten years the following mixture :
1^ — Tinct. ferri chloridi S j. •
Syr. simplicis . 3 iij — M.
Sig.— One teaspoonful hourly in waler.
If the stomach cannot tolerate this dose, it is advised that half a
teaspoonful be given every half-hour.
Prof. Joseph E. Winters,^ of New York, says that he has administered
to a child of eight years as large and frequent doses of the tincture of
the chloride of iron as two drachms, in combination with glycerin, every
half-hour for forty-eight hours with marked benefit. And J. Lewis
Smith cites an instance in which a woman, aged twenty-two years,
greatly prostrated, having an excessive amount of exudate in the
throat, and a very fetid breath, took daily one and a half fiuidounces
of the iron for ten days. But, he remarks, "it is only in tlie most severe
or malignant form of the disease, the form described by Sanne as septic
phlegmonous, that such large doses are proper or are required." He
1 Diphtheria and its Management, 1SS5.
702 DIPHTHERIA
believes, as do most physicians of the present day, that in the average
case of diphtheria five drops given hourly is the proper dose for a
child of three years.
We have used in our hospital work for many years the ferric chloride
in doses practically the same as those last mentioned; but we prefer
to combine it with the bichloride of mercury, as in the following formula :
^ — Hydrargyri chloridi corrosivi g^- %
Tinct. ferri chloridi 5j.
Syrup, simplicis S j.
Aquae q. s. ad fS iij.— M.
Sig. — For a child of three years, one fluidrachm iu a little water every two hours.
The internal use of bichloride of mercury in the treatment of diph-
theria is not new. It was employed in this country as far back as 1860,
by Dr. Tappan, of Ohio, with asserted benefit. It has, however, been
used more frequently of late years, since it has been shown to be one of
the most active germicides in medicine. The accepted theory of the
microbic origin of diphtheria has led to the employment of this drug
by many practitioners in the belief that when given internally it pene-
trates all parts of the system, destroying all micro-organisms with which
it comes in contact. But as diphtheria begins as a local disease and
becomes a systemic affection later, not because the specific micro-
organisms enter the circulation — for in only rare instances have they
been found in the blood — but because of the absorption of their poisonous
products, it, therefore, may be that the remedial power of corrosive
sublimate is limited to its local eft'ect upon the organisms in the throat
and pharynx. Whichever way its influence is exerted, locally or consti-
tutionally, it has been found by many physicians to be very useful in
diminishing the virulence of diphtheria and increasing the chances of
recovery.
Though this drug has been widely employed in diphtheria, and at
times administered in what would appear to be dangerous doses, very
few reports can be found of its toxic or injurious effect. Dr. Grant^
administered to a child of four years one-half grain of corrosive sublimate
every half-hour until six doses were taken, and then hourly during the
remainder of the day, every two hours on the second day, and on subse-
quent days at longer intervals. Jacobi has also administered it freely,
but not in such heroic doses as just mentioned. He states that an
infant a year old may take half a grain every twenty-four hours — of
course, in divided doses — for many days in succession, with very little,
if any, intestinal disorder, and with no stomatitis.
While large doses may be justifiable in extremely severe cases, we
believe that smaller and safer doses are sufficient for general use. W^e
agree with J. Lewis Smith, who says: "In ordinary cases the following
may perhaps be regarded as about the proper quantities which should
be administered in divided doses in twenty-four hours: For a child of
two years, gr. | (gr. ^t every two hours) ; for a child of four years, gr. |
1 Quoted by J. Lewis Smith, Cyclopedia of the Diseases of Children, by Keating.
77//'; Till<:ATMI<:NT OF DII'IITIIF.UIA 703
(gr, -^^ every two lionrsj; for a cliild of six years, ^r. \ (\iv. .j',; every two
hours); and for a child of ten years, ^r. h (^'r. ./, every two hoursj."
Calomel. — Calomel as a remedy in diphtlieria has its advo(;ates. It
has been recommended with the purpose of securing both its cathartic
and alterative elfects. It may be useful as a gentle cathartic at the
beginning of an attack, but to continue catharsis after the flisease is
fully developed seems ol)jectionable on account of its tendency to
weaken the patient and increase the ana?mia which so soon becomes
manifest in all severe cases, whatever the treatment. Much more is
claimed for it when administered in a fractional part of a grain at
frequent intervals. Many physicians of ample experience recommend
it very highly in doses of one-tenth to one-quarter of a grain, repeated
every hour or two. Some advise that a fractional part of a grain in
powder form be placed on the tongue every hour or two, or even more
frequently, and allowed to disappear gradually. It is claimed that
when given in this way it acts both locally and constitutionally. Its
tendency to act on the bowels may be obviated by the administration
of a little paregoric at proper intervals.
Potassium Chlorate. — Potassium chlorate has been used in the treat-
ment of diphtheria for almost as long a time as the tincture of the
chloride of iron. It was formerly more often employed than at present,
but it still has many admirers. Its great efficacy in stomatitis has
encouraged the belief that it is also useful in diphtheritic pharyngitis.
But, as the results have been disappointing, and the action of the drug
tends to weaken the patient and injure the kidneys, especially when
administered in doses believed to be sufficiently large to be of service,
it has, to a great degree, fallen into disuse. Jules Simon says that
while it acts wonderfully well in stomatitis he has obtained no benefit
from it in diphtheria. Its tendency to cause albuminuria and nephritis
when taken in large doses is well known. Where death has resulted
from an overdose of this drug the kidneys have been found greatly
damaged.
Potassium chlorate in combination with the tincture of the chloride
of iron was, a few years ago, almost universally regarded as the remedy
far excellence in diphtheria. The following formula, vnXh. some variations
in the proportion of the ingredients, w^as for a long time a favorite
prescription with most physicians of this country, and is still used
by many:
P:— Potassii chlorat 5 j.
Tinct. ferri ehloridi f5 ij.
Acidi muriat. dilut gtt. x.
Syr. simplicis fS j-
Aquse q. s. ad fs iv.— M
Sig.— One teaspoonful every hour or two hours iu a little water.
A child of five years may take one-half of the above mixture in the
course of twenty-four hours.
Dr. Thomas ]\I. Drysdale, of Philadelphia, who has had considerable
experience in the treatment of diphtheria, claims that chlorate of potash
704 DIPHTHERIA
is so efficacious as to be almost a specific in this disease. He employs
it in large doses. To an adult he gives fifteen grains, and to a child of
tv/elve years seven and a half grains, every two hours. In such doses
he does not fear any deleterious effect on the kidneys. In laryngeal
diphtheria he recommends the following formula :
Jfc — Potassii chlorat 5 ij.
Syr. limonis . . fX j.
Aquae fS iij.— M.
Sig.— For a child under two years one teaspoonful, and for a child from two to ten years two
tuaspoonfuls, every half-hour in urgent cases.
After an extensive use of potassium chlorate in diphtheria, and failing
to obtain the favorable results claimed for it, we have abandoned it
entirely. We feel inclined to agree with that noted clinician of his day,
J. Lewis Smith, who says: "From what is known of its action, it would
probably be better to abandon its use in diphtheria, since it is a remedy
of doubtful efficacy for throat affections. If it be employed, it should
certainly be administered in small doses sufficiently diluted. If it be
prescribed, it should not, I think, be in larger quantity than half a
drachm in twenty-four hours for a child of five years."
Turpentine. — Turpentine has its advocates in the treatment of this
disease. It has been employed both locally and internally, with the
result, as some writers believe, of arresting the formation and spread
of the exudation, and preventing the secondary toxic effects. Cases
have been reported in which severe croupy symptoms quickly dis-
appeared under teaspoonful doses of pure turpentine, and the patient,
in one instance, recovered without tracheotomy, which was before
thought necessary. The dose more commonly employed has varied
from ten minims to a teaspoonful, one to three times daily, in milk,
sweetened water, or gruel.
Good results have been reported from the use of this agent by men
of large experience and good judgment, among whom may be mentioned
Baruch and Jacobi. Dr. Llewellyn, of Washington, D. C, speaks favor-
ably of the action of turpentine when vaporized and inhaled. Its sup-
posed efficacy is attributed to the fact that it is antiseptic and germi-
cidal in its action. J. Lewis Smith says he has employed the vapor of
turpentine with apparently good results. The mixture he recommends
for vaporization is as follows :
P;— Acidi carbolici,
Ol. eucalypti ad S j.
Spts. terebinth S viij. — M.
Two tablespoonfuls of this mixture are added to one quart of water,
which is placed in a shallow vessel with a broad surface, and maintained
in a constant ebullition or simmering upon a gas or other stove. He
thinks that the vapor thus generated, "in passing over the inflamed
surfaces, which are the seat of the exudate, with every inspiration,
probably produces more or less local disinfection, apart from the
systemic disinfection which it may cause by entering the blood and
77//'; TUJ'JATMl'JNT Ol'' l>l I'llTII KKI A 705
the tissues generally." We feel that, such ;i result is scarcely to be
expected from turj)entine. As to its alleged cHicacy in dij)hth(Tia, how-
ever, we are unable to speak from any personal experience.
Sodium Benzoate. Sodium benzoate, for internal as well as local use,
has been highly reconunciuJed by a nnnd)cr of writ,(*rs. Dr. I. N. Ix>ve
regarded it as efficacious in from five to fifteen grain doses. Some;
observers claim to have shown that it arrests the growth of micro-
organisms. According to J. Lewis Smith, II(;lferich, Graham Brown,
and Sanne beli(>ve that it is a specific against the virtis of diphtheria.
Smith says: "On the other hand, M. Dumas, surgeon to the Hopital
de Cette, has not derived any marked benefit from its use, and Prof.
A. Jacobi says that it does not deserve the eulogies bestowed upon it
from theoretical reasonings."
Such drugs as pilocarpine, copaiba, cubebs, resorcin, hyposulphite of
sodium, and many others, have been recommended from tim(! to time,
but none of them deserves any prominent place among the therapeutic
agents useful in the treatment of diphtheria. Of the internal remedies
to which prominence has been given we would consider most useful
the tincture of the chloride of iron and bichloride of mercury. To
these we would add strychnine, digitalis, and alcohol. But as diphtheria
is a disease of variable type, we must treat each case according to the
indications.
Strychnine.— Strychnine is useful to combat cardiac depression. It
may be given combined with tincture of the chloride of iron, or it may
be administered separately. It is often advisable to inject it hypo-
dermically. The dose should be adapted to the age of the child, but
the amount which children of tender years will bear without harm is
astonishing, especially when in a condition of toxaemia. A child of
three years will take y^-g- of a grain every four to eight hours; in an
emergency a larger dose will be borne.
Digitalis. — Digitalis is also of advantage when the heart action is
weak. In case of irritability of the stomach, which always occurs in
profound toxiemia, digitalin may be administered hypodermically.
Strophanthus, sparteine, caffeine, and the like, are also recommended
to combat cardiac failure. To a child of five years two drops and some-
times as much as four drops of the tincture of digitalis may be given
every four hours, or from one to six drops of the tincture of strophanthus.
In a great emergency one or two unusually large doses of these drugs
may be administered, followed by the more ordinary dose at proper
intervals.
Citrate of caffeine may be used in doses from \ grain to 5 grains.
Jacobi says: "For subcutaneous injections the salicylate (or benzoate)
of caffeine and sodium, which readily dissolves in 2 parts of water,
is valuable for emergencies, in occasional doses of from gr. 1 to 5
(6 to 30 cgm.), in from 2 to 10 minims of water."
Alcohol. — There are but few other diseases which demand more
imperatively the use of alcohol than does diphtheria. Mild cases will
frequently do well without stimulants; but no case, however mild it may
45
706 DIPHTHERIA
seem to be, should be considered out of danger until recovery has taken
place. In view of the well-known depressing effects of the poison of
this disease, even mild cases should receive small doses of some stimulant.
Severe cases require a very liberal amount of alcohol in some form;
it should be commenced early in the disease by giving small doses at
first, and increasing the amount as the indications for its use become
more pronounced. Whenever the heart action shows any loss of force,
or the first sound of the heart becomes less distinct, or pallor is noticed,
or the patient's strength is declining, large and frequent doses of some
active stimulant are required. It matters little how the stimulant is
administered, whether plain or in the form of milk punch or wine
whey, provided that sufficient is given to produce the desired effect.
Whiskey is more often employed, for the reason, doubtless, that good
whiskey can be more easily obtained than good brandy. If whiskey
disagrees with a patient brandy should be tried. Either of these
stimulants may be administered in teaspoonful doses properly diluted,
to a child of five years. In septic cases the amount of alcohol which
a child may take without showing evidence of intoxication is nothing
less than astonishing. In this type of diphtheria it is not unusual for
a child of five years to take one teaspoonful or even two teaspoonfuls
of whiskey every hour, making the daily amount ingested from three
to six ounces. While alcohol is ordinarily contraindicated in albuminuria
or nephritis, yet rather than lose the support of so important an ally
in combating toxsemia, it should, nevertheless, be cautiously em-
ployed.
If the toxaemia be well marked, alcohol in doses however large will not
save the life of the patient, but it may prolong it somewhat. When
the heart's action begins to wane, it is difficult to restore it. W^e cannot
recollect of ever having seen a patient recover when the pulse was
once lost at the wrist. Hence, the great importance of beginning the
use of alcohol early. If the stomach will not tolerate either whiskey
or brandy a good wine should be substituted. We have found cham-
pagne useful when the stomach is irritable. Aromatic spirit < f ammonia
is a good stimulant, and may be used temporarily, if it be found more
agreeable to the stmoch.
Attention should be given to the diet of a diphtheria patient throughout
the entire illness. In the acute stage of the disease all food should be
of a fluid character, consisting of milk, beef-tea, broths, and the like.
It may be necessary to peptonize these, though, as a rule, the digestion
is not bad. Ice and iced drinks may be allowed. Should there be a
craving after cold articles, cold junket, frozen custards, and frozen
beef-tea may be given. Soft-boiled eggs are useful when the patient
is able to take them. Later, corn-starch, rice pudding, bread and
butter, fruit and vegetables may be added. As early as possible a full,
liberal diet should be allowed.
In regard to the complications of diphtheria, we feel that but little
time need be spent here in discussing their treatment. Adenitis, otitis
media, bronchopneumonia, and nephritis are the more common com-
77//'; TREATMENT ()/<' 1)1 1'llTII IIIU A 707
plications ericoiintcnHl, and they j)rcs(;nt no incjicatioiis for treatment
at all (liiTerent tlian wlicui these; all'ections oeeiir from other causes.
The paralysis of diphtlieria, however, dillers from the; other compli-
cations, in that it is [jcculiar to the disease. It cannot be prevented;
and drugs avail but little in hastening the cure, ""d'he most dang<;rous
form is cardiax; j)aralysis. It is well to anticipate this cf>nflition by
keeping the patient (juiet, and endeavoring to sustain th(; strength of
the heart by administering digitalis, strychnine, alcohol, and other
cardiac tonics. As we have already seen, cardiac paralysis often develops
suddenly, and the patient may die before the })hysician can be summoned.
The earliest symptoms of this affection should receive prompt attention.
The patient should remain as (juiet as possible in lied, with his head
low. It is sometimes advisable to raise the foot of the bed slightly.
He should remain in the recumbent position when taking food, water,
or medicine. Under no circumstances should he be allowed to leave
the bed to empty his bladder or rectum. Whiskey or brandy should
be given in doses sufficiently large to be of service. If the stomach be
at all irritable, champagne is to be preferred. In case of a sudden
seizure of heart-failure, hypodermic injections of brandy should be
administered. The hypodermic use of strychnine will also aid in
sustaining the heart action. Ammonia, camphor, musk, and the like
sometimes serve as useful auxiliaries. At the same time the general
strength of the patient should be well sustained with a liberal amount
of nourishing and easily digestible food, such as peptonized milk,
beef-tea, broths, or some of the concentrated foods designed for invalids
with feeble digestion. For large children and adults soft-boiled eggs
are useful, unless the digestion be very feeble. When improvement
takes place the physician should see that the patient does not get out
of bed too soon.
For the multiple paralysis which follows diphtheria the patient
requires sustaining remedies, such as iron, quinine, strychnine, and
alcoholic stimulants. Particular attention should be given to the diet,
as there is ordinarily marked debility and anaemia, with a feeble digestion.
Beyond the employment of a sustaining treatment we do not believe
that much can be done to hasten the cure of diphtheritic paralysis.
Some physicians believe that they have derived benefit from electricity,
but a large number speak doubtfully of its efficacy.
As strychnine is known to be efficacious in many other forms of
paralysis, it is frequently employed on general principles for the neuroses
of diphtheria. Some observers have reported good results from its
use, while others question its utility, except as a tonic. Prof. Henoch,
Reinard, and Gerasimow claim to have hastened the cure of diphtheritic
paralysis by hypodermic injections of strychnine. This drug is said
to have been employed in one case (a boy, aged three and one-half years)
with marked improvement in the tonicity of the muscles within twenty-
four hours after the first dose, wdiich consisted of about -^ oi & grain,
and this was repeated each day for fifteen days, when the patient was
considered cured. In. another case (a child, aged six years) a complete
708 DIPHTHERIA
cure is reported from hypodermics of about -^-^ of a grain daily for
seven days, followed by ^V of a grain each day for twelve days longer.
We are not convinced that strychnine possesses any special value
as a remedy in diphtheritic paralysis. It is our opinion that tonics
and a sustaining diet will do more toward helping a patient through
an attack than anything else. The paralysis is seldom permanent.
We have never known it to be so. In most cases complete recovery
takes place in from two to four months.
There is, however, one thing connected with the treatment of multiple
paralysis of diphtheria which is of great importance. We refer to the
care a patient should receive when unable to swallow. In all severe
cases deglutition is difficult and sometimes impossible. It is necessary
then to sustain the strength of the patient by nutritive enemata, or by
introducing food into the stomach by means of an oesophageal tube.
The latter is preferable, as it gives us a better idea of the amount of
nourishment that is utilized. The patient should be fed every four
hours, and with each feeding there should be administered also such
medicine, stimulants, and the like, as may be required. It is not often
that a patient has to be fed with the oesophageal tube for a longer time
than two weeks. We recall one case of paralysis in which this means
of feeding was employed for sixteen days. By holding the jaws slightly
apart with the gag of the intubation set, it is not difficult to introduce
the tube through the mouth into the stomach. The tube will slip
down more easily if slightly oiled. If a patient be safely carried over
the period of difficult or impossible deglutition, his chances of complete
recovery may be considered very good.
Treatment of Laryngeal Diphtheria (Membranous Croup).
It is deemed most convenient to consider the treatment of laryngeal
diphtheria under three heads:
1. Prevention.
2. The means of promoting the separation and expulsion of the
pseudomembrane.
3. The adoption of such operative measures as will overcome the
mechanical obstruction to respiration.
Prevention. — ^There is no certain way of preventing laryngeal diph-
theria, unless it be to guard the child against exposure to the infection
of the disease. But when diphtheria begins in the fauces something
may be done in the way of diminishing the liability of the membrane
extending into the larynx. We have seen that a mucous membrane
which is inflamed or congested is thereby predisposed to the diphtheritic
process. It is advisable, therefore, to guard the patient, as far as
possible, against the development of a catarrhal affection of the larynx.
As soon as faucial diphtheria is recognized, the physician should see
that the child is placed in a room of equable temperature and free from
draughts. If the case occur in the winter season, and the atmosphere
of the room is warmed by dry heat, it would be well to moisten the air
TIIK rilF.ATMKNT Ol'' 1)1 1'lll'll HIU A 70f)
by the addition of a little steam. It has been suggested that the steaui
be impregnated with eiicaly|)tol or some other fragrant essential oil,
but we do not tliink tliat this is of any great importanee. (^are should
be taken not to overcharge tiie air of the room with irioisture,, as this
would be more harmful than benefieial. in the sununer months fresh
air should be freely admitted, with precautions against draughts, and
steam may, be dispensed with.
Drugs are of no avail in preventing laryngeal involvement. Anti-
toxin may be of great service as a preventive measure, but we have
seen the pseudomembrane in the fauces extend into the larynx on a
number of occasions even after the administration of antitoxin.
Means of Promoting Separation and Expulsion of the Pseudo-
membrane. — When false membrane has formed in the larynx, constitut-
ing membranous croup, nature's method of effecting a cure consists
in the gradual disintegration of the membrane, or its separation and
expulsion. How this process may be best promoted has always been a
problem difficult of solution. Emetics have been freely employed,
and of these turpeth mineral was for a long time believed to be espe-
cially useful. But they can be of no service unless the membrane be
in good part detached. The persistent use of emetics is objectionable
on account of their depressing effect. When, however, a flapping
sound is heard in the larynx, indicating the presence of partly detached
membrane, an emetic should not be withheld except in cases of profound
asthenia. The one selected should be of that class which excites
prompt and efficient vomiting without producing prolonged nausea
and depression. Among those to be preferred we would mention ipe-
cacuanha, powdered alum, and sulphate of zinc.
Warm Steam. — For the purpose of hastening the separation of the
false membrane in croup there is a general consensus of opinion in
favor of the continuous inhalation of warm steam. This is frequently
impregnated with an alkali, like lime, or with some mild antiseptic
agent, like eucalyptol, the compound tincture of benzoin, or turpentine.
But it is the steam upon which the chief reliance is placed. Oertel
believes that the energetic use of hot vapor causes a rapid and abundant
suppuration of the diseased tissue, until finally the pseudomem])ranous
layer becomes completely detached from the rapidly regenerating
tissue of the mucous membrane, and is expelled either piecemeal or
in its entirety. He regards this as nature's process of resolution in
favorable cases.
The inhalation of warm steam is undoubtedly at times of much
benefit, but we are inclined to believe that this treatment is often carried
to excess. When shut up in a tightly closed tent in which a basin of
water is kept constantly boiling, the child receives not only a diminished
supply of oxygen, when the blood is already suffering from an oxygen
dearth, but his skin is kept bathed in moisture, and his clothing and
bedding are constantly damp. The effect of such treatment is certainly
depressing. Warm steam inhalation should therefore be employed with
some care. Lennox Browne savs that the bed should be curtained
710 DIPHTHERIA
and the hot vapor "brought near it by means of a steam-kettle, but
the croup-tent bed, which gives the httle patient a continuous vapor
bath, is as unnecessary as it is depressing."
Slaking Lime. — Inhalation of the warm vapor which arises from
slaldng lime in water has been highly recommended as a remedy in
membranous croup. The vapor thus generated, being strongly alkaline,
is believed by some to act as a solvent of the membrane. Oertel found
that when a piece of pseudomembrane weighing three grains was placed
in lime-water it swelled up in fifteen or twenty minutes into a loose,
flaky mass, which could easily be divided, and after from thirty to
forty minutes was completely dissolved. The assumption that lime-
water acts in the same way when inhaled in the forai of vapor as it does
in the test-tube is not, we think, borne out by experience. At any rate
this treatment is not so frequently employed now as formerly.
Calomel Sublimation. — ^The inhalation of sublimated calomel has
been extensively used for the last twenty years or more with some
degree of success. It is said to act not as a germicide, but by hastening
the separation of the pseudomembrane, through, possibly, an influence
exerted both locally and constitutionally. We have employed it fre-
quently, but with only indifferent results. The number of cases which
were materially benefited was small. The method of using it is very
simple. Place the child in an improvised tent, not so large but that
it may be fairly well filled with the fumes. The calomel may be sub-
limated by placing it on a small fire-shovel containing a few hot coals;
or it may be placed on a red-hot shovel, or on a piece of sheet iron
or tin, or in an iron spoon, either of which can be heated by means of
an alcohol lamp or a Bunsen burner. Eight or ten grains should be
sublimated every hour, or at longer intervals.
The Internal Use of Mercury. — The internal or constitutional
treatment of membranous croup is to be carried out on the same lines
as in the other varieties of diphtheria. Mercury in some form has
long been employed, and most physicians believe that it gives better
results than any other internal remedy that has been recommended.
Calomel is much used in small and frequent doses, to the extent of
causing slight ptyalism. Many practitioners confidently expect improve-
ment as soon as this effect is produced. Dr. T. Clarke Miller,^ of
Massillon, Ohio, expresses great confidence in mercuric chloride in
the treatment of all forms of diphtheria. He gives y ^^ grain of calomel
every hour for twelve to twenty-four hours, and then continues the
same dose every two hours. He says: "If I find that the exudate has
originated in or extended to the larynx, I use antitoxin at once. If
the nose is involved seriously, it is well to use antitoxin, though not
to the exclusion of the calomel. I would omit the antitoxin rather
than the calomel." The bichloride, cyanide, and iodide of mercury
have also been highly recommended by some writers.
1 The Diagnosis and Treatment of Diphtheria, read at the Toledo Meeting of the Ohio State ^
Pediatric Society.
THE THEjVTMENT OF Dl I'llTII l<:iiIA 711
It is a pleasure to quote so often an author whose articles on rJiph-
theria are everywhcTe regarded as classic. We refer to Prof. Jacobi,
who says: "For nearly twenty years I have employed the bichloride
in doses of 1 ingin. (gr. ,.,,) or more once every hour. The smallest
babies take one-fourth or one-third of a grain daily for days in succession.
Almost never will a stomatitis follow, and no gastric or intestinal irrita-
tion, provided the dilution be in the proj)ortion of at least 1:8000.
An occasional slight diarrlux'a jnay re((uire the addition of a few drops
of camphorated tincture of opium. 1 can repeat a fonner statement,
that never before the antitoxin period have I seen cases of croup getting
well in such numbers, either without or with tracheotomy or intubation,
as when under mercurial treatment." We have already expressed
much confidence in the mercurial treatment of diphtheria, including,
of course, membranous croup.
Operative Measures. — If it be found that the laryngeal symptoms
do not improve under the treatment recommended, but, on the contrary,
become more and more marked, or if the patient be not seen until
the symptoms of mechanical obstruction have become alarming, recourse
must be had at once to operative measures. The operation which is
necessary to overcome the difficulty is either tracheotomy or intubation.
Formerly tracheotomy was universally employed, but of late years
it has been almost entirely superseded, in this country particularly, by
intubation.
Intubation.^ — This procedure is viewed more favorably, mainly
because it does not require the use of the surgeon's knife. We all know
how reluctantly parents give their consent to the operation of trache-
otomy on their child. When this operation was the only means of
overcoming the obstruction to the entrance of air through the larynx,
it was too often postponed until the child was almost moribund, and,
consequently, the results were discouraging. Intubation being a blood-
less operation, and not requiring an anaesthetic, parents do not hesitate
to give their consent to this procedure, and hence the lives of many
children who suffer from membranous croup are now saved that would
otherwise be lost. It is a matter of great importance that operative
interference, whether intubation or tracheotomy, be not delayed too
long. It is almost criminal to allow a child to die from suffocation
without making an effort to save its life by resorting to one or the other
of these mechanical measures. W^hile intubation is to be preferred
in most cases, it cannot always take the place of tracheotomj/. A
physician without experience in intubation would be likely to fail in
the operation, and if no one possessing the necessary skill is available,
he would be obliged to resort to tracheotomy. Or the latter operation
may be preferred, or even become necessary, when the membrane
extends far down into the trachea. In such cases the intubation tube
will not afford relief. Tracheotomy may also become necessary when
the intubation tube is repeatedly coughed up.
The procedure for relieving the stenosis of membranous croup by
placing a tube in the larynx with its upper end below the epiglottis
712 DIPHTHERIA
was first adopted by Bouchut in 1858. But, as his devices were crude,
and as the operation was deemed impracticable by his confreres, and
even ridiculed by them, he was discouraged from pursuing farther his
conception of intubation. It remained for Dr. Joseph O'Dwyer, of New
York, to devise and perfect the instruments necessary for the operation,
and to demonstrate beyond question the utility of the procedure.
O'Dwyer's work of devising the intubation tubes was begun in 1880,
without, it is said, any knowledge of the previous experiments of
Bouchut. It required, however, some four or five years of diligent
experimentation before the set of intubation instruments, herein
described, was evolved into its present state of perfection. The New
York Academy of Medicine has in its possession a complete collection of
all the instruments used by O'Dwyer in his long series of experiments.
The collection is interesting as showing the various changes in the
size, shape, and construction of the intubation tube in its evolutionary
process.
Intubation Instruments. — In their completed state the O'Dwyer
intubation instruments consist of a series of seven tubes, a scale for
measuring the size of the tubes, an obturator, an introducer, a mouth gag,
and an extractor. The tubes vary in size, both as to their calibre and
length, so as to fit the larynx of a child at any age. Tubes are also
made suitable for adults, though they do not form a part of the regular
outfit. The head of the tube is irregularly oval, with its anterior surface
flush with the tube itself, so as not to interfere with the epiglottis, while
posteriorly it projects backward so as to rest, when in situ, upon the
rima glottidis. A tube that is too small for a patient may slip down
into the trachea. In the left side of the head of the tube there is a
small hole into which a string may be inserted. The object of this
string is that the tube may be withdrawn in case it is introduced into
the oesophagus instead of the larynx. The circumference of the tube
is somewhat larger in its centre. The anterior and posterior surfaces
of the tube are straight, while a central bulging is seen on either side.
This is called the "retaining swell,'^' as it helps to keep the tube in
place, and to a great extent prevents its expulsion by the act of coughing.
The lower end of the tube is rounded off and blunt, and its lumen
throughout is elliptic (Fig. 99).
The tubes were originally made of white metal plated with gold;
but later the inventor had them constructed of hard rubber overlying
metal. This is considered an improvement, as the tube is much lighter,
and more easily coughed out when the lumen becomes occluded with
fragments of the false membrane. It is believed, too, that it is less
liable to injure the larynx when worn for a long time. Certainly, it is
less irritating from the fact that lime deposits do not form on it, as on
the metal tube. The latter, when worn for a few days, is quite sure to
become rough from these deposits. All intubation sets made at the
present time contain only hard-rubber tubes.
Each tube is provided with an obturator which is fitted to the intro-
ducer. The obturator extends throughout the lumen of the tube,
Till': Tli'l'JATMI'JA'T OF I )l I'll'I'llilUI A
71i
projectinfT .sH^^Iitly from the Iowcm- cihI, wIkwc it is rouiHleation of the
tube may also be recognized by the fact that the string grows shorter
as the tube descends into tlie o'sophagus. It should Ix- pulh-fJ oni at
once.
'^rhe tube being properly placed, it is well to remove the mouth gag
and allow the child to cough and expectorate for a minute or two, anrl
at the same time to be sure that there is no obstruction in tlic tube
Everything being satisfactory the gag should be reintroduced, the
string cut and withdrawn, while the; tip of the index finger rests on
the head of the tube to prevent its displacement. 'J"'he child should then
be released and put to bed.
If the child is very young, having no molar teeth, and the operatfjr
distrusts his ability to remove the tube with the extractor, the string,
instead of being cut and withdrawn, may })e looped over the ear of
the child and secured to the cheek with a strip of adhesive plaster. In
this case the hands of the child must be muffled, else the offending
string will be caught with the fingers and the tube pulled out. In
children with teeth this procedure is not to be recommended, as the
string is soon chewed off and rendered useless. Experienced operators,
however, prefer to remove the string in all cases.
There are still some other points in connection with the operation
that the beginner should know. In the first step of the operation the
operator's hand containing the introducer should be close to the chest
of the patient. The tube should be pushed backward on the median
line of the tongue until it reaches the chink of the glottis, then the
handle of the instrument must be raised, and the tube should slip
down into the larynx without much force being used. The tube, during
its introduction, sometimes causes a slight spasm of the parts, in which
case the operator should pause for a few moments, when the spasm
will probably relax and the tube slip into place. It should be remem-
bered that the epiglottis must be kept out of the way; if not the operation
will surely fail. It is important, too, that the child should be under
perfect control in the arms of the nurse, and that it should squarely
face the operator. The position of the child's head and neck should
be, as Northrup says, as if the child were suspended from the top of
its head.
In case the first attempt at placing the tube is unsuccessful, rather
than exhaust the patient with repeated trials at one sitting it is better
to remove the gag and allow the child a few seconds to rest, or to cough
and expectorate. A beginner rarely succeeds the first time; it is far
better that he should make several short attempts than a prolonged
one.
A vigorous cough following the introduction of the tube is favorable
rather than otherwise, as it shows that the parts have not lost their
sensitiveness, and it clears the mucus from the trachea. If there is
no cough, and the breathing ceases and the cyanosis deepens, there is
surely an obstruction at the lower end of the tube; in which case it
718
DIPHTHERIA
should be removed immediately. If the same result follows a repetition
of the operation, tracheotomy should be performed.
Some operators prefer to have the child in the recumbent position
during the act of intubation. The advantages claimed for this position
are that the operation can be performed with but a single assistant,
and that there is less danger of heart-failure if the patient be greatly
prostrated. The child should be rolled up in a sheet or thin blanket,
as already described, and placed squarely on its back. (See Fig. 102.)
In other respects the operator should proceed as before. At the present
time the resident physicians in the Municipal Hospital employ this
method altogether. It is also employed in the Willard Parker Hos-
FlG. 102
Showing the lirst steps of intubation in the dorsal position.
Dr. B. Franklin Royer.)
(Photograplied by
pital, New York, and is recommended by Casselberry, of Chicago, and
Carstens, of Leipzig.
Dangers and Difficulties of Intubation. — The operation cannot be
said to be dangerous when performed by an experienced operator.
It is true, instances have occurred in which exudate has been pushed
down into the trachea by the tube, causing suffocation and instant
death. This condition, however, is easily recognized at once, and the
prompt removal of the tube is usually followed by forcible expulsion
of the detached mass of false membrane. When this occurs the dyspnoea
may be so greatly relieved that reintubation is not necessary. But fre-
quently the membrane reforms and the operation is again called for.
77//'; TIU much
delay the sensitiveness of the parts soon becomes so blunted that cough,
Fk;. 103
Fixation of the larynx. (Lejars. )
Fig. 104
The tube guided by the index linger. (Lejars.)
on which the safety of the patient depends, is not excited, and death
speedily results from suffocation.
The inexperienced and clumsy operator may incur other dangers, such
as asphyxia from prolonged attempts at intubation, lacerating the
720
DIPHTHERIA
tissues, or forcing the tube into a false passage. All of these accidents
can be avoided with care.
There are but few serious difficulties liable to be encountered by
the experienced operator. It has been said that the tube may be
Fig. 105
The tube penetrates the larynx. (Lejars.)
Fig. 106.
The tube in its proper position . CLejars.)
obstructed m its course by entering one of the ventricles of the larynx.
This, we are sure, hardly ever happens Avith the O'Dwyer tubes which
are so nicely rounded at their ends. Besides the pushing down of
membrane before the tube, or the occurrence of a slight spasm of the
TIIF. TltKATMNNT OF 1)1 1'llTII I'llil A
721
muscles of the larynx, as dcscrihcd alxjvc, in inlrofliir-Irif^ tlif tnljc the
operator will soinetinics meet with (h"(licnlty caused hy swelHn^', inflam-
matory thickening, or anlema of the subglottic tissues. \Vh(;ri it is
found that the tube adapted to the age of the child will n(jt enter readily,
it is advisable to try a smaller one. After this has been worn for a
short time there is usually no difficulty in introducing (me of tiie j)roper
size. The narrowest part of the lumen of the larynx is in the region
of the cricoid cartilage. We have seen a few instances in girls in which
the cricoid ring was abnormally small, a fact which we have been able
to demonstrate post-mortem,. When this condition exists only a little
sweUing or a^dema of the lining membrane is needed to ninkc the intro-
Withdrawal of the thread. (Lejars.)
duction of the tube difficult. The only thing to do in such cases is to
use a smaller tube.
Treatment and Feeding After Intubation. — It is advisal^le not to
make any local applications to the throat while the tube is in the lar^iix;
at least, irrigation or spraying should not be practised. The applications
to the nose, if required, need not be omitted. Internal treatmeat,
stimulants, and the like, may be continued as before.
The feeding of the child is the thing that frequently gives us the most
concern. Some children swallow with but little difficulty after intuba-
tion, while it is really distressing to see others drinking liquids of any
kind. The act of swallowing excites coughing, and this may be still
further excited by some of the liquid running down the tube into the
^ 46
722
DIPHTHERIA
trachea. The cough is often violent, causing a large part of the liquid
in each act of swallowing to be forcibly expelled, not only through the
mouth but through the nose also. Children, however, usually persevere
in drinking, and after a little while they frequently get along better.
Semisolid food is not so liable to cause coughing, and is, therefore,
preferable. When a child is old enough, we prefer to have it fed on
bread soaked in milk. This forms a bolus which can be swallowed,
as a rule, without exciting much cough.
Fig. 108
Casselberry's position for feeding intubated cases. (After Nortlirup.)
It is claimed that the difficulty of swallowing, even of liquids, may
be overcome by placing the child on its back with the body and legs
elevated, while the head hangs over backward at an angle of forty-five
degrees or greater. It is thought that any liquid that may get into the
tube will, with the child in this position, run out again rather than into
the trachea. The placing of the child in this position during feeding was
first recommended by Casselberry, of Chicago. He and many other
physicians who have tried this method speak of it very favorably. In
our experience it has not proved so satisfactory. In bottle-fed babies
77//'; TRMATMIiNT Oh'lDII'UTII l-:i{IA 723
it sometimes answers fairly well. It should ])C stated that soirie [jhysieians
believe that the child swallows b('tt<'r lyin^ on the; abdomen with the
head hanging forward.
If it be found that the child is not getting sufficient nourishm(;nt by
either of the methods mentioned, gavagi; should be resorted to. This
may be done by introducing either a small o'sophageal tube or a flexible
catheter through the nose into the stomach. If this route is found
inconvenient or dilficult, the child's jaws may be slightly separated
and the tube introduced through the mouth. If one catheter should
not be long enough another may be joined to it by means of a short
glass tube. Some prefer rectal feeding, but v^'e have never found it.
satisfactory.
Removal of the Tube, or Extubation. — The time for remo^'ing the
tube will depend very much on the age of the child and the stage of the
disease. In older cliildren the tube may be removed earlier than in
those who are younger. Likewise, when the tube is not required until
a late stage of diphtheria, it may l)e removed sooner than when intro-
duced at an early stage of the disease. We have seen it stated some-
where that O'Dwyer recommended that the average time of wearing
the tube should be seven days; and if the patient's residence is a long
distance from the physician's office the time had better be eight days.
It has been our rule to allow the tube to remain in place six days before
removing it. Frequently, however, the resident physicians remove it
earlier, but they often find it necessary to reintroduce it. Northrup
thinks that five days for a child over two years is long enough for the
tube to be worn in the average case. He says: "At the Willard Parker
Hospital the time allowed is four days; at the New York Foundling
Hospital, three days." He, with many other writers, believes that the
length of time which the tube is required in membranous croup has
been materially reduced by the use of antitoxin; also, that reintubation
is now less often required.
Cases are not infrequently seen in which the tube, after having been
worn for only a short time, is coughed up and expelled, together with a
mass of membrane. Such cases sometimes recover without reintubation
being required. There are other cases in which the tube is not retained
longer than it is needed; that is to say, in the course of four or five days,
when the membrane in the larynx has disappeared and the oedema sub-
sided, autoextubation takes place through the agency of the cough. This
result is always gratifying, and especially so to the inexperienced operator.
Whenever the tube becomes obstructed it must, of course, be instantly
removed. Fortunately, in most cases it is coughed up. Wlien coughed
up, the tube is either expelled or the child removes it from the mouth
with his fingers. In rare instances it is swallowed. Should this occur,
no great uneasiness need be felt, as we have never known a tube that
was swallowed fail to pass through the intestines.
The Technique of Extubation. — Up to a certain point the technique
of the operation of extubation is exactly the same as that of intubation.
After being rolled up in a blanket or sheet, as before, the child should
724 DIPHTHERIA
be held in the upright position on the lap of the nurse, or placed in the
dorsal position, according to the choice of the operator. It is equally
important that the child's head should be held steady, and that the
axis of the head, neck, and trunk should correspond. The mouth gag
being in position, the operator passes his index finger of the left hand
backward over the dorsum of the tongue until he feels the tube and
determines its position. He should then tilt the epiglottis forward and
control it. Holding the extractor in his right hand, with the handle
of the instrument near the chest of the child, he should pass it backward
along the side of the finger until the tube is reached; the handle of the
extractor should then be raised to a horizontal position, and, with the
aid of the tip of the finger which is controlling the epiglottis, he inserts
the beak of the instrument into the opening of the tube. Having suc-
ceeded in doing this, he presses down the lever at the upper part of
the extractor with his thumb, which causes the two parts of the beak
of the instrument to separate, and thus the tube is caught and held,
very much as a glove stretcher holds the finger of a glove. The operation
is completed by lifting the extractor with the tube until it impinges on
the hard palate, then depressing the handle and withdrawing the
instrument and tube from the mouth. If the tube should slip off, as it
often does, after having been lifted from the larynx, its removal can
easily be concluded by means of the finger.
It is important to properly regulate the distance of separation of
the two parts of the beak of the extractor. This may be done by
means of the screw in the handle. If the jaws of the instrument are
allowed to open too widely the orifice of the larynx may be lacerated
by a clumsy operator. Tlie extractor should be held in the hand lightly,
as no great force is required to remove the tube. Be careful not to
place the thumb on the lever until the beak of the instrument is well
within the opening of the tube.
If the operator should have difficulty in grasping the tube, it is better
to make repeated short attempts, allowing the child to rest for a minute
or two in the intervals, than to make a single prolonged effort. As
extubation is more difficult than intubation, beginners often become
nonplussed in their efforts to extract the tube. In such a dilemma,
enucleation, or removal by pressure, is recommended. Park^ says:
" It is possible in an emergency, in the majority of cases, to easily expel
the tube by placing the child face downward with the body slightly
elevated, and pressing gently against the trachea along its anterior
surface, just below the end of the intubation tube." One of the writers
tried this expedient a few years ago, but did not succeed. It was feared
that the amount of pressure required to accomplish the purpose might
injure the larynx.
After the tube has been removed the patient should be placed in bed
and carefully watched for a while to see that the respirations continue
easy. In family practice the physician should not leave the house for
1 Loomis-Thompson, American System of Practical Medicine.
r///'; trmatmi<:nt of dii'IitiiI'Uua 725
at least thirty minutes. Tf tlu'rc is any Hifliculty in })r('afliinf( lio sliouM
remain until lie feels reasonably sure that tin; jjaticnt is going to get
along without the tube. Reintubation is often necessary. When dyspncjea
returns after extubation the condition of the patient not infrequently
becomes critical so (juickly that if })rompt aid be not afforded fleatli
from suffocation will siu'ely result. It is, therefore, highly im[>fjrfant
that the physician should be within easy call ff)r some hours. Having
seen not a few children perish at this stage of the disease when their
lives might have been saved by prompt aid, we feel that the importance
of the advice just given cannot be emphasized too strongly. To lose
a child (hu-ing the height of an attack of membranous frr)up is bad
enough, but to see it die after the danger has apparently passed, and when
the brightest hopes are entertained for its recovery, is much worse.
Such a result may not inaptly be compared to the sinking of a ship in
the harbor after it has weathered the storms of the ocean.
For lessening the nervous excitability of the patient, as well as for
its relaxing effect, a little morphine may be given just before removing
the tube. Park says that at the Willard Parker Hospital, "immediately
after the extraction of the tube, the child is given -^^ grain of morphine
hypodermically, and an ice-bag is applied to the larynx. It is sought
in this way to lessen the irritation and swelling of the larynx. The
child is still kept in a recumbent position for one or two days." Perfect
quietness at this time is of great importance. A few hours of quiet
sleep after extubation is quite desirable, as it will sometimes tide a
patient over the period at which the indications for reintubation are
most likely to develop.
Prolonged Intubation. — Despite the free use of antitoxin, and the
greatest possible care in the operation of intubation and extubation,
it frequently happens that the tube must be w^orn for a much longer
period than five or six days. In other words, when the tube is removed
at the time just indicated, the dyspnoea returns, making reintubation
necessary; and this sometimes happens over and over again in the
same patient through a long series of intubations and extubations.
We know of nothing connected with the work of intubation that is
more perplexing to the operator, or more distressing to the patient,
than this unfortunate occurrence. Some of these cases require months
and in rare instances years of intubating until recovery takes place.
Indeed, a large proportion of the most obstinate cases perish from one
cause or another before the difficulty is overcome.
Prolonged intubation is not always due to the same cause; it may
result from one of several causes, such as persistence of the false mem-
brane in the larynx, oedema of the tissues, subglottic lar}Tigitis with
thickening of the soft parts, ulcerations, exuberant granulations, cica-
tricial contractions, destruction of the cartilages and collapse of the
larynx, atony of certain muscles, or abductor paralysis. But it must be
admitted that it is often difficult to differentiate between these various
pathological conditions of the larjTix, or to explain satisfactorily the
exact cause of the difficulty.
726
DIPHTHERIA
Fig. 109
Some writers believe that the conditions rendering the prolonged
use of the tube necessary are rare, or even extremely infrequent. We
have met with very many cases in which it was necessary to continue
the use of the tube longer than the usual period of five or six
days without development of the pathological changes which lead to
chronic stenosis. Such cases are able to get along without the tube
in the course of two weeks, or three, at the longest.
But postdiphtheritic stenosis occurs, according to
our experience, in from 1 to 3 per cent, of all
cases of intubation. Dillon Brown is reported
as saying that he has encountered it in the pro-
portion of about once in 75 or 100 cases.
In discussing the causes of prolonged intuba-
tion but little consideration need be given to
traumatism resulting from the introduction or
removal of the tube. While it is true that the
unskilful use of the introducer or extractor, or
too much pulling upon the epiglottis during the
operation, may cause abrasions and oedema of
the soft parts, and thus make reintubation neces-
sary, yet it is certain that the principal cause of
"retained tubes" is not due to such an injury, but
to traumatism in the larynx occasioned by the tube
itself. It is important that the tube should prop-
erly fit the larynx; it certainly should not be too
large. But no matter how well it fits, it some-
times causes ulceration. It should, therefore, be
dispensed with as soon as possible. It, however, should not be removed
until there is reason to believe the patient can get along without it; for
removing it too early would necessitate its reintroduction, and thus the
risk of traumatism would be increased.
When the tube is required longer than the usual length of time on
account of the persistence of false membrane in the larynx, the con-
dition, from our present point of view, is not serious, for as soon as
the membrane disappears the tube can be dispensed with.
We believe that the most common cause for retention of the tube,
at least primarily, is subglottic laryngitis with oedema. Later, as the
tube is worn longer, and has been removed and reintroduced many
times, tissue changes of a destructive character sometimes take place
in the larynx, with a marked tendency to terminate in chronic stenosis.
We have removed, post-mortem, larynges which showed considerable
loss of tissue from ulcerative action. These ulcers heal by granulation
and the formation of cicatricial tissue, and hence permanent stenosis
to a greater or less degree is liable to result in such cases.
Many of the cases with subglottic laryngitis and oedema improve
after two or three intubations, and recovery follows without any un-
toward symptoms. Other cases are more troublesome, especially those
which develop also atony of the muscles or abductor paralysis. With
Pressure ulcer due to intu-
bation. (Baginsky.)
PLATE LIX.
Larynx and Trachea Renioved at Autopsy.
Sho'v\nng a large roundisli ulcer caused by pressure of the intubation tube.
The lower linear -wound -was the result of a tracheotomy. From a patient in
the Municipal Hospital. (Photographed by Dr. E. N". Fought.)
77//'; r/U'JATMJ'JNT OF 1)1 1'lmi Hiu A 727
this complication it may be necessary to repeat intubation many times,
and the patient is fortnnate if he escapes ulceration of the larynx. He,
however, rarely escapes bronchopneumonia, more or less marked.
When there is marked ulceration of any part of the larynx, with
little or no oedema, the child may get along fairly well witliout the tube
for a few days, but as cicatrization takes place the lumen of the larynx
becomes gradually diminislied, with a correspondingincrease of dyspna-a.
In attempting to perform intubation in such a case, it has been found
impossible to introduce the tube. We have been confronted with this
difficulty more than once, and in order to save the child's life have
resorted to tracheotomy.
In cases of ulceration of the larynx we believe it is good practice to use
the tube intermittingly until the ulcers have cicatrized. If there is difficulty
in introducing the tube it had better be left undisturbed for a long time
— i. e., from one to two weeks at least. In cicatricial stenosis, however,
after the difficulty is overcome of introducing a tube, though small,
but of sufficient calibre to supply the lungs with air, it is comparatively
easy, after this tube has been worn for a day or two, to introduce a
larger one. Having thus restored the normal lumen of the larynx, it
is advisable to insert the tube two or three times a week for a while,
leaving it in place from twelve to twenty-four hours. Later, as the
conditions improve, it need not be introduced so frequently. But the
tube should not be dispensed with until the tendency to recontraction
of the cicatricial tissue has been overcome.
In cases of prolonged intubation the vulcanite tube should by all
means be preferred. The calcareous deposits which always form on
metallic tubes make them very objectionable. They cannot be worn
long without causing irritation and often ulceration of the larynx. As
these deposits do not form on hard-rubber tubes, they may be allowed
to remain in position for a long time without doing harm. One of our
cases of four years' standing has worn a vulcanite tube continuously
for periods of three months each, and once as long as five months
without removal, with no unpleasant consequence except, as the parents
say, an offensive breath. The tube never showed any calcareous
deposits. It is worthy of remark that when the tube has been worn
for a long time the child acquires the ability to swallow with little or
no difficulty.
We have called attention to the fact that in some cases of prolonged
intubation, after the tube has been removed for a few days, it is impossible
to reintroduce it, and that tracheotomi/ becomes necessary. Likewise,
this operation may be deemed expedient when the tube cannot be
retained in position. We have seen cases in which the tube was con-
stantly coughed up, even when it was two or three sizes too large. In
such a case it sometimes happens that the head of the tube enters the
postnasal space and suffocation threatens if the tube be not immedi-
ately removed or pushed down into the larjTix. To keep it in place
would require a constant attendant. Under such circumstances it is
better to perform tracheotomy.
728 DIPHTHERIA
In this troublesome class of cases we are, however, reluctant to
recommend tracheotomy except as a dernier ressort. This is because
of the difficulty we have many times experienced in getting rid of a
retained tracheal cannula. One such patient is at the date of writing
in the hospital^ having worn the cannula for about two months.
After returning to their homes, three of our patients of this description
were taken to a general hospital in this city and placed under the care
of a surgeon. An operation was performed with the view of overcoming
the stenosis due to contraction of the cicatricial tissue in the larynx,
but in each instance the operation was unsuccessful, and the tracheal
cannula had to be continued. Two of these unfortunate children subse-
quently contracted pneumonia and died. There are three other ex-
patients of whom we have knowledge with retained tracheal tubes;
in one the retention, at the time of writing, has extended over a period
of six months, and in the other two of about four years each.
The difficulty in getting rid of the tracheal cannula in this class of
cases may not be due alone to cicatricial tissue in the larynx caused by
the intubation tube. In addition to this a later obstruction is not
infrequently developed as the direct result of the inflammation caused
by the long-retained cannula. This occurs at the upper angle of the
wound and may be in the nature of a stricture, or the larynx may be
completely occluded by cicatricial tissue. This condition is even of
more serious import than the former. We have seen two such cases in
which it was impossible to pass a probe through the lumen of the larynx,
either by way of the mouth or the tracheal wound; and the voice, even in
the faintest whisper, was lost, which proved that no air passed through
the larynx. According to O'Dwyer, a stricture of this description
develops in a large proportion of young subjects when the operation
is high, involving the cricoid cartilage or its immediate vicinity. He
says: "When the wound is still higher, that is, wholly within the larynx,
complete occlusion with adhesion of the vocal cords is very liable to
occur," etc.
As to the treatment of chronic stenosis of the larynx, we believe that
long-continued intubation offers the best results. As soon as the tube
is once introduced, no matter how small it may be, the chief difficulty
is overcome. After this, tubes of graduated sizes should be employed,
one after the other, until the one suited to the age of the child is reached.
As already stated, the tube may have to be worn intermittingly for a
very long time before the cicatricial tissue loses its power to contract.
The physician should not become discouraged too soon, but persevere,
as it may sometimes require years to remedy the difficulty.
^Vhen occlusion of the larynx is complete, or nearly so, whether
caused by the intubation tube or a long-retained tracheal cannula, it
will be found impossible to introduce a croup tube of the smallest size.
Such cases are difficult of management by the general practitioner
and had better be referred to the laryngologist. We believe, however,
that instead of attempting to force an entrance from above downward,
it is better to etherize the patient and enlarge the tracheal wound at
rilK TREATMENT OF J)I I'llTII Kill A 729
its upper angle so as to admit of tlic introduction of a soniul from hfilow.
In this way the sound is h'ss Hable to injure the parts by catching in
the ventricles. The intubation tube should then be introduced and
worn continuously for one or two weeks, after which it should be
employed intermittingly until a cure is eff('ct(;d. This procedure was
recommended by 0'J)wyer in a ])af)er read l)('for(! the; British Medical
Association in 1804, on "Treatment of Chronic Stenosis of the Larynx
by Intubation." In this paper O'Dwyer says: "The length of time
that intermittent intubation will be required to effect a permanent cure
will be influenced largely by the amount of cicatricial tissue present,
and its location. If confined to the chink a more S})C(;dy result may
be expected, because of the stretching which is exerted by the expansion
of the glottis with every breath. After the normal lumen of the larynx
has been restored, or at least ample breathing room secured, a tube
should be inserted once or twice a week, and allowed to remain in
position from twelve to twenty-four hours. This interval can Ije gradu-
ally increased according to indications, and continued imtil the tendency
to recontraction has been permanently overcome."
After the introduction of the intubation tube in these cases of chronic
stenosis in which tracheotomy has been performed, it is desirable that
the tracheal wound should be kept open for some time. If it could be
kept patulous — a thing difhcult to accomplish in a child — the liability
of the tube being coughed out would be greatly lessened. A special
tube or combination of tubes that would meet this indication seems
to be an important desideratum. At any rate, O'Dwyer's advice should
be heeded. It is as follows: "In practising intubation for the removal
of a tracheal cannula, the wound under all circumstances must be kept
open until sufficient breathing room through the natural passage has
been secured to sustain life, in case the tube should be coughed out.
This is, as a rule, extremely difficult to accomplish, especially in cliildren.
The hard-rubber plug devised by Drs. Pitts and Brook, and used in a
series of cases, appears to be most practicable for this purpose. It is
provided with a collar similar to that on a tracheal cannula, by which
it can be held in position."
Shurly,^ of Detroit, believes that the cure in cases of prolonged intu-
bation may be hastened by smearing the tube with an ointment com-
posed of alum and vaselin. Louis Fischer, of New York, likewise
recommends 10 per cent, alum or ichthyol-gelatin.
1 A paper read in the Section on Diseases of Children, American Medical Association, 1903, on
" Prolonged Intubation Tubes, with a Method Leading to their Extraction."
CHAPTEKXIY.
DIPHTHERIA {Continued).
THE SERUM TREATMENT OF DIPHTHERIA.
The antitoxin method of treating infectious diseases may be said
to have had its origin in the scientific investigations of Pasteur in 1880.
He then made the discovery that an unusually mild attack of fowl
cholera may be produced in chickens by inoculating them with an
attenuated or non-virulent virus of that disease. Chickens thus inocu-
lated, he found, were thereby rendered immune to this affection. He
also applied this discovery to anthrax in sheep with similar results.
Later — in 1886 — Salmon and Smith showed the great practical value
of Pasteur's discovery by an application of this principle to the protec-
tion of swine against hog cholera.
With a knowledge of the fact that the rat and the frog were peculiarly
refractory to the operations of the anthrax bacilli, Behring showed by
experiment that the blood taken from these animals was, within cer-
tain limits, efficacious against the production of anthrax in other
animals.
In 1890 Behring and Kitasato startled the medical world with the
announcement that if an animal be immunized against tetanus or
diphtheria the serum of the blood of that animal, when injected in
sufficient quantity, is capable not only of immunizing other animals
against an attack, but also of effecting a cure when attacked. These
observers published their discovery in the follovdng language: "Our
researches on diphtheria (Behring) and on tetanus (Kitasato) have led
us to the question of immunity and cure of these two diseases, and we
have succeeded in curing infected animals and in immunizing healthy
animals, so that they have become incapable of contracting diphtheria
or tetanus."^
In this connection it is due Aronson to state that, with equal diligence
in this field of labor, he also succeeded soon afterward in immunizing
animals against diphtheria.
After the investigations of these men, it is only fair to mention the
confirmatory experiments of Fraenkel, Wernicke, Roux, and others,
who likewise succeeded in producing in animals an immunity against
diphtheria by inoculating them with virulent or somewhat attenuated
cultures or with diphtheria toxin. But, as already shown, Behring
carried these researches one step farther by demonstrating that the
blood of immune animals contained a substance which antagonizes
' Quoted by Lennox Browne, Diphtheria and its Associates.
THFj Sr<]RJIM TRMATMMNT OF DH'II'I'II FltlA 7.';]
tho (liphtlicria, toxin. Tlicsc iinporlaiii studies fDiisfiliitc tlic foiiriflufion
upon which has been based the mocJern antitoxin treatirif-nf of rjiph-
theria.
The last link in the chain of these interestinff investigations having
been forj^ed, it now remained to apply the dis(;overies tiiat liad been
made to their special purpose of ciwin^ (Hj)htlieria in human beings.
Here, as in the entire field of this research, the work of Behring was
most productive. Tie succeeded in reaching the goal of his investigations,
and, together with Kossel, in 1898, recorded 30 cases of fiif)htheria
in human subjects which had been benefited l)y the use of serum
from the blood of animals artificially immunized.
In 1894, Ehrlich, Kossel, and Wassermann reported 223 cases treated
with antitoxic serum, with a mortality rate of 23 per cent.
In June, 1894, Katz, a colaborer of Baginsky, reported to the
Berlin Medical Society 128 cases of diphtheria which had been treated
with serum produced from one of Aronson's horses. This number was
subsequently increased by Baginsky to 163 cases, with the surprisingly
low death rate of 12.9 per cent.
While the announcements of the foregoing results were received
with intense interest, the culminating point of enthusiasm was reached
at the Eighth International Congress of Hygiene and Demography,
held at Budapest in September, 1894, when Roux presented his brilliant
paper on the subject of the serum treatment of diphtheria (I>ennox
Browne). He announced that he had confirmed, by experiments in the
Pasteur Institute, all the important statements made by Behring and
others who labored contemporaneously, and presented the records of a
large number of cases in which the serum treatment had been employed
successfully in the human subject, "and," as Lennox Browne so aptly
says, "by comparative statistics, enforced the attention of the whole
medical world to a consideration of its claims."
Theory of the Action of Antitoxin. — There seems to be very Uttle
known as to the modus operandi of antitoxin in the treatment of diph-
theria. It exerts no bactericidal effect upon the Klebs-I.oeffler bacilli,
although it is supposed to arrest the inflammatory process caused
by these organisms. It is also believed that it does not act chemically
or otherwise upon the toxin circulating in the blood, but rather upon
the living cells of the body, through whose agency the cure is effected.
Park says: "After the cells have been to a certain extent affected by
the toxin, the protective power of the antitoxin can no longer be exerted
and the lesions progress in spite of it."
While the mode of action of the antitoxic serum cannot be satisfac-
torily explained, yet there is no doubt that it is capable of neutrahzing
the effect of the toxin of diphtheria in animals. This has been demon-
strated thousands of times in the laboratory by bacteriologists. Park
says: "We have every reason to expect that, since the toxin in human
diphtheria is, so far as we can determine, exactly the same toxin as that
in diphtheria in animals, tliis power of the antitoxin to make harmless
the toxin will manifest itself in man under similar conditions."
732 DIPHTHERIA
Preparation of Antitoxin. — As already pointed out, to render an
animal immune to the diphtherial poison it is held to be sufficient to
gradually accustom that animal to the action of the poison. The
serum of an animal thus treated is believed to possess not only prophy-
lactic but also .curative qualities. The goat has been used in this way
for the production of antitoxin; but in order to obtain a more abundant
yield — as well as for some other reasons — the horse is the animal now
generally preferred.
Having eliminated the possibility of the existence of glanders and
tuberculosis by the proper tests, the horse is brought into a good con-
dition by rest, diligent grooming, and careful feeding, preparatory to
beginning the process of immunization. According to Park, the follow-
ing method is employed in the production of antitoxic serum by the
Health Department of New York City:
To prepare a strong diphtheria toxin a virulent culture of the Klebs-
Loeffler bacillus, grown under special conditions, is, at the end of a
week's growth, rendered sterile by the addition of 10 per cent, of a
5 per cent, solution of carbolic acid. In twenty-four hours it is filtered
through sterile filter paper and stored in bottles in a cool place. A
number of horses are injected with an amount of toxin sufficient to
kill ten thousand guinea-pigs of 250 grams weight each (about 44 c.c.
of strong toxin). With each injection of toxin 10,000 units of antitoxin
are given. After from three to five days, when the fever has subsided,
a second injection of a slightly larger dose is given. Increasing doses
of toxin are then given at intervals of five to ten days, until, at the end
of two months, from ten to twenty times the original amount is given.
The horses are then bled and the blood serum tested for antitoxin.
Those animals yielding less than 200 units in each cubic centimetre
are discarded.
The remaining horses are then further treated with ascending doses
of toxin. At the end of three months the serum should contain from
300 to 800 units of antitoxin to each cubic centimetre. The best horses
will furnish high-grade antitoxin for years. A three months' freedom
from toxin injection should be given the horses each year.
The blood is obtained by plunging a sharp-pointed cannula into the
jugular vein. It is received in Ehrlenmeyer flasks and allowed to clot,
the serum then being siphoned off.
Antitoxin is a proteid substance of unknown chemical composition.
It is destroyed by heat 55° C, and is precipitated from its solution in
the- same manner as globulins.
As already pointed out, antitoxin possesses the property of neutral-
izing, within certain limitations, the diphtheria toxin within the body.
That is to say, when a given amount of antitoxin is injected into an
animal with or just before a certain quantity of the toxin, it abrogates
the poisonous effect of the latter.
Behring and Ehrlich applied the term "antitoxin unit" to an amount
of antitoxin capable of protecting the life of a guinea-pig weighing
250 grams from one hundred fatal doses of toxin. Ehrlich later
Till': HI': HUM Tia<:ATMi:NT oi'' Dii'iiriiHiaA 733
pointed out the variability of ihv. (Ilplithcria toxin, and tlicreFore tli(!
liability of error in such standardization. Park, who experimented
with toxins of did'erent potencies, gives the following definition of an
antitoxin unit: "The amount of antitoxin necessary to f)roteet the
hfe of a guinea-pig from one himdred fatal doses of a toxin similar
to that adopted as a standard, namely, one liaving th(! cliaraeteristics
of toxins in cultures at the height of their toxicity." lie .says: "This
amount of poison is produced by the growth for one week of a virulent
baciHus in 1 c.c. of bouillon."
The Serum. — The serum varies considerably in color, though it
should be clear and free from anything that looks lik(! bacterial growth.
It is maintained in an aseptic state by putting it into sterilized bottles,
which are hermetically sealed and kept in a cool place. It is fpiite
common to use some preservative, such as camp»hor, carbolic acid,
trikresol, and the like.
The serum on the market varies greatly in antitoxin units. It is
believed that each cubic centimetre should contain at least 100 anti-
toxin units, but it is desirable to have it much stronger. Originally,
Behring's firm put up three strengths in vials of about 10 c.c. each, as
follows :
No. 1, containing 600 units, which was regarded as a suitable dose
for a child at the onset of an ordinary attack of diphtheria.
No. 2, containing 1000 units, for a severe attack in children.
No. 3, containing 1500 units, for adults, or a very severe form of
the disease in children.
The serum prepared in this country is put up in vials containing
from 5 c.c. to 10 c.c, and represents a strength of 100 to 500 antitoxin
units to each cubic centimetre. The number of units in each vial
should appear on the label.
Dosage. — In considering the dose one should think of antitoxin
units rather than the quantity of the serum; but it must be admitted
that there is no fixed dose. In the present state of our knowledge it
is impossible to fix the dose on the basis of age, as in the case of drugs.
Perhaps most practitioners inject as many antitoxin units into a child
as into an adult. This does not seem unreasonable when we consider
that the amount of toxin absorbed, and which we seek to neutralize
or counteract, is in all probability as great in the former as in the latter.
It is also not improbable that the younger the child the greater the
susceptibility to the toxin of the disease, with a less power of resistance,
and "consequently," as Lennox Browne remarks, "if, as has been
suggested, the remedy acts by cell stimulation, the greater the necessity
for a large dose of the serum; or, in other words, since the young cell
elements are so extremely sensitive to the diphtherial poison, they
require to be fortified all the more strongly in order to exercise an
effective resistance." We may state, on the authority of the writer
just quoted, that Roux, in his first announcement, speaking of the
serum prepared at the Pasteur Institute, advised that 20 c.c. (repre-
senting, probably, 2000 units) be given to every patient — adult, or child
734 DIPHTHERIA
above one year — so soon as seen, and even in advance of the bacterio-
logical diagnosis, stating that for children under one year the first dose
should be as many cubic centimetres as the child is months old. In very
severe cases, he said, the dose should be as much as 30 c.c, or even more.
It has been deemed advisable by the most competent observers to
regulate the dose according to the time that has elapsed since the onset
of the disease and the severity of the attack. As we have just shown,
Behring believed that a dose of 600 units was sufficient for a child at
the onset of an ordinary attack, but if the case be a ery severe, or far
advanced when first seen, the dose should be increased to 1500 units.
We feel that what Park^ has said on the subject of dosage is worth
quoting. He writes: "The size of the dose should be measured chiefly
by the extent and intensity of the disorder; also, but to a less degree,
by the size of the patient and the duration of the illness. For young
children, with but moderate lesions of the tonsils or palate, a single
dose of 1000 to 1500 units will suffice. For older children and adults
1000 to 2000 units should be given. In children who are already
seriously ill or who already show the toxic effects, or in whom the
larynx is involved, a dose of 1500 to 3000 units ... is necessary.
"If the symptoms do not abate, another 1000 to 2000 units may
be given on the following day. In a few cases still a third injection is
required. Exceptionally, a week or ten days after administering the
antitoxin, a slight return of exudate may appear; here another moderate
injection is indicated. Where these doses have not benefited it is
doubtful if larger ones will succeed.
"At the New York Hospital for Contagious Diseases for several
months one-half of the severe cases received on admission 3000 units,
and again on the following day 3000 more. If no improvement followed,
a third 3000 units were given. The other half received 2000 units on
admission, and a second 2000 in eighteen hours. So far as one could
judge, those receiving the lesser amount did as well as those receiving
the very large amounts. On the other hand, no additional disagreeable
effects were noticed from the larger quantities."^
McCollom,^ of the South Department Hospital, Boston, recommends
that antitoxin be administered in large doses. He advises that 4000
units be given at once, and that this dose be repeated at intervals of
1 Loomis-Thompson, American System of Practical Medicine.
- While these pages are going through the press we note in the Archives of Pediatrics, December,
1904, an abstract of a discussion in the New York Academy of Medicine on the dosage of diphtheria
antitoxin In which Dr. Park's views are given as follows : He said that for three years he had experi-
mented with antitoxin in doses greatly varying in size : during one year the dose was 10,000 to 20,000
units; the next year it was between 5000 and 10,000 units; the third year it was between 3000 and
5000 units. Hfe said it was very difQcult to find out which dosage produced the best results.
In bad cases of diphtheria Dr. Park advocated using large doses. In mild cases, either early or
late, involving tonsils and pharynx, he used 2000 units ; in severe early cases 4000 units ; in ordi-
nary laryngeal cases 5000 units; in malignant cases, tonsillar, pharyngeal, or nasal, 10,000 units, and
repeating this dose at the end of twelve hours unless the patient is distinctly better. He emphasized
the fact that the antitoxin should be given for the diphtheria and not for any accompanying condi-
tion like pneumonia.
3 A Plea for Larger Doses of Antitoxin, Medical and Surgical Reports of the Boston City Hospital,
1900, eleventh series.
77//'; sf<:ni/M tiiilished
data, Biggs and Guerard arrived at the following conclusions:' "It
matters not from what point of view the subject is regarded if the
evidence now at hand is properly weighed, but one conclusion is or
can be reached — -whether we consider the percentages of mortality
from diphtheria and croup in cities as a whole, or in hospitals, or in
private practice; or whether we take the absolute mortality for all the
cities of Germany whose population is over 15,000, and all the cities
of France whose population is over 20,000; or the absolute mortality
for New York City, or for the great hospitals in France, Germany,
and Austria; or whether we consider only the most fatal cases of diph-
theria, the laryngeal and operative cases; or whether we study the
question with relation to the day of the disease on which treatment
is commenced, or the age of the patient treated; it matters not how^
the subject is regarded or how it is turned for the purpose of comparison
with previous results, the conclusion reached is always the same, namely,
there has been an average reduction of mortality from the use of anti-
toxin in the treatment of diphtheria of not less than 50 per cent., and
under most favorable conditions a reduction to one-quarter, or even
less, of the previous death rate. This has occurred not in one city at
one particular time, but in many cities, in different countries, at different
seasons of the year, and always in conjunction with the introduction
of antitoxin serum and proportionate to the extent of its use."
Among the earlier effects of antitoxin is the whitening process which
the false membrane undergoes. Following tliis, the membrane begins
to separate, and, according to Roux and many other observers, entirely
disappears in four or five days after the injection of the serum.
The subjoined table shows the day of the disease w^hen antitoxin
was administered to 350 patients in the Municipal Hospital, Phil-
adelphia, and the day on which the throat was declared free of mem-
brane. These were not selected cases, but taken at random.
1 Quoted by Park, Twentieth Century Practice of Medicine.
740
DIPHTHERIA
The Day of the Disease on which the Throat was Declared
Free of Membrane.
Day of disease
on which anti-
toxin was
administered.
No.
of
cases.
i
•6
(N
CO iTJi
si
.£3
00
OS
g
.0
CO
S
J3
^'
01
o3
First . .
Second .
Third .
Fourth .
Fifth
25
118
91
53
26
12
8
12
4
1
1
2
3
8
6
17
6
■5
19
16
1
3
18
16
7
2
2
12
15
8
8
2
10
10
7
3
2
1
10
9
10
6
3
4
1
12
7
5
2
1
4
2
1
4
2
3
1
1
2
1
2
2
3
1
1
1
1
1
2
1
1
1
1
3
3
1
1
4
1
1
1
1
2
1
2
1
1
On the 28d, one.
Sixth
On the 30th, one.
Seventh
Eighth .
Ninth .
On the 27th, one.
1
2
Tenth .
!
I
Total
350
1
2
11
29' 41 46
1
45
35
42
35
15
10
8
7
6
1
5
3
3
1
It may be seen in the above table that the earher in the disease the
antitoxin was administered, the sooner the membrane disappeared.
Lennox Browne, however, beheves that antitoxin is not a very im-
portant factor in hastening the separation or disappearance of the mem-
brane. He shows comparisons between 92 cases treated with serum
and 67 without, as follows:
Day op Treatment on which the Throat was Declared Free of
Membrane.
Day.
Series A, without serum.
Series B, with serum.
Second .... 4 cases or 6 per cent.
1 case or 1.08 per cent
Third
13 " 20
4 cases or 4.3 "
Fourth
14 " 21
9 " 9.8 "
Fifth
14 " 21
18 " 19.5
Sixth
8 " 12
18 " 19.5
Seventh
6 " 9 "
10 " 10.8
Eighth
5 " 7.4 "
2 " 2.1
Ninth
1 case or 1.5 "
1 case or 1.08 "
Tenth
1 " 1.5 "
1 " 1.08
Eleventh
1 " 1.5 "
"
Twelfth .
2 cases or 2.1 "
Thirteenth
2 " 2.1 "
Fourteenth
2 " 2.1
Seventeenth
1 case or 1.08 "
Twenty-fourth
1 " 1.08
Twenty-eighth
Thirty-ninth
1 " 1.08 "
1 " 1.08
74 + 18 =
The author of this table says: "In Series A this fact (the day on
which the membrane disappeared from the throat) was noted in only
77//'; HNIiUM 7'n/<:ATMl'!NT OF 1)1 1'llTII EHIA 74]
67 of the cases, and in 02 in Scries li. Only I occnrntfJ (in Scries Aj
in which membrane reappc^arccJ, and that on the foijrtccnt}i day after
a(hnission; whereas, in Series B there were 5 cases of reappearance,
18 cases in which d(>ath occurred Ix^forc; it hiid cleared entirely, anri in 1
case it was observed as latrurn application."
Kassowitz reproduces graphic charts from an article published by
de Maurans/ in which it is shown that the mortality from diphtheria
in Birmingham, Liverpool, Dublin, and Stockholm has strikingly risen
during the serum period. The rise began in some instances a year or
so before the use of serum and in others after its use.
This writer still further shows that the curves of diphtheria mortality
were not influenced by the introduction of serum treatment in Budapest,
Glasgow, Zurich, Lille, Cologne, Berne, Christiana, Beriin, Lyons,
Brussels, Leipzig, Edinburgh, Paris, Geneva, Copenhagen, Havre,
Nantes, Toulouse, Turin, Antwerp, Stuttgart, Munich, Hamburg,
Buenos Ayres, and London.
As tending to show the inutility of antitoxin, Kassowitz says that in
1897, according to the German Imperial Board of Health Reports, 42.9
per cent, of those who died of diphtheria were given serum within three
days of the onset of the disease, and 22 per cent, within two days.
The value of the antitoxin treatment is forcibly demonstrated in the
reports of the Metropolitan Asylums' Board. In 1894, 3042 patients
of all ages were treated without serum, in the hospitals controlled by
the Board, with 902 deaths — a death rate of 29.6 per cent. In 1895,
the first year of the serum treatment, 3529 patients were thus treated,
with a death rate of 22.5 per cent. This shows a fall in the mortality
of 7.1 per cent. In the annual report of the Metropolitan Asylums'
Board for 1901, it appears that, in that year, (i499 cases of diphtheria
were treated with antitoxin in the Board's hospitals, with 817 deaths —
a death rate of 12.5 per cent. There has, therefore, been a reduction
in the mortahty from 29.6 per cent, in 1894, without antitoxin, to
12.5 per cent, in 1901, with antitoxin. The treatment in other respects
is said to have been the same.
According to this report, the laryngeal cases treated in the Board's
hospitals in 1901 with antitoxin numbered 753, of which number 159
died, yielding a death rate of only 21.1 per cent.
1 Semaine modicale, 1901, p. 401.
746
DIPHTHERIA
Goodall/ of London, presents the following compilation of statistics
from reports of the statistical committee of the Metropolitan Asylums'
Board, showing the case mortality of the city of London, before and
since the advent of antitoxin:
Mortality per cent, of all notified cases
Mortality per cent, of notified cases admitted to )
Asylums' Board hospitals J
Mortality per cent, of notified cases not admitted
Per cent, of notified cases admitted to hospitals
Before antitoxin.
1892 1893 1894
23.8
24.8
21.5
30.1
24.8
27.1
23.7
24.5
24.7
25.0
24.5
38.8
Since antitoxin.
1895 1896 1897
21.2
18.3
23.3
41.5
19.9
17.7
21.3
39.9
17.4
14.9
20.1
51.4
Goodall also shows the case mortality of diphtheria treated in the
hospitals of the Metropolitan Asylums' Board, as follows:
Table I.
1892. 1893. 1894. 1895. 1896.
29.5 30.4 29.2 22.8 21.2
" Later years contain larger number of adults."
1897.
17.6
Table II. — Mortality in children under five years of age.
1892. 1893. 1894. 1895. 1896. 1897.
51.5 53.3 43.9 39.5 30.3 24.9
" Including fatalities from other diseases combined with or following diphtheria."
The annual reports on the work of the Metropolitan Asylums' Board
for the year 1903 show that the Board received during the year notifica-
tions of 7582 cases of diphtheria; of these 5072 were treated in the
hospitals, with a death rate of only 9.6 per cent. The average death
rates in the Board's hospitals in quinquennial periods since the year
1887 are as follows:
1887 to 1891.
33.6 per cent.
1S92 to 1896.
25.5 per cent.
1897 to 1901.
13.7 per cent.
1902 and 1903.
10.4 per cent.
According to a pamphlet issued by the authorities of the Institute
for Infectious Diseases, of Japan, the serum treatment of diphtheria
has affected the statistics of this disease in that country as follows:
Previous to the sale of serum the average death rate of diphtheria
patients was 50 per cent.; but since the sale began it has gradually
decreased to 38 per cent, in 1896, 36 per cent, in 1897, and finally as
low as 28 per cent, in 1902.^
Most of the statistics collected in this country are equally positive
as showing the value of antitoxin in the treatment of diphtheria. The
1 British Medical Journal, 1899, vol. i. p. 197.
2 It is surprising to note in this pamphlet that, while the death rate from diphtheria in Japan has
been greatly reduced since the advent of antitoxin, there has been a large increase of both cases
and deaths annually,
Till': ^i<:uiiM Tui:ATMiii'irriih:niA 747
comparative mortality from this disease in (^liiea^o, l)cJV>n' and aft<'r
the introchietion of tlie serum treatment, as shfjwn in tlic linllcliit of
February 13, 1004, of the Health I)<'[)artment of that eity, is as follows:
During the preantitoxin period the deaths amujally J)er 10,000 of
population were 12.4r) j)er cent., while since the serum has been uscfj
the ratio of deaths has been reduced to 4.55 per cent. 'J'hc increase of
population amounts to 52 per cent.; the decrease of diphth(;ria deaths,
63.4 per cent. Between ()ctol)er 5, 1895 (date of first case treated)
and December 31, 1003, th(> Tlealtli Department treated 7435 ca.ses of
bacterially verified (Jiphtheria, of which number 470 died, yielding a
death rate of 6.44 per cent. It is stated that the average mortality
without antitoxin still remains about 35 per cent.
We are indebted to Dr. J. H. McC-ollom, of Boston, for the following
table, showing the ratio of m()rl)idity and of the mortality of diy)htheria
in Boston, per 10,000 of population, for ten years — 1S04 to 1003 inclusive:
^, , ^. „ Ratio of T^ ^u Ratio of
Years. Population. Cases. ,.,., Deaths. _ . ,» ,
morbidity. mortality.
1894 .... 4«6,830 3019 61.01 878 18.03
189.5 .... 501,083 4059 81.00 654 11.73
1896 .... 516,305 4489 86.94 572 9.80
1897 .... 528,912 3398 64.24 -456 7.77
1898 .... £41,827 1661 30.65 185 3.15
1899 .... 555,057 2836 51.08 304 4.99
1900 .... 560,892 4977 88.73 537 9.57
1901 .... 573,579 3319 57.86 353 6.15
1902 .... 588,741 1940 34.72 225 3.82
1903 .... 600,929 2091 34.79 211 3.51
McCollom says the South Department Hospital of Boston was opened
for patients September, 1895, and antitoxin has been given to every
case of diphtheria admitted. In 1896 he published the following table,
which shows the number of patients, by ages, admitted to the hospital
from September 1, 1895, to May, 1896, together with the mortaUty rate in
each age period:
Age. Cases. Deaths. Mortality per ct.
Under 1 year 17 3 17.64
1 to 2 years 74 20 27.02
2 " 3 " 136 37 27.2
3 " 5 " 329 55 16.71
5 " 10 " 410 39 9.51
10 " 20 " 189 9 4.76
20 years aud upward 206 7 3.38
1359 170 12.5
In presenting these statistics McCollom says that from February,
1891, until February, 1894, there were 1062 cases of diplitheria, with
493 deaths — a death rate of 46.42 per cent.
The cases treated in the South Department Hospital, Boston, since
the introduction of antitoxin have vielded the following annual mortalitv :
748 DIPHTHERIA
Year. Cases. Deaths. Mortality per ct.
1895 844 96 11.37
1896 1,779 276 15.54
1897 1,291 181 14.02
1898 : 892 103 11.54
1899 . 1,672 180 10.78
1900 ? . . « . . ' . . 2,600 294 11.3
1901 ' . . 1,448 172 11.87
1902 1,018 103 10.11
Total 11,544 1405 12.17
In an interesting^ paper detailing the results, of antitoxin in New York
City in 1902, by Dr. J. S. Billings, Jr./ the following diagram appears:
TABLE SHOWING DEATH RATE PER (0,000
FROM DIPTHERIA IN THE BOROUGHS
OF MANHATTNaN and the BRONX
FROM 1888 TO 1902
YEAR
64
1888 89 90 91 92 93 94 95 9fi 97 98 99 1900 01 20
18
GO
17
S
50
\,
16
52
>- 48
^44
<
H 40
a:
1 36
UJ 32
en
< 28
^^ 24
20
IG
12
\
15
o
14 §
o
13 --
tc
12 u.
11 UJ
1-
10 <
9 I
1-
82
7^^
6
\
A
z
\
/
/ \
\s
4
\<
\
/
\
K'
N
LU
\^
V
^
ID
K
>
\
o
\,
3
\
\
O
K
\
z
V-
-^
Y^
^
-^
^
6^
Lv
\
8
4.
DOTTED. --CASE MORTALITY
SOLID DEATH RATE
l^his diagram shows in a very striking manner how greatly the mor-
tality from diphtheria in New York City has diminished since the
introduction of the serum treatment.
After presenting considerable statistical evidence, Billings concludes
his paper by saying: "There is no longer any doubt as to the curative
action of antitoxin in diphtheria. Of 15,792 cases injected with anti-
toxin furnished free of charge by the Department of Health or by its
inspectors, 1860 died, a case fatality of 11.8 per cent. If the cases
moribund when injected (722 in number) are deducted the case mortality
is further reduced to 7.5 per cent."
1 New York Medical Journal and Philadelphia Medical Journal, December 12, 1903.
Tiii<: si'Ua/M Tui<:ATMierio(J. We are infiennox Hrowne
he found that paralysis was more common than in ])revious years when
antitoxin was not employed.
Goodall,^ of Ivondon, lias shown that paralysis became more frcfjuent
in the Metropolitan Asylums' Board hospitals after the introduction of
antitoxin. He presents the following table showing the percentage inci-
dence of paralysis in the Board's hospitals from 1S9.3 to 1897, inclusive:
Non-antitoxin.
1893. 1894.
189.i.
Antitoxin.
1896
1897.
Eastern Hospital .
. 12.1
10.8
16.0
21.4
15.1
Northwestern Hospital
. 14.0
11.1
18.9
14.1
12.8
Western Hospital .
. 18.1
8.2
17.7
21.5
11.0
Southwestern Hospital
. 14.3
18.3
22.0
20.6
20.5
Southeastern Hospital .
. 16.2
20 2
34.7
42.3
45.9
Total.
. 14.3
13.2
20.1
21.3
20.3
Alleged III Effects of Antitoxin. — In the vast majority of cases no
immediate ill effects are noticeable. An abscess at the site of the
injection may occur, but this is preventable.
Many observers believe that antitoxin has increased the incidence
of nephritis. It does seem that albuminuria is more frequently seen
now then formerly. Referring to the results in his 1000 cases of diph-
theria, Lennox Browne says his figures show a very considerable and
undoubted increase in the proportion of cases of nephritis under serum
treatment as compared with the old. Speaking of Baginsky 's experience
to the contrary, he remarks: "It is only fair to quote the experience of
Professor Baginsky. . . . On a comparison of 993 cases without
serum and 525 with serum, he has come to the conclusion that the
injection of serum does not increase the frequency of nephritis. gi\ing
tables in support of his contention. This observer is careful to give
separate and widely different figures for clinical nephritis, as distin-
guished from that observed post-mortem."
Hansemann, Washbourn, Goodall, and T>ennox Browne have noted
the liability to anuria under serum treatment. The last-named writer
says he was particularly unfortunate in his own early experience in
this respect, as 6 out of a series of S patients died Avith anuria as the
most prominent symptom.
R. W. Marsden," of London, believes that the early use of antitoxin
1 British Medical Journal, 1S99, p. 197. s Ibid., 1900, vol. ii. p. 65S.
4S
754 DIPHTHERIA
lessens the liability to albuminuria, and that when it appears late in
diphtheria it may be due to antitoxin. He says that "though it may
have an irritant effect upon the kidneys, yet this is by no means the rule,
and in any case its action is only temporary."
Winters/ of New York, one of the attending physicians to the Willard
Parker Hospital, believes that pneumonia in diphtheria has become
mo]*e frequent since the employment of the serum treatment. He says
that "the pneumonia of the antitoxin cases of diphtheria differed from
the pneumonia we were in the habit of seeing in diphtheria; that it was
a totally different disease from that' seen before in the course of diph-
theria; that it occurred as a sequela and not as a complication." He
regards it as septic in character.
In an earlier part of this article we called attention to the frequency
of bronchopneumonia in the laryngeal form of diphtheria, and expressed
the belief that it resulted from diphtheritic involvement of the respiratory
tract. It is true that bronchopneumonia often occurs late in the disease,
and. even at times during convalescence from the faucial form of diph-
theria, but we have never felt that it was due to the serum treatment.
Before concluding it may be well to mention the fact that more than
one death has been reported as immediately following the injection of
the serum. This accident has been almost entirely confined to the use
of the serum for immunizing purposes. While no very satisfactory
explanation has been given for the occurrence of these sudden deaths,
it is not believed that they were caused by the serum fer se.
The only ill effect which we are able to attribute to antitoxin with
any degree of certainty is a peculiar exanthem, often attended with rise
of temperature and more or less joint pains.
Antitoxin Eruptions. Frequency. — The use of antitoxic serum in
diphtheria is followed, in a certain proportion of cases, by a train of
phenomena, the most conspicuous of which is the development of a
cutaneous eruption. The proportion of cases in which antitoxin rashes
develop is most variable. Hartung has collected from the literature a
series of 2661 injections, of which 294, or 11.4 per cent., developed
rashes. 253 of these eruptions are accounted for in the following table:
Eruptions. Injections. Per cent.
Heubner (Berlin cases) 54 298 ]8.1
Heubner ........ 22 77 28,5
Baginsky 49 525 9.3
Soltmann 5 89 5.6
V. Ranke 5 118 4 2.
Seitz |20 140 14.3
I 4 180 2.22
Forster 7 73 4 9.6
Schucolty 4 38 10.5
Gunther 3 33 9.0
Bokai ;il 120 9.1
< 30 147 20.4
Moizard, Paris 33 231 14 2
Risel, Halle 6 114 5.2
253 22S-3 11.08
1 Medical Record, June 20, 1896.
Rflsh.
Percent.
18
17
■23
2.'}
19
33
22
33
77//'; SI'Jh'f/M rUI'JATMMNT Of DI I'llTII IIRI A 755
The Imperial Board of Health of Germany reports 4358 cases of
diphtheria injeeted with seru?n from January to July, 1805, with the
production ol" 354 rashes, or 8.1 per cent.
Among 7S cas(\s of diphtheria treated in the Scarlet P'ever and I)ij)h-
theria Hospital of New York, in lOOl, rashes occurred in 25.4 per cent.
The Investigating Committee of the Clinical Society of London
collected records of 663 cases; 220 of these, or 33.1 per cent., develf>ped
antitoxin rashes.
liCnnox Brown(^^ noted 38 eruptions in UK) cases. Herg^ gives the follmv-
ing figures for the Willard Parker llos})ital of New Yoi-k for four months :
Canes.
May 107
June 103
July 02
August . , fi5
Total 337 «2 24
The great variability in the frequency with which antitoxin eruptions
develop may be best appreciated when it is stated that Monti, of \^ienna,
observed rashes in 52 per cent, of one of his series of cases, whereas
Hager did not observe a rash in a single instance among 61 cases.
In our own experience an eruption has developed in about 20 per cent,
of the cases injected.
Date of Appearance of Eruption. — The rash may appear in from
one day to one month after the injection of the serum. The subjoined
table will show the day of occurrence of 120 antitoxin eruptions observed
by us in the Municipal Hospital of Philadelphia. It will be seen that
the greatest number of rashes occurred upon the sixth, seventh, and
eighth days after the administration of the serum. Indeed, by actual
computation over 49 per cent, of the total number appeared on these
days.
The date of appearance of the rash depends much upon the particular
serum employed. A few years ago we used a serum the rashes from
which quite uniformly appeared about the end of fourteen days.
Days upon which Antitoxin Eruptions Developed in 120 of Our Cases.
Eash appeared in 1 case on the second day after the serum injection.
6 cases
fourth
6 "
fifth
18 "
sixth
17 "
seventh
24 "
eighth
5 "
ninth
7 "
tenth
5 "
eleventh
7 *•
twelfth
5 "
thirteenth
5 "
" fourteenth
1 case
■' fifteenth
8 cases
sixteenth
3 "
seventeenth
1 case
eighteenth
1 ■'
twentieth
1 Diphtheria and its Associates, London, 1S95. - New York Medical Record, 1S9S, pp. S65-S73.
756 DIPHTHERIA
In the report of the Clinical Society of London, the largest number
of rashes appeared from the seventh to the twelfth day; the figures
are as follows:
Day of Appearance of Antitoxin Eruptions.
First to sixth day 33 cases.
Seventh to twelfth day 147 "
Thirteenth to eighteenth day 34 "
Nineteenth to thirty-first day 6 "
The rashes noted by I^ennox Browne appeared for the greater part
from the seventh to the twelfth day. The statement is made by some
writers that the scarlatinoid rashes are prone to occur early, in the
neighborhood of the third day. We have seen some rashes of this
character occur quite early.
Character of the Eruption. — In our experience the vast majority
of the rashes have been of an urticarial character, either made up of
frank wheals or consisting of an urticarial erythema. Next in frequency
have been the rashes belonging to the class of polymorphous erythema.
These may consist of irregular marginated and non-elevated patches
of redness, or may show a distinct tendency to annular or gyrate con-
figuration. It is not uncommon to see an erythema made up of small,
round, red patches with perfectly pale centres.
In other cases the erythema may be of the scarlatinoid type and bear
a close resemblance to the exanthem of scarlet fever. These appear
to have occurred much more frequently in New York City than in
Philadelphia. In other cases the rash may be a morbilliform erythema,
looking not unlike the eruption of measles.
Vesicular and bullous eruptions are quite uncommon; but we have
observed one well-pronounced case, which is shown in the accompanying
photographs. We have also observed a case in which there was
extravasation of blood into the vesicles. Purpuric antitoxin eruptions
are not very frequent, for of many hundreds of rashes that have
occurred in the Municipal Hospital we have seen not more than eight
or ten characterized by hemorrhage into the skin.
Antitoxin eruptions are frequently polymorphous, exhibiting wheals,
patches of non-elevated erythema, and occasionally papules and vesicles.
Mixed urticarial and erythematous lesions are frequently obserA'ed.
Indeed, all of the lesions which may occur in erythema multiforme
may be present in the rashes following serum injections. Most of the
rashes are accompanied by severe itching; this is particularly complained
of by adults, who are, perhaps, better able to give expression to their
discomfort.
(Edema of the skin is commonly noted in association with antitoxin
rashes. The face is puffed, particularly about the eyelids, and not
infrequently the penis, scrotum, and feet are oedematous.
Among the 220 rashes recorded by the Clinical Society of London,
161 were erythematous, 37 were urticarial, 17 were mixed, and 5 were
petechial; 2 of the 5 petechial cases died. Of 33 rashes noted by Moizard,
PI. ATI: LX.
An Unusual Antitoxin Eruption exhibiting Erythematous Patches
on the Trunk and Vesicular Lesions on the Face.
PLATR I.XI,
The Saine Patient as Plate LX. , showing the Vesicular
Character of the Lesions on the Face.
THE SI'JIiUM TREATMENT OF hi I'llTII l-llll A 757
14 were urticarial, .sciirlaliiiiforin cin l,liciii;i, !) polymorplioiis erythema,
and 1 purpura.
DiS'i'iuiuri'ioN. 'Ilic (lisli-ihiilioii of tlic ii of the culaiieous surfaee.
It is noted with particular frequency about the arms, lej^s, and huttock.s,
although the trunk is scarcely less commonly atta(;ked. The face often
escapes, but by no means always.
The most frecjuent region for the ajjpearance of the rash is the site
of the injection. It is quite common for an erythematous or nrtiearial
eruption to appear about the cutaneous puncture and the surrounding
skin within twenty-four hours after the injection; this frequently dis-
appears only to return some days later as the herald of the general
eruption. Among the 220 antitoxin rashes recorded by the C'linieal
Society of London, 40 were first seen at the site of the injecticMi.
The eruption may consist of but a few scattered patches, or it may
be so profuse as to involve the greater part of the cutaneous surface.
The eruption ordinarily persists for about forty-eight hours, although
in some cases it may last three, four, or five days. The purpuric rashes
continue much longer. Occasionally the rash will begin to fade and
almost disappear, and then in twenty-four or forty-eight hours reappear.
Recurrent Rashes. — The eruption following the use of diplitlieria
antitoxin is occasionally subject to recurrence. The rash may disappear
and return in a few days or several weeks afterward. Among 134
rashes observed by us within a year and a half, there were 14 recurrent
rashes. The earliest relapse occurred three days after the first eruption
and the latest seventeen days. There is sometimes more than one re-
currence. The GHnical Society of London reports 11 recurrent rashes
among 220 eruptions collected. The following table gives the day of
appearance and of recurrence of the cases observed by us:
Eecurrent Antitoxin Eruptions.
Primary rash appeared in :
1 case 7 days after serum injection, and again 3 days later.
" " " " " 5 " "
" " " ■' " ]" "
" " •' " 4 "
" 14 "
4 ..
' 7
' 4
' 7
' 6
' 10
'■' 6
" 8
' 8
' 8
' 6
' 10
' 6
' 6
Total 14
Constitutional Symptoms. — Antitoxin rashes are commonly accom-
panied by constitutional disturbance of a more or less pronounced
character. In the majority of cases there is elevation of temperature
758 DIPHTHERIA
with its usual concomitant symptoms. The pyrexia is extremely variable ;
in some cases there may be hyperpyrexia.
We have occasionally observed temperatures in children of 104° and
105° F. More commonly the fever does not rise above 101° or 102° F.
In the 220 rashes reported by the Chnical Society of London, fever
accompanied the eruption in 136 of them.
The fever lasts ordinarily from twenty-four to seventy-two hours,
although it may persist longer. It declines, as a rule, with the subsidence
of the rash. Headache is commonly associated with the fever and a
variable amount of prostration is present. In some cases the prostration
is quite pronounced.
Vomiting occurs occasionally in children, and now and then there is
diarrhoea. Where the temperature is high delirium is said to occur
(Sevestre and Martin). We have not observed delirium in any of
our cases.
A very commou symptom accompanying the antitoxin rash is pain
in the joints; adults often bitterly complain of this arthralgia. Articular
swelling is noted in a certain proportion of cases. The wrists, elbows,
shoulders, knees, and ankles are the joints most commonly attacked.
The swelling usually subsides in a few days.
The Clinical Society of London reports arthropathies 40 times among
663 cases of diphtheria; in 35 of these cases the joint symptoms accom-
panied the antitoxin eruption.
Causation of the Serum Phenomena. — The phenomena which develop
in a certain proportion of cases after the administration of antidiph-
theritic serum are without doubt dependent upon something which is
contained in the injected fluid. Inhere is strong reason to believe that
the antitoxic principle itself has little or nothing to do with the eruption
and other manifestations produced. It has been quite conclusively
proven that plain horse serum when injected into individuals will
produce eruptions of the character described in about the same pro-
portion of persons as the diphtheria antitoxic serum.
The serum of non-immunized horses was injected by Bertin into a
number of children suffering from diphtheria with the development of
rashes in a considerable proportion of them. Four children suffering
from an ordinary sore throat were injected by Sevestre with serum of
non-immunized horses, with the production of an erythema in each one.
Johannsen,^ of Christiania, administered hypodermically 2 to 15 c.c. of
pure blood serum from a healthy non-immunized horse to 23 persons free
of diphtheria. The serum given to 19 of the individuals was filtered;
4 received unfiltered serum. A more or less generalized erythema
developed in 12 of the 23 patients in from one to eleven days. The
filtered serum produced less disturbance than the unfiltered.
It has long been known that the injection into an animal of an alien
or heterogeneous blood serum — i. e., a serum derived from an animal
of another species — is followed by toxic symptoms.
1 Johannsen, Bertin, and Sevestre. Cited by Berg, loc. eit.
THE SI'IRUM TRKATMl<:Nr Oh' Dl I'llTII FJUA 759
Rumno^ believes that the toxic vi^i^x-i of blood serum depends upon
tli(; aetioii of sj)eciiil toxalbninins. Alexander Selinii(P is of the opinion
that the toxie elVeet is (hie to the; action of the sohibh' fibrin ferment
of OIK! l)lood sennn u])on the second ;mini;i,l.
If Ehrlich's side-chain theory stands the test (A time it will pnjbably
be found that the serum injected contains a substance which acts as
an intermediary body.
Herg, aft(M- using antitoxic serum filtered tliroiigh a T'liamberland
filter, and comparing th(> results with unfiltered sennn, ef)nchided that
filtered antitoxin is less likely to give rise to rashes. Park, of New York,
is not convinced that this is actually so.
The wide variability in the production of serum rashes Is doubtless
due to two factors: 1. Individual susceptibihty or predisposition, and,
2, peculiarities in the blood serum of certain horses. There can be no
question that the serum of some horses gives rise to a larger percentage
of antitoxin rashes than that of others.
Where the serum of an animal produces an unusually large num-
ber of eruptions, that animal had better be given up as a source of
antitoxin.
Diagnosis of Serum Rashes. — It is often a matter of difficulty to dis-
tinguish between an antitoxin eruption and the eruption of measles
or scarlet fever, more particularly the latter. Secondary infection with
scarlet-fever poison during the course of diphtheria is not an uncommon
occurrence. When a scarlatiniform rash develops in a patient who has
been given antidiphtheritic serum, the question arises. Is the rash the
result of the serum, or is it an expression of scarlet fever?
No more difficult problem in differential diagnosis arises than in
these cases. The diagnosis may be easy when the scarlet-fever SMiiptoms
are complete and well marked. When there is vomiting, rapid rise of
temperature, an aggravation of the existing angina, a characteristic
tongue, and an intense, diffuse, punctated rash, the nature of the phe-
nomena may be readily divined. But when, as so often happens, there
is moderate pyrexia (100° or 101° F.), and a diffuse rash of moderate
intensity, the solution of the diagnostic problem is at times impossible.
The difficulties are increased 'by reason of the fact that diphtheria
patients suffer from an angina and from glandular enlargement, and
the antitoxic serum may produce fever, a scarlatinoid rash, vomiting,
and prostration.
In our experience at the Municipal Hospital, scarlatinoid eruptions
have formed but a very small percentage of the serum rashes. We
have observed from time to time a large number of scarlatinoid rashes
accompanied by more or less fever in the diphtheria wards, but we
have regarded such cases as scarlet fever and have sent them to the
"mixed ward" w^here cases of double infection with diphtheria and
scarlet fever are treated. Although these wards always contain some
well-pronounced cases of scarlet fever, the patients sent from the diph-
' Quoted by Berg, loc. cit. , - Ibid.
760 ' DIPHTHERIA
theria wards with the scarlatinal rashes have rarely contracted scarlet
fever. This experience has seemed to us to afl'ord confirmatory, though
we admit not conclusive, evidence that the diagnosis was correct.
In the city of New York scarlatiniform rashes after the injection of
antitoxic serum seem to have been more common than in Philadel-
phia, and within recent months, during which time there has been
used, at the Philadelphia Municipal Hospital, the New York Board of
Health serum, it has appeared to us that scarlatinoid rashes from the
serum have been more frequent.
The features Vvhich tend to indicate that the rash is of serum origin
and not the exanthem of scarlet fever are: its development at about
the proper time after the injection, the moderate grade of the accom-
panying fever, the presence of severe itching, the absence of a recurrent
angina and the scarlatinal tongue, the occurrence of joint pains or
swellings, irregularity in the development or distribution of the rash,
the brevity of its duration, and the absence of consecutive desquamation.
It must be remembered, however, that all of these phenomena have
but a relative value in the diagnosis and that in many cases, after due
weighing of all the symptoms, the diagnosis remains obscure. Other
observers of experience have recognized similar difficulties in diagnosis.
CH A PTER X V.
i)isiNFir,
Embalming with strong solutions of foniialin or arsenic destroys all
but the surface infection, and this may f)e treated with solutions of
carbolic acid, (;orrosive snblimate, or formalin.
Vehicles.- -Airdjulances, carringcs, street ears, and th(; like, an; best
disinfected by running tiiem into a tightly closed ec^mpartirutnt which
may be quickly filled with large quantities of strong formaldehyde gas.
In a specially built structin-e of this kind satisfactory disinfection may
be effected in an hour. Vehicles which can b(; tightly clf)sed may be
thoroughly sprayed with a 5 to U) per cent, solution of fonnalin and the
vapor allowed to act for about six hours.*
* In preparing the above article tiie writers have consulted the excellent book on " Disinfection
and Disinfectants," by Dr. M. J. Rosenau, Director of the Uygienic Laboratory and Passed Assisiant
Surgeon U. S. Public Health and Marine Hospital Service.
INDEX.
Ar>l)()MINAL coiiiplicaXions in siiuili-
pox, 287
Abortion in smallpox, 21G
Abscesses in smallpox, 229
Accidental cowpox in man, 142
Actinomyces in va(!cine virus, 103
Adult chickenpox, 327
scarlet fever, 347
Aerial transmission of scarlet fever con-
tagium, 357
of smallpox infection, 161
Age incidence in smallpox, 112
in measles prognosis, 530
Air transmission of smallpox infection,
161
Albuminuria in smallpox, 226
Alopecia after smallpox, 191
Altitude, influence of, on scarlet fever,
352
America, introduction of smallpox into,
147
of A'accination into, 25
Angina scarlatinosa, 390
Anginose scarlet fever, 382
Animal transmitted virus, 97
vaccination, 93
advantages of, 94
in America, 93
Anomalous measles, 497
Antipyrin eruptions and measles, diag-
nosis of, 527
Antistreptococcus serum in scarlet fever,
474
Antitoxin of diphtheria, action of, 731
curative power of, 738
effect of, on local process, 735
limitations of, 736
prophylactic power of, 737
eruptions and measles, diagnosis of,
529
preparation of, 732
prophylactic influence of, in Munici-
pal Hospital, 738
treatment of diphtheria, 730
unit, 732
An ti vaccination arguments, 114, 115, 119
Apepox, 143
Atmospheric conditions and smallpox,
156
transmission of smallpox infection,
161
Attack rate of smallpox, 120
BACrElMOLOGICAI. diagnosis <>i
(liplitheria, 077
impurities of vaccinr-, virus, 102
Bacteriology of diphtheria, 612
of measles, 521
of scarlet fever, 430
of smallpox, 256
of tvphus fever, 572
Baths in smallpox, 299
lieaugency lymph, 92
Bed-sores in smallpox, 231
Bills of mortality, smallpox deaths, 109
Black smallpox, 204
Blattern, 145
Blood changes in chickenpox, 335
in diphtheria, 670
in scarlet fever, 436
in smallpox, 253
Boils after vaccination, S3
iu smallpox, 229
Bousquet's lymph, 92
Bovine lymph, 31
vaccination in America, 93
Bullous eruptions after vaccination, SO
CALF-TRANSMITTED virus, 94, 97
Calf vaccination, 93
Camel, smallpox in, 143
Camp measles, 499
Carbuncles in smallpox, 230
Casual cowpox in man, 142
Chauveau's experiments with variolation,
88
Chemnitz smallpox statistics, 118
Chester smallpox statistics, 113
Chickenpox, 316
in adults, 327
blood in, 335
complications and sequelte of, 329
diagnosis of, 335
disseminated gangrene in, 330
eruptive stage of, 322
er3'sipelas complicating, 330
etiology of, 318
history of, 316
incubation period of, 320
nephritis in, 332
pathology of, 334
prodromal erythema, 322
prognosis of, 339
pyaemia complicating, 330
768
INDEX
Chickenpox, scarring after, 326
second attacks of, 319
and smallpox coincident, 333
symptomatology of, 321
synovitis and arthritis in, 330
treatment of, 339
with other exanthematous diseases,
332
Chloral eruptions and measles, diagnosis
of, 528
Clavelee, 135
Climate, influence of, on scarlet fever,
349
Cohasset lymph, 93
Coincident chickenpox and smallpox, 333
Comparative mortality rates of variola
and varioloid, 278
Comparison of course of vaccinia with
different virus, 96
Complications of chickenpox, 329
of diphtheria, 640
of measles, 501
of rubella, 561
of scarlet fever, 395
of smallpox, 229
of typhus fever, 583
of vaccination, 58
Compulsory vaccination law in Germany,
123
Confluent measles, 494
smallpox, 199
superficial, 212
Conjunctivitis in smallpox, 232
Contagious impetigo complicating vac-
cination, 70
period of measles, 484
Contagiousness of desquamating epithe-
lium in scarlet fever, 357, 462
Contraindication for vaccination, 32
Copaiba and cubebs eruptions and
measles, diagnosis of, 529
Copeman and glycerinated lymph, 98
Corneal ulcer in smallpox, 233
Cowpox, 17
in cow, 142
Crede's ointment in scarlet fever, 469
Croup and diphtheria, diagnosis of, 674
meinbranovis, 633
Cutaneous gangrene in smallpox, 194
Cytoryctes variola^, 264
life cycle of, 265
of Guarnieri in vaccinia, 85
DEATH rate of smallpox among vac-
cinated and un vaccinated, 117
Decline of smallpox after introduction of
vaccination, 107
Decrustation in smallpox, 186
Definition of chickenpox, 316
of diphtheria, 598
of measles, 476
of rubella, 547
of scarlet fever, 341
of smallpox, 144
of typhus, 566
Delayed vaccination, 38
Delirium in smallpox, 182
ferox in smallpox, 182
Derivation of word smallpox, 144
variola, 144
Dermatitis bullosa after vaccination, 80
exfoliativa in smallpox, 196
herpetiformis after vaccination, 80
Desiccation in smallpox, 185
Deterioration of humanized virus, 95
Dewsbury smallpox statistics, 118
Desquamation, contagiousness of, in
smallpox, 482
in measles, 497
in rubella, 556
in scarlet fever, 374
duration of, 376
Diagnosis of chickenpox, 335
and impetigo contagiosa, 338
and smallpox, 335
of diphtheria, 672
of measles, 523
of rubella, 562
of scarlet fever, 447
of smallpox, 266
and acne, 272
and acute gastritis, 268
and chickenpox, 269
and drug eruptions, 272
and eczema, 274
and glanders, 274
and impetigo contagiosa, 273
and la grippe, 267
and measles, 268
and meningitis, 267
and roseola vaccinosa, 272
and scarlet fever, 269
and syphihs, 270
and typhoid fever, 267
and typhus fever, 267
of typhus fever, 586
Diet and stimulants in smallpox, 301
Diphtheria, 598
age factor in prognosis of, 679
incidence, 611
albuminuria, 362
alleged ill-effects of antitoxin, 753
antitoxin in, action of, 731
alleged ill-effects of, 753
curative power of, 738
dosage, 733
effect of, on local process, 735
on paralysis, 753
eruptions, 754
fever with, 758
morbilliform, 756
recurrent, 757
scarlatinoid, 756
ill-effects of, 753
laryngeal form, 741
limitations of, 736
mode of administrating, 736
preparation of, 737
prophylactic power, 737
rashes, causation of, 754
date of appearance, 755
I NT) MX
7G0
I )i))liLli('ri!i,, ;i,nl.il,()\in niHlics, (li,'i,fi;ii(i.si.s of,
fever in, 758
frequency of, 754
results in, 743
in (Jhicjimo, 750
iti .lap.'ui, 74()
in l-lii' Mutiiciiwil Ho.spital
in I'liiludclplii.'i, 749, 752
in N(W York (.'il.y, 7 IS, 751
in Willanl l';i.rk(',r Il().si)itiii,
New York, 749, 751
treatment of, 730
unit 732
value of, 743
avirulent diphtheria bacilli, 616
bacilli of biolofrical characters of,
614
in blood and internal orj^ans, 617
distribution of, in body, 617
in lungs, 663
in lymph nodes, 668
in scarlet fever throats, 399
in throats of exposed persons,
619
of healthy persons, 618
persistence in the throat, 618
staining properties of, 613
types of, 613
virulence of, 616
bacillus, general infection with, 617
growth of, on bouillon, 615
on gelatin, 615
on glycerin agar, 615
on Loeffler's blood serum,
614
in milk, 615
on potatoes, 615
Neisser's stain of, 614
morphology of, 613
pathogenesis of, 615
bacteriological diagnosis of, 677
bacteriology of, 612
blood changes in, 670
in Boston City Hospital, mortality
of laryngeal form,
743
results of antitoxin in,
747
bronchopneumonia in, 641
at autopsy, 661
bacteriology of, 662
catarrhal croup, diagnosis of, 674
causation of serum rashes, 758
changes in adrenal bodies, 670
in alimentary cjuial, 664
in blood, 670
in heart muscle, 660
in intestines, 665
in Iddneys, 667
in liver, 665
in lungs, 661
in lymph nodes, 668
in nervous s^'stem, 670
in panci'eas, 670
in pituitary bod}^ 670
I )iplil liiii;i, changes in pliiiml ni'-ni-
branes, fi63
in salivary gl;i,nd.s, 670
in skeletal inuscles, 669
in Hpl(!en, (i64
in testicles, 670
in thymus gland, 669
in (liyroid glund, 670
in (Miicago, aniiloxiri n-sults in, 750
(4iroiiic stenosis of larynx in, 726
circulatory symptoms, 631
coni])licatirig scarlet fever, 397
corn})lications of kidneys, 667
of lung, 641
of lymph glands, 642
ol' scarlf^t fever, 644
Mild sequela; of, 540
conjiuictival, 626
constitutional predisposition to, 609
course of, 636
cultures of, for diagnosis, 677
ciitaneous, 627
definition of, 598
diagnosis of, 672
of serum rashes, 759
dissemination of infection, 607
duration of, 636
of membrane in throat, 740
ear inA^olvement in, 626
endocarditis in, 66
epistaxis in, 625
eruptions after antitoxin, 754
erythema in, 627
etiology of, 602
examination of cultures of, 678
exudate in, 624
location of, 658
of e3^es, 626
favorable cases of, 637
fever in, 630
folUcular tonsillitis, diagnosis of. 675
gangrenous pharj-ngitis, diagnosis of,
676
general paralysis in, 650
geographical distribution, 604
heart changes in, 660
failure in, 641
hemiplegia in, 647
hepatic changes in, 665
herpetic pharjTigitis, diagnosis of,
675
liistopathologv of membrane, 658
histoiy of, 598
indications for operati^•e interfer-
ence, 715
infection in milk, 608
influence of domestic environment,
606
of race, 613
of rainfall, 605
of schools, 60S
of season, 605
of sex, 611
isolation of well persons harboring
baciUi of, 619
intubation in, 711^
49
770
INDEX
Diphtheria, intubation in, prolonged, 725
technique of, 715
in Japan, results of use of antitoxin,
746
kidney changes, 667
complications of, 642
laryngeal, 633
antitoxin in, 741
operative measures in, 711
leukocytosis in, 671
liver changes, 665
lobar pneumonia, 642
location of membrane, 658
Loeffler's solution as local applica-
tion, 693
of methylene blue, 613
lung changes, 661
making of cultures of, 677
malignant type of, 638
measles complicating, 645
membrane in stomach, 664
mercurial applications in, 692
in Metropolitan Asylums' Board
Hospitals of London, antitoxin
results, 746
middle-ear involvement, 626
mild type of, 636
mortality of intubation cases in Wil-
lard Parker Hospital, 742
in Mvmicipal Hospital, 743
of tracheotomized cases, 742
in Municipal Hospital of Philadel-
phia, antitoxin results,
749, 752
mortality of intubation, 743
myocardial changes, 660
myocarditis, 660
nasal, 624
irrigations in, 697
treatment of, 697
nephritis in, 642, 667
nervous symptoms, 633
in New York City, antitoxin results
in, 748, 751
of nose, 624
nose-bleed, 625
oedema in, 628
after antitoxin, 756
paralysis, 646
general, 650
incidence, 753
of cardiac and respiratory
nerves, 649
of soft palate, 649
pathology of, 658
pericarditis in, 660
period of incubation in, 620
pleurisy in 642
prognosis, 678
prognostic significance of age, 679
of exudate, 682
of nasal involvement, 683
of paralysis, 686
of pulse, 685
of race, 682
of renal involvement, 686
Diphtheria, prognostic significance of
sex, 681
of temperature, 684
of toxaemia, 684
pulse in, 631
rash in, 627
rashes of, 754
after antitoxin, 754
recurrence of, 640
recurrent attacks of, 610
in Russian Hospitals, antitoxin re-
sults, 744
septic cases of, 638
variety of, 629
serum rashes in, 754
severe type, 636
site of infection in, 610
of skin, 627
smear preparation for diagnosis of,
677
statistical table of antitoxin results
in Boston City
Hospital, 747
in Chicago, 750
in Metropolitan
Asylums' Board
Hospitals, 746
in Municipal Hos-
pital of Phil-
adelphia, 749,
752
in Russian Hos-
pitals, 744
in St. Petersburg,
745
in Willard Parker
Hospital, 749
752
indicating duration of mem-
brane in throat, 740
of date of appearance of
antitoxin rashes, 755
of mortality from laryngeal
form in Boston City
Hospital, 743
from laryngeal form,
742
in tracheotomy, 742
of intubation in Muni-
cipal Hospital,
743
in Willard Parker
Hospital, 743
of recurrent antitoxin
rashes, 757
of stomach, 664
St. Petersburg results of use of anti-
toxin, 745
stomatitis, differential diagnosis of,
676
sj^mptomatology, 622
syphilitic sore throat, differential
diagnosis of, 676
termination of, 636
throat appearances in, 622
tincture of the chloride of iron in, 700
IN/J/'JX
771
DipliUK^ri.'i,, loxiciiiiji, of, 628
tmclH'()(,()my ill, 727
iiidiciitioriH for, 71 I
treatiiKMil, of, 0X7
nlcoliol ill, 705
iUi(.iH(\|)ti(t .Mnijlic'itions in, (HM
of jLiinil, ()iW
biciiluridc oT incnMiry in, 702
(■;ilnmcl in, 70;{
snMiin.'i.l ion in, 707
(•;uisU(! applic.'Uions in, 000
cliloratc, of potash in, (iOI
oonstitiitioiijil, 700
digitalis in, 7or)
ol' clijilit.iicril ic con jnncl i\i-
tis, 099
emetics in ineinhnmoiis croup,
709
extubation, 733
technique of, 723
gargles in, value ol', 091
internal, 700
indications for, 700
irrigation in, 69(5
with saline solution, 698
intubation in, 718
dangers and difficulties of,
718
feeding after, 721
prolonged, 725
technique of, 715
lactic acid in, 695
of laryngeal form, 708
local, 690
Lfiefller's solutions in, 693
of membranous croup, 708
mercury in, 709
steam in, 709
mercurial applications in, 692
of ocular, 699
operative, indications for, 715
measin-es in laryngeal form,
711
of paralysis, 707
potassium chlorate in, 703
preventive, 687
removal of intubation tube, 723
serum, 730
slaked lime in, 710
sodium benzoate in, 705
solvents of exudate, 694
spraj's in, 696
strychnine in, 705
tincture of the cliloride of iron
in, 700
turpentine in, 704
whiskey in, 706
ulcerations from pressure of intuba-
tion tubes, 726
urine in, 632, 642
in ^^'illard Parker Hospital, mortal-
ity in intubation, 742
results of antitoxin,
749, 751
with scarlet fe\-er, 644
with measles, 645
DiphthrTitic [jaralyHis, 610
Disinlcction, 761
of bcr|(lin(r, 761
of books, 761
of cadaverw, 764
of (:arj)ets, 764
of letters, 764
of money, 764
prcp.'ir.'ition of room for, 761
in sin.'illpox, 285
by spniying with loriiialin w>liitinris,
762
with paraforni pastils, 763
with sulphur dioxide, 763
of v(4iicl(;s, 765
Dissenting views as to air transmission of
smallpox infection, 164
Domestic animals, tran.«mission of small-
pox inf(!ction by, 165
EAR complications in smallpox, 235
Eaux aux Jambes, 138
Eczema following vaccination, 79
Effect of glycerin on bacteria, 101
Egyptian plague, 145
En anthem of measles, 489
of scarlet fever, 373
of smallpox, 180
Equination, 140
Equine variola, 138
Eruption of measles, 493
Eruptive stage of smallpox, 173
Erysipelas comphcating smallpox, 230
after vaccination, 72
Erythema multiforme complicating vac-
cinia, 70
scarlatini forme in smallpox, 196
scarlatinoides, 419
Etiology of chickenpox, 318
of diphtheria, 602
of measles, 478
of rubella, 549
of scarlet fever, 344
of smallpox, 150
of tA'phus fever, 568
Exceptionally mild smallpox, 206
Exfoliative dermatitis in smallpox, 196
Extubation in diphtheria, 723
Eye complications of variola, 231
FALSE vaccination, 42, 49
Favorable s^•mptoms in smallpox.
281 ■
FeA'er in measles, 489
in scarlet fever, 366
in smallpox, 183
First vaccination of .Tenner, 91
Foetus, smallpox in, 221
Formalin, 761
Formaldehyde disinfection. 761
effects of. on vennin. 761
French and German Armv, smallpox sta-
tistics. 121
French measles. See Rubella, 547
Furunculosis after vaccination, S3
772
INDEX
GAIjBIATI and animal vaccination, 93
Gangrene, in scarlet fever, 422
in vaccination, 67
of skin in smallpox, 194, 231
Gangrenous angina in scarlet fever, 396
Generalized vaccinia, 60
German compulsory vaccination laws,
123
and French army smallpox statis-
tics, 121
German measles. See Rubella, 547
vaccination commission, 123
Germicidal action of glycerin, 100
value of glycerin in lymph, 98
Glossitis variolosa, 181
Gloucester smallpox statistics, 118
Glycerin, effects of, on bacteria, 101
germicidal action of, 100
Glycerinated lymph, 97
advantages of, 101
duration of activity of, 105
preparation of, 103
value of, 98
Goat pox, 138
Golden rule of vaccination, 28, 31
Grease, 138
Guarnieri's bodies, 263
in vaccine lesions, 85
HEART complications in smallpox, 236
Heifer vaccination, 93
Hemorrhagic measles, 499
scarlet fever, 387
smallpox, 202
pathological changes in, 251
typhus fever, 585
vaccinia, 63
varioloid, 206
History of chickenpox, 316
of dijjhtheria, 598
of measles, 476
of rubella, 547
of scarlet fever, 341
of smallpox, 144
of typhus fever, 566
Histology of skin in smallpox, 242
of vaccine lesions, 83
Hornpox, 213
Horsepox, 138
Human equination, 140
ovination, 138
smallpox from material from vario-
lated cows, 89
Humanized virus, 30
deterioration of, 95
Hygiene of vaccination, 30
ILLNESS, initial, of smallpox, 167
Iodine used locally in smallpox, 311
Impetigo contagiosa complicating vac-
cination, 70
varicellosa, 325, 330
variolosa, 192
Immunity of vaccinated physicians and
nurses against smallpox, 127
Incubation period of chickenpox, 320
of diphtheria, 620
of measles, 487
of rubella, 550
of scarlet fever, 363
of smallpox, 166
of typhus, 575
Infected articles, persistence of smallpox
poison, 160
Infection of smallpox, 157
carried in garments, 160
transmitted in the air, 161
Infectious period of smallpox, 157
Infectiousness of blood in smallpox, 255
Infectivity, period of, in scarlet fever, 355
Initial stage of smallpox, 167
Inoculation, 148
declared illegal, J 15
with ovine lymph, 138
practice of, in England, 114
of smallpox in America, 25
and smallpox prevalence, 114
Inoculated smallpox, 214
Inoculability of measles, 478
of scarlatinal virus, 354
of varicellous fluid, 319
Insanity after smallpox, 237
after typhus fever, 584
Insects, transmission of smallpox infec-
tion by, 165
Institution epidemics of measles, 531
Insusceptibility to smallpox, 150
to vaccination, 43
Intrauterine smallpox, 222
Intubation in diphtheria, 711
dangers and difficulties of, 718
instruments, 712
prolonged, 725
treatment and feeding after, 721
Invasive stage of measles, 488
Involution of eruption in smallpox, 185
Iritis in smallpox, 235
Irregularity in measles eruption, 500
in scarlet fever, 388
Itching in smallpox, 189
Isolation in scarlet fever, 461
of smallpox patients, duration of,
287
JAIL fever. See Typhus, 566.
Jefferson's letter to Jenner, 133
Jefferson, Thomas, and vaccination, 28
Jenner, Edward, 17
Jefferson's letter to, 133
on relation of cowpox to smallpox,
90
Jenner's first vaccination, 91
Joint disease in smallpox, 237
KINEPOX, 17
Kindpocken, 112
Kilinarnock smallpox st^-tistics, 113
INDEX
773
Klcihs-T/Ocmcr h.-utilliis, discovrTy of, 502
KopliU'.M spol.s in incjislcs, 'lOl
(liiif^iio.sMc v.'iliK' of, r)2.'i
Kiili|)i)ck('n, 17
LA I'ETITE VEROI.E, Ur,
Lady Montague and inoculalion,
148
Laryngeal dipliihoria, 033
Jioiwislcr smallpox statistirn, IIK, 1 H),
121
Leprosy after vaccination, 70
Leidvocytosis in scarlet fever, 137
Fjoeal irealnient of sniall|)ox, :i(J()
Jjoelller's solution of methylene blue, 613
Long humanized virus, 07
Lord Ma(^aulay on the ravages of small-
pox, 147
Louis XV. attacks of smallpox, 152
liupus vulgaris after vaccination, 78
Lymphatic glands in scarlet fever, 378
Lymph, glycerinated, 07
advantages of, 101
natural sources of, 91
preparation of, 103
Lyons Commission on variolation oi'
cows, 88
MACAULAY, on the ravages of small-
pox, 147
Malignant measles, 499
scarlet fever, 385
Marseilles smallpox statistics, 118
Martin's lymph, 93
Measles, 476
in adults, 482
age incidence, 481
albuminuria in, 512
anomalous cases of, 497
aphthous stomatitis in, 505
bacteriology of, 521
blood changes in, 520
bronchopneumonia in, 503
bullous eruptions in, 508
camp, 499
cancrum oris in, 512
capillar}^ bronchitis, 503
changes in blood in, 520
in the liver in, 520
in lungs in, 520
in lymphatic glands in, 520
in nmcous membranes in, 519
in skin in, 518
in spleen in, 520
character of epidemic and prognosis
of, 532
chorea after, 508
climate and prognosis of, 533
complications of, 501
alunentary tract, 505
ear, 510
eye, 509
glandular, 512
heart, 511
Measles, compliraf ions of, kidney, 511
laryngeal, 501
lung, 502
nervous, 506
skin, 508
confluent, 494
contagious period, 484
deaf-mutism and, 51 1
desquamatif)n, 497
drug eniptions, differential diaiBfnoHiB
of, 527
diagnosis of, 523
diarrluea in, 506
disseminated sclerosis in, 507
eczema after, 509
effect of, on chronic disea.sf^s, 519
season on, 483
exanthem, 489
endocarditis in, 511
epidemics of, 482
in institutions, 531
eruption in, 493
hemorrhagic, 499
irregularity of, 500
presence of papules, 494
of vesicles, 494
eruptive period of, 493
erythema nodosum after, 509
etiology of, 478
fever in, 489
gangrene of lungs in, 505
of skin in, 508
gangrenous stomatitis in, 512
hemorrhagic, 499
herpes facialis in, 508
history of, 476
incubation period of, 487
influenza, differential diagnosis of,
525
inoculabihty of, 478
insanity after, 506
isolation of, 537
utility of, 538
KopUk's spots, 490
lobar pneumonia in, 504
malignant form of, 499
membranous laryngitis in, 502
meningitis in, 508
mental disorders in, 506
mild form of, 497
type of, 498
mode of contagion, 479
morbilhform erythemata, differential
diagnosis of, 527
noma in, 512
notification of, 536
paralysis after. 507
pathology of, 518
pericarditis in, 511
pigmentation in, 496
pleuris}-, 504
post-rubeoUc rashes in, 501
pre-eruptive rashes. 492
pregnant women. 517
pre\-ious health of patient and prog-
nosis of, 532
774
INDEX
Measles, prodromal or invasive stage of,
488
prognosis of, 529
prophylaxis of, 535
pulmonary tuberculosis after, 504
purpura- in, 512
recession of rash, 501
relapses in, 486
rubella, differential diagnosis of, 524
scarlet fever, differential diagnosis
of, 524
season and prognosis of, 533
smallpox, differential diagnosis of, 525
susceptibility, 480
symptomatology, 487
favorable, 535
unfavorable, 535
syphilis, differential diagnosis of, 527
third attacks, 486
treatment of 535
of bronchopneumonia in, 544
of cancrum oris in, 543
of complications in, 542
of conjunctivitis in, 543
of itching in, 542
of laryngitis in, 543
of nose-bleed in, 543
of otitis in, 545
temporary immunity, 481
tuberculosis cutis after, 509
typhoid form, 499
typhus fever, differential diagnosis
of, 526
ulcerative stomatitis in, 505
urticaria in, 508
vulvitis in, 512
with other infections, 518
without catarrhal symptoms, 497
without eruption, 498
fever, 497
Membranous angina in scarlet fever, 396
croup, 633
Mild measles, 497
type of smallpox, 206
Miliary vesicles in scarlet fever, 370
Milk, scarlet fever, infection in, 357
Miscarriage in smallpox, 216
Mitigated smallpox, 209
Modified smallpox, 209
Monkey, smallpox in, 143
Montague, Lady, and inoculation, 148
Montreal epidemic of smallpox, 159
Morbid anatomy of scarlet fever, 439
Morbilli confluentes, 494. See measles,
476
hemorrhagic, 495
Iseves, 494
miliaris, 494
papulosi, 494
vesiculosi, 494
Morphine in smallpox, 298
Mortality of smallpox in the prevaccina-
tion period, 275
Mucous membrane eruption in smallpox,
180
Multiform erythema after vaccination, 70
NATURAL cowpox in cow, 142
Negri and animal vaccination, 93
Negroes, smallpox in, 154, 276
Neisser's stain for the diphtheria bacillus,
614
Nervous complications of measles, 506
in smallpox, 237
Noma in scarlet fever, 422
OCULAR complications of variola, 231
(Edema of glottis in smallpox, 181
Orchitis in smallpox, 237
Otitis media in scarlet fever, 400
in smallpox, 235
Ovination, 137
human, 138
PALMAR lesions in smallpox, 187
Paraform disinfection, 763
Paralysis in smallpox, 238
Paraplegia in smallpox, 239
Passy lymph, 92
Pathology of chickenpox, 334
of diphtheria, 658
of measles, 518
of scarlet fever, 436
of smallpox, 242
of typhus fever, 573
Pathological changes in hemorrhagic
smallpox, 251
Pearson's lymph, 91
Pemphigus after vaccination, 80
Period of incubation of chickenpox, 320
of diphtheria, 620
of measles, 487
of rubella, 550
of scarlet fever, 363
of smallpox, 166
of typhus fever, 575
Petechial fever. See Tj^phus, 566.
Phimosis in smallpox, 237
Phlebitis after smallpox, 237
Pigmentation after measles, 495
after smallpox, 190
Plantar lesions in smallpox, 187
Pleurisy in smallpox, 236
Pneumonia in smallpox, 236
Pock diseases of lower animals, 135
Pocken, 145
Postrubeolic rashes, 501
Postvaccinal lupus vulgaris, 78
Postvariolous rashes, 196
Prague, effect of introduction of vaccina-
tion in, 107
Precocious vaccinia, 41
Pre-eruptive rashes in measles, 492
Pregnancy, influence of, in scarlet fever
359
Pregnant women, smallpox in, 215
Prevention of pitting in smallpox, 308
Prodromal erythema in chickenpox, 322
rashes in smallpox, 171
stage of smallpox, 167
iNi)i<:x
77r,
l^r()f!;ru)His ol' cliiclu'ripox, XV.)
of (li|)li( licria,, ()7X
of mcMslcs, 520
(if fiilicll.'i,, r>(')\
of sciiJ-lcl. f(tvcr, •If)?
of siii;i,lli)()X, 27r)
of I yplms f(!vcr, 589
I'fopliyliixi.s of nitiiiIli)ox, 2 fc^vcr, I'A'.i
in Viifiola .'uid vaccinia, 2(12
l's(Mi(lo(li|)litJicr'ia, ()r)2
bacilli, ()l!)
coinnuinicabilily <>f, 0.^;^
(liiiSnosis of, <)75
Ij-calmcnl. of, (ir)7
Psoudokcloidal fj;rowths after sniaIli)ox,
2:^0
Psoriasis after vaccination, 82
i'lKM'pcral scarlet fcvor, 359
I'uerperium, influence of, in scarlet fever,
359
Purpura hemorrhagica in scarlet fever.
420
variolosa, 203
Pustular hemorrhagic variola, 205
J'ya^mia after vaccination, 64
in smallpox, 241
QUARANTINE in scarlet fever, 461
in smallpox, 283
Quinine eruptions and measles, diagnosis
of, 528
RACE, influence of, on scarlet fever,
353
Raspberry tongue in scarlet fever, 374
Recurrent eruptions in scarlet fever, 393
smallpox, 151
Red light treatment of smallpox, 304
Relapse in rubella, 562
Relation of horsepox to cowpox, 139
Relationship of cowpox to smallpox, 87
of vaccinia to smallpox, 87
Respiratory complications in smallpox,
236
Retained intubation tubes, 726
Retroequination, 142
Retrogression of eruption in smallpox,
185
Retrovaccination, 51
Revaccination, 45
statistics of, 120
Rhazes' description of smallpox, 145, 146
Roseola vaccinosa, 37, 68, 171
Rotheln. See Rubella, 547
Royalty, smallpox deaths among, 149
Rubella, 547
age, incidence of, 550
albuminuria in, 561
coincident with other diseases, 562
complications and sequela^ of, 561
cough in, 558
definition of, 547
desquamation in, 556
HubcMa, diagnosis ol', 562
diiratioii of isolation in, 565
of rash, 555
eruptions of, anomalous, 555
character of, 554
(Miology of, 549
f(!ver in, 557
history of, 557
hoarseness in, 558
influenza, dilfercntial diagnosis of,
561
it,cliiiig in, 559
lymphatic glands, 559
measles, differential diagnosis of, 562
nausea and vomiting in, 559
period of eruption in, 552
of incubation in, 550
of invasion in, 551
prognosis of, 564
pulse and respiration in, 559
relapses in, 562
second attacks of, 562
scarlatinifonn variety^ of rash, 556
scarlet fever, differential diagnosis of,
564
sneezing in, 557
sore throat in, 558
symptomatology of, 550
synonyms of, 547
treatment of, 565
tongue in, 558
Rubeola. See Measles, 476
SACCO'S lymph, 92
Sanitation and vaccination in Glas-
gow, 116
Scaling in scarlet fever, 374
Scarlatina. See Scarlet fever, 321
anginosa, 382
faucium, 390
hemorrhagica, 387
maligna, 385
miliaris, 370
papulosa, 370
pempliigoidea, 371
simplex, 365
sine angina, 392
eruptione, 390
exanthemate, 390
febre, 388
with desquamation, 392
vesicularis, 370
Scarlatinal infection, mode of reception,
355
rheumatism, 419
virus, inoculability of, 354
Scarlatinifonn erythema, 449
in smallpox, 196
Scarlet fever, 341
abscesses in, 425
of brain in. 403
in adults, 347
afebrile cases of, 368
age influencing prognosis, 45S
776
INDEX
Scarlet fever amblyopia, 405
anginose form of, 382
antistreptococcus serum in, 474
and antitoxin rashes, 451
bacteriology of, 430
blebs in, 424
blood in, .436
bronchial catarrh in, 381
care of patients in, 465
changes in bone-marrow, 443
in gastrointestinal tract,
442
in heart, 443
in kidneys, 445
in liver, 442
in lungs, 445
in lymphatic system, 440
in skin, 439
in spleen, 441
in tongue, 440
chorea after, 430
choroiditis in, 405
circumoral pallor in, 372
complicated by diphtheria, 397
complications of, affecting ali-
mentary canal, 425
bones, 429
nervous system, 428
the respiratory organs,
427
ear, 399
eye, 404
heart, 406
liver, 426
respiratory organs, 427
and sequelae,. 395
skin, 423
contagiousness of desquamating
epithelium, 357
of scales, 462
contagium, aerial transmission
of, 357
Credo's ointment in, 475
deafness after, 404
definition of, 341
dermatitis gangra;nosa in, 424
desquamation, 374, 448
diagnosis, 447
diagnostic value of desquama-
tion, 448
of strawberry tongue,
448
diet, 465
diphtheria, differential diagnosis
of, 454
bacilli in throat in, 399
disinfection, 465
dissemination of, in schools, 460
drug rashes, differential diag-
nosis of, 453
duration of desquamation of,
376
of quarantine in, 461
eczenia after, 424
empyema in, 428
exanthem in, 373
Scarlet fever, endocarditis in, 406, 444
enteritis in, 426
etiology of, 341
facial palsy in, 403
family predisposition to, 349
fever in, 366
furuncles in, 425
gangrene in, 422
of neck .in, 385
gangrenous angina in, 396
hemiplegia in, 428
hemorrhagic, 387
hemorrhage from erosion of
bloodvessels, 409
herpes in, 424
history of, 341
hot pack in, 472
hydrotherapy in, 467
hygiene of sick apartments in,
463
hyperpyrexia in, 368
hypodermoclysis in, 474
immunity and susceptibility to,
345
incubation period of, 363
infection in milk, 357
influence of pregnancy and puer-
perium, 359
of race, 353
influenza, differential diagnosis
of, 454
insanity after, 429
irregular, 388
isolation of, 460
itching in, 373
involvement of antrum of High-
more in, 444
jaundice in, 426
keratitis i.n, 404
kidney changes in, 445
laryngitis in, 380
leukocytosis in, 437
lymphatic glands in, 378
malignant, 385
mastoid disease in, 403
measles, differential diagnosis of,
453
membranous angina in, 396
meningitis in, 403, 428
mode of transmission of con-
tagium, 344
morbid anatomy of, 439
multiple neuritis in, 429
myocarditis in, 406
noma in, 422
oedema of lungs in, 427
optic neuritis in, 406
orbital cellulitis in, 405
otitis media in, 400
paraplegia in, 429
partial eruptions, 389
pathology of, 436
pericarditis in, 444
period of infectivity of, 355
phlebitis in, 425
pleurisy in, 428
INDEX
777
SoaTlcl. I'(!vcr, prKMinifniiji in, .'Wl, 427
\.nv.\i\\('.nw. <»r, iiifliic'dcc, of ulM-
l,u(l<^ on, '.Wl
ol' cliiii.'U.t! on, .'M!)
ol' Jocniil.y on, 1352
of a(!ii.son on, '.ihO
prognosis oF, 457
prognostic infliuincc of age, 458
ol' (;oinj)lic!il.ion,s, 459
ol' viruldiicy, 45S
prophylaxis ol', 45!>
protozoa in, 'V,V,i
puerperal, 359
purpura heinorrJiagica in, 420
rccurronces of, 393
relapses of, 393
respiratory symptoms, 380
return cases of, 356, 4()1
rubella, differential diagnosis of,
454
second attacks of, 392
secondary angina in, 397
septicitniia and otitis media in,
401
septic erythema in, 391
form of, 382
sequelae of, 430
serotherapy in, 374
simplex, 365
smallpox, differential diagnosis
of, 454
stage of eruption, 369
of invasion, 365
strawberry tongue in, 448
streptococcus, 434
suppurative arthritis, 420
surgical, 361
symptomatology of, 363
symptoms, gastrointestinal, 381
respiratory, 380
throat, 369
synonyms of, 341
tetany in, 429
thrombosis of lateral sinus in,
403
tongue, 374
tonsillitis, differential diagnosis
of, 454
treatment of, 374
of ears, 470
of enlarged glands, 469
of fever, 467
of gastroiiitestinal tract, 473
of heart, 473
of joints, 471
of Ludwig's angina, 470
medical, 467
of noma, 469
of purpura, 473
of purulent rliinitis, 469
of throat, 468
of uraemia, 472
typhoid, 387
urticaria in, 424
use of blood serum of convales-
cents, 475
I Scarlet fever virulencf; influenr-ing fjrog-
nosis, 458
vomiting in, 3(>(i
vvitlioiit angina, 392
desquamation, 392
eruption, 390
fever, 388
Scarring after ehiekenpox, 32(i
Scars after smallpox, 190
vaccination, 51
Scratchy heel, 139
Season and smallpox incidence, 154
iiifhu^nce of, on scarlet fever, 350
Second attacks of ehiekenpox, 319
of measles, 485
of rubella, 562
of scarlatina, 392
of smallpox, 151
Secondary angina in scarlet fever, 397
fever in smallpox, 183
toxic or septic rashes in smallpox,
196
umbilication in smallpox, 180
Septic diphtheria, 629
scarlet fever, 382
Septicaemia after vaccination, 64
in smallpox, 241
Sequelae of cliickenpox, 329
of diphtheria, 640
of rubella, 561
of scarlet fever, 395
of smallpox, 229
of typhoid fever, 583
Serum treatment of diphtheria, 730
of smallpox, 306
Sheeppox, 135
Sheffield smallpox statistics, 118, 119, 121
Ship fever. See Tj-phus, 566
Simple scarlet fever, 365
Skin complications in scarlet fever, 423
Sloughing of vaccine site, 63
Smallpox, 144
abscesses in, 229
age incidence of, 112
albuminuria in, 226
alopecia after, 191
in America, 147
atmospheric conditions and, 156
bacteriologv of, 256
baths in, 299
continuous warm, 300
bed-sores in, 231
blood in, 253
boils in, 229
in camel, 143
carbuncles m, 230
changes in bone-marrow in, 250
in heart in. 250
ixx kidneys in, 249
in liver in, 249
in hTnphatic glands in, 250
in skin in, 242
in spleen in, 249
in testicles in, 251
complications of abdominal, 237
ear, 235
778
INDEX
Smallpox, complications of, heart, 236
nervous, 237
ocular, 231
respiratory, 236
and sequelae of, 229
confluent, 199
superficial, 212
conjunctivitis in, 232
corneal ulcer in, 233
in countries where vaccination is
neglected, 132
critical days of, 279
cytoryctes variolse, 264
deaths among royalty from, 149
decline of, after introduction of vac-
cination, 105
delirium in, 182
diagnosis of, 266
diet and stimulants in, 301
disinfection, 285
disseminated spinal sclerosis in, 241
dviration of isolation of, 287
effect of season on, 154
eruption upon mucous membranes
in, 180
erysipelas complicating, 230
etiology of, 150
exfoliative dermatitis in, 196
fever in, 183
in foetus, 221
gangrene of scrotum in, 231
of skin in, 194, 231
hemorrhagic, 202
incubation period of, 166
infected sick-room objects, 160
infection of, 157
carried by healthy persons, 160
transmitted in the air, 161
infectious period, 157
infectiousness of blood in, 255
initial stage of, 167
inoculation of, in America, 25
insanity after, 237
insusceptibihty to, 150
involution of eruption in, 185
iritis in, 235
isolation of patients in, 282
itching in, 189
joint disease in, 237
local use of tincture of iodine, 311
macules, 174
mild type of, 206
modified, 209
in monkey, 143
mortality in prevaccination period,
275
in negroes, 154, 276
number of lesions present, 179
oedema of glottis in, 181
orchitis in, 237
otitis media in, 235
papules, 174
paralysis in, 238
paraplegia in, 239
pathology of, 242
of mucous membranes, 248
Smallpox, peripheral neuritis in, 241
phimosis in, 237
phlebitis after, 237
pigmentation after, 190
pleurisy in, 236
pneumonia in, 236
in pregnant women, 215
prevalence of, before discovery of
vaccination, 106
prevention of pitting in, 308
prodromal rashes of, 171
prognosis of, 275
prophylaxis, 282
pseudokeloidal growths after, 230
pustules, 177
quarantine of, 283
rashes in, 196
scarlatiniform erythema, 196
scars of, 190
second attacks of, 151
septicaeinia and pysemia in, 241
in sheep, 135
sore throat in, 181
stage of decrustation, 186
of desiccation, 185
of eruption, 173
of suppuration, 176
streptococcus pyogenes in, 261
symptomatology of, 166
symptoms, favorable, 281
unfavorable, 281
toxic or septic rashes, 196
treatment of, 282
of eye complications, 313
local, 306
of nervous svmptoms, 297
red light, 304
serum, 306
of throat, 297
urine in, 171, 225
use of morphine in, 298
vaccinated and unvaccinated, 116
vaccination during the incubation of,
290
varieties of, 199
vesicles, 174
Sore throat in smallpox, 181
Spontaneous cowpox, 142
at Cohasset, 93
Spotted fever. See Typhus, 566
Spurious vaccination, 42, 49
Stage of decrustation in smallpox, 186
of desiccation in smallpox, 185
Statistical evidence of efficacy of vac-
cination, 105
Statistics of the German Vaccination Law,
123
of revaccination, 120
of smallpox mortality before and
after introduction of vaccination,
108
Strawberry tongue in scarlet fever,
374
Streptococcus pyogenes in smallpox,
261
in scarlet fever, 434
INDEX
779
Siilplmr (linxidc (liHiiii'cctJoii, 7(»;i
inclliod of, IM
(Siipixinilivc lever in ,sin;ill|)o\, \K',
.sl.'ifie ol' sMi.'illpox, I7(>
Siir^ie.'il se.'irlel. lexer, ;',(il
Siiseepliliilily to VMceiiii.'M)!' irifjirirs horn
of \;ifi()l()iis niolliers, 221
Sweden, iiil i-()diiei'ioii of \;icein;il ion in,
107
v;icein;ition made eoinpnlsory in,
107
smallpox (leaXlis before and after
introduction of vaccination, 11
Symptomatoloify of cliici