>V!U'. fyxmll IMwmtg plrmg BOUGHT WITH THE INCOME PROM THE SAGE ENDOWMENT FUND THE GIFT OF 3*em*g m t Sage 1891 A 4 S±QJiM */M/&d. Cornell University Library RL 75.N53 Selected monographs on <] er, "*] t 7 l l °9y- 3 1924 012 173 229 a Cornell University J Library The original of this book is in the Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924012173229 THE NEW SYDENHAM SOCIETY. INSTITUTED MDCCCLVI11. VOLUME CXLIII. SELECTED MONOGRAPHS ON DERMATOLOGY. TJNNA. NIELSEN. DTJHBLNG. BBONSON. BLANC. BEBGEB. PBINCE-MOBBOW. LONDON: THE NEW SYDENHAM SOCIETY. 1893. c*^ PBINTED BY ADLAED AND SON, BABTHOLOMEW CIOSE, E.C., AND 20, JTANOVEB SQUARE, W. CONTENTS. Selections from the Dermatological Writings of Dr. P. G-. Unna. [Translations, chiefly in Abstract. Edited by Phineas S. Abraham, M.A., M.D., B.Sc, F.K.C.S.I.] ...... 1 On the Appearance of Herpes Zoster during the Administration of Arsenic. By Ltjdwig Nielsen, M.D. . . . . . . .167 A Collection of Dr. Duhring's Papers on Dermatitis Herpetiformis . . . . .177 The Sensation of Itching. By Edward Bennet Bronson, M.D. . . . . . . .299 Beport of a Case of the Mycosis Fongoide of Alibert. By Henry Wm, Blanc, M.D. With Lithograph . 317 Pellagra. By Ludwig Berger, M.A. [Translated and Abridged by Frank H. Barendt, M.D.Lond., F.RC.S.Eng.] . . . . , . 341 Drug Eruptions. A Clinical Study of the Irritant Effects of Drugs upon the Skin. By Prince A. Morrow, A.M., M.D. [Edited by T. Colcott Fox, M.B.Lond., FRCP] With an Index . . 355 Researches on Psoriasis. By Ludwig Nielsen, M.D. [Translated by Frank H. Barendt, M.D.] . .569 SELECTIONS PBOM THE DERMATOLOGICAL WRITINGS OP Dr. P. G. UNNA/ TRANSLATIONS, CHIEFLY IN ABSTRACT. EDITED BY PHINEAS S. ABRAHAM, M.A., M.D., B.Sc, F.R.C.S.I., LECTUEEE IN PHYSIOLOGY AND HISTOLOGY, WESTMINSTER. HOSPITAL MEDICAL SCHOOL; PHYSICIAN TO THE WESTERN SEIN HOSPITAL, LONDON; AND EDITOR OP THE ' JOURNAL OP THE LEPROSY INVESTIGATION COMMITTEE.' PREFACE. Dr. Uota's contributions to dermatological literature are so numerous that, with the space at disposal, translations or abstracts of only a few could be included in this volume. The editor, indeed, is quite aware that several important papers by the author will not be found in the series; and he wishes to state that, with one exception, the selection has been taken from a number of reprints which Dr. Unna him- self sent to the Secretary of the New Sydenham Society for the purposes of this work. A complete list, however, of the author's publications is appended. The translations are, for the most part, given in abstract. The Editor desires to record his thanks to Dr. Chichester May, and Messrs. H. Felkin and A. D. Abraham, who have materially helped him in preparing the translations and abstracts ; and to Dr. Alfred Eddowes, who is responsible for the article on Pavus. The proofs have been submitted to and kindly approved by Dr. Unna. P. S. A. LIST OF DR. UNNA'S PAPERS (TRANS- LATED m ABSTRACT). i. Lectures on the General Pathology of the Skin 2. On Circular Patches of Exfoliation of the Palm and Tongue 3. On a Case of Cured Lepra Tuberosa 4. Syphilis and Eczema Seborrhoicum 5. Lichen Euber and its Treatment 6. Hyphogenic, Coccogenic, and Bacillogenic Sycosis 7. Three Varieties of Favus . 8. Becent Advances in the Therapeutics of the Skin 9. Contributions to our Knowledge of Lanolin . 10. Medicated Superfatted Potash-soaps (Ointment Soaps) 1 1 . On the Use of Ichthyol in Internal Diseases . 12. On the Treatment of Trichophyton Capitis 13. Advances in the Anatomy of the Skin 14. On the Normal Surface and Covering of the Tongue 15. On the Insensible Perspiration of the Skin . 16. On Skin Varnishes 17. The Action of Carbolic Acid and Oil of Cloves on Lupus 18. On the Cultivation of Epidermic Fungi 19. The Staining of Micro-organisms in the Horny Tissues 20. On Plasma-cells, especially in Lupus 21. On Waldeyer's Plasma-cells and Ehrlich's Mast-cells 22. Some Observations on Rodent Ulcer 33. Contributions to Dermatology PAGE I 46 50 54 59 62 64 68 9i 95 99 103 107 119 122 125 129 132 140 145 149 151 152 LECTUKES ON THE GENERAL PATHOLOGY OE THE SKIN. DELIVERED IN THE WINTER SESSION, 1888-89.1 I. Anjemia. The vessels of the skin undergo greater changes of calibre within physiological limits than do those of any other organ, and this is due to the great development of its muscular and nervous apparatus. In its pathology, too, contraction of the vessels plays an important part, but here other factors are also at work in producing anaemia, viz. qualitative and quan- titative changes in the total amount of blood in circulation. If the anaemia be caused by contraction of vessels, the skin feels cooler and often less succulent ; but if the tone of the vessels remain normal, the temperature and the amount of fluid in it may be as before, although it may be anaemic. Hence anaemia of the skin may be divided into two great groups : (1) Anaemia due to general alterations in the total quantity of blood, and (2) Anaemia confined to the skin. Anaemia consequent on qualitative blood-changes may be due to a deficiency of red, or an increase of white, corpuscles, or to a combination of both factors. A want of red cor- puscles makes the skin and mucous membranes anaemic in true chlorosis, in acute and chronic inanition where the 1 " Vorlesungen liter allgemeine Pathologie der Haut, gehalten in Winter- semester," 1888-89 — 'Monatsh. fur prakt. Derm.,' ix Bd., 1889, Nos. 1, 2, 6, 8, and x Bd., 1890, Nos. 3, 4, 6, 7— I. Anamie. 1 2 tjnna's dermatological papers. patients cannot take food, in those recovering from con- suming febrile diseases, in pseudo-leukaemia, and in hydrsemia; but in leukaemia there is also an absolute and relative in- crease in the number of the white corpuscles, and in certain forms of anaemia and cachexia — e.g. in absolute starvation and • advanced tuberculosis and cancer — in addition to a deficiency of haemoglobin, there is also a diminution in the total quan- tity of blood. Not only is there here a change of colour of the blood, but there is an adaptation of the vessels of the skin to the diminished supply, i. e. the stream-bed of the skin becomes contracted in simple diminution of the blood. This is seen, too, after loss of blood from wounds and opera- tions, and in cases of intestinal parasites, as in pernicious anaemia. After severe haemorrhage in young persons, the skin becomes waxy, yellow, and transparent, from the regu- lative contraction of all the vessels of the skin and absorption of tissue-fluids by the veins and lymphatics. The ashy-grey colour of the skin in cholera is similarly due to a general contraction of the cutaneous vessels, com- bined with increasing cyanosis of the blood, as the velocity of its current diminishes. The fall of temperature and in- crease of the vascular tone of the skin resulting from these quantitative anomalies of the blood, approximate such cases to the isolated anaemia, which we shall now consider, and in which qualitative changes are of course excluded. This anaemia may involve the whole skin or only parts of it. When the whole skin is anasmic, either the circulation in general or the central nervous system must be affected. Contraction of the cutaneous arteries always runs parallel with the anaemia, and sometimes this contraction follows a diminished blood supply ; but whether the arterial constric- tion or the diminution of blood in the skin be primary in any given case, is often as difficult to determine as in phy- siological experiments. Arterial constriction is certainly primary in the death agony, and it causes that unfortunate pallor which makes the post-mortem study of most dermatoses so difficult, and that of the circulation anomalies impossible. The paleness accompanying cardiac weakness, especially that which precedes fainting and obviates a dangerous fall of blood-pressure, is also probably primary in nature. To the GENERAL PATHOLOGY OF THE SKIN. 3 same category belongs the anaemia which accompanies or precedes nausea (ah injectio medicamentis, chloroform, swing- ing, and sea-sickness), and in which there is often an accom- panying inhibition of the splanchnics, causing plethora of the intestinal tract, the anaenria of the skin being here regulative. Reflex spasm of the cutaneous arteries is also often caused by the prodromata of an epileptic fit, by psychical disturbances (fear, sudden terror), and by strong stimulation of sensory nerves, especially of the abdomen, as in colic. The goose- skin due to mental perturbation indicates, moreover, powerful stimulation of all the unstriped cutaneous muscular tissue, including the vascular. A secondary adaptive contraction of the dermal vessels gives rise to the pallor following night-watching and exces- sive muscular or cerebral activity, when there is a collateral overfilling of the vessels of internal organs, according to their needs. The most important example of a general contraction of the cutaneous vessels is seen in the signs of all acute infec- tive diseases. Here the poison circulating in the blood supplying the vaso-motor centres, gives the stimulus which results in the periodic contraction of the peripheral vessels. If the rigor be severe the vessels of the superficial muscles are also affected, and those of the internal organs become abnormally full. Hence the temperature of the surface falls, and that of the deeper parts of the body rises. Influences which paralyse the vessels, such as warmth, can partly over- come their tonic contraction. As is well known, during the rigor the temperature of the closed axilla is already rising. On the other hand, cold accelerates the rigor, showing that the tone of the vessels, in the interval between the rigors, is really raised, and only kept in check by the greater warmth of the blood and the increased cardiac action. Certain organic poisons, especially strichnine and ergotine, increase the tonic contraction of the peripheral vessels, although there is not the arterial spasm of rigor ; and the pallor after acute poisoning with alcohol is similarly pro- duced, by the products of its decomposition. It thus appears that it is not a slight irritation which causes, reflexly or directly, a general cutaneous ansemia, but 4 unna's debmatological papers. pathological circumstances which attack profoundly the whole constitution. This is easily understood when we con- sider that the normal constriction of the vessels is consider- able, and that the vaso-motors must be intensely stimulated in order to produce universal visible pallor and sensible cold. We may, therefore, safely ignore a paralysis of the dilators in the production of general cutaneous anaemia. In contradistinction to the general causes which produce universal anaemia we have to look for local causes for the production of localized anaemias. These can be more easily classified into those due to primary vascular constriction, and those in which the narrowing of the calibre of the vessels is secondary to a diminished blood supply. We make frequent use of the latter principle, and increase the vascular tone ; for instance, when we raise the extremities to an unwontedly high position, for the purpose of quieting the circulation or lessening pain. Ligaturing an artery causes immediate contraction of it& trunk and branches on the distal side of the ligature, and in the case of a vein, on the proximal side as far as the first collateral branch; and the contraction accurately represents the pressure of the column of blood which has been removed. Perceptible paleness is rarely produced in these cases — only temporarily, indeed, even after ligaturing a large artery such as the femoral, for the collateral circulation is soon established. The anastomoses of the superficial and deep cutaneous net- works of vessels are far too extensive for the ligaturing of a few of them to make any impression on an area of skin. A partial emptying of the vessels through external pres- sure is another cause of local anaemia. The compression may be from without the body, as from the finger, articles of dress, bandages, &c, or from within, from tissue masses, &c, beneath the cutis. While arterial ligature generates localized anaemia with difficulty, pressure on the arterioles and capil- laries produces it with ease, but only so long as the pressure lasts ; on its removal, the anaemia is replaced by a relaxive hyperaemia — the vessels having become paretic through the pressure. In this manner, too, act tumours of recent date which stretch the skin, collections of fluid and foreign bodies, as well as rapidly growing abscesses, temporary oedemas, GENERAL PATHOLOGY OE THE SKIN. 5 injections, and urticaria. But if the pressure on the cuta- neous vessels has lasted for weeks or longer, as in atheroma, uric acid concretions, chronic oedema, myx oedema, tumour- like infarcts of the lymph-spaces, such as occur in dermal leprosy — an organic narrowing of the vessels takes place, "the whole cutaneous vascular network is diminished, and many capillaries are obliterated. Further on we shall see that this is the cause of many forms of anaemia ; the skin remaining pallid and anaemic, like a cicatrix, after pressure has been removed and swelling has subsided. Local anaemias, due to primary arterial constriction, may be subdivided into those arising from spastic contraction of the arterial muscle-tissue, and those due to an organic nar- rowing of the vessels. The former, of course, are generally temporary, and the latter permanent ; but a spastic narrow- ing may occasionally last for some time — hence it is best to retain the division just mentioned. A classification based ■on a narrowing of arteries on the one hand, and on a con- traction of capillaries on the other, however useful in single cases, cannot be generally maintained ; for, although every narrowing of capillaries is not due to arterial constriction, the lessened calibre of an artery always results in a capillary narrowing, at any rate in the stretched elastic skin. Cold is the commonest cause of increased tone in the cu- taneous vessels ; but to produce the effect the cold must be considerable, as from an ice-bag or ether spray. If the difference of temperature between the cold body and the skin be inconsiderable, or the abstraction of heat be made difficult in any way, the temporary arterial spasm, in healthy individuals, is followed by a paresis of the vessels, and the heat may continue to be lost. This is the case when the body is submitted to a cold stream of air, or immersed in a moderately cold bath. In fact, there is a subjectively pleasant relaxive hypersemia, the vessels being expanded beyond their normal calibre, and thus the skin is rendered to some extent inert to the heat-abstracting agent, the in- creased flow of warm blood compensating with accuracy the loss of heat. The effect of slight cold, such as normally acts on the exposed parts of individuals dwelling in northern countries, b TJNNA S DERMATOLOGICAL PAPEKS. thus does not produce anaemia, but a slight hyperaemia of the exposed skin — the result being what we call a fresh, healthy colour. On the other hand, the inhabitants of warm countries have the face and hands normally pale — like the covered parts of those living in cold climates. The pale face and hands of southerners, and the pale bodies of northerners, do not generally show the reflexly produced pulsating hyperaemia : we have evidently here to do with a greater normal contraction of the vessels ; and we shall probably be right in regarding this increased tone as com- pensatory to the relaxing effect of warmth on the cutaneous vessels, just as we formerly considered red cheeks as produced by an action compensatory to the effect of cold. In spite of this, the inhabitants of warm countries are not anaemic, it is only that their cutaneous vessels have contracted in a regulative manner. No doubt this is a purely peri- pheral condition, an idiospasm of the vessels, and its import- ance will become evident when we are considering the patho- logical departures from the normal. To this class of anaemias, due to self- regulative contraction of vessels, may be added that of limbs which have been paralysed for a considerable time. This has been a bugbear to pathologists, for a paralysis of the dilators could scarcely produce recognisable anaemia ; and, on the other hand, paralysis of the vaso-motors ought to produce hyperaemia > and even if this hyperaemia be transient, it would at the most give place to the norma] condition, and not to anaemia. In consequence, however, of the paralysis, not only would relaxive hyperasmia occur, but later on there would be a constant hyperaemia of stagnation from the defective muscular movements, and the now greater effects of gravity. We shall not go far wrong, therefore, in considering the anaemia, which is certainly there, to be due to a peripheral self- regulation, or an idiospasm, of the vessels, which counteracts the effect of gravity and the loss of action of the voluntary muscles. This explanation is rendered more probable by the fact that paralysed limbs become not only anaemic but often cedematous, from an increase of venous as well as of arterial tone, a phenomenon which has not hitherto been satis- factorily explained, but which can be easily understood by GENERAL PATHOLOGY OE THE SKIN. 7 assuming it to be a part of the peripheral self -regulative arrangement. The following instances of arterial spasm cannot be regarded, like the above, as within physiological limits. Hemicrania spastica and Raynaud's disease of the hands and feet are truly morbid affections of the tone of peripheral arteries. The former need only be mentioned here, because pallor of the skin is of course one of its characteristic symptoms ; for the rest, it comes among the diseases of the vascular and nervous systems. Raynaud's disease, however, demands special consideration. In the mildest form, found especially among washerwomen, the hands and feet, particularly the digits, are only veryanaemic, and in some cases bluish white. In the cold, shooting pains occur, which rapidly pass off, and when the patients are warm in bed, or immerse the extremities in warm water, itching sensations are felt. The temperature is objectively loweredj and the tactile and temperature senses are dulled. Long- enduring anasmia of this kind can, of course, only develop where all the arteries of a given area are uniformly and syn- chronously narrowed ; and, as we should expect, the extre- mities alone are attacked by this disease — for in them alone can a peripheral cause easily affect all the cutaneous vessels in such a manner that compensation becomes impossible within the area. That the branches of the cutaneous arteries, and not their trunks, are affected is proved by the normal condition in which we find the ulnar and radial arteries of the upper limb and the dorsal and plantar of the foot. It is also obvious that even the most profound anaemia is not followed by any hemorrhagic venous accumulation of fluid — terminal arteries in Cohnheim's sense do not exist. The only effect on the circulation, beyond the narrowed arteries, is a pro- found anaemia of the capillaries and veins, with correspond- ing fall of pressure and of velocity of the blood current. The capillary stream-bed is doubtless diminished ad maximum by the same cause, and this may be the reason why the permanent specific anaemia of these cases does not lead to a damaging of the vascular walls — such as always occurs after prolonged mechanical constriction of an artery, and which might be expected here, seeing that the contraction 8 unna's dermatological papers. often passes off for a time. Bat no trace of such damage, or of hasmorrhagic oedema, is to be seen after reducing the contrac- tion by hot bathing. On the other hand, one effect is never absent in severe cases of true Raynaud's disease, viz. a partial necrosis of the skin, which always takes place at the balls of the toes and fingers, and bed of the nails, where a com- pensating circulation from deep-lying vessels is quite im- possible : in some cases this goes on, in the course of years, to successive necrosis of all the phalanges. The primary cause of this peripheral idiospasm is quite unknown ; cold, of course, is the most important assisting influence ; and not only in this respect, but in its whole aspect, this disease has many analogies to the so-called "frost-bite," which is a sort of spastic, stagnating dermatosis. Before considering the true organic narrowing of the cuta- neous arteries, we may shortly discuss the anaemia artificially produced for therapeutic or cosmetic purposes. The con- ditions demanding such treatment, may be either real morbid processes accompanied by hyperaemia, or their erythematous remains, or simply redness of the face and hands, which is still within physiological limits. In these cases, stimulation of the vaso-motor nerves and vascular ganglia would be of little use, for the effect would soon pass off, and be followed by an undesirable paresis of the muscular tissue of the vascular walls ; the means we possess, moreover, for producing this effect are very few. It is, however, easy to produce a diminution of the hyper- aemia by the intelligent use of the group of reducing, oxygen- binding remedies. The following substances possess a chemical action of this kind, viz. sulphur and its prepara- tions, pyrogallol, resorcin, ichthyol, and certain metals and oxides — mercury, oxide of zinc, and oxide of lead. The arterial constriction thereby produced is not rapidly gene- rated and evanescent, but slowly developed and permanent ; and is most nearly allied to organic narrowing, or thickening of the vascular walls, by the growth of young connective tissue ; but up to the present, its nature is not accurately known. Since the lessening of the hyperaemia is always accompanied by diminution of any concomitant inflammation, we must probably regard it as an organic reduction of volume GENERAL PATHOLOGY OF THE SKIN. 9 of the whole vascular tree — the vascular pores being dimin- ished and the outbreak of inflammation thus made more diffi- cult. The thickening of the walls of the valved arterial branches of the frog's web, as described of Klemensiewicz, iwhen the blood-pressure is falling, offers an acceptable physio- logical parallel. In the really organic diminution of calibre of the cutaneous vessels, the capillaries, many of the arterioles and venules, and some few larger branches, are actually converted into cellular or fibrous connective tissue. Embolism and throm- bosis, as causes of anaamia, play an important role in dermal pathology ; but on account of the very frequent anastomosis •of the cutaneous vessels, only infective embolisms have serious ■results. Innocent emboli, indeed, may be carried and lodged in the cutaneous network without producing symptoms, and the same is true for local thrombosis following such emboli. Careful search would no doubt reveal them, in cases of general embolism, to be much more frequent in the skin than is com- monly supposed. We often find, quite unexpectedly, in the examination of tumours, thrombi of apparently harmless bac- teria, of secondary importation, or hyaline thrombi in wider areas, the former being too small, and the latter allowing the blood-stream too much room, to produce any perceptible anaemia, although they must obviously increase the resist- ance to the blood entering the capillary area. For the production of real anaemia, there only remains a narrowing of the capillary region, leading to obliteration of lumen by young connective tissue. The process called endo- arteritis obliterans by Friedlander, is of much greater im- portance in the pathology of the skin than we might suppose. This fibrous vascular degeneration does for the skin, what the embolic and thrombotic closure of the vessels does for ■other organs in producing anaemia. A review of the dis- eases of the skin will show that it may follow infective in- flammations as well as ulcerative processes, and progressive as well as retrogressive disturbances of nutrition. Without enumerating all the individual instances, we may point out the general characteristics ; and for this purpose it seems appropriate to distinguish two kinds of obliterating closure of vessels. In some cases, the cutaneous vessels are oblite- 10 unna's dbrmatologioal papers. rated from the capillaries backwards, after being extremely narrowed for some time by external pressure. This atrophy, due to pressure, follows abnormal stretching of the muscular and elastic tissue of the skin, as in cases of long-standing scleroderma, pruriginous eczema, and ichthyosis, as well as in cases of prolonged pressure from atheroma, uric acid con- cretions, and chronic oedema. Obliterating atrophy, after thinning of the vessels by traction, we find in cicatrisations, and especially in the strise gravidarum. Syphilitic processes, on the other hand, cause a peculiar affection of both the larger and the smaller vessels — but chiefly of the former, in which a more or less cellular connective tissue is developed within the lumen, from the endothelium. Proceeding as it does with sclerosis of the already existing connective tissue, the production of large anaemic tumours of cartilaginous hardness may be the result. Anaemia lio- dermia may be similarly produced, but •without sclerosis of the connective tissue, in the extremities of certain patients with tabes ; and, in the same way, are initiated changes which lead to a whole host of fibrous hypertrophies and atro- phies, as in sclerosis of the skin, morphoea, and keloid. In all these cases there has been no preceding pressure or trac- tion ; the obliteration of the vessels does not follow but pre- cedes the existing anaemia. II. General Considerations concerning the Hyperemias of the Skin. 1 The various anaemias of the skin are, upon the whole, of a very uniform character, because in them there is no very great departure from the normal state of the circulation. The general term hyperasmia, on the other hand, includes conditions differing considerably from one another, and to understand them clearly it is necessary always to have the physiological facts of the cutaneous circulation in one's mind. The appended diagram indicates the nerve-tracts concerned in the regulation of the blood-flow through the skin. 1 " Allgemeines iiber Hyperamien der Haut " — ' Monatsh. f . prakt. Derm.,' ix Bd., 1889, No. 2. GENERAL PATHOLOGY OE THE SKIN. 11 DlAGBAM OF AETEEIAL NeBVE ApPABATTJS. (TO Cerebral Ganglion Vaso-motor Ganglion (of Medulla) Heart Sympathetic Dilator Constrictor Ganglion of Artery (Tonic and Dilating) Sensory Endothelial Nerve \ (Dilator) ^E Sensory Muscle Nerve (Constrictor) The tube in the diagram represents a piece of muscular cutaneous artery, just where it is about to enter the cutis vera. The lines represent nerves, the circles with dots in their centre, ganglia, and the points, nerve terminationSi Two terminals are within the muscular wall of the artery, a motor at a and a sensory at sm. On the internal surface of the tube is a sensory endothelial nerve, se. The vascular ganglion g gives off two nerves to the motor terminal a, the fine filament g a taking origin from it, and a thicker so-called vaso-motor, m a, which only passes through it. This gan- glion also receives h g, a centripetal sensory nerve from the skin, and a centrifugal branch of communication, m g, from the higher centre m, or a so-called dilator. The vaso-motors and dilators generally run together in the case of the skin, e. g. the sciatic carries those for the leg. The centre m re- presents a series of vaso-motor ganglia distributed along the medulla and cord. In addition to the nerves already men- tioned, branches are received by this centre m from the cerebrum (p — m), from the heart (c — m) , from the skin (h — to), and from the endothelial coat of the vessel (se — m), each of which conveys a psychical or sensory stimulus from the organ in question. If we wish to ascend from the favoured 12 unna's dermatological papers. alternative — by which all hyperemias, without distinction, are attributed, either to a paralysis of the vaso-motor nerves, or to an irritation of the inhibitory (dilator) nerves — to definite pathological pictures of the so various clinical ano- malies of the cutaneous circulation, we must shortly review the physiological experiments which have led to the doctrines current to-day on the normal circulation of the skin. These experiments justify the diagram given above. Ostroumoff's observations 1 showed that tetanising the newly-cut nerve produced with certainty great arterial con- striction and lowering of temperature (by the tract m — g — a) . The inhibitory (dilator) nerves, on the other hand, were chiefly affected by weak stimulation, by rythmic stimulation at intervals of five seconds, and by strong tetanic stimula- tion when the vaso-constrictors were already dead (on the fourth day for the sciatic) . In all these instances, hyperemia, with rise of temperature, resulted, i. e. not only a removal of the tonic influence (by the path m — g — a) of the vaso-motor centre, but also an inhibition (m g) of the spontaneous action (by the path g — a) of the vascular ganglia, and hence a maximum dilatation. The nature of the conditions justifies the conclusion that the dilatation is not due to an independent muscular action of the artery (Bxner), but to an inhibition of all vaso-constricting influences at the peripheral ganglion, which is the point best suited for this purpose. For, with this assumption, we can understand how it is that weak stimuli produce an effect so prodigious as the removal of the contraction of the strong circular muscular fibres of the arteries ; further, that rhythmic, *'. e. cell stimuli, are par- ticularly effective ; and that after commencing degeneration of the vaso-motors a still further dilatation must ensue, since now by strong stimulation of the inhibitory fibres, which probably degenerate just as quickly, only inhibitory impulses can be started in the ganglia. By mapping out the path m to a in the way shown in the diagram, we avoid having to assume two different kinds of nerves with antagonistic muscle apparatus in the artery, for which the histology of the cutaneous vessels gives us no warrant. Neither do we 1 "Experiments on the Inhibitory Nerves of Cutaneous Vessels," ' Pfliiger's Archiv,' 1876, p. 219. GENERAL PATHOLOGY OP THE SKIN. 18 introduce unnecessary complications ; for peripheral ganglia, with the definite function of inhibition, we must assume to exist in the skin in any case. It is a well-known fact, noticed by all experimenters alike, that after section of all nerve tracks connecting the vessels with the central organ, the vessels gradually contract again, and acquire new tone, which, how- ever, never regains the old delicacy in reacting to external stimuli or the former resistance. The contraction can be explained by introducing between the passive stretching of the muscle tissue by the blood-pressure and the contraction of the muscle, a sensory element, sm, which, stimulated by the stretching of the muscle, leads the latter to contract (by the path sm — a). An independent tone, admitting of regu- lation within narrow limits, can, however, be established only by peripheral ganglia. According to our diagram, g remains intact, exercising an independent influence by the path g a, and counteracting the stretching of the vascular tube by the blood-pressure. The further reaction of the centrally paralysed cutaneous vessels, compared with that of unparalysed vessels, shows us how to decide with certainty by what paths the remaining active stimuli must travel. OstroumofE found that nicotine poisoning, or poisoning by C0 2 (by suspending artificial respiration), only produced cutaneous hyperaemia when the nerves of the vessels were untouched. These stimuli hence travel by the path se — m — g, if we assume that the poisoning starts from the blood itself ; or by the path m — g, if it affects the vaso-motor centre directly. Only very severe nicotine poisoning also dilated the vessels paralysed from their centre. Must we therefore also assume a direct path se — g ? Probably not, for this paralysis may be looked upon as a direct action of the poison on the terminal of the tract g — a, independently governed by the vascular ganglion. Latschenberger and Deahna 1 found, moreover, that cen- tripetal fibres run from all vessels, and that their stimulation causes dilatation in the vascular area of the artery, and tends to lower the pressure which has been raised by arterial con- striction in a self -regulative manner. These impulses travel by the path se — m — g. Starting with the proof of such 1 ' Pfliiger's Archiv,' 1876, p. 157. 14 unna's dermatological papers. sensory vascular depressor nerves, and reasoning by analogy, these authors assume the existence of similar sensory anta- gonistic constrictor fibres, which, when the vessels are di- lated, produce a regulatory contraction by stimulation of the vaso-motor centre. This path, se — m — a, constructed, as it were, for the sake of symmetry, may be considered super- fluous, since its existence is not proven. We can conceive the same effect to be produced in a simpler manner — by the expansion of the vascular tube stimulating directly the sen- sory nerve-endings situated in the stretched muscle-tissue, and thus reflexly causing a degree of contraction correspond- ing to the amount of expansion. We then have need only of the path sm — a, which we have already used to account for the vaso-constriction after section of the vaso-motors, to explain, without making use of the centres in the cord, all those cases of constriction which originate from the interior of the tube itself. This assumption of only two kinds of sensory nerves in the vessels, viz. endothelial- and muscle-nerves, suffices for all experimental as well as pathological facts hitherto observed. The former, stimulated by pressure of the blood or of the vascular wall, produce contraction reflexly through the cord centres ; the latter, stimulated by the stretching or tension of the vascular wall, cause a muscular contraction purely peripherally and directly. The gradual rise of pres- sure, increasing and diminishing rythmically with the heart- beat, is the natural stimulus of the inhibitory ganglia, by the path se — m — g, and it produces the dilatation of the arteries. The rapid and maximum expansion of the arterial wall, which occurs during arterial blood transfusion, leads (by the path sm — a) to so energetic a reaction in the direc- tion of constriction, that complete occlusion of the arteries may result (Cohnheim). The gradual constriction of the cutaneous arteries when blood-pressure is falling {vide Anaemia) occurs without pres- sure on, and stimulation of, the sensory nerves (se), and is therefore chiefly due to the toxic action of m and g, which accommodates the tension of the arterial wall to the dimi- nished internal pressure. The investigations of Bernstein, 1 1 ' Pfliiger's Archiv,' 1877, p. 575. GENERAL PATHOLOGY OE THE SKIN. 15 on the other hand, have shown that the experimental pro- duction of arterial dilatation is veiy much facilitated by a previous strong constriction, such, e. g., as is caused by cold. The production of anaemia by cold, the blood-pressure being normal, accumulates, by compressing the endothelial nerves se, a latent stimulus for the inhibitory nerves ; and this becomes manifest when weak and otherwise ineffective stimuli are superadded. We have, moreover, already seen that the pallor due to external cold easily passes over to hypersemia in the case of the healthy skin (normal reaction of cold). This happens even when the blood-pressure is only a little raised, as, e. g., during quick awakening. It may also be caused by sensory stimuli, such as gentle rub- bing of the skin. All these events hence occur through the intermediation of the path se — m — g, and, as far as we can see, the assumption is sufficient of sensory endothelial nerves which are at the same time dilators, and of sensory muscle-nerves which are also constrictors of the cutaneous vessels. The former may be considered to be identical with the nerves seen by the author and by Bremer. We have to thank the experiments of v. Bezold, 1 and of Ludwig and Thiry, 3 for our knowledge of the fact that stimulation of the central end of sensory nerves causes rise of blood-pressure, and that the latter is the result of the contraction of peripheral arteries. This process takes the path h — m — a. Heidenhain, 3 much earlier, had observed a rise of temperature, i. e. dilatation of the cutaneous arteries, to follow stimulation of sensory nerves ; and this was not obtained after section of the vaso-motors. Snellen and Loven* found, further, that stimulation of the central end of the auricular dilated the arteries of the ear, and that stimulation of the dorsal nerve of the foot dilated the saphenous artery. A sensory stimulus thus caused dilata- tion of the cutaneous artery supplying the same region, i. e. a reflex travelling by the path h — g. Finally, Goltz and Ostroumoff observed a rise of temperature, or arterial dilata- 1 ' Untersuchungen iiber die Innervation des Herzens,' Leipzig, 1863. 5 ' Sitzb. d. Wiener Akademie,' 1864. 3 ' Pfliiger's Archiv,' 1870, p. 504. * ' Sitzb. d. Sachs Akad. d. Wissensch.,' 1866. 16 unna's dermatological papees. tion, even of the opposite, but symmetrical, region, after sensory stimulation. This would correspond to a stimulus taking the path h — m — g. The changes of cutaneous circulation, due to the stimula- tion of sensory end-organs in the skin, come then from im- pulses travelling either by sensory cutaneous nerves directly passing to the vascular ganglia of the same region, or by cutaneous sensory nerves connected with the vaso-motor centres of the cord, through which symmetrically situated cutaneous arteries are affected. The commonest example of stimulation by the direct path. h — g is furnished by the redness of the skin which rapidly follows a simple scratch or cut, and which then vanishes in a short time. The stimuli travelling by the roundabout way, through the vaso-motor centres of the cord, are gener- ally weak, and only stimulate the peripheral inhibitory centres g. They play an important part in the spread of nervous and parasitic dermatoses : in the latter case by producing a hyperemia which makes the skin a more favorable soil. Constriction -of all the arteries of the skin, by cutaneous stimuli travelling along the indirect path, occurs, as we have already seen in anaemia, only if the stimuli are very violent. Universal cutaneous anaemia is the precursor of cerebral anaemia (fainting), which generally soon follows. There are only the two sets of fibres, h — m and h — g, for the action of sensory nerves on the cutaneous circulation. Ludwig and Cyon 1 found that the stimulation of a cer- tain cardiac nerve in the rabbit caused all the cutaneous arteries to dilate. Considering the abundant supply of regu- lative machinery for the peripheral vessels, it would have been surprising if no means had existed for the direct inter- ference of the centre itself of the vascular system, viz. the heart, in the action of the vessels of the skin. In the de- pressor nerve of the rabbit this means has been found. When the blood-pressure rises, the heart relieves itself by more vigorous and slower beats (vagus stimulation), as well as by paresis of the peripheral vessels. The path c — m in the diagram is open for this process. 1 ' Sitzb. d. Sachs Akad. d. Wissensch.,' 1866. GENERAL PATHOLOGY OP THE SKIN. 17 We have, finally, to consider stimuli travelling from the cerebrum to the vaso-motor centres (p — g in the diagram). These explain the influence of psychical emotions on the cutaneous circulation. As is well known, the unstriped muscle of the cutaneous vessels is as little under the influ- ence of our will as any other tissue of the kind ; our con- scious thinking has not the slightest effect upon it. But certain conceptions, especially those causing shame or anger, can also, when they cross the threshold of consciousness, unconsciously affect in such a manner the vaso-motor centres that the arteries of the skin in certain regions are paralysed for the time. The stimuli passing down the path p — m — g are generally only strong enough to stimulate the peripheral inhibitory centres, and these too not even universally, since the blush for the most part only pervades the skin in the region of the head. Thus the effect produced differs from the above considered universal pallor caused by psychical disturbance (by the path p — m — d). Now, looking back at ■our diagram, we see that the path m — g is the most impor- tant ; it is, so to speak, the most active of all. In m a number of internal and external stimuli continually run together, to be conducted to the arterial tube, increased in number by the arterial stimuli originating independently in m. Instead of allowing antagonistic sets of muscular appa- ratus to counteract one another in the wall of the artery itself, by there being a second similar nervous mechanism with its subordinate muscles, there is the simple arrangement that all the stimuli for the arteries, which unchecked would lead to constriction, must pass through peripheral ganglia, in which they can be wholly or partially inhibited, according to the requirements of the individual artei'ies. As a single workman can hold in check the whole latent water-power behind a flood-gate, so very weak stimuli affecting this par- ticular spot suffice to keep all those tonic influences away from the artery and to paralyse it. Hence it is chiefly with paralysing or inhibiting influences that we have to deal in the chapter on hyperaemia. The peculiarity of the cutaneous vessels is their powerful tonic contraction (in contrast, e. g. with the vessels of the lungs) . Hyperasmias, or at any rate the so-called arterial ones, are hence, without exception, para- 2 18 unna's dermatological papers. lytic phenomena ; and we see how inappropriate, and even misleading, is the expression " active hypersemia," which is so often used. The "hypersemias of stagnation" might be much more appropriately termed " active," for here the tone of the vessels comes much more into consideration than their name indicates. It would, indeed, be better to avoid altogether the misleading terms " active " and " passive." If we do not wish to speak of " paralytic " hypersemias, we might very well employ the words "relaxing" or "fluction- ary," which also contrast well with the expression hyper- semia of " obstruction." Clinically, then, two classes of hypersemias are known by the bright red colour of the former, and the bluish-red (cyanotic) tint of the latter ; anatomically they are distinguished by the accelerated blood-stream in the former and the retarded in the latter. The terms " hyper- semia of relaxation" and "hypersemia of obstruction" hence cover the most important external characters. III. Eelaxive Hyperemia. 1 Cohnheim has taught us that the best cure for all injuries to the vessels is an increased flow of blood through them. An increased supply of blood to the vessels is only possible by a removal of the normal obstructions to the circulation ; and this, especially for the arteries of the skin, means a diminution of their tone. The capillary area of the skin, especially the papillae, is immediately exposed to the full force df the blood-pressure, which is usually broken in the arteries. The skin becomes red, gets hotter, and gives off more heat. While no pathologist would look upon the pus- tules of smallpox as the result of a toxic angioneurosis, such a view of the nature of a prodromal exanthem is, at least, plausible. The former condition is a type of an 'in- fective embolism of the skin ; the latter is the result of the action of the poison on the central vaso-motor system. 1 " Wallungshyperamie," ' Monatsh. f. prakt. Derm.,' Bd. ix, 1889, No. 6. [I have been unable to find an accurate and altogether satisfactory transla- tion for this expression, which literally means a " welling up." — Ed.] GENERAL PATHOLOGY OF THE SKIN. 19 The prodromal exanthem seldom affects the whole body; it has a predilection for the flanks and for the flexor sur- faces of the arms and legs. Hebra showed that the later eruption does not affect these regions, and he tried to prove a connection between these two facts. The author agrees with Curschmann that no such connection exists. The above-mentioned regions are generally free from the erup- tion of smallpox, even when no prodromal rash has appeared ; and we know that in leprosy these same districts are usually unaffected, although no previous hypersemia of them has taken place. In contradistinction to this is the roseola which appears in the convalescent stage of cholera. In this case the acute intoxication of the body is over ; the blood once more cir- culates through the contracted arteries and capillaries, and causes, where the stasis was most marked, at the tips of the extremities, a red, patchy (less often an urticarial) exahthem. There is here no question of embolism or of poisoning of the vaso-motor centres, but only of a flooding of the most con- tracted, and probably the most injured vessels with blood. The general contraction of the vessels in the algid stage, as in the resolution of Eeynaud's disease, probably accounts for the fact that these paralysed vessels show no symptoms of inflammation. To understand the occurrence of this roseola we must study the arrangement of the vessels of the skin. The arteries and corresponding veins of the skin, from the time they enter the hypodermic tissues, form cones, the apices of which lie in the subcutaneous tissues, the bases in the papillary bodies. According to the fibrous nature and thickness of the cutis, the axes of these cones lie either vertically, or more usually obliquely, to the surface of the skin. These cones are cut by the under surface of the epi- dermis into rounded or elliptical conic sections, and as a result the papillae are composed of round or oval portions of greater or less diameter. Even when the skin is well supplied with blood these vascular .cones can only touch each other at various points, and lacunse are left between them. In most parts of the body, especially in tie extremities, 20 UNNA's DERMATOLOGICAL PArERS. tlie vascular cones are bounded by or embedded in a large mesh-work of capillaries, which have no direct supply and return of blood. "We can easily see that there are many disturbances of the circulation which must cause such an unequal distribution of blood as to produce differences of colour. The roseola of cholera arises when, after prolonged stasis in the capillary area, the blood presses forward into this district : the stasis here is not so quickly overcome as that in the papillary areas. Characteristic of simple vaso-motor disturbances is the erythematous circular syphilide which arises in the later secondary stages. It is distinguished from all circular ser- piginous eruptions of the same period by the fact that the circles do not enlarge, that they have no sharp external edge, and that their centres are usually quite healthy. It is, in fact, not a syphiloma of the skin itself, but of the nerves of the vessels. The circles themselves correspond to the collateral capillary network, their centres to the papil- lary vascular elements. Similar erythemata arise in lepra nervorum j besides sharply defined erythemata, spots and circles appear, which later form circular or gyrate patches, that in time become pigmented. A whole series of toxic erythemata is allied to these in- directly infective eruptions. The first group comprises the erythemata caused by atropine, amyl nitrite, and chloral. These are transient, diffuse, and are like a blush called forth by shame or anger, especially as they affect the head and neck. Atropine erythema affects the upper part of the trunk ; chloral rashes the wrists, ankles, elbows, and knees. No desquamation takes place, and no subjective symptoms accompany them ; they are merely paralytic phenomena. A draught of cold water calls forth an enormous hyper- aemia of the head in patients who habitually take chloral. Here we have a latent weakening of arterial tone, which is only manifested by additional influences — a godd example of a slight chronic angioneurosis of the skin. We may regard quinine erythema as a prototype of a second group. This rash is more universal, of longer duration, it causes desquamation and oedema, is accompanied by subjective GENERAL PATHOLOGY OP THE SKIN. 21 sensations and by fever, and is liable to be confounded with scarlatina. The internal administration of salicylic acid, carbolic acid, stramonium, veratrine, and digitalis causes general hypersemia of the skin. And these rashes are not brought about by a vaso-neurosis alone ; the toxic material injures the vessel walls, and thereby causes the symptoms of a slight cutaneous inflammation. A third group is represented by the antipyrin rash ; this drug gives rise to discrete, raised, somewhat cedematous, itching papules, which are not unlike the rash of measles. It affects chiefly the neighbourhood of joints, seldom the trunk, and less seldom the face, neck, and genital organs. The subjective symptoms are more pronounced, desquama- tion less so, than in the erythemata of the second group. To this group belong the morphia, cubebs, and copaiba rashes, and those resulting from the administration of tur- pentine, hyoscyamus, and chlorate of potash. We now turn to the relaxive hyperemias that have a more local character, and we may divide them into three groups. i. The first group includes those erythemata in which the paresis of the muscular coat of the arteries is called forth by physical causes. We must mention first of all the hypersemia which results from the cessation of any pressure upon the skin, such as is seen after the application of an Esmarch's bandage, or in the red lines left on the skin by drawing one's finger-nail across it. The author looks upon this as a pressure paralysis of the individual capillaries and arterioles — as an idio-paresis, and not a paresis brought about by the intervention of the vaso- motor centres. 2. Hypersemia caused by variations in temperature is seen in newly born children. Cold has a paralysing effect upon the vessels only when they have been exposed to its influence for some time. The reactionary paralysis brought about by low temperatures lasts only as long as the application of the cold continues. 3. The paralysis of the vessels caused by heat must be differently explained. Warming the skin does not directly paralyse the vessels ; it causes a more rapid and consequently 22 unna's dekmatological papers. warmer flow of blood through them, and so indirectly causes a paresis of the muscular coat. At a temperature of 50 to 6o° the hyperemia gives place to slight degrees of inflammation. We have here an irritant which, according to the extent of its action, causes either muscular paresis or injury to the vessel walls. To this class of irritants the rubefacients belong, as do also the mineral acids, iodine, mercury, &c. We may class the erythemata caused by inoculation of poisonous substances given off by insects (bees, wasps, &c.) in this group. The aetiology of the infective hypersemias is still doubtful. They show no relations to the anatomical arrangements of the cutaneous blood-vessels. The closer we examine these exanthemata (scarlet fever, measles, typhoid rash), the more we are convinced that each of them has characteristics of its own, dependent upon a particular infective germ. IV. Obstructive Hyperemia. 1 The author has defined " relaxive hypersemia " as a congested condition of the skin, in which the resistance in the peripheral vessels is abnormally small while the blood- current is quickened. By " obstructive hypersemia " he understands a condition of increased vascularity, in which the resistance is abnormally increased while the blood-current is slowed. The increase of resistance which causes congestion may occur at any point in the circulation, in the right or left heart, in the arteries or veins. Congestive hypersemia of the skin is, however, more simple, and he divides it into two classes according to the general or local character of the congestion. A dark bluish colour and an objective, sometimes subjective, lowering of temperature, are characteristic of all 1 "Stauungshyperamie," ' Monatsh. f. prakt. Derm.,' Bd. ix, 1800 No. 8. GENERAL PATHOLOGY OF THE SKIN. 23 congestive hyperemias, and oedema of the tissues often occurs. The functions of the skin are mostly suspended, though, an increased secretion of sweat is common enough. Hypertrophy of the tissues does not occur even in long- standing congestion ; more often pressure atrophy and in- creased vulnerability are noticed. After discussing the causes of cyanosis, the author points out that we cannot explain the bluish fingers, ears, and noses of patients with weak hearts on the ground of the distance of these parts from the heart. He thinks that the vessels of these parts contract under the influences of decreased pressure and external temperature, because they are from their position normally exposed to greater losses of heat. He looks upon the contraction as a compensatory phenomenon. The author then describes the occurrence of congestive hyperaamia as a result of pressure on large vein trunks by tumours, the pregnant uterus, &c. Besides an inflammatory acne rosacea, he describes another non-inflammatory form. In both forms obstructive hyperaemia plays an active part ; isolated, large, dilated veins appear about the aim nasi, the tip of the nose, and on the cheeks ; later a network of dilated capillaries arises, giving a diffused redness to the organ. The obstruction to the circulation in the inflammatory form (rosacea sebor- rheica) may lie in the inflammatory process in the skin; in the non-inflammatory form the congestion may be caused by obstructions to the circulation in the nasal mucous membrane or about the fauces. Auspitz first pointed out that circumscribed bright red patches appear on the congested, bluish-grey surface of an arm round which a ligature has been placed. Besides these red patches, in cases of extreme congestion white patches appear. The author agrees with Auspitz that these white patches are due to ansemia, and he thinks that they are cau'sed by contractions of some of the arteries supplying the skin. Auspitz considers that the red colour of the above- mentioned patches depends upon the presence of haemo- globin in the exudation. The colour changes from a &4 tjnna's dermatological papers. yellowish to a fiery red, and it disappears when the congestion is relieved, leaving brown pigmented patches. Cold is an important factor in the causation of obstructive hyperemia ; it not only causes contractions of the arteries and veins of the skin, but it also acts upon the vessel walls, indirectly by slowing, and eventually cutting off the blood supply. It also cuts of£ the supply of oxygen to the muscular coat of the vessels. The vessels contract until their lumen almost disappears, by which the antagonistic nerve apparatus of the vessel walls is stimulated, and the anaemia is transformed into a relaxive hyperemia. Under greater degrees of cold, however, this antagonistic nerve mechanism is interrupted, and the skin turns suddenly white and becomes like a piece of frozen snow. This is well seen when the skin is frozen with ether spray. The veins of the skin have a muscular coat as well as the arteries, and this coat when acted upon by cold contracts, and so gives rise to an obstruction in the circulation which causes congestive hypersemia. When the arteries and veins contract equally the flow and return of the blood are proportional ; but when the return of the blood is in any way hindered, peculiar appearances arise. Chilblains have nothing to do with frostbite ; they are " angioneuroses," and depend upon a perverse reaction of the vessel tonus to differences in temperature. The arteries of the affected parts contract somewhat under the influence' of cold, the veins contract more strongly, and the result is a slowing of the blood-current, which is evidenced by a bluish colour and slight swelling of the parts. No paresis of the arteries, which would lead to a compensatory relaxive hypersemia, takes place. The supply of blood to the parts is not large enough, and the obstruc- tion to the return of the blood is too great. Dry cupping causes an obstructive, and not a relaxive hypersemia of the skin. It leads, if the cup is left on the skin long enough, to complete stagnation and diapedesis of red corpuscles. The force of gravity may cause a congestive hypersemia, as is well seen in the well-known blue death-marks on dependent parts of the body. During the death-agony a GENERAL PATHOLOGY OF THE SKIN. 25> general contraction of the arteries drives the blood into the veins ; when the rigor mortis ceases the blood from these regurgitates into the capillary areas, which become enlarged and of a bluish-black colour. The author then describes the congestion of the legs and feet which occurs in people who stand a great deal ; and he traces the steps by which the veins, from being merely over-filled in the earlier stages, become varicose later on. V. CEdema. 1 We must distinguish between two kinds of oedema, inflammatory and mechanical. The pathology of mechanical oedema of the skin has not been sufficiently studied, and is generally misunderstood. Experimental pathology has taught us that the closure of all the lymphatic channels of a limb does not cause oedema in it, while an obstruction in the veins never fails to give rise to oedema. As a natural conclusion from these two facts, the author states that the lymphatics of the skin are only an occasional channel for the return of lymph. The lymphatics of the skin carry back to the blood only that small fraction of lymph which does not return by the venous capillaries into the veins. The skin is able, by means of its permanent elasticity, to drive along the lymphatics the small quantities of lymph which they normally contain. A more extensive employ- ment of the lymphatic channels is abnormal, and leads to a softening of the tissues, — to, in fact, oedema. We do not, of course, deny that obstructions in the lymphatics themselves, especially when they are numerous and high up, may increase oedema. The discovery of such obstructions, however, even the complete obliteration of the thoracic duct, does not by itself explain the occurrence of oedema of the skin. In every case of oedema we have to determine what has prevented the lymph of the skin from returning by its proper channels, the veins. 1 "Oedem," 'Monatsh. f. prakt. Derm.,' Bd. x, 1890, Nos. 3 and 4. 26 unna's dermatological papers. Tlie amount of oedema depends not so much upon the intensity of the obstruction in particular vein-trunks as upon whether all, or at any rate most of the veins of a region are pressed upon. i . The most certain way to produce oedema quickly is to compress the upper part of a limb with a bandage. The veins are more easily compressed than the arteries, and the return of blood is thereby impeded, while the amount of supply is not decreased. In this case compression of the lymphatics takes no part in the production of the oedema. 2. The second chief factor in the production of mechanical oedema is gravity. 3. General venous congestion causes oedema of the whole skin, which shows itself first in particular places — ankles, eyelids — depending on the structure of the skin in these localities. The oedema of heart disease is of mechanical origin; no changes in the vessels of the cedematous skin occur. 4. Yenous thrombosis. — This generally takes place in the smaller veins, such as the crural ; the amount of the consequent oedema depending, first, upon the number of available collateral branches ; and secondly, upon the presence of other causes of oedema, such as inflammatory complica- tions, general hydrsemia, &c. In otherwise healthy people, thrombosis of the crural vein causes only slight oedema about the ankles and feet. Phlegmasia alba dolens, and inflammatory conditions of the skin leading to elephantiasis, were usually looked upon as a lymphangitis with retardation of the flow of lymph. We now know, however, that obstructions to the lymph- stream never cause oedema of the skin. In phlegmasia alba dolens the fact of the lymph being richer in albumen shows that we have to do with an inflammatory process, which, starting in an infective phlebitis, spreads to the surrounding tissues. We can speak of it as an inflammatory oedema — a combination of inflammation and stagnation. In elephantiasis filariosa, and the lymphorrhoea connected with it, great weight has been always laid on the plugging of the lymphatics by filarias, although the presence of the embryos in the blood-vessels has long been known. It is i n GENERAL PATHOLOGY OF THE SKIN. 27 the veins, and not in the lymphatics, that we must search for the obstructions to the lymph-stream, even when plugging of the lymphatics can be demonstrated. 5. Among the mechanical cedemas the author places the collateral oedema which is often noticed above some deeper seated abscess, as on the the cheek in empyema of the antrum, &c. The cedematous skin is not hot or red, and the oedema disappears when the abscess is opened. Cohnheim, Rindfleisch, and Ziegler look upon these serous swellings as inflammatory. Zimmermann pointed out that this oedema occurs over the sternum or ribs in cases of pleuritic effusion, which, he says, disproves its inflammatory origin, as does also the fact of its rapid disappearance after abscesses are opened. Billroth and v. Eecklinghausen look upon this collateral oedema as brought about by a stagnation which might easily be caused by compression of neighbour- ing veins. The author thinks that this oedema is a mechanical one ; and if the fluid from the cedematous tissues contains little albumen and few white corpuscles, he looks upon the stagnation theory as justified. We know, he points out, that veins coming from inflamed tissues are dilated : stagnation of blood in the tissues surrounding the focus of inflammation must, therefore, easily occur ; and if a relaxive hyperaemia spread into this same area, an obstruction oedema will result. 6. Contractions of the walls of the veins as a cause of stagnation of the blood. The author has pointed out that this factor has been entirely overlooked in the study of oedema ; and he says we only need recognise it in order to understand the spastic cedemas of the skin — urticaria^ and the circumscribed oedema of Quincke. This theory, based on the tonus of the walls of the veins, explains the origin of urticarial skin diseases. The author found, in every case of urticaria on the arms or legs, that if a bandage were tied round the limb as soon as the general venous congestion set in, the urticarial swellings became flattened and depressed, and itching ceased. Indeed, at some distance from the ligature one can easily see that the urticaria disappears before a general 28 tjnna's deematological papebs. swelling of the skin is noticeable. These facts agree very well with the theory according to which the urticarial swellings are caused by a local obstruction to the return of the blood. The increased pressure in the larger veins of the skin (caused by the ligature) overcomes the spasm of the smaller veins. By spasm of the veins he understands a sudden contraction of the musculature of these vessels, which may last a variable time, and disappear quickly or slowly. This contraction must always.be greater than the corresponding contraction of the arteries ; and the dis- proportion between the arterial and venous tone is the chief factor in the occurrence of spastic oedema. We must include in this group the oedema of erythema multiforme, and the so-called rheumatic and neuralgic oedemas. (Edema occurring in paraplegic and paralysed people must be differently explained. When, in these cases, the vaso-motor nerves of the limb are paralysed, the peripheral vaso-motor centres take over the regulation of the calibre of the vessels ; hyperemia gives place to anaemia ; and, if the tonus of the veins preponderates, oedema occurs. To this group of nervous oedemas, which have all a more or less local character, the author adds the toxic oedemas. These have all the common property of causing, by some material circulating in the blood, a disproportion between the tone of the arteries and veins. This is seen in morphia poisoning, in curari poisoning in frogs, and in the oedema occurring before death from snake-bites. Until a more plausible explanation be forthcoming, there may be added to this group the oedema occurring in renal disease and scarlet fever. The so-called climatic dropsies which occur, sometimes epidemically, in hot climates may be regarded as of a toxic nature, and something akin to " urticaria ab ingestio." Circumscribed, slight, transient oedema (without albu- minuria) is sometimes noticed in people living in the tropics ; this may be caused by an inco-ordination in the tone of the arteries and veins. This increased tone of the vessels is antagonistic to the relaxing effect of the heat ; an increased arterial tone would give rise to anaemia, and increased venous o n e to oedema. GENERAL PATHOLOGY OP THE SKIN. 29 The author thinks that the cedema seen about the ankles in cases of cachexia and phthisis is due to an auto-intoxica- tion which affects the vaso-motor system. Inflammatory (Edema. — We can ouly speak of inflam- matory cedema when actual acute, subacute, or chronic inflammation exists. Whenever the skin is inflamed, it becomes swollen, because the power of absorption of the veins is small, and the increased amount of lymph has to be carried ofi by the lymphatics. Inflammation of the skin, therefore, more than of other organs, causes abnormal conditions of circulation of the lymph, and more readily induces swelling. Inflam- matory cedema of the skin occurs chiefly in acute inflamma- tions, especially in those brought about artificially by drugs, e. g. vesicants, tar, resorcin, &c. Cohnheim and Lichtheim, and later Jankowsky, showed that if in hydraemic animals the skin were inflamed it became also cedematous. Our experience teaches us that this does not occur in man. Inflammatory skin diseases in wasted, badly nourished, anaemic people tend to decrease to a minimum or disappear, and to show themselves again when the circulation and condition of the blood have been improved. This important difference is explained by the fact that in the experiments on animals an hydraemic plethora was present, while in the other cases there is merely a diminution in the solid constituents of the blood. (Edema, whatever its cause may be, represents the differ- ence in amount between the arterial and venous blood ; and this definition applies to the inflammatory as well as to the mechanical variety. We thus admit that the fluid of cedema and the physiological lymph are the same ; but we only speak of cedema when the above-mentioned difference is very large. Every oedema which lasts any time, whether it has arisen suddenly (rheumatic oedema) or slowly (renal cedema), causes a gradual loosening of the tissues, and the normal elasticity of the skin becomes lost. The tissues pit when pressed upon, and one can judge of the loss of elasticity in the skin by the length of time that such pitting lasts. 30 tjnna's dermatological papers. If, on the other hand, a sudden obstruction to the venous circulation arises (as in urticaria, where abnormal nervous impulses raise the tone of the veins), a tense elastic swell- ing results, which is sharply denned from the surrounding tissues, because the normal lymph-spaces only allow a small amount of the fluid to be carried off. In cases of extreme oedema, when the cutis is thin, blebs form in the epithelium, which burst, and allow of a constant trickling of lymph (lymph scrotum). The pressure of the fluid may cause necrosis in cases when the skin is greatly thickened. The secretory functions of the skin in all mechanical cedemas are suspended. The surface is dry, fatless, dull, and often slightly desquamating. In the simple oedema of heart and renal disease, only symptoms of pressure atrophy show themselves. The -skin becomes thinner, the elastic and muscular tissues atrophy, fat disappears, and the veins and lymphatics become dilated. Prom this the author thinks that the well-known hyper- plastic processes in elephantiasis nostras and filariosa, as well as in long-standing, artificial, inflammatory oedemas, are not consequences of the oedema, but of the preceding inflam- matory changes (erysipelas, eczema, dermatitis artificialis) . In the course of these the skin swells enormously ; the collagenous network grows to a great size ; the epidermis of the skin and follicles forms deep depressions and warty outgrowths ; the blood-vessels and lymphatics become not only thickened, but, as their twisting shows, also elongated ; the hyperplastic process extends to the swollen glands. These changes are ascribed to an infective cause ; simpl& mechanical oedema, like venous congestion, is associated with retrogressive changes in the tissues. VI. H.EMORBHAGE. 1 Hemorrhage in the skin may occur per rhexis or per diapedesis, being blood effusion in the one case, and blood 1 "Blutung," 'Monatsh. f. prakt. Derm.,' x Bd., 1890, Nos. 6 and 7. GENERAL PATHOLOGY OF THE SKIN. 31 filtration in the other. Although neither the causes, sym- ptoms, concomitant circumstances, nor final results are the same, we cannot in every case say whether a given haemor- rhage has resulted from rupture or from filtration, and to avoid repetition they may be both considered together, under the common term hasmorrhage. It is, moreover, obvious that the chief causes of diapedesis may act as assisting causes of rupture of blood-vessels and vice versa. It is, however, important to accentuate the marked differences of the two processes. We can more easily decide, in the case of the skin, whether rupture of a vessel has occurred ; and im- bedded, as the latter is, in a firm, tough tissue, haemorrhage from it must always be more difficult, and when it occurs, more easily ascribed to either process than in the case of the vessels of internal organs. When rupture takes place, red blood is poured out through a wound of the vascular wall ; but when the hasmorrhago is due to diapedesis, lymph passes through, poor in albumin, fibrin factors, and white corpuscles, but abnormally rich in red discs. In the former case a blood pool rapidly forms in the tissue, its size being determined by the surrounding resistance, and this pool is soon converted into a thrombus ; but in the latter case the haemorrhage increases slowly, and its elements are diffused through the neighbouring tissue without becoming a con- tinuous clot. If the haemorrhages are small, these differ- ences may not be detected by the microscope, especially when the specimens have been hardened. Hemorrhages due to rupture may give rise, if small, to " ecchymoses," and if large, to "blood-boils" or " hasmato- mata." The cause is nearly always some gross traumatic lesion. The flea-bite is an example of the former, and large "and more permanent blood suffusions may be produced by blunt force over large areas, without penetration ; the result in this case depending more on the actual vascularity of the skin at the time. Hence, all factors producing stagnation hyperaemia increase the liability to hasmorrhage from rup- ture. One kind of blood-boil is the ot-haematoma of lunatics ; but the cephalo-haematoma of infants and hasmatomata of the vulva in parturition do not belong solely to this class; for there is at first a stagnation oedema leading to diape- 32 unna's dermatological papebs. desis, and these forms show how difficult it is sometimes to draw the line between the two processes. By cupping, the hypersemia of stagnation may pass into rupture of the ab- normally distended capillaries ; but the diminution of pressure up a high mountain or in a balloon is not sufficient to cause haemorrhage in the skin, although it may from mucous mem- branes, often, no doubt, from the bursting of the inelastic •and superficially dried surface covering. A similar result has been attributed to increased pressure within the vessels, but wrongly so in the case of the skin, for the great mus- cularity of the cutaneous arteries is able to resist the most powerful cardiac action. The case is different if there be great general venous congestion, as during the paroxysms of whooping-cough, epileptic and asthenatic fits, parturition, ■&c, when small cutaneous vessels may occasionally burst. They are insignificant, however, as compared with those occurring under similar conditions in the conjunctiva, retina, and brain. Squeezing and suction are, therefore, the most important and certain causes of rupture of the well-protected cutaneous vessels. The causes of rhexis, indeed, are mainly trau- matic. Formerly, too much importance was attached to changes in the vascular walls. Although atheroma and thinning of the wall are doubtless important factors in the case of other organs, the small cutaneous arteries are far more subject to the opposite, conditions — endarteritis obliterans and thicken- ing of their walls. The theory of fatty degeneration of the ■cutaneous vascular endothelium must be received with cau- tion, for the fat globules deposited by the lymph are by no means a sign of a degenerative process. Two kinds of vascular changes, however, remain, which -may predispose to hssmorrhage :— (i) Atrophy of the venous walls from pressure, as we see now and then in old varices, ;and (ii) an imperfect embryonic nature of the cutaneous vessels. The first causes not only profuse haemorrhages, •but also circumscribed ecchymoses in old people, whose skin is already atrophic. Arrested vascular development often gives rise to hemorrhage from tumours, especially the sarcomata ; but here there is also considerable dilatation of GENERAL PATHOLOGY OF THE SKIN. 33 the larger blood-vessels. It seems probable that some of the haemorrhages of newly-born syphilitic infants are also due to imperfect development of cutaneous vessels, but true (embolic) purpura also occurs. The so-called cachectic haemorrhages, however, must not necessarily be attributed to atrophic or degenerative vascular changes. They chiefly belong to processes of diapedesis ; a cutaneous haemorrhage in a cachectic individual is hardly ever due to cachexia of the vessels. An affection of the general vascular system may be men- tioned, which alone deserves the name of a hssmorrhagic diathesis, viz. haemophilia, in which Schonlein and others found a thinness of the vascular walls. The condition is hereditary, and the male members of the family, with thin, little pigmented skin and fair hair, are chiefly affected. Sponta- neous haemorrhages in the skin, without laceration of the cutis may occur; and the slightest mechanical injury may entail serious haemorrhages and haematomata. As there is no want of coagulating power in the blood, the difficulty of stop- ping the bleeding from insignificant wounds can only be the result of deficient retraction and elasticity of the arterioles. But here trauma is also the important exciting cause. In proceeding to the cutaneous haemorrhages resulting from diapedesis, we enter the wide and dark field of pur- puric diseases. Only in those occurring in simple venous congestion, have we a satisfactory experimental basis in the observations of Strieker, Cohnheim, Auspitz, &c. But these are of less interest to us than those occurring in connection with infective processes and neurotic disturbances. They have been generally classed as " mechanical," in distinction to those forms of purpura supposed to be dyscrasic and toxic, and due to a change in the blood rather than of the condi- tions of the circulation. This idea, however, on careful in- vestigation, is untenable, for we may also give a " mechani- cal " explanation to the toxic and infective forms. It is hence necessary to give the so-called mechanical forms of purpura another name. They mostly result from "simple congestion " (stagnation) ; and they are the simplest forms of cutaneous haemorrhage from diapedesis. Their prototypes from experimental pathology are the petechise, which we can 3 34 tjnna's dekmatological papers. produce at will below a venesection bandage ; and Auspitz first showed us, by his stagnation experiments, that venous congestion alone suffices to produce macroscopic haemorrhages, even in healthy skin. The congestion must border* on stasis, but in certain diseased conditions lesser degrees of conges- tion suffice. In scarlatina and erysipelas a purpuric erup- tion is easier induced than with the normal skin ; and still more so in a acute dermatitis, acute eczema, urticaria, and measles. Cutaneous haemorrhage is enormously increased by simple congestion in the case of purpura variolosa, the whole limb showing a suffused black colour. In one cate- gory of cases under this group the stasis of blood in the larger veins is the sole cause of the haemorrhage,, as in the rare petechiae after thrombosis, e. g. in phlegmasia alba dolens. Extravasations in varicose legs, although belonging to the same class, are not so easy to explain. Yarices are not due simply to gravity, but to a chronic gravitation-hyper- semia in connection with an increased tone of certain vessels of the limb, and consequent diminution of the vis a tergo. Extravasation is the result, especially where the skin is atro- phic, as in the neighbourhood of chronic ulcers. The pre- agonal purpura, developed on dependent parts shortly before death, is related to this. It originates from the general venous congestion and gravitation-hyperaemia caused by deficient vis a tergo, and is an example of so-called " cachectic " pur- pura. Here, too, spasm of the small cutaneous veins so resists the pressure in the venous capillaries, that diapedesis of red disks can take place. This is also the case in very chronic urticaria, urticaria perstans (Pick), erythema multiforme of the legs, purpura urticans, and in lichen lividus of old people. Bateman's purpura senilis may be here mentioned, which occurs chiefly on the extensor surface of the forearm in old women, and is very chronic and accompanied by dark pig- mentation. The larger group of infective and toxic pelioses were formerly explained by " blood-dissolution," the poisou being supposed to produce so profound a change in the blood that it passed easily through the wall of the vessels, as in purpura variolosa and severe yellow fever. This idea is erroneous : before such a diapedesis of red discs, considerable cedema GENERAL PATHOLOGY OP THE SKIN. 35 would first be seen, and we should also have to assume severe lesions of the vascular walls, or a common inflamma- tory exudation. It has been abundantly proved experiment- ally that heterogenous substances, so long as they do not •cause coagulation, may be added to the blood without haemor- rhage resulting. Medical practitioners mean by the term a peculiar un- known lesion of the vessels leading to the diapedesis ; but inflammatory changes in the skin occur only exceptionally in the various forms of purpura, e. g. in P. urticans ; and diapedesis from circulating blood, without previous and •concomitant exudation of inflammatory lymph, cannot be accepted. The case is different, however, if simple conges- tion or stasis is present. Haemorrhagic inflammations, indeed, are to be regarded as composed of inflammation plus stasis, the cause of the latter being unknown. Inflammation with- out stagnation cannot give rise to the diapedesis of red disks. Hayem has recently supposed the coagulation of blood by " precipitation grumeleuse " the cause of these " dyscrasic " haemorrhages. He found that ox serum introduced into a dog's circulation produced haemorrhage in the intestine, serous membranes, spleen, &c, and that these were often ■embolic, the capillaries being plugged by changed haemato- blasts ; but they were not observed in the skin, hence, if the •explanation be even correct, it is not applicable to human pur- pura. Simple emboli produced by chemical blood changes are not sufficient to explain suffusions, &c, in the skin. Here there are no terminal arteries ; and the permanent plugging of even small vascular areas would require very numerous emboli. In general embolism, moreover, haemor- rhages are observed much more frequently in internal organs than in the skin. Nor can cutaneous haemorrhages be accounted for by iso- lated venous thrombi, which are difficult to distingnish histo- logically from columns of stagnating blood. The collateral •circulation is too good for thrombosis to cause haemorrhage or oedema in the skin. The thrombus, moreover, may be a consequence of the same changes in the capillaries which cause the haemorrhages. V. Kogerer found venous thrombi in thirteen cases examined by him, but they alone are not 36 UNNA'S DEEMATOLOGICAL PAPERS. enough to explain the petechias. It is more likely that the fibrinous clots, also found by him, in the capillaries and arteries were the primary cause. The continuous blocking of whole capillary areas, due partly to changes in the vas- cular walls and partly to a continuous formation of thrombi, goes much further towards explaining the infective cutane- ous haemorrhages. Amyloid capillary degeneration, with cutaneous hemor- rhage, was found by Wilson Fox in a case of syphilis ; but this is exceptional. Hyaline degeneration is often found in chronic dermatoses, but never amyloid. Askoro described considerable endothelial thickening in specimens from a scor- butic gum ; and Leloir observed a peculiar proliferation of endothelium, and its partial detachment in cutaneous haemor- rhages, which occurred shortly before death in a case of cirrhosis of the liver with interstitial nephritis and athe- roma of the aorta. The vessels were dilated, especially in the papillae, and there was vigorous emigration of leucocytes ; but no fibrin plugs were formed. He attributed the oblite- ration of the capillaries, partly to a stagnation of white discs, and partly to the desquamating endothelium. Hayem has similarly attributed cutaneous haemorrhages, in a case of phthisis and peliosis rheumatica, to endarteritis obliterans. It is not likely, however, that this process, which occurs so- commonly in the skin without producing anything of the kind, should by itself cause haemorrhage. Endophlebitis obliterans, on the other hand, might cause stagnation dia- pedesis, &c, but it is not known to occur. The plugging of the arteries with finely granular matter, also observed by Hayem, is of more importance. Endarteritis can only assist- by lowering the pressure and velocity of the blood-stream. In purpura haemorrhagica Letzreich found bacilli and spores imbedded in gelatinous plugs, produced, he thought, by the- action of the organisms on the serum albumin, and completely filling the capillaries. It is likely that in Hayem' s cases,, and in many other forms of purpura, a similar process of bacterial emboli is in question, with clotting of plasma along extensive tracts, consecutive stagnation and diapedesis. Klebs was the first to connect cutaneous haemorrhages- with bacteria. He found colonies of his " monas haemorrhagi- GENERAL PATHOLOGY OF THE SKIN. 37 cum " blocking the vessels and causing haemorrhage in a form of purpura of new-born infants. Diarrhoea ushered in the disease, and a parasite in the intestine was probably prim- arily concerned. In his steps followed Cornil, Martin de Geniard, Coppinger, Petrone, Cohnheim, and Weigert. The infective forms of purpura are most simply explained in this way ; and the theory of bacterial coagulation thrombi will probably in future play an important role. That thrombi may form around other bodies than micro- organisms is not to be denied ; but we cannot believe in spontaneous coagulations as a cause of haemorrhage in the skin. Harris has observed cutaneous haemorrhages in three cases of lympho-sarcoma of the mediastinum, and in some of the specimens there were sarcomatous plugs in the capillaries. A connection between sarcomatous growths and haemorrhage in the skin has also been maintained by Fagge. In the present state of our knowledge, we must accept the following serologically different forms of purpura : (i) The simple pelioses due to congestion (stagnation). These are not so common as is generally assumed, for the venous congestion is often accompanied by other causes of purpura. (2) The acute haemorrhages occurring in infective diseases. The notion of " blood-dissolution " is obsolete, and Hayem's theory of coagulation of granular precipitation must yield to the view of mixed fibrino-bacterial or hyalo-bacterial thrombi. (3) Those rarer cases due to obliteration of capillaries from leucocytes, sarcomatous masses, &c, and in which throm- bosis from fibrin formation may subsequently take place. (4) Those following widely spread degeneration of capil- laries (capillaritic desquamation and amyloid degeneration). The changes in the larger vessels of endarteritis obliterans can only, like venous congestion, promote the capillary throm- bosis. (5) The hypothetical toxic purpura, occurring in acute poisoning and in certain chronic diseases. Hayem's theory of spontaneous coagulation around haamatoblasts is more likely to be true in these cases. 38 unna's dermatological papers. (6) The nervous hemorrhages of French observers. Strauss found petechias in tabetics, over painful spots, and Faisans observed them in neuralgia. Many haemorrhages in cancer and tubercle of the spine may, perhaps, be here included, as well as the angio-neuroses, urticaria, and erythema multi- forme. It is conceivable that a venous spasm may be present, and that if the congestion be enduring, exudation of red disks will result. Accurate clinical and histological observations are here needed. It is time to discard the notion of " cachectic purpura " as well as that of "blood-dissolution." When occurring in cachectic, ill-nourished, alcoholic, or old patients, these haemorrhages probably belong to one of the first three groups ; but the debilitated action of the heart, and the lowered blood- pressure in the capillaries in such cases, are no doubt favour- able to the formation of thrombi by bacilli, &c. VII. Angio-neuboses. To Auspitz we must give the credit of having first sepa- rated a series of skin affections, under the name of " Angio- neurotic Dermatitides," from the ordinary inflammatory processes, and for having clearly defined this class. The author gives a quotation from Auspitz's work, in which the necessity is pointed out of forming a distinct class of " Angio-neurotic skin affections." Auspitz considers that the changes in the tone of the blood vessels are independent of local inflammatory processes, but are dependent upon injuries which act upon the vascular nerve-centres ; therefore, according to him, the localisation in the skin in each particular case arises from two sources — the nerve disturbance and the local injury to the skin ; but he has no very clear ideas as to how the alteration of the vessel-tonus is combined with the local inflammation. It is necessary that we should clearly understand the mode of action of the neurosis in every case of inflammation, more especially as the vast differences in the exanthemata are determined by different combinations of 1 " Portesungen iiber allgemeine Pathologie der Haut," 'Monatsh. f. prakt. Derm.,' xi Bd., Nos. io — 12. GENERAL PATHOLOGY OP THE SKIN. 39 these two factors. In a large number of cases we have not to deal with a widely distributed neurosis and a local cir- cumscribed inflammation of the skin, but the angio-neuroses and inflammation occur in the same small vascular areas, and run a parallel course, e. g. Hebra's erythema multiforme of the dorsum of the hand. In such a case we must imagine that the specific virus is seated in the skin at these places and calls forth a localised inflammation and an equally circum- scribed angio-neurosis. Such a double action is difficult to imagine, if we merely take into consideration, as Auspitz does, a stimulation or para- lysis of the vaso-dilators, or the vaso-constrictors. In no case can we convert a simple inflammatory erythema into an erythema multiforme by stimulating the vaso-constrictors. In a former lecture the author enunciated a theory to account for some special varieties of pure angio-neuroses. Every dis- proportion in the amount of contraction of the arteries and veins of the skin which limits the amount of blood returning by the veins, causes a spastic oadema of the skin ; and the varieties of urticaria are types of this condition. To this group of angio-neuroses must be added a large number of skin diseases — numerous drug exanthemata, a number of infective erythemata and most of those papular and papulo- bullous dermatoses which are caused reflexly, and lastly some diseases of unknown aetiology, which are akin to E. multiforme and E. nodosum. When we study these cases more closely, we see that such angio-neuroses can only occur upon erythematous bases ; for simply anaemic angio-neuroses, as in Raynaud's disease, can never lead to insufficiency of the venous blood return. " In all cases the chief characteristic of an angio-neurosis consists in the fact that the engorgement of the capillaries is not normally compensated for by an adequate fluctuation in the calibre of the veins, and by an increased rate of flow, but that, on the contrary, a stoppage takes place." The whole process takes place somewhat in this way. At first local hyperemias occur of the size of macules, or groups of macules in the form of rings, which from their usually symmetrical occurrence point to an irritation of the central ganglia. This first stage cannot be looked 40 unna's debmatological papbes. upon with certainty as angioneurotic ; its appearance only suggests it. After a longer or shorter period these spots become, by swelling of the cutis, converted into an E. papu- latum. At the same time, the colour changes to a more bluish-red, cyanotic tint. A spastic obstruction to the return of blood has now been added, and the veins can no longer cope with the amount of blood which is brought to them. The author thinks we may presuppose a special irrita- bility of the musculature of the venous vessels, which reacts in this unsuitable way upon the increased blood-pressure. Most of these eases occur in anaemic, neurasthenic or neuro- pathic people, in whom muscular spasms of other kinds easily occur. We may suppose that the arteries have the same character of reacting to variations in blood-pressure as we have ascribed to the veins ; bnt the much greater arterial blood-pressure presses upon the paretic arteries, and overcomes any tendency in them to spasm, The obstruction, which is the characteristic of the angio- neuroses, is caused by a tendency of the whole cutaneous vascular system to reply to a stimulus, such as the increased blood-pressure, by a quick and intense increase in muscular tone. Our study has now led us to a clear pathological founda- tion which we may describe as " an intense irritability of the musculature of the cutaneous blood-vessels," which underlies a large number of inflammatory as well as non-inflammatory angio-neuroses. When the muscular stimulus goes on increasing, a time must come when the muscles of all the cutaneous vessels remain in a condition of tetanic spasm. The clinical picture then changes. There is no incongruity in the calibre of the vessels, as only a very small stream passes along the arteries and veins. This condition is an exact picture of those appearances which have been described as Raynaud's disease and " dead fingers " in the lecture on antemia. The stimu- lus of blood-pressure is not sufficient to call forth these appearances ; to it must be added the intense cold of the extremities in order that this tetanus of the vessels should be produced. GENERAL PATHOLOGY OP THE SKIN. 41 In some persons a flea-bite only causes an arterial con- gestive hyperasmia, which does not alter its character when acted upon by new stimuli. In other people the same injury gives rise to an angio-neurotic erythema, because in them the virus is a sufficient stimulus to bring about the irritability of the muscular coats of the vessels. Various stimuli give rise to angio-neurotic erythemata in different people, such as the weals left on some hands by stroking them with a pencil ; urticaria ab ingestis and the rashes which occur after the use of certain drugs are of the same nature. In relation, to the cause, an angio-neurosis is the result of a particular or adequate stimulus ; in relation to the indi- vidual, it is the result of an idiosyncrasy. In the second place a typical, usually rapid, course (synchronous with the cause) is common to all angio-neuroses. As the third sym- ptom common to all angio-neuroses, one must mention their symmetrical distribution. The character of the eruption is various; papules, vesicles, tubercles, &c. occur, though they are all mostly formed on one type. The author goes on to discuss the classifications of angio-neuroses as adopted by Auspitz,Le win, and Schwimmer, and gives a list of eruptions which he thinks should be counted among the infective angio-neuroses ; — namely the roseola of cholera, the prodromal rashes of variola, the evanescent erythemata occurring after vaccination, and, perhaps, the roseola seen in tubercular meningitis. The erythemata, on the other hand, which occur in the course of typhus, typhoid, diphtheria, dysentery, and pneu- monia, &c, he looks upon as either embolic or caused reflexly, the latter especially when, instead of simple ery- themata, papular or urticarial eruptions arise. To this latter group he would add, the ephemeral roseola- like rashes which occur in childhood, and which are usually classed under the name Roseola infantilis. The author does not agree with Auspitz in his classifica- tion of toxic angio-neuroses. He would class under this heading only the erythematous, erythemato-papular, herpetic, pemphigus-like and urticarial forms. 42 unna's debmatological papebs. , Auspitz called his third group of angio-neuroses the " essential " one. The word essential means in this con- nection, as everywhere else, that the astiology of the cases in this group is unknown. It comprises the idiopathic angio- neuroses whose nature is only known to us by the character of the eruptions, and consists of " urticaria chronica " (Cni- dosis) and the group of Erythanthema essentials, which, besides Hebra's B. multiforme and nodosum, contains a number of herpetic and pemphigus-like eruptions, and finally Peliosis rheumatica. Auspitz in his system advocated that the terms E. multi- forme and nodosum should be given up ; the author does not agree with this, but urges that they should be more accu- rately defined. Hebra in the first edition of his work described the peculiarities of a disease which he called " Erythema exsu- dativum multiforme," and if we pay due regard to these we can easily differentiate between E. multiforme and similar diseases. The author then quotes Hebra' s description of E. multiforme, and gives the differential diagnosis between it and E. nodosum, and goes on to say that from the stand- point of the infection theory, E. nodosum is comparable with Herpes zoster, and E. multiforme with a recurring H. labialis. No one will deny the connection between the two processes, but anyone who is a lover of accurate diagnosis will try and distinguish between them. It is doubtless the superficial similarity in the form of the exanthema which has caused so many observers to include under the name "E. multiforme" or "Erythema" a large group of toxic, reflex, and chronic dermatitides. We are in a position to set up beside Hebra's E. multiforme and nodosum a group of characteristic well-defined types which must be setiologically, as well as clinically, distinguished from them. Some cases bearing upon this are cited. Case i. — Unna was attending a young man in 1877 with pericardial effusion. When the effusion was greatest (no drugs had been used) a peculiar exanthem appeared. A bluish-red papular eruption formed symmetrical semicircles round the angles of the mouth ; following this discrete spots GENERAL PATHOLOGY OP THE SKIN. 43 appeared on cheeks, chin, and nose. The spots were sym- metrical, and the two corresponding ones always appeared at the same time. The next day the eruption had spread down- wards over the neck, and abdomen and arms, and upwards over the forehead. By the third day the disease, always sym- metrical, had spread down the legs to the tips of the toes. ; The individual spots and papules were always separated, arranged in circular incomplete lines, did not enlarge or run together and went through their involution in the same place., Involution began about the fourth day at the angles of the mouth, and spread downwards. By the fourteenth day the exanthem had entirely disappeared. There was no itching. The patient was nnder observation for a long time after- wards, and there was never a recurrence of the eruption. This was certainly not a case of B. multiforme. Did the. pericardial effusion cause pressure on the sympathetic ganglia of the heart ? It was a case of reflex angio-neurosis, but not of the type of Hebra's E. multiforme. Case 3. — A young healthy man was without any apparent reason attacked .by an B. papulatum. The backs of the hands and forearms were affected, but it was remarkable that the trunk was thickly covered with, spots and that the eruption was said to have begun here and then to have spread over the whole body. There was no itching ; the patient complained only of anorexia. On the next day some new spots had appeared, and the conjunctivae were yellow ; on the following day icterus was well marked all over, and the urine contained bile, the fasces containing but little. There was no itching at this time. While the icterus increased for some days the exanthem diminished in the same degree, and finally disappeared. Cases of E. multiforme as a complication of jaundice are common enough ; but in this case the exanthem appeared as- soon as the gall-bladder became distended, and disappeared again as soon as the constituents of the bile entered into the blood. It was evidently caused, not by the presence of bile in the vessels of the skin, but reflexly by the distension of the gall-bladder ; just in the same way as sudden irritation of 44 unna's dermatological papers. the diaphragm (by changes in size of uterus, bladder, burst- ing of hepatic and diaphragmatic hydatid cysts, &c.) gives rise to erythema and urticaria. The mode of occurrence of the exanthem, its topography, its sudden disappearance prove sufficiently that this was not a case of Hebra's E. multiforme exudativum but an evanescent reflex angio-neurosis. Polstebnoff mentions that in his two cases of E. papulatum in jaundice the dorsa of the hands were not affected. The author gives details of five other somewhat similar ■cases, and claims to have shown that there are a number of angio-neurotic exanthemata, which are entirely different from, and easily distinguishable from Hebra's E. multiforme. Following Auspitz, he proposes to call these angio-neurotic exanthemata "Erythanthemata" (epu0poe=red ; av0oe=blos- som), and defines them as " angio-neuroses of an erythemato- papular type." Urticaria is included in this group, but E. multiforme and nodosum (which Auspitz included in it) do not belong to it ; no more does E. neuriticum, which is a con- gestive dermatitis, and, as Charcot and Mitchell have shown, somewhat akin to chilblain. The author in conclusion gives a classification of angio- neuroses : Type I. A nsemia. (i) Angio-spasm of the fingers (" dead fingers "). {2) Local asphyxia resulting in necrosis (Raynaud's disease). (3) Ergotism. Type II. Cyanoses. (1) Livedo annularis and frigore. (2) Pemiosis. {3) Cyanotic form of local asphyxia. Type III. (Edema. (1) Acute circumscribed oedema (Quincke's disease). {2) Urticaria factitia. GENERAL PATHOLOGY OF THE SKIN. 45 Type IV. Erythanthema. (a) Symptomatic erythanthema. (a) Reflex, caused by — (i) Heart disease. (2) Uterine affections. (3) Urethral affections. (4) Peritoneal irritations. (5) Teething (Urticaria infantum). (6) Taste and smell. (6) Toxic, caused by — (1) Bites of insects (Urticaria traumatica). (2) Drugs. (3) Digestive disturbances. (4) Uraemia, (c) Infective — (1) Roseola cholera. (2) Eoseola variolse et vaccinae. (3) Eoseola infantilis. (4) Prodromal erythemata of variola. (5) Rotheln-like disease of children. (6) (?) Remittent fever with phlyctenous eruption. (Wunderlich, Gerhardt, and Heubner). (7) (■) Japanese river-fever (Baelz). (8) (?) Exanthema of meningitis. (b) Idiopathic (essential) erythanthema. With no known aetiology, therefore clinically divided into — (a) Erythanthema of maculo-papular form. (6) Erythanthema of papulo-bullous form, (c) Erythanthema of urticarial form. (1) Urticaria communis chronica. (2) Urticaria necrotica. (3) Urticaria pigmentosa. (4) Urticaria infantum. Type V. (?) Haemorrhages. (a) Symptomatic — (a) Reflex (in neuralgia, hysterical). (6) Toxic (iodine, salicylic acid). (c) Infective (prodromal haemorrhages in variola). (b) (?) Idiopathic — Peliosis rheumatica (Auspitz). ON CIRCULAB PATCHES OE EXEOLIATION OE THE PALM AND TONGUE. 1 (Exfoliatio Areata Palmse Manus et Exfoliatio Areata Linguae.) The author understands by this a benign disease, limited to the skin of the palms, which has hitherto been, as far as he knows, undescribed. He saw the first case of this disease in a young girl, on whose palms and digital palmar surfaces circular patches were scattered, as large as sixpenny or shilling-pieces, where the epidermis looked as if it had been punched out. The bases of these shallow depressions were somewhat smoother than the surrounding skin and somewhat reddened, and the edges were raised. Some were smooth, some jagged, and some undermined. By the coalescence of these circular patches larger areas were formed, especially on the palms. The patient complained of some tenderness over the affected areas, but there was no itching. The usual symptoms of eczema were absent, and treatment directed against that disease failed. A year later he saw a similar case in a man of thirty, who had been ill only a few days — the disease only troubled him through the unsightliness of his hands. There 1 " Ueber Kreisfleckige Exfoliation der Hohlhand und der Zunge," ' Vierteljahresschrift fur Derm. u. Syph.,' 1881. EXFOLIATION OP THE PALM AND TONGUE. 47 was no history of syphilis or of any acute illness. A sulphur ointment was ordered, and in two days the man was cured. He saw a third case two years ago, but could form no conclusions as to the sstiology or character of the disease. He believes that this disease is related to the affection, de- scribed by Caspary and others as the " map-tongue," Lingua geographica, which occasionally occurs in apparently healthy people. This disease is not of syphilitic origin, and causes the patient no pain or discomfort. Unna describes fourteen cases of the affection which he has had under his care, and distinguishes three degrees of it. (i) Numerous circular patches, varying in size from a pea to a sixpenny piece, are scattered about upon a healthy- looking tongue. They are mostly discrete, and only occa- sionally do they touch at their peripheries. They are de- pressed, and are distinguished from surrounding tissues by their colour. Their usual seat are the margins of the tongue, more rarely the median portions of the upper or under surface. The edges of the patches are yellowish grey or bluish in colour, the centres slightly depressed and red. The patches tend to disappear suddenly after a few days or hours, while other similar patches may make their appearance. They never creep over the surface of the organ. Their increase in size takes place by the addition of new patches, and not by the enlargement of existing ones. These patches of exfoliation lie quite superficially in the •epidermic layer, and are due to a swelling of the epithelial •cells. These cells are more swollen and looser in the centres ■of the patches, and are therefore more easily removed by the movements of the tongue, &c, the cells at the edges, being less swollen and softened, are less easily removed, and in this way the central depressions are brought about. (2) The whole tongue, or nearly the whole of it, is affected. (3) The author has seen two cases of an extreme degree of this affection. The disease extends much deeper, and desquamation is more marked, so that regular ridges and furrows are formed. He gives details of eleven cases of the affection, and then discusses its aetiology. 48 unna's dekmatological papers. He agrees with. Caspary that it is not caused by syphilis. Mercurialisation does not give rise to it, he thinks, although one of his patients dated her affection from the beginning of a course of mercurial inunctions ; for in six other cases, where the same mercurial treatment was adopted, the exist- ing tongue affection underwent no change, and most certainly got no worse. Anaemia appeared to be a predisposing cause in one half of his cases. Dyspepsia and bad teeth have no connection with it. In two of the cases the disease began in early childhood, but it could not be determined whether the children were born with ib or not. The disease may be, he thinks, of neuropathic origin, or a sort of tropho-neurosis. He would define it as follows : — " Exfoliatio areata lingum is a benign disease confined to the tongue, which makes its appearance in circumscribed circular patches which tend to coalesce. It is a painless superficial affection of the epithelium, and the mucous membrane is never affected." The author then points out the differences between it and (i) Aphthae : these cause more loss of tissue, the ulcers are consequently painful ; the mucous membrane of the mouth, and gums especially, is affected in this disease. (2) So-called catarrhal swellings are somewhat like the disease in question, but are more painful, are not so circum- scribed, and extend down deeper as far as the prickle-cell area. (3) Leucoplakia (Schimmer) occurs in streaks and not in rings, is not confined to the tongue, but affects the mucous membrane of the lips and cheeks. (4) Irregularly occurring exfoliations are usually evanes- cent, and rarely return ; they run a different course, and are due to an irregular desquamation of the whole tongue. As regards treatment, Dr. Unna recommends sulphur : $> Flor. Sulph., io-o. Mixt. Gummos., 2oo - o. M. Or 9> Flor. Sulph., io'o. Bmuls. Amygdal., 200 - o. M. EXFOLIATION OP THE PALM AND TONGUE. 49 to be used locally. He found the greatest benefit, however, from sulphurous acid, either in the form of a gargle or used undiluted. He recommends the following prescription : |k Aq. Sulphurosae, Aq. Mentha), aa ioo'O. Flor. Sulph., Syr. Simpl., aa 2o - o. G-umm. Tragacanth., 2 - o. M. The patient, after having cleansed his mouth, takes a mouthful of this mixture, keeps it in his mouth five minutes, during which time he moves it about with his tongue. This may be done several times a day. ON A CASE CUBED LEPEA TUBEEOSA. 1 Gentlemen, — It was my intention to bring before you to-day something unique, viz. a living cured case of tuberous leprosy. The subject is a lady who acquired leprosy two years ago in Brazil, and arrived in Hamburg last December, when she came under my treatment. In this case I have been fortu- nate enough to cure, according to my view, completely, a disease which until now has generally been considered to be absolutely incurable. She had promised, in an exuberance of gratitude, to accompany me hither to-night, but at the last moment she changed her mind. Fortunately, I had her photographed before and after treatment. In the original picture, front view, you will see that the case is one of leprosy, of rather severe degree. The tuberosities on the side of the face and neck can be seen in the portrait taken in the recumbent position. The photograph taken after the cure will give you an idea what changes one can therapeuti- cally produce in leprosy. I had last year the pleasure to study, with other German physicians, leprosy in Bergen, under the guidance of Armauer Hansen and of the venerable Danielssen, and it impressed me deeply that with the extraordinarily rich material there at hand, little or nothing could be attempted therapeutically. 1 " Ueber einen Pall geheilter Lepra tuberosa," ' Separat-Abdruck aus den Verhandlungen des Congresses fur innere Medicin in Aufton°-e der Geschaf ten-Commission,' Wiesbaden, 1885. CUBED LEPBA TUBEBOSA. 51 When I inquired into the matter, the general reply was, "We have tried everything that has been proposed, and nothing has been successful ; leprosy is incurable ! " Danielssen, however, said to me later that if I would come to Norway for a space of time, he would be ready for new experiments. This remark incited me to try everything should I ever obtain a leper to treat, and I had not long to wait for the event. The above-mentioned patient, sent by Herr Schede, entered my consulting-room the middle of last December. The diagnosis was plain, at the first sight, to anyone who had ever been in a Leper House, and there was the characteristic smell, which made a deep impression upon me when I visited the asylums. I have since spoken on this subject with a physician from South America, and he confirms me, and states that it is not difficult to recognise a leper by the smell. The lady entered my clinique on December i8fch, and I have arranged in periods the seventeen weeks during which she was under my care. Before entering upon the treat- ment, I had designed a plan. It seemed to me probable, from certain histological facts, that the leprous bacilli lived in oxygen, and that without a good supply of this they could not exist, I determined therefore to treat the leprous tubers with the whole series of our modern " reduction remedies," the chief of which are pyrogallic acid, chrysarobin, resorcin, and lastly ichthyol. I mapped out the patient in four skin regions ; the right arm I treated with pyrogallic acid, the right leg with chrysarobin, the left arm with resorcin, and the left leg with ichthyol — all in 10 per cent, ointments. I was able to arrive at some conclusions even in eight days. I found that all four preparations had worked favorably, the most satisfactory being chrysarobin and resorcin; the ichthyol had done well but more feebly, and the pyrogallic acid had acted too strongly, it had raised the horny layer into many blisters. For the next experiment I divided the body into two parts, treating the right half with ichthyol, and the left with resorcin — the former drug in a 50 per cent, and the latter in a 20 per cent, ointment. The ichthyol preparation was much pleasanter to the patient, the resorcin causing pain, but otherwise doing well. In a third experi- 52 UNNA'S DERMATOIiOGICAL PAPERS. ment I tried a purely ichthyol treatment, which lasted for twelve days, and after a few days I began to give the remedy also internally. There was an enormous effect on the skin, and also on those parts which had not been directly treated, especially the eyes. The patient had exhibited that greyish red hypersemia which is the forerunner of the severe leprous ophthalmia, characterised by photophobia and pain in the eyes upon effort. All these symptoms lessened from the day when the ichthyol treatment was carried out, and the general health ameliorated. The patient arrived in a thin and miserable, and almost helpless condition, caused either by the leprosy itself, or perhaps by an antisyphilitic treatment to which she had been subjected. Although the general health, the appetite, and nutrition improved, it was evident that only a certain point was reached with ichthyol. Many tuberosities had indeed disappeared, but some had left behind them hard remains. I took up the resorcin again ; and as the affection was no longer general, but confined to a few places on the skin, I applied the remedy no longer as an ointment, but in the form of " salve- and plaster-mulls." In addition I used a 10 per cent, pyrogallic ointment, but this again proved too strong. As after five days the resorcin had not the desired effect on the hard nodules, a 5 per cent, pyrogallic ointment was used for the whole body. Now pyrogallic acid is a very dangerous substance. I employ it, indeed, constantly, but I so arrange that only the neck, head, and hands are treated by it, and in consequence of this I have never had a mishap to deplore. The 5 per cent, pyrogallic ointment over the whole body had for some time a good effect, and, becoming bolder, I applied a pyro- gallic plaster to the especially obstinate tubers. Unknown to me, the patient covered half of her body with the plaster, with the result of producing alarming symptoms of prostra- tion. In such an event, large doses of hydrochloric acid internally are to be recommended. It is known that the reducing remedies act particularly in alkaline media, and we can weaken their effect on the system by giving at the same time copious doses of hydrochloric acid. In this way I was able to control this severe accident. The invalid was in- deed, feeble for weeks, but on the other hand, the pyrogallic CURED LEPRA TUBEKOSA. 53 acid had an excellent effect on the leprous tubers, which almost entirely disappeared. I gave the patient time to recover, only using, meanwhile, milder remedies, so that she gained strength for a final effort, which consisted in a com- bined treatment with all the four drugs at the same time. Chrysarobin was used from the shoulders downwards, pyro- gallic acid on the upper parts, ichthyol internally, and resorcin as a salve-mull to the mucous membrane of the nose. This final treatment carried out for eighteen days gave the result, in my opinion, that the patient was cured. I watched her for three weeks, and during that time only attempted to treat superficial matters — where the skin was somewhat bloated, although not thickened, salicylic plaster was applied, and a mercury plaster to remove pigmented spots. Tou perceive, gentlemen, that with care and energetic treatment much can be attained in this disease. The case was a somewhat severe universal one of lepra tuberosa, the arms and legs were, indeed, extensively attacked, and the eyes and nose were affected. I cannot say whether any affection of the internal organs was present. The treatment was not only external ; moreover the application of the above remedies to the skin is constitutional, for all these drugs become absorbed. The disease having so obviously disap- peared from the skin, we may well imagine that the visceral leprosy is also cured. We cannot even declare to a syphilitic patient that he is absolutely cured of his disease, although we may promise that every subsequent attack can be simi- larly cured. If we can attain to so much in leprosy, I think that we have accomplished what we may provisionally quote. as a cure. SYPHILIS AND ECZEMA SEBORRHOICUM. As this important paper has already appeared in English in the ' British Journal of Dermatology, 5 1 an abstract only will here be given. The author in the first place alludes to the careful work of Fournier and others, who have shown that the polymorphism of the syphilides may be resolved into a series of clinically recognisable fixed types which are in- fluenced by various conditions. The well-known though infrequent form of acneiform syphilide, hitherto looked upon as a simple type, may really be regarded as a mixed infection — a papular, follicular, or lichenoid syphilide which has become simultaneously infected by a pus-forming coccus ; for suppuration is not a character of syphilis. We must, moreover, regard a number of other well-known syphilides as mixed infections of syphilis and eczema seborrhoicum. The author's attention was first directed to the co-ex- istence of these two exanthems in attempting to diagnose certain doubtful cases of so-called " corona veneris ;" and a like symbiosis was recognised in many other cases of papular or crusted-papular, and especially of serpiginous syphilides of the late secondary stage. Whenever secondary syphilis presented itself, it corresponded in its distribution and in- flammatory intensity with the seborrhceic process. Three grades of the latter may be distinguished ; one slight, the others more severe. It almost always commences 1 ' British Journal of Dermatology,' vol. i, Nos. I and 2, 1888. " Syphi- lis raid Eczema Seborrhoicum, 61 Naturforscherversammlung in Koln," 'Monatsh. f. prakt. Derm.,' Bd. vii, 1888, No. 217. SYPHILIS AND ECZEMA SEBORRHOIOUM. 55 as a squamous eruption, with but slight inflammatory character, and easily escaping notice. There may be defined, circular, pale or reddish, scaly spots (pityriasis capitis, barbae, faciei, corporis) ; slightly raised, irregularly bordered or coalescing, yellowish-red, scaly papules (eczema sebor- rhoicum, papulosum corporis, rosacea seb. faciei), or regularly formed, serpiginous, yellowish-red, papular plaques or rings, with eroded edge and yellow depressed centre (ecz. seb. annulatum, sterni, dorsi, and flexuosum, and certain ecz. marginata nuchas) . From these squamous forms the others may develop by intensification of the inflammation ; and thus we may get, on the one hand, the scabbed or crusted varieties (many cases of so-called psoriasis gyrata and annulata, and many dry eczemas), or, on the other hand, the weeping varieties (ecz. seb. madidans capitis, aurium, genitalium, flexuosum). The crusted forms are particularly associated with the ringed squamous variety, and the weeping forms with the papular. In whatever way seborrhoeic eczema manifests itself, it is able to prepare the ground for the papular syphilide, and to bring on that eruption. The papulo-crusted syphilide (s. papulo-crouteuse of Fournier) , which always occupies the favourite sites of sebor- rhoeic eczema, viz. the scalp and face, is a striking example of mixed syphilis and eczema seborrhoicum. The yellow seborrhoeic edge spreads chiefly on the temples and brow, extending beyond the papules, which under the syphilitic influence become larger, more raised, flesh to copper coloured, and pigmented. The crusts are dry and fatty. In the hairy scalp, beard, and mons Veneris, the crusted papules here and there coalesce, and form raised masses, depressed in the centre and with sharp serpiginous borders. The mingling of the two affections is particularly well marked in the naso-labial furrows — the area of hyperhydrosis oleosa — where large sweat-glands exist which may become affected with seborrhoea and inflammation. On other parts of the body, particularly on the legs, ser- piginous papulo-crusted syphilides chiefly occur. The secondary papular syphilide has in itself no tendency to spread in a circinate manner, although the papules may 56 UNNA's DJ5BMAT0L0GICAL PAPEBS. become confluent, and portions of skin may become invaded by a continuous growth of young papules between the older ones. An uninterrupted uniform advance indicates an affection of the epidermis or of the papillary layer of the corium, for these are the only layers of the skin which have a uniform structure in all regions ; and unless, there be necrosis, lesions of the cutis do not proceed in a uniform serpiginous manner. Hence itisnot extraordinary that seborrhceic eczema, creeping on in the superficial layer, assumes a serpiginous character, which the papular syphilide by itself does not. A hyperaemie condition of the cutis, no doubt, influences the development of a syphilide, which will always appear in those parts of the skin which have been irritated. Thus a miliaria rubra can determine the onset of a small papular syphilitic rash, and an attack of scabies may promote an eruption in the interdigital folds and gluteal regions. The author lays down the proposition that "a serpiginous parasitic eruption of the upper skin is able to impress the eruption of a syphilitic exanthem with the stamp of a truly serpiginous lesion, in that, it, by its continual progression, keeps rendering new and hitherto healthy ring-shaped tracts of skin fit for the development of syphilides." He gives a case in illustration, in which the patient had been the subject of seborrhceic eczema, and had subsequently acquired syphilis with the development of a typical serpi- ginous, papulo-crusted eruption on the neck. That form of syphilitic so-called " psoriasis palmaris " which gradually appears late in the secondary period, spreads in a serpiginous manner, and is so resistent to constitutional treatment, is an example of the mixture of an obstinate seborrhceic eczema of the palm with a papular syphilide. Another mixed form is observed in the scalp, where an ordinary syphilitic alopecia may be accompanied by scurfiuess and small itching papules. A nummular syphilide on the forehead, nose, or cheeks may also unite with slight sebor- rhceic rosacea to form large dark red papules or patches, which must be locally treated in order to ensure rapid dis- appearance. Weeping seborrhceic eczema, combined with syphilis, ex- plains the so-called " syphilis vegetans." The moisture of SYPHILIS AND ECZEMA SEBORRHOICUM. 57 these condylomatous outgrowths lias usually been ascribed to uaacleanliness, and to secretions from adjoining parts. But the growths also occur in the: anal region, the axillae, and ■even on the hairy scalp ; and whatever effect the above con- ditions may have, these positions are certainly sometimes the seat of seborrhceic eczemas. The presence, indeed, of ooz- ing, exuberant papular syphilides on the scalp is a sure sign of the mixed infection. Certain cases make it probable that some tertiary tubercular syphilides are likewise developed upon a sebor- rhceic basis ; such, e. g., as the serpiginous ulcerating or non-ulcerating forms on the. face, scalp, neck, breast, and axillae. The author believes that here, too, the serpiginous character is determined by the seborrhceic eczema. Secondary syphilides resemble seborrhceic eczema in show- ing a preference for the flexor surfaces of the extremities, as well as the head and genitals. The eczema keeps up in these situations a slight but continuous irritation, and a hyperemia which can be at any time intensified. When a patient so affected becomes syphilised a " facies seborrheica " is im- pressed upon the syphilide. There are, however, many morphological, subjective, and therapeutic differences between the two pure diseases. The syphilitic papule tends to be sharply circumscribed, remains not bigger than a pea or lentil, is never very scaly, but frequently quite smooth and merely surrounded by a fringe of scaly epithelium, and it is stiff and elastic to the touch. It is generally of a dull brownish-red tint, and pigment is often deposited in its site and in its neighbour- hood. Although, when numerous, there may be some con- fluence, there is no regular continuous serpiginous character. It never itches or smarts ; and, apart from the head and genitals and flexor surfaces of the limbs, it is mostly seen on the front and sides of the lower parts of the trunk. Syphi- lides come out approximately at the same time over all parts of the surface attacked ; and they yield promptly to mercurial treatment, but not to such applications as sulphur, resorcin, or zinc oxide. The seborrhceic papule, on the other hand, is only cir- cumscribed in special localities (sternum, axillae, forehead), 58 tjnna's dbrmatological papers. generally has irregular outrunners, is variable and more polymorphic in character and extent, and is always more or less scaly or even crusted. It is not dense and elastic ; in colour it is yellowish red, with a characteristic yellow tone around, and without pigmentation. In addition to the regions common to both affections, it prefers the sternum, the interscapular space, and the sacral region. The course of the eruption is slow, from above downwards, and it is frequently limited to the upper parts. It readily yields to sulphur, resorcin, and zinc oxide. An interlocking of the seborrhoeic and syphilitic processes may therefore be assumed when (i) the separate spots are very various in size, confluent, and not sharply defined ; (2) the specific syphilitic colour is replaced by a fresh yel- lowish red ; (3) the greater part of the papules are covered with scales and fatty scabs ; (4) the arrangement is serpi- ginous ; (5) a yellow colour is present around and in the centre of the serpiginous circles ; (6) there are eczematous characters, oozing, heat, and tension ; (7) there is itching of greater or less intensity ,- (8) the eruption occurs on the scalp margin of the forehead, in the naso-labial furrows, on the sternum, between the shoulder-blades, and over the sacrum ; (9) it is concentrated on the hairy regions, or on places of contact; (10) the eruption is unusually obstinate to constitutional treatment, but improves under local anti- seborrhceic applications. The practical deduction is that " whenever we recognise, in accordance with the above-mentioned signs, the co-exist- ence of a syphilide with the seborrhoeic process, or wher- ever we find a purely seborrhoeic eruption side by side with a syphilide, the treatment must consist from the very first in the application of an antiseborrhoicum locally, in con- junction with the general internal administration of mercury or iodine." LICHEN EUBEE AND ITS TEEATMENT. From an experience of thirty eases met with in four years* the author is enabled to compare the various forms of " Lichen " with the descriptions of German, French, English, and American authors. He gives notes of fourteen cases and the treatment adopted, and discusses at considerable length the views of Wilson, Hebra, and many others. He divides "Lichen ruber" intoL. acuminatus, L. dbtusus, and L. planus, the papule in the first being acute and pointed, in the second obtuse, and flat in the third. The papules in all varieties have the common characters ; they have a livid, bluish or yellowish-red tint, a hard consistence, a peculiar dryness, they are more or less itchy, and more or less per- sistent. They never become vesicular or pustular. At times, when the disease is universal, the different forms may be combined. L. acuminatus consists of small papules i to 1*5 mm. in diameter, the size of a millet or mustard seed, conical, and covered at the point with a small, scaly, intensely itchy ele- vation, which corresponds to the orifice of a hair follicle. When the skin between them reddens, swells, and becomes thickened, they may appear confluent, forming large plaques. The itching is more severe than in the other varieties. The affection generally sets in acutely, after profuse perspiration, chill, or rigors. Properly treated, it may be localised and cut short ; otherwise it may extend all over, and become- chronic, and lead to death from marasmus, &c. Hebra's 1 " Zur Klinik und Therapie des Lichen Ruber," ' St. Petersburger medicin. Wocbenschrift,' No. 45, ff, 1884 ; and " Clinical History and. Treatment of Lichen Kuber," ' Med. Bulletin,' Philadelphia, 1885. 60 unna's dermatological papers. treatment by large doses of arsenic takes long to act ; Kobner's arsenic injections have a somewhat quicker effect, but the most rapid and agreeable method is by carbol-subli- mate inunctions, which may cure recent cases in a week, and older ones in two to four weeks ; the itching diminishes almost from the first day. L. dbtusus consists of papules 3 to 5 mm. in diameter, raised but flattened on the top, with a small indentation in the centre, hard, dry, waxy, and translucent, bluish- or brownish-red and without scales. It is less acute, less itchy, and more circumscribed than L. acuminatus. Left to itself it may spread, but then leaving large intermediate areas of healthy skin. The neighbouring papules may form together large plaques ; and, when cured, brownish pigmented, thin,, scar-like spots remain. Hair and nails never suffer, nor does it end in marasmus. Arsenic has less effect, but it may be quickly cured by the carbol-sublimate inunction, or single, papules may be removed by strong paints or plasters of chry- sarobin, sublimate, or salicylic acid. L. planus shows perfectly flat red spots, but slightly ele- vated, depressed in the centre, and 6 mm. to 4 cm. in dia- meter ; the surface is smooth, or often with a thin scale. They may develop either by a coalescence of very small, flat papules, or by a gradual increase in size of a single spot ; they may also be formed from " obtusus " papules which are commencing to heal, and even from a group of "acuminatus " papules. Thus there may be primary and secondary "planus " papules. Their character is due to the fact that the papil- lary area is evenly affected, while in acuminatus and in obtusus the parakeratosis is more apparent in the former in the hair follicle, in the latter in the sweat-pore. The planus, papules are more prone to remain isolated, and they increase more slowly and do not influence the general health . Arsenic has less effect, but the isolated spots have been cured by mercury and arsenic plaster-mulls, sublimate and salicylic collodions. In this form, superficial bullje may at a late period appear. Much that has been described in England and America as " Lichen planus " is L. obtusus. The author gives an historical and critical review of the whole subject; comparing the original descriptions of F. LICHEN RUBER AND ITS TREATMENT. 61 Hebra's "Lichen ruber" (i860) and Erasmus Wilson's- "L. planus" (1869), and maintaining that the former ob- server was acquainted only with the " acuminatus " variety, while the latter only knew the " obtusus " and " planus " forms — especially the first. He refers to the remarks of Tilbury Fox, Piffard, Robinson, &c., in England and America, and of others in Germany and Prance. He has had no personal experience of Weyl's "L. acneique or L. circinatus" nor of Vidal's " L. corne " and Chambard's " L. hypertro- phique ;" and he admits that we are yet far from a com- plete knowledge of the lichen group. The author's original carbol-sublimate ointment consisted of— Ung. Zinci Benz., 500. Acid. Carbol., 10 — 20. Sublimate, "5 — 1. With or without 01. Olivse, 20. HYPHOGENIC, COCCOGENIC, AND BACILLOGENIC SYCOSIS. 1 The author refers to the progress made in dermatology through, the principle of parasitism, even in connection with those diseases which have been long, ascribed to micro- organisms. We cannot now say that a particular fungus, like Trichophyton, is the cause of a trichophytosis without absolute demonstration, viz. isolation, inoculation, and cul- tivation. Sycosis furnishes a striking example. The idea of a differentiation of sycosis into a parasitic and non-parasitic form is now obsolete. Since, indeed, Bockhart in 1887 showed that pus cocci could produce the typical phenomena of the disease we know that all sycoses are parasitic. The two forms hitherto described are the hyphogenic and cocco- genic ; but a third form has lately been demonstrated by Tommasoli, in the author's laboratory, to be bacillogenic. Hyphogenic sycosis {herpes tonsurans barbse) starts in the hair itself, the fungus — not developing in liquids — being in the narrow clefts between the horny cells, beyond the region where the lymph circulates. Staphylococci, on the other hand, attack the hair-bulbs in a very different manner ; they thrive in the lymph-spaces, and afterwards invade the fibrous and epidermic structures of the follicle. This is rendered possible when they get into the space between the hair and the root-sheath, when the cleft which is normally closed above (Pinkus) is mechanically opened. The hair never becomes brittle, as in the hyphogenic form, but kinks up, and epilation is painful. The tubercles which result are 1 ' St. Louis Medical and Surgical Journal,' August, 1889. HYPHOGENIC, COCCOGENIC, AND BACILLOGENIC SYCOSIS. 63 smaller, harder, more hot and painful, and lie entirely in the cutis ; and inflammation of the entire cutis may ultimately ensue. The hyphogenic folliculitis is more acute, and spreads from hair to hair, only stopping at the scalp ; and for this reason, while the fungus may be closely allied to T. tonsurans, it may not be identical. Coccogenic sycosis is everywhere ■endemic, hyphogenic epidemic ; any suppuration may give rise to the former, but only specific inoculation to the latter. The hyphogenic form is easily cured, even by weak parasiti- cides ; the coccogenic most difficult to treat — the best results being by a therapeusis of exclusion. If left to itself, the latter may lead to the total suppuration of the follicles with the formation of scars, i. e. if the prickle-layer of the lower part of the hair-bulb be attacked. In old cases a coccogenic sycosis may be superadded to a hyphogenic ; and it is questionable whether the large tuber- cles of the latter be not due to an infiltration of cocci. Prom an apparently mild case of sycosis in the author's ■clinic, Tommasoli obtained a pure culture of bacilli with no admixture of pus cocci. The rods were short, rather thick, ejliptical, and with rounded ends. They did not liquefy gelatine ; and by inoculating with a needle, yellowish- white " nail "-cultures with smooth heads were developed. They grow best on potatoes as a thick mucoid growth and with a green discoloration around, and with unpleasant odour. It is distinguished from B. parvus-ovatus (Hoffler) by being in- nocuous to rabbits, and from B. pyogenes-foetidus (Passet) by its whitish -yellow colour on potatoes. The author and Tommasoli name it Bacillus sycosiferus-foetidus. On inocu- lating skin, typical sycosis appeared, with red indurated papules at the sites of the hair-bulbs, with small apical pus- tules, painful to the touch and on epilation. Pus cocci as well as the bacilli were found in plate-cultures from the pus. It is probable that some of the mild cases of supposed -coccogenic sycosis are really bacillogenic, especially where -.there is mild interfollicular disease with scanty suppuration. The rapid development or revolution in the study of sy- cosis during the last few years illustrates the value of sys- tematic experiment. THREE VARIETIES OE EAVUS, The original paper on this subject was read at Halle in September, 1891, .before the dermatological section of the sixty-fourth meeting of German scientists and physicians. The following is a short abstract. Through the work of Quincke the study of favus has received a great impulse, and the facts which have now come to light show how very short-sighted we have been in the past with regard to our clinical observations of this disease. Dr. Prank recognised that among the collection of favus, in the author's laboratory there were three different varieties. Experiments, numerous and varied, were then undertaken to determine the exact differences which the diseases produced by the various fungi presented clinically. The fungi were numbered I, II, III. Dr. Frank inoculated himself with a pure culture of No. I, obtained from mice. In three weeks the disease was clearly established. At the author's request Dr. "Williams inoculated himself on the leg with fungi I and III, at a little distance apart. The skin of the leg was chosen because the author had observed how firmly favus adheres to the skin in this region. On the third day following inoculation from No. 1 the part was inflamed ; on the fourth day some minute vesicles had formed ; on the fifth the whole surface of the inoculated patch was swollen and painful on movement ; on the sixth day crusts began to form, and great pain was experienced ; so great was the discomfort that the horizontal position had to be maintained. The site of inoculation with No. Ill caused by far less serious symptoms, and developed more slowly. Throughout their whole course the two inoculated 1 "Drei Favusarten," ' Monatsh. f. prakt. Derm.,' Bd. 1892, No. 1. THREE VARIETIES OF FAVUS. 65 patches exhibited distinct differences. i. The scutula of. Favus I were less numerous, and not so concentrated as those of Favus III. Some of the scutula of Favus I formed only half-rings, whereas Favus III was specially disposed to build up typical cupped crusts. 2. Scutula of Favus I were greyish yellow, while those of No. Ill were dark sulphur-coloured. The former pre- sented much the appearance which we find in the ordinary favus of mice. 3. Scutula of No. I were much softer and more brittle than those of No. III. 4. Scutula of No. I adhered more firmly than those of No. Ill to the horny epithelial substratum. The above characteristics were sufficiently well marked to enable us to differentiate the two affections with ease. The author was the sixth of those who inoculated them-; selves with fungus No. II, the result being negative in each instance. White and black mice, white and black rats, guinea-pigs, rabbits, cats, and chickens were inoculated with, the three varieties of favus. On white mice and rats, black rats and chickens, the fungus did not take effect well, at least no typical scutula were developed. Throughout the numerous inoculation experiments, however, the differences between the scutula formed by each variety were maintained. Microscopic examination also showed individual peculiari- ties of growth upon the skin, as well as differences in the filaments of the fungi themselves and their mode of sporing. For the fungus of No. I the name proposed is " Achorion enthythrix " (i.e. possessing straight running hairs). For the disease produced by it the term " Favus griseus " is suggested, on account of the greyish-yellow colour of the scutula. The term " griseus " is apothecary's Latin, but has the advantage of being more easily understood than ravus, which would be more classical. No. II the author calls " Achorion dikroon " (not to be confounded with dichroon), on account of the forked ends of the hyphse. The disease will be termed in future " Favus sulphureus tardus," owing to its sulphur colour and slow growth. For variety No. Ill the term " Achorion atakton " appears suitable, ,in consequence of the irregular course of 5 66 unna's debmatological papebs. the hyphaa ; and the disease which it produces receives the name " Favus sulphureus celerior," because the crusts are of a sulphur-yellow colour, and the growth of the disease is relatively quicker than that of No. II. Three practical points are specially referred to with respect to the study of the fungi cultivated on artificial media. i . In order to remove any doubt as to the real difference between the various fungi, they should be grown upon the same plate. If cultivated closely alongside each other, they can be stained, cut, and examined microscopically upon the same slide and in one section. 2. The best cultivating material so far has had the following composition : — Agar, 4 per cent, j peptone, 1 per cent. ; levulose, 5 per cent. ; common salt, i per cent. It requires a steam filter for its satisfactory preparation, and should be put through it twice. 3. For obtaining pure cultivations, the employment of a rather dry nutrient material is recommended. It is also advisable not to neutralise the agar, but allow it to remain slightly acid. In this way the favus can more easily outgrow the development of any micrococci present. Cultivations from the crusts are obtained by taking a small portion from the middle of the latter and smearing it upon the drier upper end of the agar in a sloping tube. To obtain cultivation from hairs, their free ends should be singed off up to near the roots, and the latter then transferred to the agar, being placed upon the dry upper end of the tube. According to the author's experience, the following is the best method for protecting and transporting favus material intended for cultivations. A piece of good sticking plaster is pressed upon the closely clipped favus patch, whieh should first have been well washed with soft soap or other- wise disinfected. After a time the plaster should be plucked off, when it will be found to have extracted numerous hairs, many of which carry the fungus. The plaster should now be attached to the lid of a sterilised tin box, and the box closed so that the hairs hang free. Pre- served in this dry condition, cultivations can be obtained satisfactorily after the lapse of some weeks. THREE VARIETIES OE FAVUS. 67 Prom the results of eight attempts to produce favus on the non-hairy parts of adults with fungus of F. sulphureus- tardus the author concludes that this variety probably only excites on man a short-lived superficial disease, known as " Favus herpeticus." The cheeks of the common house-mouse were inoculated with the three forms of fungus, and exhibited well the points of difference between the scutula which form in each case. Some of these distinguishing characteristics are as follows : Favus griseus. — Scutulum of moderate size, about that of a lentil, and as thick. On the upper surface flat or raised, not cup-shaped. G-rey-yellow, like old wash-leather, neither shining nor smooth. Penetrated at all points by the fine and tactile hairs. Favus sulphureus-tardus. — Scutulum very large, covering the whole cheek, and thick. Cup-shaped on the surface, and covered by small humps, gathered into folds, yellowish white, cream-coloured, smooth as leather, shining in some parts, and pressing back the hairs, which do not penetrate it. Favus sulphur eus-celerior. — Scutulum remains small, about the size of a peppercorn, cup-shaped on its surface, smooth but not shining ; of a light ochre-colour towards its peri- phery, in the centre whiter, and on the folded margin of a horn-like brown. It presses back the finer hairs, but is penetrated by the larger. [A. E.] EECENT ADVANCES IN THE THERAPEUTICS OE THE SKIN. 1 At the request of the publisher of the journal, 1 Dr. Unna sketches the present position of Dermato-therapeutics, limit- ing himself to the most important skin diseases, but going with exactness into those details interesting to the general practitioner. Since 1881, when the late Oscar Simon wrote on this sub- ject in the same journal, the principal matters to note are improvements in the technical methods of therapeutics ; and these may be illustrated by a few typical examples. They belong more to general therapeutics, aud are of importance to every practitioner. Indeed, the treatment of slight but troublesome skin ailments has gained more by these technical methods, than that of the severe dermatoses which come before the clinics and specialists. Before entering into these new therapeutic measures, we may consider the new medi- cines which have been able in the last few years to gain a certain position. They are salicylic acid, the ichthyol pre- parations, calcium sulphide, resorcin, and cocain. Until its invaluable keratolytic property was discovered, salicylic acid was only used by dermatologists, in weak doses, as a means of killing fungi. We have hitherto possessed no drug which will remove so well and quickly the normal, or pathologically thickened, horny layer. The dose, indeed, for this purpose must be particularly strong, and moisture must be excluded. These conditions are only properly combined in the salicylic plaster-mull (5, 10, 20, to 50 grammes per ' 'Aerzlichen Vereinsblatt f iir Deutschland/ 1885, No. 158. THERAPEUTICS OF THE SKIN. 69 roll) ; hence, a constantly increasing interest in this prepara- tion has lately arisen in all countries. The most obstinate cir* cumscribed dermatoses, strongly infiltrated patches of eczema, psoriasis and lupus, can clearly be treated locally, with much greater prospect of result, after the epidermis has been thinned by means of salicylic plaster-mulls. It differs from all other hitherto known substances of the kind, in its action, however intense, being limited to the horny layer alone. The prickle-cell layer of the epidermis is never affected ; and, therefore, so long as it is used alone, vesicles and blisters never form, as e. g. with sublimate. Its keratolytic action is in no way an ordinary corroding one ; the salicylicated horny layer can be scraped off as a soft, whitish, compact membrane. This point is mentioned at length, because it will doubt- less be of great importance in the dermato-therapeutics of the future ; there is enormous advantage in thus being able to commence the treatment of obstinate circumscribed skin diseases. At the same time it is possible that we may dis- cover other potent drugs for the same purpose, by studying the peculiar chemical action of the salicylic acid. But salicylic acid does more than this. Under its action infiltrations and granulations disappear, just as well as with caustics and alkali soap, which until now were our chief means of obtaining these results. Naturally in a concen- trated form it affects deleteriously many skin parasites ; and hence mycotic eczema of long standing can be attacked by nothing more quickly and surely than by strong applica- tions of salicylic acid. Lupus infiltrations are affected by it in the same way as by arsenic and mercury : while psori- asis patches are certainly thinned, although not cured, as with chrysarobin. As a rule, when a universal dermatosis shows especial obstruction to treatment on account of the firmness of the epidermis, 2 per cent, to 5 per cent, of salicylic acid may be added to the remedies otherwise indicated, in order to obtain a quicker action. The salicylic acid can be com- bined unlimitedly with almost all our drugs, with the excep- tion of alkalies and soaps. , The value of sulpho-ichthyolate of ammonia (soda, &c.) lies in its large percentage of sulphur, its solubility, and its 70 unna's dekmatological papers. absolute indestructibility. As it easily blends witb the tissue juice, and can be continuously taken internally without danger, very considerable and unusual effects of sulphur can be attained by its means. Like the usual sulpbur remedies it has a favorable local action on horny anomalies (Parakera-* toses), and so especially on pityriasis simplex (Alopecia pity- rodes), Seborrhcea sicca, ichthyosis, and desquamation after acute exanthemata. In slighter cases of psoriasis, a favor- able effect is also unmistakable. While the usual sulphur preparations can only be used with care in eczema and by constantly watching their action, a weak addition (2 per cent.) of ichthyol salt to the most useful anti-eczematous- remedies, acts well under all circumstances, and quickens the drying up, particularly in the much crusted eczema of children. The internal administration of ichthyol (grm. ro per diem, 0*2 to o'5 for children) is of still more importance, particularly in all those eczemas which we must ascribe to- nervous origin. To this class belong the dentition eczemas of children, Lichen urticatus, leading to pruriginous eczema, the commencement of true prurigo, and those eczemas of adults with circumscribed herpetic characters, by choice loca- lised in the region of the radials and remarkable for their symmetry and pre-eminent tendency to relapse. In these cases, ichthyol deserves to replace the commonly used arsenic — which it will probably supplant. It is also of great use as an anticatarrhal just after leaving off arsenic, when the latter cannot be borne. The principal r61e, however, of ichthyol salts is played in acne, which is also to be classed among the corneous ano- malies, and in rosacea. The firm horny layer and the ob- structions of the follicular mouths disappear under its influ- ence just as quickly as the enlarged vessels and the thicken- ings of the cutis. It is a special advantage that we can here use sublimate at the same time, as it is not contra-indicated with this sulphur remedy. Finally, the ichthyol preparations have proved themselves useful as external applications in certain infectious skin in- flammations, particularly in furunculi, erysipelas, lymphan- gitis, and panarites, also in acute exanthemata, and lately, moreover, in leprosy. THERAPEUTICS OF THE SKIN. 71 Calcium sulphide, a very old remedy, which on account of the uncertainty of its preparation, and from the results of decades, was long left in oblivion, has been, again lately re- commended by English authors. It is a reducing remedy of great effect in interstitial suppurations, especially at their beginning, and should be given internally only in small doses (grm. o"oo5 — o - oi, three to four times a day). It should, of course, be as pure as possible, carefully prepared, and sub- sequently preserved in charcoal. Pleasantness and certainty of action, however, are only guaranteed when the remedy is given in the form of " small-intestine pills ",- and from its uncommonly easy decomposition by acids it forms a sure means of testing the insolubility of such a pill in the stomach. After its administration there should be absolutely no eruc- tation of H 2 S — such as occurs when given in other ways. Eesorcin, as an acknowledged anti-putrefactive remedy, was first tried in infective skin diseases ; and indeed it has well justified our expectations. From its freedom from smell, it is preferable to the ichthyol preparations in acute processes, like common erysipelas (in 10 to 20 per cent, ointment), lymphangitis, &c. ; but as it is not quite so harm- less, we can only apply it with care in universal and chronic skin affections. A favorable result has been obtained with it in all the parakeratoses, including psoriasis and pityriasis rubra. Among eczemas, also, there are some which clinically present a parasitic character, and for these, resorcin is the best remedy. To this class belongs that dry very itchy eczema of the eyelids, which easily passes on to fissures, and is typically accompanied by a similar form around the mouth, anterior nares, and sometimes the scrotum — a rare but serious kind of multiform eczema. Resorcin, as an oint- ment, of 10 to 30 per cent., here rapidly leads to a cure. The r61e of this drug will probably soon be enlarged, for it has only been recently introduced in the therapeutics of skin diseases. Cocain here deserves mention, although it is only a quite recent acquisition. There are two troublesome affections in particular for which it is already used, and with great success, in a 1 per cent, solution or 1 per cent, ointment. These are the painful fissures of the anus and nipple. 72 DNNA'S DERMATOLOGICAL PAPERS. Cocain is at present the only remedy on which we can confidently recommend mothers and wet-nurses to continue Buckling, even when there is soreness and fissure of the nipple. To these chemical remedies, which are selected as by far the most important of those most newly introduced, we may add two physical house remedies which are always at hand ; viz. hot water and the powder bag. The uses of hot water, and its comfort to the patient if properly applied, are so considerable, that it is surprising that dermatologists have not hitherto adopted it to the same ex- tent as the gynaecologists. Thanks to the example of the latter, it has now, however, been lately adopted by us. A sponge is dipped into water just hot enough to be borne by the patient's hand. The sponge, partially squeezed, is then firmly applied to those parts of the skin which are hyper- asmic, weeping, irritating, or bleeding, and, in spite of the smarting from the heat, kept on for about half a minute. This proceeding may be repeated several times at short inter- vals. The damp skin is then exposed to the air, or powdered, if it be desired to increased the cooling effect ; and in either case, when dry, all rubbing must be avoided. Patients with rosacea, who frequently suffer from flushes of blood to the head, are most thankful for the recommendation of these deterent hot applications. Their instinct has rarely led them to combat their symptoms with hot water ; for they usually indeed wash as often as possible in cold water, which although of momentary comfort always makes the evil greater — the primary contraction of the vessels producing, as a re- action, a lasting paralysis. After every meal, excitement, or exertion a short hot bathing is especially advisable. If the hot sponging be continued too long, the effect is not so considerable — the subsequent contraction of the vessels being lessened. We proceed in a like manner if we wish to stop the bleed- ing quickly after scarification for lupus, rosacea, &c. ; if, however, the bleeding is to be promoted, the water should be of a temperature of 20° to 25 C. The hot sponge acts particularly well in all itching affec- tions, without exception. In Pruritus ani and scroti an immediate result follows ; and as in these cases the itching THERAPEUTICS 01* THE SKIN. 73 is just most acute when dressings have been on for some time and must be changed, it is well to rapidly bathe the parts with hot water immediately before applying the fresh dressing (salve, plaster-mull, or jelly). In all affections also, accompanied by a thickened horny layer (acne, psoriasis, &c), hot bathings are the best ; we may indeed lay down the rule that they are preferable to cold in most diseases of the skin. A remedy, also of simplicity, which only recently has begun to be valued, is the powder-bag. Every physician in hia daily practice, meets with a number of circumscribed obsti- nate skin affections, particularly of eczematous type, in which, from maltreatment on the part of the laity, it is often diffi- cult to determine what is the true affection and what is super- imposed irritation. Moments, moreover, come to the physi- cian in the treatment of such diseases, when it is hard for him to decide whether a sudden turn for the worse, or a cessation of improvement, is to be attributed to a remedy or to the disease itself. In such cases, the application of the powder-bag soon brings back the affection to its natural condition, and then it may be more clearly known what had best be done. Many eczemas are quite cured by this treatment, after they have previously defied the ordinary measures. The powder-bag is as useful for simple powdering as the salve- mull dressing is for simple inunction. It represents the most concentrated action of a simple powder, all the more because any sort of meal filtered through the bag deposits a dust-like powder of greater fineness than that of even the very best powder which can be bought. The bags should be made of old used linen, or other mate- rial not too dense, the pieces being evenly cut and sewn together in the form of a bag, except at one border — which remains open for filling with a moderate amount of simple rice or potato meal. After closing, the bag is sewn with quilt stitches through and through, in order to keep the meal evenly distributed ; and it is then tied directly on to the skin. Fats must not be applied to the skin at the same time, as they stop up the pores of the powder-bag. For arms and legs, we take two pieces of sleeves, thin stockings, drawers, &c, one placed inside the other, with the space 74 TJNJSTa's DERMATOLOGICAL PAPERS. between filled with powder; for the genitals the bag is fastened on with a suspensory bandage ; a trunk bandage is used for the body, and whole masks, in the form of a bag, can be constructed for the face. Turning now from the simple remedies to the few derma- toses in which improvement can be shown under the new methods of treatment, we may commence with eczema — to which, as the chief representative of these skin affections in which the barrier between the tissue juice and the outer world is broken down as in surgical wounds, the first real attempts were naturally directed after the perfection of surgical technique gave the first impulse to these advances. As these attempts were quickly crowned with success, a rapidly developing reform ensued of our whole healing apparatus. The first step took the form of salve-mulls, which continued the old principle of fatty applications. Instead of lappets of cloth covered with ointment, as recommended by the elder Hebra, we have ready at hand for the patient a plastic plaster, which can be cut and folded according to will, consisting of the lightest bandage-mull impregnated with ointment. After a mass of rich experience, we may regard the use of salve-mulls for all circumscribed eczemas of the face, ears, nostrils, arms, hands, feet, and legs, as well as the genital organs, as one of the best and most effective methods of treatment. The more complicated the surface, the more apparent are the advantages ; and for this reason they are especially useful for the concbse and nostrils — eczema of these parts now taking by their means half the length of time for cure. The extremities and neck can also be advantageously treated with them ; but not the trunk, and universal eczema, on account of the cost. Binding-mull of different widths may usually be used for keeping on the salve-mull, and, if softening of the skin is to be promoted, a piece of gutta-percha tissue may be inserted between the salve-mull and the mull binder. The most useful forms for these eczemas are the " zinc-ichthyol," the " zinc-salicylic," the "zinc-thymol," the "zinc-sublimate," the "zinc-red precipitate," the "white precipitate," the " lead- carbolic," and the simple " boric," " lead," and " zinc " salve-mulls. THERAPEUTICS OF THE SKIN. 75: For circumscribed patches on the face and back of the hand, the salve-mull can be prepared only on one side, so that it can be pressed on, outwardly presenting a dry surface, and retained without bandaging. If the salve-mulls leave anything to be desired it is that (i) they do not alone possess sufficient adhesive power to hold on, and (2) that they do not absolutely dry outside. A considerable technical advance was made by using in their manufacture two materials of conspicuous adhesive power, india-rubber and oleate of clay, the former being inert with regard to the disease, and the latter showing anti-eczema- tous properties. The "plaster-mulls" thus made stick admirably, and are perfectly dry on the surface — characters which have made them much liked. Two plaster-mulls have shown themselves especially suit- able for eczema, the "zinc" and the " salicylic " (5, 10, 20 grms. per roll). If the salve-mulls, through their fatty con- stituents, keep back the watery exudation of the skin, this effect is still greater when plaster-mulls are used — and herein lies their strong, as well as their weak side. It is difficult to imagine an application which guarantees a deeper action of the medicaments. The remedy is enclosed in these plaster- mulls, in a pure, almost undiluted condition, between the epi- dermis and an absolutely water-tight, firmly-adherent mem- brane. The diffusive conditions of the horny layer are in consequence quite novel, and by far more favorable. Swell- ing as it does from the excess of the warm skin vapour, and becoming almost like a mucous layer, the soluble and vola- tile ingredients of the plaster pass in a weak but uninter- rupted stream from the lower surface of the mull into the skin. Hence these plaster-mulls are indicated in obstinate circumscribed skin diseases, in diseases of deep-lying organs (muscles, tendons, joints, bones, serous cavities, testicles, larynx, &c), and as agents for the treatment of chronic con- stitutional diseases (syphilis). On the other hand, in consequence of being waterproof and soddening the skin, they could scarcely be expected d priori to be of much use in eczema. As a matter of fact, however, the zinc and salicylic plaster-mulls are of especial value in. eczema, and this shows that their energetic deep action quite 76 tjnna's djkkmato logical papers. compensates these collateral effects. Whilst the zinc plaster- mulls suffice for the superficial slight eczemas (e. g. of the fingers, hands, and face), the salicylic mull should be used for all severe cases, in a strong form at first, and in a weakef form at a later period. The concentration of fatty action in the salve-mulls, natu- rally however, soon led to the study of the very opposite method of treating eczema, viz. by the pure drying-in reme- dies. If the fatty salves occasionally prove themselves un- reliable, this has been shown, by a use of exclusively fatty salve-mulls, to be due merely to individual peculiarities. Among drying-in vehicles for eczema remedies, glycerine jelly takes the first place. 1 This is mentioned here at length, because it has hitherto been adopted much less than it deserves. What makes glycerine jelly so suitable for eczema is the combination of absolute permeability to the skin vapour, of slight but advantageous pressure on the parts beneath, of firm adhesion, utmost cleanliness, and relative cheapness in using large quantities. Simple zinc jelly, or better still, zinc-ichthyol jelly (2 per cent, ammonia sulphich. thyolate) comes in wherever salve- mull is inapplicable, as on the trunk of the body, wherever ointment cannot be borne, where fixation is desired without bandaging, &c, and where, on account of oedema, some pres- sure is necessary. These jellies are especially useful in all acute eczemas — where formerly only powder was used. These affections — ■ always vesicular, spreading, and accompanied by shooting pains and great tension — disappear, under the influence of a quickly painted-on film of zinc-ichthyol jelly, just as rapidly as they came. For circumscribed favorably-situated patches, powder bags are almost equally efficacious, but for large areas of the body the jelly painting cannot be surpassed. We need not be afraid moreover of applying it thickly, even to the muck swollen eyelids. Should a specially increased pressure be desirable, tbere is no simpler or more pleasant method than to paint, over the whole part affected, a suitably prepared jelly, and then to 1 ' Monatshefte,' 1883, No. 2. THERAPEUTICS OP THE SKIN. 77 apply a simple mull bandage, which can be painted over again with the jelly, and serve as a foundation for another bandage. In this manner, in addition to a soothing and anti-eczematous effect, any desired \ pressure can be per- manently maintained by means of zinc jelly and mull band- age. It has been especially developed as a treatment of congested exanthems of the lower leg, due to stagnation — particularly ulcers. The jelly is painted on the skin around, leaving the sore free, and a double-headed bandage is so applied to tbe leg as to diminish the ulcer. If there are no sores present, the bandage serves to reduce the leg, which is usually eczematous. The application of the zinc jelly necessitates its being previously melted in a water-bath, but this small trouble is amply compensated for in the comfort of the small, clean, and lasting dressing. On the face the jelly application may be allowed simply to dry ; in other parts it should be covered with some dry material. For this purpose, besides the mull bandages, common silk and tissue paper and cotton wool are suitable — the former on the trunk, neck, face, and central parts of the extremities ; the latter on the points where movement would tear the paper. In addition to their independent healing and mechanical uses, the jellies above named have proved themselves almost as useful as supplemental applications with salve and plaster-mulls. For instance, in a child with eczema of the head and face, to the head may be applied the zinc-ichthyol salve-mull, but in order not to interfere with suckling, the parts about the mouth and nose must be left free. These are to be painted over with zinc-ichthyol jelly, and covered with small pieces of tissue paper, as are likewise the edges of the skive-mull. The whole of the bandages may also be smeared over with the jelly, making a sort of firm mask. The jelly is also conveniently combined with plaster-mull, .as we shall see later on, in connection with psoriasis. For obvious reasons, very hot weather and profuse per- spiration are contrary indications for the jelly treatment in eczema; the less soluble pastes are then preferable. An eczema paste may be prepared by the poor, by boil- 78 unna's deematological papees. ing in water, meal (ioo), and adding to the stiff paste, while hot, oxide of zinc (ioo), glycerine (50) — and, according to indications, sulphur (20), tar (50), or other substances. A very serviceable lead-paste, especially recommended for eczema of the hands and fingers because it resembles the ■colour of the skin, may be thus made : ft Amyli Oryza3; 10 ; Lythargyri and Glycerini, aa, 30 ; Aceti, 60 ; M. Coque ad 80. It also acts very well in painful eczema of the anus and scrotum leading to fissures. Gum arabic and dextrine have proved useful, as soluble adhesive ingredients, which can be conveniently worked into pastes. These gum pastes are made by rubbing together mucilage, glycerine, and equal parts of dry powder : e. g. ft Zinci Ox., Amyli, Glycerini, Gummi Arabici, aa 20*0. M. Among the dextrine pastes, the ichthyol paste may be particularly mentioned as a rapidly-drying treatment for all kinds of intertrigo, in slight eczemas of the face and hands which cannot stand grease, and also in universal eczemas. It may be thus prepared: ft Ammon. Sulpho-ichthyol., ro — 3 - o, Aquae, Glycerinas, Dextrini, aa io'o. M. leni calore. This mixture forms a sort of liniment which quickly stiffens the skin, smarting for a moment on eroded surfaces, but soon stopping the itching and pain. These pastes, like the jellies, are quite permeable to the skin moisture, and act, on drying, in a cooling way, like powder. But while the jellies can be made in large quan- tities and kept in stock, the pastes can only be prepared in small quantities and kept for a short time. Intermediate between these pastes aDd the fatty ointments, are pastes made up with fatty substances, and they form on the skin a thick putty-like layer. Such are the " Bolus pastes," e.g. ft Boli Albas, 01. Lini, aa 30-0; Zinci Ox., Iiiq. Plumbi Subacet., aa 20-0. M. ; and also the starch- vaseline pastes, e. g. ft Zinci Ox., Amyli Oryzae, aa io"o, Vaselini 20*o. M. The fatty nature of these ointments is, as it were, advan- tageously corrected by the addition of drying powders. In cases where an emollient is desirable, but not a pure fatty ointment, cold cream (Ung. refrigerans) may be suit- able. The chief property of this is its constant cooling TEERAPEUTIOS OF THE SKIN. 79 effect, from the evaporation of the water, which, it should contain in large amount: R Cerise, Cetacei, aa i'oj 01. Amygdalae, Aq. Rosarum, aa 10*0. M. f. cremor refrig. Common cocain is a substitute for this, as well as the well- known cooling mixture of lime water and linseed oil, with which pastes can also be prepared by the addition of oxide of zinc, &c. While the external treatment of eczema has gained by the introduction of the above remedies, the ichthyol salts are the only new remedies which have enriched the internal therapeutics of the disease to any great extent. They possess an undeniably favorable effect, particularly in those obstinate recurrent cases which can be ascribed to a central nervous origin. Valuable as these new methods may be for the majority of ordinary circumscribed eczemas, as well as for those forms which, on account of their unfavorable position (ear, nose, ankle, scrotum, &c), have been hitherto amongst the most difficult to cure, and although, if wisely selected, they can at the outset cope with even universal eczemas, nevertheless, it must not be supposed that the old methods with fatty ointments have become altogether superfluous. The latter have only been relegated to their proper sphere, viz. the treatment of the various long-standing universal eczemas, especially when the dry skin needs lubricating ; and for this purpose the ointments retain their dominant position. The efficacy of the fatty ointments depends, on the one hand, on the easy permeability of the epidermis by fats, and on the other hand, the excess of grease obstructs the normal evaporation of water from the skin — gaining, therefore, for the absorption of remedies similarly favorable conditions, but in a less degree, as obtain under the impermeable plaster- mull. As Hack has shown, fats even increase absorption on granulating wounds, almost as much as water-proof bandages (Lister's protective). Universal inunction is not, therefore, as lately stated, an unscientific method, but it is the easiest and relatively most pleasant way of ensuring a powerful influence on the whole cutaneous organ, and a constitional effect at the same time. We can, indeed, thus obtain a double effect — externally on 80 unna's dermatological papers. the skin itself, and internally through the blood which sup- plies the skin. Where vigorous action is indicated, we still,, therefore, employ the universal inunction method. With certain reservations, inunction is applicable to psoriasis as we see it to-day ; for in this obstinate dermatosis the strongest action is generally not too much. The reme- dies recommended in this journal four years ago, chrysarobin. and pyrogallol, are still the corner stones of our external treatment ; and where a rapid and complete removal is desired of an extended and inveterate psoriasis, we must even now resort to a universal inunction with these drugs. The best plan is to combine the two, by rubbing the patient (mean- while clothed in wool or flannel shirt, trousers, &c), twice daily, from the feet to the shoulders with 10 per cent, chry- sarobin ointment, and from the shoulders to the crown of the head with 10 percent, pyrogallol ointment. It is advisable also to treat the hands of the patient with pyrogallol, and not with chrysarobin — to avoid conjunctivitis, by his inadver- tently touching the eyes. To the genitals also, chrysarobin should not be applied ; if they show psoriasis spots, they may be rubbed with pyrogallol ointment ; if not, left alone. The most rapid colouring, irritating, and antipsoriasis action is observable on the flexor surfaces, especially of the joints, and on the genitals ; and as soon as the irritation becomes unpleasant to the patient, these parts are to be excluded from the treatment by successively painting on zinc gelatine, and applying wool, so that the more obstinate places can steadily be treated further. By means of these precautions, we generally succeed in obtaining a rapid, full, and uniform effect in four, eight, to twelve days (according to the amount of irritation produced), without chrysarobin conjunctivitis or pyrogallol discoloration of the urine necessitating intermission of the inunctions. After this maximum action is reached, the disintegrated horny layer is scraped off in a second cycle of treatment, in which either sublimate baths, i in iooo (or ichthyol, 2 in ioo), are used, or a course of ointments, or sulphur baths com- bined with the latter (tar and ichthyol ointments). When the skin regains its normal colour, the chrysarobin-pyro- gallol inunctions should be resumed, as there are nearly THERAPEUTICS OF THE SKIN. 81 always some patches remaining, and then in a fourth cycle similar to the second, or the treatment may be more local. The technical advances of the last few years have not been without influence on the local treatment of psoriasis. The combination of pyrogallol and chrysarobin with gelatine, at first welcomed with acclamation, has not quite justified expectations ; the results did not compensate the intensity of its action. The introduction of the so-called " traumaticin " l as a solvent for chrysarobin, has been on the other hand most important. Comparative experiments as to the action of equally strong solutions of chrysarobin in traumaticin, collodion, and elasticin (india rubber in benzol), have shown that the traumaticin solution is the most efficacious applica- tion, and that it has two special advantages : first, it is the easiest to spread in very thin layers ; and secondly, the chloroform is in itself a valuable antiparasitic. The more simple parasitic dermatoses (e. g. favus of the non-hairy skin) can be quickly cured by the application of traumaticin alone ; and the more severe (e. g. herpes tonsurans) are best treated by medicaments dissolved in chloroform. If, therefore, a spreading psoriasis is to be treated locally, the patient being allowed to go about, the most suitable method, besides the anciently proved white-precipitate ointment and the alco- holic extract of tar, is to paint all spots every two days with a 5 per cent, chrysarobin-traumaticin solution. It will be frequently found, however, that around a beautifully heal- ing patch, a wreath of young psoriasis papules will crop up without any inflammatory irritation zone, and the necessity may arise either to cease all external medication, or to fall back on the universal inunction cure. A third way in which the efficacy of both of the new remedies has been verified is by means of the plaster-mull. This method of treatment, however, should be limited to those circumscribed forms of psoriasis which have shown themselves refractory to other means. The following precautions should always be taken : the psoriasis spots should be margined separately with zinc gelatine, or wher& the spots are close together, the whole may be included in one ring, and the pieces of plaster, cut rather larger than. 1 ' Vgl. Vierteljalu-sclir. f. Derm. u. Syph.,' 1883, p. 538. 6 82 unna's deemato logical papers. the spots, but not so large as the zinc-gelatine frames, should be so applied as to partially overlap the former. The plaster-mull in the centre, and the zinc gelatine around, should then be smeared all over with zinc gelatine and covered with tissue paper. In eight to fourteen days the bandage may be removed, and even the most obstinate spot of psoriasis will be found to be nearly or quite cured. If it be not quite gone, the process may be repeated. By this means, the chrysarobin (or pyrogallol) will not hurt the skin, the application will retain its place, and new spots will not arise in the neighbourhood. There are inert skins which will bear thin plaster-mulls without any precautions, but these unfortunately are rare. The internal treatment of psoriasis has been advanced by the exhibition of large and surprisingly bold doses of iodide of potassium, 10 to 35 grammes (?) per diem ; and there is no doubt that by this means alone, rapid cures have been effected. This method can scarcely become general, but we may mention that in former times it was far more pushed as an auxiliary remedy in the treatment of psoriasis. It appears to be advisable to prescribe both iodide and arsenic in medium doses, separately, at different periods of the day, whereby better results are often obtained than by giving only the one drug. With children, if arsenic be not borne, ammonio sulphoichthyo- late (o - 5 to i - o grammes per diem), given in watery solution, has been found useful as an auxiliary. The ichthyol salt (2 grammes per diem) has also given good results with adults, either alone, or in union with iodide, but the facts concerning this are not yet made out. We cannot, however, leave the subject of psoriasis with- out shortly indicating the prophylactic and curative measures which are at our disposal against the unpleasant bye effects of chrysarobin and pyrogallol. If the very painful chrysa- robin conjunctivitis occurs, we have dressings with lead lo- tion, cooled with ice, cocain drops, and protective glasses for the photophobia, and as a prophylactic, we should during the whole treatment with chrysarobin — from its commence- ment till after its cessation — drop into the eyes, every three hours, a 2 per cent, solution of zinc sulphocavbolate (or a i per cent, solution of cocain) . To avoid the toxic effect THE RAPED TICS OP THE SKIN. 83 of pyrogallol, a small dose of hydrochloric acid, every two hours, is advisable ; and the larger the area of skin in con- tact with the pyrogallol the larger should he the dose of acid. If there be black urine, a small pulse, violent vomit- ing, &c, very large doses of the acid should be given day and night. 1 The acidulating of the blood acts as a direct antidote to the pyrogallol, the action of which only proceeding, as a rule, in an alkaline medium. Of course, in such a case, the external treatment must be suspended for a time, and the skin may be advantageously bathed with vinegar. The treatment of acne has also made some advance in the last few years ; and in the foreground stands now, as ever, the mechanical treatment. No medical man who wishes to obtain a quick and satisfactory result should neglect, at least at first, to scrape thoroughly, with a sharp spoon, every few days, the skin which is covered with pimples and come- dones. This is to thin the epidermis in general, and to rub off the horny roofs of the follicles, and to open the pustules. A damp compress, made of wool drawn out, allays the pain and bleeding at once. If many comedones be present, they can be easily removed by means of a special compressor, which has the advantage over the watch-key instru- ments that it can be pressed on not only perpendicularly, but also obliquely. The sharp side of the ring cuts open the corneous cover of the follicle, and the smooth side, by easy manipulation of the instrument between the finger and thumb, extracts the comedo in the direction of the hair sheath. The scrapings can be replaced, as soon as obvious im- provement has taken place, by rubbing every evening with fine marble dust ; and this can be done by the patients them- selves. A damp sponge is dipped in the dry powder, and the skin rubbed and evenly polished without pressure, until slight throbbing pain be felt. Then, instead of the usual sul- phur paste, a stronger ichthyol paste is applied : ft Amnion. Sulpho-ichthyol, 3*0; Aq. Dest. Glycerini, Dextrini, aa io - o. M. leni calore. This is to be washed off in the morning with soap and warm 1 We may order : — Jfc Ac. Mur. Dil., Spt. iEther. Mur., aa 40 ; Aq., 3,50 ; Syr. Eubi, go. M. S. 6 to 4, and later 2, tablespoonf uls every hour. 84 tjnna's dermatological papers. water, &c, weak sublimate solution used during the day : ]& Aq. Eosarum, 200*0 ; Muc. Gummi Arab., Glycerini, aa 5 - o ; Zinci Oxid., io - o; Hydrarg. Perchlor., 0*5. M. S. " To be sbaken and applied after wasting with warm water, and then, on drying, to be gently wiped off. ' In all forms of acne which are complicated with rosacea, the prolonged internal use of ichthyol is also to be recom- mended j and, if in acne, the substitution of the ichthyol pre- parations for sulphur is to be called an advance — the eyes being never affected, and no sulphides bring deposited in the epidermis — it is of far more importance in rosacea. Thanks to the ichthyol preparations, the cure of this affection has been converted from a very troublesome, often thankless, and always lengthened process, to a very simple, gratifying, and comparatively short one. The puncture of the dilated vessels, which was formerly undispensable, is now required only for the very worst cases, and it can generally be omitted. Ichthyol internally is our chief remedy : R. Ammon. Sulpho- ichthyol, 5"o — io - o ; Aq. Dest., 2o - o. M. S. "15 — 30 — 50 drops, increasing the dose gradually, to be taken morning and evening in water." The aversion of patients to the smell can be overcome in all cases in two or three days, for the taste is not proportionately nasty, especially if the drops are well diluted with water, and taken at a gulp, on rising and retiring. Of course, we can prescribe pills of the neces- sary strength, but the watery solution is preferable. Ichthyol favorably influences not only the circulation anomalies of the nose, but also the commonly concomitant disturbances of other organs, e. g. hypersemia and swelling of the mucous membrane of the nose and throat, 1 hypersemia and chronic inflammation of the conjunctiva, congestion and chilblain erythema of the hands and feet, coldness of the extremities, haemorrhoids, anomalies of menstruation, spasms from con- gestion of the pelvic organs, 2 &c, &c. The digestive organs are always improved by the internal use of ichthyol ; the bowels are not forced but regulated, the appetite is gene- rally improved, old gastro-intestinal catarrhs are cured, and the patients regain their elasticity. If there be palpitation 1 Douches and gargles of 1 per cent, ichthyol are here serviceable. 2 In this case rubbing in a 10 per cent, salve acts well. THERAPEUTICS OF THE SKIN. 85 and fulness in the head, Hallersch's acid, with or without digitalis, should be taken as well, and is by no means inter- fered with by the ichthyol. The latter should not be discon- tinued during the periods. The use of cold water for the head in rosacea, is to be prohibited ; bathing should only be with very hot water, and this should always be done after meals, and when the heat is increasing. The best soap to use is the superfatted ichthyol : indeed, slight forms of rosacea require no external remedies besides this soap. Further treatment depends upon whether the skin approaches to the acne type or to the eczema type. In the former we have, besides a more venous redness, an indolent habit, acne tubercles, pustules, come- dones, and indurated epidermis ; in the latter, more arterial injection and quicker change of blood, a weak skin inclined to scale, and often smarting and itching. The acne form requires strong measures, the best being those described above for acne, with ichthyol pastes at night, and sublimate solutions by day. The eczema form, if severe, should be treated with the remedies mentioned for eczema — lead paste, or zinc-ichthyol gelatine, or the powder bag by night, with powder after bathing during the day ; or the above lotion may be prescribed without sublimate. In turning now to lupus, we tread upon ground upon which it has been lately declared that we are setiologically now as much clear on the subject, as in the case of the above-mentioned commoner dermatoses we are in the dark. The disproportion between our knowledge of the disease and the insufficiency of its therapeutics, has here been lately ventilated — as with tuberculosis generally ; but we must neither fall into the errors of the too sanguine, who believe in everything setiologically indicated — e. g. that because sublimate kills the spores of tubercle bacilli outside the body, it will also act well in the living tissues — nor allow ourselves to be influenced by pessimists, who, because the results do not correspond at once, give up the problem as insoluble. Eecent experiments with the object of energetic- ally attacking the tubercle bacilli in the skin, partly suc- cessful and partly unsuccessful, have taught us two facts with certainty. 86 unna's dbrmatological papers. In the first place, to destroy these micro-parasites in the skin, it is usually safer and simpler to modify those proper- ties of the tissue which are necessary for the life of the parasite, than to attack the parasite directly, maintaining the full integrity of the tissue. It is especially necessary to get rid of the prodromal erythema which precedes the lupus tubercles. In this sense, every organ will have its certain •antimycotic. Further, we must endeavour to find a remedy, or combination of remedies, which will, at the same time, impoverish the nourishing medium, and kill the parasite and its spores : this would really be a specific. The study of lupus must therefore be of the greatest importance for the therapeutics of tuberculosis in general : for here we can constantly control our discoveries with the eye. The cure of an ordinary case of lupus always commences best with a scraping — as thorough as possible — under an anassthetic ; and it has not been hitherto proved that this sanguinary method gives rise to any auto-infection ; it certainly curtails enor- mously the course of treatment. After scraping, the mar- gins and floor which contain bacilli should be treated ener- getically, either with lunar caustic, chloride of zinc, or sub- limate ; or, as these cause lasting pain, with a wool tampon dipped in a concentrated solution of pyrogallol, by which means the bleeding is stopped immediately. It must be remembered that in the neighbouring tissue, too firm to yield to the scoop, and along some of the dilated vessels, are lying undisturbed bacillary pioneers of lupus ; and hence an energetic chemical treatment must now be adopted. The most agreeable method for the patient is to paint on, two or three times a day, the pure ichthyol salt — the burning which lasts for a short time being followed by a complete absence of pain. The redness promptly disappears, and the growth of new epidermis makes rapid progress : no bandage is necessary with it. A stronger effect is obtained by a 10 to 20 per cent, pyrogallol ointment ; but the greatest depth action is attained by the use of plaster-mulls, particularly the arsenic-mercury, the pyrogallol, the salicylic, the sali- cylic-mercury, the salicylic-iodoform, the iodoform, the iodide of lead, and the mercury-carbolic plaster-mull. These are directly applied to the surface of the wound. THERAPEUTICS OP THE SKIN. 87 The addition of sublimate to these remedies has been proved to be painful, and not necessary — the results not being better. "We must now bear in mind the dilated vessels, endeavour to get the whole skin to contract, and to lessen the supply of oxygen to the bacilli. If this method of treatment prove impracticable, it is then best to thin the horny layer as much as possible with a strong salicylic plaster-mull, and afterwards to apply the plasters just mentioned, separately, or in turn, until all the tubercles are healed. The scarification of lupus, although of good effect by the destruction of the vessels, has rightly fallen into disrepute, because, operating in the dark, auto-infection can easily take place. For the same reason, simple punctures of the edges are not to be recommended ; but in their place, puncture injections have been lately introduced as a well justified operation ; as the whole depth is bathed by a concentrated medicament, the possibility of auto-infection is excluded. The accompanying sketch 1 shows such an injector. By gentle pressure of the forefinger on the upper elastic membrane, we are enabled to introduce the medicament in drops close to the point of the puncture knife ; and in this way large surfaces of lupus can be treated mechanically and chemically at the same time. As injection fluids, the following can be recommended : — 50 per cent, ichthyol solution, with or without tincture of iodine, a 10 per cent, solution of pyrogallol, a 2 to 5 per cent, solution of potash, or a 5 per cent, solution of creasote, &c. Sublimate solutions are unfortunately inapplicable, as they destroy the instru- ment too soon. These puncture injections are advisable as the treatment for solitary lupus tubercles, for they can be applied without narcotics. This review of some of the principal dermatoses may terminate with furunculosis and erysipelas, the treatment of which, even before their aetiology was clearly known, has been much more successful under the dermatologist than under the general surgeon. An experience of five years has shown that all those suppurations which we know under the names of "furuncles/' "carbuncles," "abscesses," "panarites," and 1 [In the original paper.] 88 unna's dermatological papers. "phlegmon," — and which are traceable to infection from certain kinds of cocci — can frequently be cut short if treated early, always running a more benign and milder course, with lessened suppuration, and needing incision in but rare cases. The universal remedy for all these suppurations is the mercury-carbolic plaster-mull ; and how it acts depends upon the stage when it is used. Applied to a commencing boil or on a just emerging panuritium, over a large surface, it causes a disappearance with only a slight remaining redness. Laid on later, it limits the suppuration to the central most infected part, and quickly gives rise here to a spontaneous and painless rupture — the aperture, which is much smaller than could be made by incision, soon closing again under the plaster. In larger suppurations which are nearly ripe, the application of the plaster-mull at least shortens the time of bursting, or if an incision has been made — which should be made as small as possible — the time of healing is considerably quickened. The pain, moreover, is greatly alleviated. The necrotic sloughs are frequently quite absent under this treatment, and in carbuncles they are much smaller than when left to them- selves. The favourite aperture in the centre of the plaster is to be omitted with these plaster-mulls — for it would defeat their main feature — viz. water-proofness. Should any considerable amount of pus collect between the skin and the plaster-mull, it may be washed off after raising the latter, and the plaster-mull, or a new piece, may be replaced. Where the position of the skin permits, and if it be convenient to the patient, an ordinary linseed poultice over the plaster is very advantageous. In panuritia and furuncles of the hands and feet, especially where the skin is already broken, soaking in an alkaline bath is useful (with soft soap, potash, or soda) . Of course, no physician would hesitate to open at once a highly-developed suppuration about to burst, and very painful ; but, even then, subsequent treatment with the plaster-mull is the most agreeable for the patient, changing the large opening to an inconsiderable fissure, and improv- ing the subsequent scar. From the dermatological stand- point, we must decidedly protest against the unnecessary torture of constantly cutting recurring boils, and also against the painful and, as far as the patient is concerned, useless THERAPEUTICS OF THE SKIN. 89 — although classical — cross-cutting of carbuncles. A furun- culous patient who has once experienced the good effects of the plaster will anyhow lose the taste for the knife j as soon as all his boils are properly covered with the plaster-mull, their subsequent development will stop. Carbuncles may be advantageously bathed with solution of ammonia, or of alkali, before each application of a new plaster. In cases where recovery cannot take place without some suppuration, it is better to leave undisturbed the plaster- m nil and the skin : by covering the whole region with plaster, a deep- lying necrotic bone splinter, whose course was quite un- certain, has frequently come to the surface, painlessly and gradually, at an unexpected spof. Where hair makes the use of the plaster impracticable, e. g. for furuncles after eczema capitis, or in frequently recurring boils of the axillae, a rapid cure can be attained by the ap- plication, twice daily, of a 10 per cent, ichthyol ointment — which is also a very good substitute for the plaster in dissem- inated furunculosis. The best internal remedy for cutting short a suppuration is calcium sulphide (about o - oi grm. ter die), administered as " small -intestine pills." The reducing remedies, already so often mentioned (pyro- gallol, resorcin, and ichthyol salts), have lately been success- fully used for erysipelas in place of turpentine and iodine ; and their action is quicker and generally more painless. They may be smeared on as ointments — the ichthyol salt in strength of 20 to 50 per cent., resorcin in 10 to 20 per cent., or pyrogallol, 5 per cent. ; or they may be applied in salve- mulls. Prom its freedom from smell, and absence of all danger of intoxication, resorcin is to be preferred in well- circumscribed erysipelas ; but in the ambulatory variety it is better to apply ichthyol ointment to the whole skin. In every case desquamation takes place, the horny layer becoming brown and shrivelled, and bringing the process to an end. We may also remember the equally pleasant silicate of potash ("water-glass"), a simple paste which acts partly by pres- sure and partly by setting free its alkali, and which has wrongly fallen into oblivion. Having mentioned only some of the most important points concerning modern dermatotherapy, we may well say on 90 tjnka's dermatological papees. looking back that the last few years have not been barren in regard to the practical side of our special branch. Our goal has been a reform of the dermatological armamentarium ; and this is by no means yet complete. Some most important work still awaits perfection; e. g. the preparation of medicinal soaps and of medicamental pencils and pigments — under- standing by these, remedies to be painted on the skin and leaving a permanent impression. The medicated ether-spray also deserves a crucial trial on a large scale, for in certain cases it has worked wonders. Lastly, the endermatic and subcutaneous methods require new trials in dermatology. The time, indeed, is approaching when general researches must be carried out in this direc- tion, and it will then be only a matter of working them out for special drugs and special dermatoses. The coming three years will mean more for dermatology than laying down general rules for its therapeutics, of which the foundation walls already stand. From the seed sown by Koch, it is to be hoped that work on the aetiology of diseases of the skin will spring up, which will soon clear up the question lately raised by Aussitz as to the entity of skin diseases, and at last release us from the system of Hebra, which has become as a strait-jacket. For this, younger forces are required, trained in new methods ; and this retrospect may therefore be concluded with an appeal to the young physicians of Germany to devote themselves with zeal to this newly revived and promising branch of dermatology. Hamburg ; May, 1885. CONTBIBUTIONS TO OTJB KNOWLEDGE OE LANOLIN. In Dr. Unna's opinion it is chiefly the chemical inertia of lanolin, and its special physical properties, that will give it a permanent and high place in the pharmacopoeia. He can- not confirm the presence of lanolin in the human skin j cho- lesterin, however, occurs abundantly. Lanolin and Plaster-mulls. — The author traces the im- provements in the manufacture of plaster-mulls, and their development from the original salve-mulls, and remarks that the reason why the German preparations are so much superior to others is that they are made under the guidance of a dermatologist who is alive to the advances of technical science. The gutta-percha plaster-mulls which were ultimately made could hardly be surpassed, being impermeable to water, more adhesive, and having a deeper action. At first benzoated lard or tallow was used as a basis, and vaseline for easily decomposed drugs, or wax for very volatile substances. The use of oleate by Beiersdorf was a distinct advance, as being more adhesive, non-irritant, and antieczematic. Since 1885 anhydrous lanolin has gradually replaced all these, being very tough, adhesive, stable, and absorbent for large quan- tities of water. Benzoated lard, however, is still used as a basis for carbolic acid, and wax for mercury and creasote. From the inertness of the new vehicle, which should then be quite dehydrated by heat, even such substances as pyro- gallol and nitrate of silver can now be incorporated in plaster- mulls. 92 unna's debmatologioal papers. Lanolin and refrigerating ointments. — In a former paper, six years ago, the author emphasised the importance Of water in certain salves, and defined the pharmaceutical and thera- peutical limits of the fatty and " refrigerating " ointments which had been long and largely used. He recommended a harder " ung. refrigerans " and a softer " cremor re- frigerans," containing a maximum of water. Dietrich then contrasted the absorption powers of lanolin and other sub- stances, and showed that — ioo parts of Ung. Paraffini absorbed 4 parts of water. 100 parts Adipis Suilli Benz. 70 parts 01. Amygd. with 30 Cerse Flav. 70 parts 01. Amygd. with. 30 Cerse Alb. 70 parts 01. Lini with 30 Cerse Alb. 70 parts Acidi Oleici with 30 Cerse Alb. 100 parts Lanolini 7 23 31 48-5 60 105 Dietrich, therefore, strongly recommended lanolin oint- ments, in the belief that the absorptive power and the amount of water contained in an ointment varied in the same ratio; but this view cannot be so generally maintained. A fruitful field, however, was opened up by Liebreich's and Dietrich's investigations. It might be expected that pure lanolin oint- ments should act as refrigerators, but although their appli- cation at first produces a cold sensation, this is soon followed by a feeling of heat, which is the expression of retardation of normal evaporation from the skin. The explanation is that pure lanolin binds water too firmly for it to evaporate with sufficient rapidity to produce perceptible cold. By altering its consistence, however, by combining it with fats, the desired effect is produced, without at the same time altering its power of retaining mechanically large quantities of water. It was found that by careful trituration 10 parts of anhydrous lanolin would take up 16 parts of water, and that 20 parts of benzoated lard would take up 2 parts of water. On mixing, an ointment was obtained containing Lanolin, 10 ; Adeps Benz., 20 ; and Aq. 18 ; but if the lanolin and lard were first mixed and then triturated with water, as much as 70 parts of the latter could be taken up. This mixture is highly and permanently refrigerating ; but such a degree of saturation is not necessary; 45 parts of water CONTKIBtJTIONS TO OUR KNOWLEDGE OF LANOLIN. 93 (150 per cent.) are enough. Experiments to determine the best proportion of the ingredients showed that — (1) Lanolin, 10+Lard, 20, could be saturated with 70 parts of water. (2) Lanolin, 15+Lard, 15, ,, „ 90 „ (3) Lanolin, 20+Lard, 10, „ „ no ,, Saturation is reached when the mass no longer sticks to the spatula, and when drops of water can be pressed out, and this will depend upon various conditions of temperature, &c. The above figures prove that with the increase of lanolin there is not a proportional absorption of water, and on apply- ing the mixture to the skin it was found that No. 1 was stable and suitable for inunction, while with Nos. 2 and 3 so much water was expelled that inunction could not be properly completed. Hence it is best to be satisfied with a propor- tion of water to fat of 2^ to 1, and the lanolin should not exceed half the amount of the benzoated lard. The consistence of these compounds is less firm than that of the ordinary cooling ointments, and approximates more to that of ordinary cream — a substance which, in the author's opinion, might be more used in dermatological practice as a cooling application, from its containing so much water for evaporation, and enough fat to keep the skin subsequently soft. As previously pointed out, there are two classes of re- frigerating ointments, differing in consistence and amount of water contained. The first are unctuous, for rubbing in on limited areas of skin, and may be considered as ordinary cooling ointments. The second are more saturated with water, and creamy, and can be applied in large quantities over erythematous, burning, or itching areas. These may be called " cream ointments," and are best prepared as above. In practice, on account of varying conditions, such as climate, and the length of time of trituration required for saturation, &c, the amount of water may be kept considerably below the maximum. As a rule, 200 per cent, of water can be easily and certainly incorporated. The best relative pro- portions of the ingredients for a " refrigerating ointment " are — lanolin 10 parts, glycerine fat 20, and water 30 ; and for a " cream ointment " — lanolin 10, glycerine fat 20, and water 60 parts. In all cases, of course, anhydrous lanolin should 94 tjnna's dermatological papers. be used. The choice of fat to be used will depend upon conditions of temperature, &c. ; and in place of the water, watery solutions of cooling drugs may be added, such as Liq. Plumbi Subacet. and lime water, or solutions of sub- stances which may assist by producing anaemia, like icthyol, resorcin, and tannin. The following are useful formulas, with their chief indi- cations : Ung. Refrigerans — Indications. . . -r, / The ordinary indications of "cold Adeps Benz. 20 S. „ , „ I cream. Aq. Rosse 30 ) Ung. Refrig. Aquse Calcis — Lanolin Anhyd. 10 ^ ■„ •, . , , , . . , , ,, I Burns, and as ointment basis in Adeps Benz. 20 > . r „ , . \ hyperssmias, rosacea, acne. Aq. Calcis 30 J Jr Ung. Refrig. Plumbi Subacet — Lanolin Anhyd. 10 ") The indications of Goulard's oint- Adeps Benz. 20 > ment, eczema, lupus, lupus ery- Liq. Plumbi Subacet. 30 ) thematosus. The basic substances contained in the last two are espe- cially useful for reducing hypersemia, as is a cooling oint- ment containing carbonate of soda. Although alkali soap has a similar action, it is, like the solvents for fats, ether, and chloroform, incompatible with these ointments. When fats are badly borne, a cooling zinc ointment can be thus made: Lanolin, 10; Ung. Zinci Benz., 20 ; Aq. Rosas, 30 ; and a refrigerating pomade — Lanolin, 10 ; Ung. Pomadini, 20 ; Aq. dest., 30. For a hot erythematous scalp the 'water may be replaced by Aq. Calcis. The cream ointments cannot be modified to the same ex- tent ; the chief are — Cremor Refrigerans — Lanolini, 10 ; Adeps, 20 ; Aq. Rosse, 60 ; Cremor Refrig. Aquae Calcis — Lanolin, 10 ; Adeps, 20 ; Aq. Calcis, 60 ; and Cremor Refrig. Aguse Calcis — Lanolin, 10; Adeps, 20; Liq. Plumbi Subacet., 60. As they readily undergo change, they should be freshly prepared and used quickly and abundantly. Even the re- frigerating ointments cannot be kept indefinitely. MEDICATED SUPERFATTED POTASH- SOAPS (OINTMENT SOAPS). 1 Medicated soaps may be classified as hard soda-, or soft potash-soaps. After many attempts the author succeeded two years ago in obtaining the former, so prepared as to meet the requirements of the dermatologist*. For their manufacture, which can only be on a large scale, the com- bined experience isnecessary of a dermatologist, a pharmacist, and a soap-boiler, free from the usual prejudices of his class. The preparation of soft soaps, on the other hand, can be undertaken by any pharmacist, without fear of their deterio- rating in quality or homogeneity, and on a small scale, with varying ingredients as may be indicated. Although non-medicated soft-soap has long been used with effect by dermatologists in chronic inflammatory con- ditions, it has not been until now employed as a vehicle for active therapeutical agents. Since Oberlander, in 1883, recommended it as a basis for the inunction of mercury, the author has largely practised the method ; and he was stimu- lated in this by the preparation by Dr. Mielck of an efficient soft-soap preparation as a substitute for the iodide of potas- sium ointment of the pharmacopoeia. The success of the ichthyolated hard-soap also suggested the preparation of a potash-soap compound, which might be stronger in absorbent and antihypersemic action. Here, too, the result surpassed expectation. His experience in the use of four medicated 1 " Medicinische iiberfettete Kaliseifen (Salbenseifen)," 'Monatsh. fur prakt. Derm.,' v Bd., 1886. p. 348. 96 ttnna's dermatological papers. soft soaps containing mercury, iodine, ichthyol, and ichthyol- tar has been so encouraging that he strongly recommends them and other preparations of the kind to his colleagues. In the manufacture of such compounds certain principles should be followed. First, it is of importance to mix the soap with an excess of unsaponified fat, for, as it has been well known since Capesser's active inunctions, the epidermis cannot otherwise bear the continued applications. A neutral soft-soap should be first obtained, and then the fat added, in quantity and quality varying with the active drug pre- scribed. As these soft-soaps take an intermediate position between soaps and ointments, they may be called " Ointment-soaps " {Sapo unguinosus). The ordinary potash-soap, prepared from oil, is too soft for the purpose. One prepared, how- ever, from lard, as suggested by Dr. Mielck, answers all requirements, and this, with the addition of 5 per cent, of benzoated lard, forms the basis of the ointment soaps. Like the hard soaps they may be employed in several ways. The most powerful and irritating effect is obtained by leaving a strong lather to dry on the skin ; but a less irritating method is to wipe off the lather with a dry cloth. Ordinary washing with the ointment soap is of no avail, unless perhaps repeated many times daily ; but a powerful action may be ensured by rubbing in the lather for five, ten, or fifteen minutes at a time with cotton-wool or with a brush dipped in hot water, and then washing off. The author generally fixes the excess of fat at 5 per cent., but a larger quantity, or other dilutents (glycerine, vaseline, lanolin), may be added as indicated. With larger amounts of fat the soap ointment gradually loses its soap character, and we may have merely a soap-containing ointment like "Wilkinson's. Mercurial ointment soap (Sapo cinereus unguinosus) differs from that of Oberlander in being superfatted. It is prepared by mixing one part of mercury with one-sixth part of Ung. hyd. cinerei, and then adding two parts of soft-soap obtained from lard. The best way of using it is to rub it uniformly over the chosen area, then to lather it for some time with warm water, and finally leave it to dry on the skin. If the MEDICATED SUPERFATTED POTASH-SOAPS. 97 latter be indolent and non-absorbent, a stiff brush should be used ; but ordinarily a pad of cotton-wool or the patient's own hand suffices. The quantity used should be regulated to the size of the area for inunction ; and to the medical man the only criteria, as regards the intensity and duration of the treatment, are, on the one hand, the disappearance of the symptoms of the disease, and, on the other, the appearance of undesirable effects of the remedy. The chief advantages of this ointment soap over the ordinary blue ointment for mercurial inunction consists, first, in being able to introduce a larger amount of the drug into the system, especially in the case of certain individuals with an abnormally fatty skin, and, secondly, in its easy application to any part of the body and in any desired quantity. Its greater cleanliness and economy are also important. On the average 30 grammes of this ointment soap are equivalent to 40 grammes of the old mercurial ointment. Patients, moreover, invariably prefer it, from its greater cleanliness, more comfortable sensation of the dry skin, and less odour. It is undoubtedly preferable also for the local treatment of enlarged glands. Iodide of potassium ointment soap (Sa-po halii iodati unguiiwsus). The inertness of the pharmacopceial prepara- tion is well known, hence the introduction of this compound will be welcomed, as there is no decomposition of the iodide until it is rubbed on the skin. Dr. Mielck, who prepared it, has written upon the subject himself. The formula is : Ointment-soap 9 parts, iodide of potassium 1 part, and water a very little. Iebthyol ointment soap (Sapo unguinosus ichthyolatus) is more active than the ichthyolated hard soap, whose indica- tions (chiefly rosacea) the author has elsewhere fully con- sidered, and hence it has a wider sphere. Intertrigo reacts promptly to it, if energetically applied by lathering and wiping off dry ;. also various forms of furunculosis, acne and rosacea ; but here we must regulate the strength and method of application according to the indolent or irritable state of the skin. In seborrhoeic diseases, from simple pityriasis capitis and dry seborrhoea to universal seborrhoeic eczema, 98 tjnna's debmatologioal papers. this ointment soap should be lathered on for a considerable time with a brush, and left to dry. It is also excellent for acute eruptions in the course of chronic eczema, for urti- caria and lichen urticatus, circumscribed chronic eczema, before applying ointments or plaster-mulls for chilblains, for the host of superficial rheumatic affections ; in short, in all cases where the action of ichthyol is as desirable as that of soft soap. The strength may vary according to the case : Ointment-soap 10 parts, Ammon. Sulpho-ichthyol. \ to 5 parts. Ichthyolated tar ointment soap (Sapo unguinosus piceo- iehthyolatus) which contains : Ointment-soap 7 parts, 01. Cadini 2 parts, Ammon. Sulpho-ichthyol 1 part, is a modifi- cation of the type introduced by Wilkinson in his tar-sul- phur-chalk soap ointment. The ichthyol replacing the sul- phur permits the concurrent use of lead or mercury, and the larger proportion of the ointment-soap does the work of the chalk in neutralising the acid constituents of the tar. This combination is especially useful in obstinate circum- scribed infiltrations, like Sycosis vulgaris, and in certain forms of eczema. It has the advantage of being useable during the day, even for the face, without being noticed, by lathering with much water and then washing off. ON THE USE OE ICHTHYOL IN INTERNAL DISEASES. In answer to a question from a correspondent, the author gives his experience in the ' Monatshefte fur praktische Dermatologie/ 1889, No. 12. Although he had used ichthyol continuously for seven years, for the past five years it was only in those internal and constitutional affections which accompanied diseases of the skin. The indications for its use, however, he has found nnmerous, and he considers that his observations may serve as hints to physicians. The diseases treated he divides into (1) Diseases of single organs or systems, and (2) General diseases. In the first class he begins with affections of the peripheral circulatory system. In many cases of seborrhoea of the head and seborrhoeic eczema of the face, in women, the symptoms finally depend on abnormal peripheral distribution of blood. There may be one or more of the following sym- ptoms : — A waxy white or yellow tint, anaemic lips and con- junctivas, oily seborrhoea of the face, recurrent hemicrania, pain in the back and loins, menstruation small or passing into amenorrhosa, habitual constipation, anorexia, abnormal sensations during digestion, palpitations, especially on exer- tion, lassitude, drowsiness, and giddiness. In such cases ichthyol does well, and it may be continued for months or 100 tjnna's dekmatologioal papees. years ; not only does it make the skin a less favorable soil for seborrhceic eczemas, but it makes new beings of the patients, and " does them so much good " that they will, on their own account, keep on with the remedy for years. Another type of general disturbance of peripheral circula- tion is found in elderly men predisposed to rosacea, who lead sedentary lives and are fond of alcohol. They are often short and thick-set and tend to obesity, with perhaps en- largement of the liver and chronic hypereemias and catarrhs of the pharynx and bronchise, &c. Here, too, ichthyol, given for the rosacea, has a happy effect on the other hyper- asmias and catarrhs. Next in importance comes a large number of diseases of the digestive tract. Under the internal administration of ichthyol — and this observation has been abundantly con- firme, — cases of old catarrhs of the stomach and intestines, accompanied by anorexia, furred tongue, irregular bowels, tympanitis, wasting and mental depression, are often cured completely, although they have not yielded to the ordinary drugs. It is desirable that specialists, in diseases of the stomach and intestines, who do not seem hitherto to have availed themselves of ichthyol, should accurately give us the indications for its use in such cases. Two points may be specially alluded to : (i) the improvement in the general health was noticed sooner than the catarrhs and circulation disturbances at the root of the matter can be looked upon as cured ; and (2) that in some cases a favorable action was observed on cholelithiasis, so much so that the yearly journey to Carlsbad became superfluous. The third class includes diseases of the respiratory organs. The topical action of ichthyol and its inhalation are disre- garded, but its internal use has been successful in several cases of bronchial asthma. In three cases, in which the attacks could only be controlled by large doses of iodide of potassium, their severity and frequency were much reduced, the bronchiolitis and cyanosis decreased, and the general health and power of resisting the effects of weather improved. In one, which had been under treatment for four years, a permanent cure was effected. An important advantage of ichthyol is that, unlike the iodide, its use can be continued ON THE USB OF ICHTHYOL IN INTERNAL DISEASES. 101 for years. In severe cases it is well to combine the two drugs, at least during the attacks. Ichthyol is also advantageous in the bronchial catarrh of old people, especially when accompanied by asthmatic attacks of dyspnoea. This affection is not uncommon in old patients with universal chronic eczema, and the author has several times observed in them a diminution of the catarrh, expec- toration, and dyspnoea, under the ichthyol treatment. In the fourth set of cases may be placed diseases of the uropoietic system. It is hoped that Tiilzer, who has had good results, will give us from his rich material more accu- rate indications for its use than can the author, whose cases have been chiefly of cystitis following gonorrhoea. In these he has seen no effect from ichthyol. internally given, but in his former practice, in 1881, an elderly gentleman with nephrolithiasis, pain in the kidney region, and digestive troubles, derived marked benefit from ichthyol, which he had continued to take regularly on his own account for four years. He was seen lately as a healthier and stronger man, with his kidney and gastric troubles totally gone. The use of ichthyol for so long a time is by no means unique ; patients have taken it for still longer periods, and have been most grateful for the cure or alleviation of their chronic troubles. Among general ailments, the first place must be given to rheumatism in its various forms — from simple muscular rheumatism to arthritis deformans. The good effect of ich- thyol in diminishing the pain and reducing the temperature in acute rheumatism, as well as its favorable influence on the disease in general, have been tested and confirmed by so many competent observers since the author's communication in 1883, 1 that further allusion to this disease is here un- necessary. The second place may be awarded to chronic and acute alcoholism, in which little has been heard, so far, of the treatment by ichthyol. The effect of a single large dose (1 to 2 grammes) was so favorable on the circulatory dis- turbances in one case, that the author has employed it largely 1 " Das Ichthyol hei inneren Krankheiten," ' Deutsche med. Zeitung,' 1883, p. 217. 102 unna's debmatological papeks. where the patients were addicted to the excessive use of alcohol. The sluggishness of the peripheral circulation, and the tremor of the hands and tongue vanish and the appetite for solid food increases, while a dislike for drink is deve- loped. The patients, indeed, are weaned from their habit ; and this hint may be taken by the managers of asylums for dpsomaniacs. There have been several encouraging cases of its use in diabetes and true chlorosis, where its undoubtedly favourable influence on the concomitant digestive disturbances may have much to do with the improvement. The author has had larger experience of ichthyol in the case of cachexias in general. In many cases of hopeless tuberculosis, carcinoma, leprosy, and in debility caused by tertiary syphilis, the general health has been raised to a higher level. Improvement in the appetite, muscular power, and general appearance, due to a strengthening of the peripheral circu- lation, is soon noticed by the patients themselves ; and they willingly take the drug in the hope that it may cure the dis- ease at the bottom of their troubles. Is the effect due only to a symptomatic influence on the circulation, to an improve- ment in the general circulation through increasing the appetite, or to an antidotal action to the ptomaines on the tissues of the body ? This question, which we cannot answer to-day, will probably soon be determined by physio- logical and therapeutical experiments. At any rate, even now, ichthyol must be classed among our most valuable drugs for the treatment of chronic infective diseases leading to cachexia. Every medical man should acquaint himself with its properties ; and the more he studies its indications, the more confident will he feel in its application. ON THE TREATMENT TRICHOPHYTON CAPITIS. The question of Trichophyton treatment was put forward for discussion at the Paris International Congress ; and with the burning interest which this question possesses, especially for London and Paris, the discussion promised to be very instructive for us Germans. In the polyclinique of every London hospital are treated yearly many hundreds of children, the subjects of trichophyton ; and similar multitudes are seen at the St. Louis Hospital in Paris. What experience is here accumulated, and what difficulties must the treatment pre- sent — reading as we do, especially in the London journals, that new remedies are constantly being tried, and, for the most part, soon laid aside ! The result of the Paris discussion was, for unprejudiced listeners, that we are still in the midst of the experimental stage of the treatment of this unpleasant disease of school children. Neither in respect of the cure generally, nor in regard to the duration, method, or time of treatment, was there any agreement whatever. On account of my very small ex- perience of the subject, I had decided not to enter into the discussion, but was drawn into it against my will by my honoured friend Besnier. Now, however, I think I may con- fidently come forward with my small experience, and at the 1 An address given in the section of Dermatology and Syphilography at the Sixty-second Meeting of the German Naturalists and Physicians in Heidelberg, 1889. 104 unna's dermatological papees. same time answer Besnier's question. If my material has been scanty, my results, at any rate, have been uniformly favorable during the last three or four years. Proceeding from the generally acknowledged fact, that we possess in chrysarobin the most efficacious remedy against most of the mycoses of the skin, I have endeavoured to use it for the trichophyton of children's heads. I may well conclude, from the surprising ciroumstance that it has not been so employed by others, that most dermotologists rightly fear its influence on the neighbouring eyes ; and I nave tried to eli- minate, in a simple manner, this very annoying contingency. First of all, the whole soalp must be cropped short (not shaved) — even though only a few bald spots be present ; for, as it soon becomes appareat under the treatment, there are always more hairs attacked than we may at first sight ima- gine. The same plan must of course be adopted if there be no bald spots, but only scattered stumps. The whole fore- head of the child, the temples, the ears, and naked parts, are then covered with strips of zinc gelatine ; and after this has been done, the scalp within the zinc gelatine margin is care- fully painted over with a strong chrysarobin ointment, e. g. my TJng. Chrysarobin co. (Chrysarobin 5, Ac. salicyl. 2, Ichthyol 5, and TJng. Simpl. 100) or any other ointment containing from 5 to 10 per cent, of chrysarobin. The hairy part of the head is then covered with some waterproof mate- rial (waxed linen, gutta-percha tissue, &c), the edge lapping over the marginal strips and gummed down with zinc gelatine, then bound with an adhesive mull binder; and, lastly, a well- fitting flannel or wax- cloth cap is tightly fixed over every- thing with strings. Once in twenty-four hours the cap is removed, the water- proof material cut along on one side and reflected, and the head washed, dried, and covered again with fresh ointment : the slit in the material is then closed with fresh mull strips, and the cap replaced. If this proceeding be really carefully carried out, on the fourth day — when the first chrysarobin cycle is terminated — only the upper edge of the zinc gelatine strips should be stained yellow from chrysarobin. Every spot of the latter is at once to be seen on the white ground of the border strips, so that an unobserved contact with the eye is TREATMENT OF TRICHOPHYTON CAPITIS. 105 impossible. Should there be any discoloration of the lower part of the marginal strips or of the neighbourhood near the eyes, it should be washed off, and smeared over again with zinc gelatine. With this bandage we can allow children to play about quite harmlessly ; they may sleep in it, and even go to school, being not contagious nor dangerous either to them- selves or others. On the fourth day, when the cap is removed, the chrysa- robin ointment is washed off, and replaced by a 5 per cent, ichthyol ointment, which is to be used for the remaining three days of the week — in order to allay the irritation pro- duced by the chrysarobin, to make the horny layer fall off quickly, and to bring the skin back to its original colour. This application may be replaced by a 5 per cent, ichthyol solution, or, not so well, by a 5 per cent, sulphur ointment — also to be applied every day for three days. Now, only at the end of the first week can we wash off without danger the zinc gelatine strips at the back, and cleanse the whole head properly with oil and soap. The diseased parts are now very apparent from their white colour contrasting with the healthy scalp around, and they frequently astonish us from their unexpected number. From all these places some stumps (about 20 altogether) are epi- lated, in order accurately to observe the condition of the fungus. After this the second cycle is commenced, and this lasts also for a week, and runs the same course as the first. At its termination, again 20 stumps are drawn out to confirm the improvement. A third and a fourth cycle, following, generally conclude the treatment. I have not found it necessary to follow on with a fifth. The total length of time required for my treatment amounts, therefore, to four weeks. Possibly the very old and severe cases of the London hospitals would need a five, or at most, a six weeks' course. This result, at any rate, is immeasurably different from that obtained by the best London dermatologists, who are accustomed to estimate the treatment of medium cases always by months, and who can even speak of cases under treatment for years. 106 unna's dekmatological papers. My observations, moreover, are much more consoling than those of Besnier, who, indeed, quite doubts a real cure by the aid of Art. It is in consequence of the results of my cultivations of the fungus during the treatment, that I venture to make such a confident statement as to the possibility of so quick and certain a cure for Trichophytia. It is a matter of very little trouble to pull out a few suspicious hairs before treat* ment, and at the end of each cycle, and to place them to grow in agar-gelatine tubes. Even before the end of the next week, we are in a position to determine exactly, according to the result of the cultivations, whether any advance has been made toward recovery. As a matter of fact, if the above method of treatment be adopted, there can be seen an advance, from week to week, up to the com- plete sterility of the hairs of the fourth sowing. Dr. von Schlen, who has lately made these experiments, will go more into details at the end of my lecture. To prove the results of treatment by cultivations from hair-stumps is so simple a matter, and so convincing, that the method is to be strongly recommended to every dermatolo- gist, even for his own satisfaction. It is nowadays, indeed, indispensable for the scientific comparison of the different methods of cure of the disease. I have seen no relapses after this chrysarobin method. The usual contra-indications will scarcely be present, unless perhaps the excess of material at the London institutions may be so regarded. The only one I know of — and this is not absolute — is where a skin possesses such sensitiveness to chrysarobin that a single application produces erythema and oedema. As a rule, the scalp reacts indolently to it; but exceptionally, after using the ointment a few times, oedema may appear with pustules. This can be treated with 5 per cent, and then 1 per cent, ichthyol solution, or else with a weaker chrysarobin and zinc ointment. The final result, however, is equally good ; indeed, by skilful management of the irritation caused by chrysarobin, these cases are cured in a shorter time than others. I hope that our London and Paris colleagues will be able to report equally good results from this method. ADVANCES IN THE ANATOMY OF THE SKIN. Nerve-endings in Human Skin. 1 About a year before this paper was written the author was induced, by some work of Pfitzner's on frogs and newts, to study the nerve-endings in human skin. He treated some sections of human prepuce, from which the fat had been re- moved, with a weak solution of osmic acid, and found that each prickle-cell was provided with two non-medullated nerve-fibres which, without communicating with each other, ended close beside the nucleus. In preparations, from which the fat has been removed, one can see that medul- lated nerve-fibres spring from the superficial and sub- epithelial plexuses which end in the touch-corpuscles, and that other shorter medullated fibres break up into delicate medullated threads, some of which end in small terminal swellings beneath the epithelial layer, while they end in the endothelium of the blood-vessels, and especially in the capillaries of the papillas. The delicate non-medullated plexus, which lies between the superficial medullated network and the epithelial layer, gives off numerous branches to the epithelium, which run in the spaces between the prickle-cells. These fibres give off lateral branches to the prickle-cells, which, after piercing the protoplasm of the cells, terminate between it and the nucleus in rounded or oval knobs. They never enter the 1 " Die Nervendijung in des Menschlichen Hani," ' Monatsh. f . prakt. Derm., 5 Bd. i, 1882, No. 8. 108 unna's dermatological papers. nucleus itself. These end-bulbs do not seem to be quite of the same material as the fibres, for they react differently to Teagents. The author has shown the existence of these nerve-endings in the whole prickle-cell area, extending as far as the granular layer, but they do not occur in the horny layer. He finds them along the whole course of the sweat- glands, and in the whole extent of the root-sheaths of hairs. He has observed them in adults as well as in new-born children. These end-bulbs also occur between the prickle- cells ; but the intra-cellular arrangement is more usual. The most remarkable feature about these nerve-endings is that they always occur in pairs. They are not merely passive enclosures between the epithelial cells, but they enter these themselves, and so stamp the whole superficial skin as an organ in the play of the nervous system. The Fibrillar Structure of the Prickle-cells, and their Communicating Processes. 1 The author reviews the various recent observations relating to the prickle- cells and their processes. In 1879 Ranvier stated that the so-called " prickles " of Max Schultze did not exist as such, but that they are the broken fragments of protoplasmic connecting threads, which can be seen in situ ; and he also maintained that the little mid- swelling of the filament is not, as Bizzozero thought, due to the soldering together of the prickles, but that it is rather of the nature of an elastic knot, which permits the separa- tion of the cells, within certain limits, without rupture of the connecting link. He stated that the swelling only exists on the shorter threads and not on the longer ones which connect cells further apart. Three years later, by a special method of staining, Ranvier observed a close meshwork of fine threads around the nucleus of the cell, with filaments from the network crossing over to neighbouring cells through the connecting processes, of which they only occupy half the diameter. He identified them with the thread-like 1 "Die fibrillar Struktur der Stachelzellen und ihre Verbindungs- briicken," ' Monatsh. f. prakt. Derm.,' Bd. vii, 1888, No. 17. ADVANCES IN THE ANATOMY OE THE SKIN. 10ff constituents of the cell-substance, as found by other histologists (Kupffer, Fleming), but did not regard them, like Kupffer, as " protoplasmic " in contradistinction to- " paraplasmic " structures. Oajal, in 1886, on the whole, corroborated Ranvier's views, except in certain details. He distinguishes in lip-cancer two kinds of prickle-cells, a smaller, opaque and granular, and a larger, transparent and fibrous variety. In both the threads form a network around the nucleus (but leaving in the former a transparent fibre- free zone next to the nucleus), and pass to the neighbouring cells through the processes. On their way across, he, like- Ranvier, finds the threads thicker, and admits an outer layer, which, however, he believes to be cuticular and not protoplasmic ; for protoplasm is fluid, while the connecting link is stiff and more refractive. He has an original explanation for the spindle-like swelling in the middle, viz, that the cuticle is often torn and rolled around, and thus giving the appearance of a knot. In the transparent cells^ which are found in the neighbourhood of the nests, the numerous fibrillse are thoroughly refractive and running parallel closely together, and often pass directly from' one cell to another. They resemble, on the whole, the- fibrillar cornifying cells of the hair-papilla and Henle's sheath, the threads being thicker, more parallel, and more distinct. Bizzozero described (in 1870) quite another fibrillar system in epithelium from the mouth, vagina, and in the- intermediate region between skin and mucous membrane, — that the cells possess a fine, short, prickle-coat, formed of fibrillse, which lay on the surface and produce saw-shaped elevations. He claimed the discovery of interspinous spaces which has been attributed to Ranvier, and we must admit that he, moreover, perceived the continuity relations of the- cells by connecting links. Heitzmann, in 1873, tried to prove in his new theory of protoplasm and cells that all epithelium was continuous through spoke-like living threads ; and, although his view of the obliteration of all chemical and histological distinc- tions in the cell constituents — the cell substance, nucleus and nucleoli — is by no one now accepted, his scheme was at first taken up by many. The author states his reasons for 110 unna's dermatological papers. believing in the histological individuality of epithelial cells and their " prickles," while accepting their continuous con- nection by means of the latter. It appears to him, from ■developmental considerations, that the sheaths of the prickles are continuous. It is, indeed, only rational to assume that the anastomising embryonal cells, which at first exist in small number, by their successive divisions never become dis- connected. But, physiologically and pathologically, this con- ception does not hold good. In quick-growing epithelial formations, and sometimes in normal epithelium, the free border of a cell, having no neighbouring cell at one side, will often show prickles springing out ; and in a simple cedema the interspinous spaces may be so expanded and filled with leucocytes that the prickles may be shrunken or contracted, and lose their connection with the neighbouring cell. If , now, the continuity were a necessary character, the persistent separation would injure the epithelial cell ; but, as the acute cedema passes off, the whole phenomena dis- appear, and we again find all the cells connected together as before. The prickles of neighbouring cells must therefore have rejoined. The continuity of the epithelium is in- teresting, and perhaps important for the transmission of nerve sensibility in the skin, but it is frequently changing, and it is not necessary for the life of the cell. Although the author approaches to the old standpoint of Bizzozero, he does not admit a mid-swelling due to a junction, like this observer, nor an elastic organ, like Ranvier, nor rolling round of a torn sheath, like Cajal, because all these ex- planations are unnecessary, as the swelling does not exist. He announced in 1883 that a simple optical effect may give the appearance of a substantial thickening of a fibre, and this can be proved by photographs from nature. Between the epithelial cells are situated nerve-fibrils, and when these lie beneath and crossing the connecting processes, but not in focus, the appearance of swellings is produced. The long bridges do not usually show the supposed thickening, because they are more seldom crossed by nerve-fibrils. The author refers to Sticker's late view (1887) that the prickles are continuations of the " hyaloplasm " of the cells, ■which is pressed in a thread-like form through the stroma ADVANCES IN THE ANATOMY OP THE SKIN. Ill of the protoplasm, and merges in neighbouring threads of hyaloplasm. That observer gives no detailed proofs of this supposition, which is against all experience hitherto. The upshot of all researches up to the present is that the cutaneous epithelial cell-body is filled with fibrillse, which encircle the nucleus, and by means of connecting processes extend from one cell to another (Ranvier) . The function of the latter is so far unknown. Bach connecting bridge consists of such a thread, enveloped by a continuation of the cell-mantle, which later becomes cornified (Cajal). The epithelial cells show their full individuality, especially in pathological formations, and their prickles merge again, if parted, without any visible swelling — which does not, as a matter of fact, exist in the connecting processes. The Nail. 1 Our knowledge of the histology of the nails has been enriched by some observations of Henle. Ranvier, before the appearance of Henle's work, has denied the existence of " Eleidin," either in the nail itself, in its matrix, or in the bed of the nail, and so far he agreed with Unna's views and Heynold's. He found, however, that a pecu- liar substance, which he called the " onychogenous material " or " onychin," occurred in the transitional cells of the matrix. This " onychin " was easily identified by its being stained brown, and not red, by picrocarmine. Suchard described this substance as occurring, not only in the matrix, but also in a thin layer in the bed of the nail. The brown colour of the zone of transitional nail-cells, first described by Unna in 1875, is recognised by all ob- servers, but is differently explained by them. Whilst Wal- deyer finds keratohyaline, Ranvier, Suchard, and Henle recog- nise a new granular material, " onychin," in this area, Buls- berg and Unna find neither of the two present. Differences of opinion exist therefore only as regards the nature of these brown granules ; all observers are of one opinion as to their existence and their position. 1 "Die Fortschritte der Haut Anatomie in den letzten 5 Jahren," ' Monatsh. i . prakt. Derm.,' Bd. viii, 1889, No. 2. IV. Der Nagel. 112 tjnna's dermatological papers. Henle states that the " onychin " extends only as far as the white edge of the lunula, and that its boundaries are here sharply defined ; he disagrees with Suchard as to its being prolonged in a thin layer over the bed of the nail. He goes on to state that 2 — 4 rows of cells contain this ony- chin, and that the breadth of this transitional zone increases from the posterior edge of the groove forwards. The author quite agrees with these observations if, instead of " onychin-holding " cells, we read transitional cells. The existence of a special nail-forming substance seems to him to have been no more proved by Henle than by Banvier and Suchard. Henle is, in Unna's opinion, quite right in now consider- ing that the epithelial swellings, ridges, and papilla at the base of the groove vary very much in different individuals, as Blascbkos has shown. From the anastomosis of the two digital arteries small vessels are given off which run forwards, lying parallel to each other, and, in the first part of their course, are very twisted. They do not give off any branches, and have only a few communications with each other and with the deeper vessels of the bed of the nail. More ante- riorly these vessels are narrower, and lie in a deeper plane ; the difference in vascularity of the posterior and anterior sections of the root of the nail depends on this fact, and not on a diminished blood-supply. The richer blood-supply of the bed of the nail, as com- pared with the anterior part of the matrix, is thought by Henle to be due to the fact that, at the groove, the nail is nourished on two sides ; on the bed, however, only on on& side ; it requires therefore a greater blood-supply in the latter situation. Prom some observations of Egenbauer, Zander, and others, on the comparative anatomy of the nail, some details in their development in the foetus become intelligible. Unna de- scribed in the human foetus a furrow which lies in front of the bed of the nail, which produces, in the last months of foetal development, a large mass of horn. He showed further that the growing nail spreads itself over this horny mass in a thin layer, and that this horny material, together with the thin edge of the nail, is mostly shed after birth. This horny ADVANCES IN THE ANATOMY OF THE SKIN. 113 proliferation at the a'irfcerior part of the bed of the nail was up till now not understood, but it is now clear. It re- presents the horny pad of animals, and its active, but eva- nescent, production is the remnant of a former greater and more lasting development of this epidermic material. The author then goes on to give an account of recent publi- cations oil the development of the nails by Zander, Brooke, von Kollicker, and Greg'enbauer. We are indebted to Zander especially, he says, for the first detailed description of the oponychium in its different segments, and for the first exact account of the granular cells which appear below it during foetal life, to disappear with it later. These cells of the embryonic nail-bed must not be con- founded with the granules of the " granular area," the root- sheath, or the medulla of the hairs ; and at present we can not speak of a " grataular layer " of the nails, but we must use the expression " granular cells of the embryonic nail." In conclusion, the author states that our knowledge of the development of the nails has been materially increased by these observers, and that the most interesting questions of the future will be as regards the nature of the granules below the primitive nail (which one might call " onychin "), and also as regards the character of the most superficial strata of the nail itself. The Nerves of the Skin. 1 Some observations of Pfitzner's on the nerve-endings in the tadpoles of frogs and newts led the author to investigate these endings in the human skin ; and he described the cutaneous nerves as ending in the prickle-cell area in two intra-cellular nerve-bulbs or swellings. His and Pfitzner's views have not been generally accepted by histologists. W. Wolff denies the existence of the subepithelial network of nerves, which, according to Pfitzsner and Canini, gave 1 " Diel Portschritte der Haiit Anatomie in den letzten 5 Jahreil," von P. G. Unna, 'Monatsh. f. prakt. Derm.,' Bd. viii, 1889, No. 5- V. Die Nerven der Haut. 114 unna's dermatological papers. off vertical branches to the epithelium. He states that the nerves end in sharp points below the epithelium. Mitrophanow published a more exhaustive account of the same subject, and arrived at the following conclusions : — That the peculiar structures described by Eberth are not nerve-endings at all, and that the fibres, given off to them from the subepithelial plexus, are not nerve- but connective- tissue fibres ; he denies the existence of this subepithelial plexus altogether. The nerves given off from the subcu- taneous, so-called fundamental, plexus he finds do form bulbous endings in the epithelial layer, but these are between, and not in, the cells. Prom his observations on the frog, he disagrees with Unna's views on the nerve-endings in the prickle-cells in man. Frenkel disagrees with Mitrophanow's idea, and finds that the cutaneous nerves in the frog have intra-epithelial terminations. - Frenkel has also published a paper on the nerve-endings in man, in which he first discusses the three chief varities of epithelial nerve-endings (viz. endings within special cells, within ordinary epithelial cells, and between the epithelial cells), and then gives the results he has arrived at by staining with chloride of gold and osmic acid. By staining with gold, numerous black threads and net- works of threads, which give off vertical branches to the epithelium, are seen ; but he cannot find that these have any communications with larger nerves, and he thinks they are caused by deposits of gold. By treating sections with osmic acid, he finds numerous threads and granules within the cells, which correspond to those described by the author, but he can find no connections between these intracellular threads and the intercellular fibres. The threads are never seen to pierce the cells, and Frenkel looks upon them as threads of protoplasm which the nucleus in shrinking has pulled inwards with it. He thinks epithelial nerves do exist. The delicacy of the sense of touch and the stiffness of the epithelial covering necessitate that the nerves should be in close relation with the epithelial cells ; the nerve-endings must, in fact, be part of the cell itself. He then raises the question as to ADVANCES IN THE ANATOMY OF THE SKIN. 115 whether all the epithelial cells are supplied with nerves or only some of them. Frenkel thinks that only some of the epithelial cells have direct nervous functions, but that all of them have them indirectly, since, by lying in continuity with each other, they are capable of transmitting nervous impulses. The most important question Unna thinks, and one upon which these observers do not throw much light, is whether the intra-cellular nerve-ending in the human prickle-cells, as described by him and Pfitzner, are of universal occurrence. Macallum has stated that, in the tadpole, Eberth's structures are the sheaths of those nerves which enter and terminate next the nucleus in the cells, whilst other nerve-terminations are found between the cells. This arrangement of nerve - terminations, partly inter- and partly intra-epithelial, is exactly the same as the author's description of the termina- tions in human skin. We are indebted to the Hoggans (' Linnean Soc. Journ./ 1882) for a close study of the nerve-endings in mammalia. They began their work by studying the habits of captive moles, and then went on to make detailed comparisons between the nerve apparatus of hairs and those peculiar col- lections of intra-epithelial nerve-terminations, which are known in the mole as " Eimersch's organs." Of importance to us is the survey of the nerve apparatus of hairs. They distinguish three kinds : (1) Medullated nerve-fibres, which are distributed to the hairs. (2) These, by breaking up, give rise to (a) branched ganglia among the lowermost cells of prickle-area of the sheath of the hair; (b) forked non-medullated parallel fibres, which, in numbers varying from one to four, run parallel to the axis of the hair; (c) a bundle of non- medullated fibres which surround the forked ends of the above, and are situated just below the mouths of the sebaceous glands. (3) Intra-epithelial non-medullated varicose fibres, which are distributed in the prickle-cell area of the hair. While 300 to 400 nerves are supplied to the large "touch- hairs" of the horse, one to two nerves supply each ordinary hair, joining it about the middle of the sheath, and dividing into 116 tjnna's dermatological papees. two or more branches, each feeing provided with a nerve- ending. G. Hoggan, in another paper, collects in five groups the^ known methods of nerve-termination in the skin of mammalia. (i) : Non-medullated nerve-fibres of the subepithelial plexus which accompanies the blood-vessels* (2) Meissner's touch- corpuscles. Groups of ganglia, con- nected to each other by non-medullated, to the centre by medullated, fibres, and which, according to Hoggan, only occur on the palmar and plantar surfaces of man, momkeya and marsupials. (3) Forked endings, occurring in ordinary hairs, less often in " touch-hairs;" (4) Pacinian bodies. (5) Segregated nerve-cells, separated by epithelial cellsj in the basal prickle-cell area; these are MerkeFsi " toucan cells." Hoggan adds to these three others modes of nerve- termination. Goldscheider examined small pieces of the skin of his forearm, and he has described the distribution of nerves to the various sensitive " points." He finds that mixed nerve- bundles run up to the surface of the sensitive areas, and that the nerves which suppy the " temperature points " run with the vessels, while those supplying the "pressure- points " lying parallel to each other are distributed. Goldscheider thinks that the difference between " cold " and " hot-sensation " areas lies in a molecular distinction between the two sorts of nerve-endings. He points out the importance of the absence of touch- bodies in the " touch-points." These bodies, from their limited distribution, were always considered not to be essential for the sensation of pressure. Goldscheider, in conclusion, points out that the " temperature nerves " do not feel the prick of a needle, and he considered them, therefore,. £0 be analgesic. ADVANCES IN THE ANATOMY OF THE SKIN. 117 The Pigment of the Skin. 1 Unna stated, in 1876, that the matrix cells of the cortex of the hair were contained in envelopes of pigment ; he acknowledged, however, that higher up in the shaft, and in cases of marked pigmentation, the pigment might find its way into the cells themselves. Waldeyer entirely opposed these views, and stated that the pigment was contained in the formative cortical cells at the lower end of the hair. Riehl, in 1884, showed that the pigment was situated in irregular-shaped migratory cells below and in the papilla, and was carried up in these into the interstices between the epithelial cells. Higher up it disappeared from these inter- stitial spaces and accumulates in the protoplasm of the epi- thelial cells. Aeby, at the same time, stated definitely that pigment is not formed in the epithelial cells, but is carried thither and deposited ■ there by migratory cells from the connective tissue. Ehrmann conducted some experiments on frogs and guinea- pigs, and found that, when ecchymoses had been caused in these animals, the colouring matter of the blood taken up by the cells was transformed into amorphous granular pig- ment, whilst hsematoidin crystals were also formed in the tissues. These same tissues were later found to contain large quantities of pigment in the cells of the cutis and the prickle- cell area of the epidermis. He deduced from these experiments that pigment originates from the colouring matter of the blood, which the connective-tissue cells closest to the vessels take up ; these cells, he states, do not mi- grate out of the cutis, as Riehl and Aeby supposed, but merely pass the pigment on to the cells of the epidermis. In man, Ehrmann states, pigment is entirely formed in the cutis, although it is almost only found in the epithelium ; he forms this conclusion from the analogy of the skin of am- 1 "Die Fortschritte der Haut Anatomie in den letzten 5 Jahren," 'Monatsh. f. prakt. Derm.,' Bd. viii, 1889, No. 8. VI. Das Pigment der Haut. 118 unna's dermatologioal papers. phibia, in which the origin of pigment in the cutis is more easily observed, and also from the fact that in cases of deep pigmentation pigment-cells are also found in the cutis. The author agrees with Ehrmann that leucopathia syphilitica, vitiligo, and poliosis depend, not upon recession of pigment from above, but upon a cessation of supplies of newly-formed pigment from below. He considers the chief value of Ehrmann's work to lie in his experimental and histological proofs of pigment-formation in the cutis, and also in his de- scriptions of the transference of pigment, without any change of position in the cells of the cutis which contain the pig- ment. He considers Ehrmann's theory of separate cells in the epidermis passing the pigment upwards to be far-fetched and untenable. Karg showed that a portion of white skin, grafted on an nicer in a negro, became very soon quite black, and a portion of a negro's skin, grafted on to a white man, very soon lost its colour He agrees with Eiehl and Aeby that the trans- ference of pigment is carried out by " wandering" cells — chromatophores. After reviewing some publications of Nothnagel and von Kollicker, Unna sums up by saying that upon one point at least all observers are agreed. Pigment does not originate in the epidermis, but is transported thither from the cutis. Further, that in the lower epide rmic strata the pigment lies between the cells, and makes its way higher up into the cells themselves, where it collects especi- ally at the distal pole of the nucleus. Disagreement exists as to the means by which the pigment is carried upwards. Curiously enough the lymph- stream has not been mentioned by any observers as a probable means of conveyance of the pig- ment, and to Unna this seems the most plausible theory. He thinks that the pigment reaches the anterior of the cells along the channels by which the intra-cellular nerve-fila- ments, described by him, are distributed. ON THE NORMAL SURFACE AND COVERING OF THE TONGUE. 1 In this paper the author does not propose to deal with the posterior part of the tongue, with its circumvallate papillae, as this region is often hardly in view. We must distinguish between the dorsum and the edges of the tongue ; and in every description of these two regions, always lay particular stress upon the colour of the organ and the con- dition of its surface. The colour is determined by the cir- culation and the condition of the epidermic layer, the smoothness of the organ by the mode of distribution of the papillae, a constantly varying factor, and also by the condi- tion of the epidermic layer. ( i ) The circulation. — Anaemia and venous congestion cause a bluish-grey colour of the tongue, while a good circulation is indicated by a more or less red, fleshy colour. When some persons put out their tongues anaemic patches are seen, especially along the median line, which are caused by contractions of a few bands of the transverse muscle. (2) The condition of the epidermic layer demands a far closer inspection. We know that this surface varies very much in the distribution of the filiform and fungiform pa- pillae. When the filiform papillae are long and cover the 1 " Ueber die normale Zungenoberflacbe und der normalen Zungen- belag," ' Separat-Abdruck aus der Vierteljabresscbrift fur Derm, and Sypb.,' 1 88 1. 120 tjnna's dermatological papers. whole surface, the tongue looks whitish in colour and very rough ; when, on the other hand, the length of the papilla?,, with the hair-like processes, is gradually lessened from behind forwards the tongue is redder and smoother towards its edges. The length and thickness of the tufts of hair- like processes of the papillae influence the appearance of the surface of the organ. The longer these processes are the whiter does the tongue appear, and, when they have reached a certain length, what we may call a normal furred tongue is the result, which the practical physician is always rather prone to look upon as pathological. The presence of a fur upon the tongue depends, therefore, normally as well as pathologically, upon the length of the processes borne by the filiform papilla? ; and, unless we know the usual condition of a tongue beforehand, it is hard to say whether a fur is pathological or normal. A patho- logical fur is formed upon the tongue by a swelling of the hair- like processes of the papilla?, which become thicker and longer, and together appear as a thick, white, homogeneous fur. The increase in thickness of the whole epidermic layer depends upon a swelling of the individual cells, and the pro- nounced whiteness upon the same cause, well as upon a loosening of these cells which leads later to the removal of the fur. This is the simplest and commonest form of fur as met with in gastric derangements. As regards the fungiform papillae, these contain more connective tissue, but a smaller horny covering, than the fili- form papilla?. The epidermic layerforms a horizontal covering over them, and is not, as in the case of the latter, prolonged up into delicate processes. Sometimes the fungiform pa- pilla? approach in construction to the filiform, and stick out on the surface of the tongue above them- More commonly, however, the filiform are shorter and thicker than usual,, and then the tongue has a markedly smooth appearance ; this is often seen in old and wasted individuals, and depends in this case upon atrophy of the papilla?. The red colour of the fungiform is in marked contrast to the whitish colour of the filiform papilla?. One can easily imagine the different types of tongue which result from the various modes of distribution of these NORMAL SURFACE AND COVERING OF THE TONGUE. 121 papillae. As the fungiform papillae affect the edges of the tongue, these usually appear red. A common arrangement is for the fungiform papillae to form clusters, as large as a pea or cherry, along the edges or dorsum of the tongue ; sometimes they form three or four parallel rows along the edges, and are entirely absent from the dorsum. They are sometimes all collected together at the tip of the tongue, which then appears red and granular. There must be mentioned, in conclusion, the linear ab- sence of papillae which causes furrows along the surface of the tongue ; a median longitudinal groove is the commonest. Rarer are vertical grooves, at a distance of about - 5 cm. from each other, which cause a most peculiar appearance of the edges of the tongue. Another curious appearance arises when the whole surface of the organ is covered with furrows, then looking something like convolutions of the brain. ON THE INSENSIBLE PERSPIRATION OE THE SKIN. ] It is certain that in the every- day treatment of skin diseases we exert, by means of ointments, powders, plasters, varnishes, &c, a considerable influence upon the physiological functions of the skin as regards the evaporation of water and the secre- tion of fat. To study the conditions of this evaporation the author closed a funnel with the skin of a fowl (cutis and epidermis) from which the fat had been removed, and con- nected it with a graduated glass tube which indicated the amount of water lost by evaporation through the skin. By this means he was enabled to judge of the difference in the amount of evaporation caused by the application of varnishes, &c, to the skin. Four of these funnels were placed side by side in a box, and the amount of water lost by each could be read off on the graduated tubes with which these were connected. The amount of water lost by evaporation was, as one would suppose, lessened by fats, and lanolin prevented evaporation more than any other. This obvervation was interesting, as it is well known that the skin becomes slightly swollen and more turgid after the application of lanolin oint- ments than after ordinary ones of the same strength, and we know that our drugs act more powerfully upon the skin, in proportion as the epidermis becomes more turgid, by the re- tention of the water of evaporation. Glycerine also prevented evaporation. In exact opposition to the fats is the action of " gums." 1 "Ueber die insensible Perspiration der Haut.' - IX. Cong. f. inner Med. ON THE INSENSIBLE PEESPIEATION OE THE SKIN. 123 It is a well-known fact that by the application of gum to the body large quantities of bodily heat are withdrawn. A man covered all over with gum shivers in a well-warmed room or in bed. This fact is explained in various publications, in which the author recommended gum in certain skin diseases, as due to an increased evaporation by the skin. This eva- poration through a porous body, as dried gum is, seemed to be natural enough. The experiments with the above appa- ratus have, however, definitely proved that, with a thin coat- ing of gelatine, the amount of water lost by evaporation is increased, and that the gelatine had therefore an exactly opposite effect to ointments. Experiments were then made with equal quantities of collodion, gutta-percha, and india- rubber. The covering of gutta-percha diminished the amount of evaportion to a third, the one of indiarubber down to one seventh, while the covering of collodion did not only not diminish the amount, but actually increased it by two thirds of its former amount. A thin covering of collodion allows therefore about ten times as much water to evaporate from the skin as does a covering of india-rubber. Further, we can state that, so long as a thin covering of collodion or gelatine sticks close to the skin, it not only does not prevent evapora tion, but actually increases it. It is a matter of every-day experience that starch-powder has a beneficial effect on cutaneous inflammations, not only on moist, secreting surfaces, but also on merely hyperaemic ones. Dusting the inflamed surface with powder has a cool- ing effect, and exerts this by increasing the insensible evapo- ration from the skin. This is brought about in the following way: — The powder removes by capillary attraction the particles of fat from the skin, distributes these over its whole surface, and thereby allows of freer evaporation through the epidermis. It is for this reason that the application of powders has its most cooling effect on the skin of the face, where the inflamed areas are most fatty. By modern physiologists the important evaporation of water by the skin is looked upon as a sort of perspiration, and no clear distinction is drawn between skin-vapour and sweat. When we consider that the amount of water lost by evapo- ration reaches in the twenty-four hours 1 kilo. (Seguin) or 124 unna's dermatological papers. \ kilo. (Weyrich), we can hardly understand how recent works on physiology have laid so little stress upon it. Some practical results must, in conclusion, be pointed out^ which may be deduced from these experiments. If we cover the skin of a healthy individual with fat, e. g. a mixture of lanolin and vaselin, he will lose very much less water through his skin. Less heat is given off, and more water is passed through the kidneys. The storing up of heat is probably the object aimed at in rubbing atrophic and wasted children with fat and oil. If, on the other hand, we have a poison circulating in the blood, which we know will certainly not be got rid of through the skin, but through the kidneys, it would seem to be rational treatment to cover such an individual with fat, so as to drive more water through his kidneys. On the other hand, we are possessed of remedies, as we have seen, which materially increase the insensible perspiration. We can effect this by the removal of fat from the skin, and, in a greater degree, by smearing the body with gum. This latter method has been in use in skin diseases for years. If, therefore, we wish to increase the amount of perspiration, we cover the body with gum ; and, to carry out this treatment effectually, the covering of gum must be washed off and renewed every third or fourth day. This seems to be a rational mode of treatment in pyrexia, where unloading of the kidneys is called for, and this method the author recommends to the consideration of physicians. ON SKIN VARNISHES. 1 In the therapeutics of skin diseases film-forming applica- tions, or, as the author prefers to call them, " varnishes," play a peculiar part. Theoretically one might not expect much benefit from their use ; but experience teaches us that these applications do good, and efforts are always being made either to enlarge their number or to improve existing ones. It is Gertain that very satisfactory and far-reaching results are obtained by the use of varnishes, which have apparently only superficial effects ; but we do not know how to specify suitable cases, nor can we give a scientific explanation of the therapeutic effects of these applications. At the International Congress in Washington in 1887, Dr. Knaggs, of London, read a paper " On a New Method of Local Treatment in Skin Diseases," and in the ensuing discussion the author gave his classification of varnishes, as follows : — (1) ^Ethereal or benzin solutions or india rubber, nitro- cellulose, gutta percha, aluminate ; (2) Spirit solutions of resins, wax, fats, oleates, and soaps ; (3) Watery emulsions of the last-named ; and (4) Watery solutions of gum, dex- trine, albumen, gelatine. The author, at the Congress in Vienna in 1890, gave some details on the different permeability of various varnishes by aqueous vapour, which were more or less diametically opposed to the popular views on this point. 1 "Zur Kenntniss der Hautfirnesse. Versamml. Deutscher naturf. in Aerzte in Halle, ' Therapeutische Monatshefte,' Berlin, November, 1891. 126 tjnna's dermatologioal papers. Elliot, of New York, has lately advocated the use of " Bassorin " as a basis for varnishes. " Bassorin " or tra- ganthin " is found in some varieties of gum plants, and is distinguished from gum by its behaviour when treated with water. It does not dissolve as gum does, but swells up ; especially in hot water, into a tough slimy mass. The author had used tragacanth, which consists chiefly of arabin and bassorin, in the form of varnishes and ointments for a number of years. Elliot, however, introduced a material, made from this traganthin, which excels the gelatin preparations in homogeneousness ; but he does not tell us how his dispenser prepared this substance ; we are merely informed that " bassorin-paste " consists of " bas- sorin, mixed with glycerine and dextrine. The author examined some samples of this preparation, which Elliot sent him, and found that the basis of it consisted not of tragacanth itself, but of the purer, slimy substance — bas- sorin. Beiersdorf has obtained a very nice, homogeneous preparation by rubbing tragacanth up with water and then filtering ; the filtrate being then condensed by evaporation and mixed with glycerine. In this way a preparation,, having the same properties as Elliot's paste, has been ob- tained, without the addition of dextrine being necessary. Beiersdorf also made a bassorin varnish, which contained a good deal of starch, by treating lumps of " Salep " with water, condensing the slimy mass by evaporation and adding glycerine. These two bassorin varnishes have the advantages over the Traganthin varnishes, formerly employed by the author, and lately recommended by Pick — in containing more bassorin — (5 to z\ per cent.), and in the film their form being, in con- sequence, smoother and firmer, and, at the same time, more delicate. They also spread themselves much more evenly over the skin. Both these varnishes are readily miscible with oxide of zinc ; while most of the varnishes in use are not. The author then goes on to make some observations on other skin varnishes, which are soluble in water, and of these the casein preparations are the best. ■Casein powder is dissolved in an alkaline solution, the ON SKIN VARNISHES. 127 best alkali for this purpose being borax. It has been found that the following proportions gave the best film on drying : — Casein, 5 ; borax, o"6 ; water, 25, or 20 per cent, casein + 2\ per cent, borax. This solution dries quickly and forms an even, smooth film, which readily takes up various drugs, such as resorcin, pyrogallol and even chrysarobin, without any oxidation taking place. If casein is dissolved in ammonia, which is allowed to evaporate, then mixed with glycerine, a fine emulsion results ; and the casein keeps its film-forming proporties. This glycerine- casein- varnish is very elastic, dries easily, forms excellent films, and is compatible with most drugs. The author gives the five best balsamic and resinous varnishes. (1) Amber varnish. — The amber-lac of commerce is a mixture of amber and turpentine, dissolved in alcohol. It is an excellent vehicle for chrysarobin and pyrogallol, drying quickly, and forming a pliant, smooth film, which can be easily removed by cotton wool dipped in spirit. (2) Gastor-oil shellac varnish. — Solutions of shellac in alcohol are useless, for they are too brittle. A good varnish is obtained by mixing shellac one part, with castor-oil one fifth part, and alcohol three parts ; and this when filtered, is miscible with zinc oxide. (3) Canada-balsam-collodion varnish. — A mixture of 16 parts collodion with 1 of Canada balsam forms a clear, pliant film, which takes up oxide of zinc better than No. 2, and is also miscible with pyrogallol, though not so well with chry- sarobin. (4) Castor-oil-collodion varnish. — Bight parts collodion and 1 part castor-oil, with 1 part zinc oxide, make an excellent varish with oxide of zinc, which undergoes no decomposi- tion. (5) Lead-ricinoleate varnish. — One part of oxide of lead is boiled with i£ parts of castor-oil; and this dissolved in 2 parts of absolute alcohol forms a good varnish. A large quantity of oxide can be incorporated with it. 128 unna's dermatalogical papbes. The author gives the following formulae (i) f!) Acid. Salicylic, 3. Canada balsam, 1. Collodion, 16. (2) $t Zinci. Oxyd., 2. 01. Ricini, 2. Collodion, 16. (3). 9> Resin, g. 01. Ricini, 1. Pyrogallol, 1. Alcohol absol., 15. THE ACTION OF CARBOLIC ACID AND OIL OF CLOVES ON LUPUS. 1 Besides tuberculin, two drugs, carbolic acid and oil of cloves, have a specific action on lupus tissues when applied locally. A concentrated solution of carbolic acid causes a dry scab, which is scarcely raised above the level of the sur- rounding skin, and the necrotic tissue is removed without any moisture. The application of oil of cloves acts differently. Only a superficial scab is produced, under which the cutis becomes raised and swollen. By continued application of both drugs, the epithelial covering of the lupus nodules is destroyed, while that of the healthy surrounding skin remains intact. Occasionally, more often with oil of cloves than with phenol, the epidermis is raised up in blisters, and then ulcers are formed. The author has examined sections of lupus nodules, with the healthy surrounding tissue, twenty-four hours, two days, and seven days after treatment with carbolic acid. The most noticeable feature in all the preparations is the scabbing of the epidermis, and later on of the cutis. In specimens in which the treatment has lasted one or two days, an upper necrotic layer of epidermis, and a lower apparently healthy layer, separated by a deep line of demarcation, cover the lupus nodule. If the action of the carbolic acid be continued, the whole 1 " Die Einwirkung von Karbolsaure und Nelkenol auf Lupus Grewebe," 4 Monatsh. f. prakt. Derm.,' xiii Bd., 1891, p. 463. 130 unna's dermatological papers. epidermis becomes necrotic, and the distinction between the cells and their nuclei disappears. The action of carbolic acid is always more pronounced on the epithelium of the lupus nodules than on that of the sur- rounding healthy tissues. A " reaction of the epidermis " takes place, which for some time prevents the further destruction by carbolic acid. These changes .are worthy of consideration. The configuration of the epithelium undergoes great changes, the sub-papillary prickle-cell area alone retaining its form ; the supra-papillary, on the other hand, is atten- uated and, in many places, is only represented by a few rows of cells. A horny layer, consisting of only a few rows of cells with horizontal rod-shaped nuclei, is spread over this prickle-cell layer, and forms the line of demarcation of the necrotic change. When the " reaction " takes place, changes are observed in the prickle-cell area. It becomes thickened and the supra-papillary portion is seen to be composed of two layers. The upper one of these is thickened by cedematous swelling of the older prickle-cells, and is composed of large clear cells with slightly stained nuclei, while the lower layer is composed of small deeply stained cells rich in chromatin. It is this altered prickle- cell area which, in conjunction with the thickened epidermis, prevents for a long time the action of carbolic acid on the under-lying tissues. Carbolic acid acts upon the cutis very much in the same way, and acts much more deeply upon lupus growths than upon healthy surrounding skin. The collagenous tissues in the connective-tissue layer lose their fibrous structure and become homogeneous ; they blend with the protoplasm of the connective-tissue cells, to form a structureless mass in which the nuclei of the cells are seen lying. The further action of carbolic acid upon the skin causes greater disorganisation. The structureless homogeneous mass becomes split up in every direction and assumes a porous, worm-eaten appearance. As carbolic acid has a preference for attacking, and causing molecular destruction of, the older and already disorganised tissues, we can easily understand its action on lupus. Accord- ing to the author's experience, applications of strong carbolic ACTION OF OAEBOLIO AOID, ETC., ON LUPUS. 131 acid have occasionally, without other treatment, caused the disappearance of lupus nodules. The number of applications must be regulated by the depth of the nodules, they must be carried out continuously without allowing the skin to recover. Pure carbolic acid must be used. We may now consider the effect of oil of cloves upon lupus and the surrounding healthy skin. After two days' treatment, we find the epidermic and granular layers of the healthy surrounding skin somewhat thickened, while those covering the lupus nodule are trans- formed into a scale. The prickle-cell area remains passive under this treatment ; and even after seven days' application, we only notice a slight enlargement of the cells and an increase in the nucleolar bodies, 2 to 3 in each nucleus. It is only after long-continued use of the oil that degene- ration of the epithelium takes place. The necrosed portion of epithelium is not so sharply defined from the simply cedematous portion, as after the application of carbolic acid, although we can, in this instance too, speak of a line of demarcation which is marked out by a row of minute vesicles. The epithelium covering a lupus nodule, after treatment for weeks with the oil, is sometimes found to be softened and permeated with serum and fibrin, but with only a few leuco- cytes ; or it may have fallen off as a scale. The action of the oil on the cutis elements is not so sharply defined as that of carbolic acid. The action extends deeper in a few days than that of the acid, but the resulting changes in the lupus nodules are very much the same. These changes, however, occur more rapidly ; even after two days, the lupus nodule is broken up by numerous cracks, and has a finely porous appearance ; and after some weeks it appears spongy, and is riddled with holes. In conclusion, the author considers that the therapeutical value of oil of cloves can not be compared with that of carbolic acid. ON THE CULTIVATION OF EPIDEEMIG FUNGI. 1 In Dr. Unna's first communication on that form of eczema to which he gave the name " Eczema seborrhoicum " (on account of its connection with the so-called " Seborrhoea sicca," and of the fatty nature of the exudation), he stated that he had no doubt as to its parasitic origin ; and he has since then been investigating the fungi occurring in the pathological products of the affection. These researches were continued with the help of Dr. P. Taenzer, and the convic- tion became paramount that, in order to determine a particular fungus as the only final cause of the disease, it was abso- lutely necessary to study all recently discovered botanical facts in reference to the skin fungi in general. By means of Koch's method of plate cultures with the scales and secre- tions of Eczema seborrhoicum, an astonishingly rich flora became apparent, and every new case of the disease added new parasites to those already found ; so that it was impos- sible to arrive at even a preliminary conclusion by this means. Twelve typical cases were thus mycologically studied, in order to become acquainted with the botanical aspect of the question, without reference to the aetiology of the disease. This inquiry gave, from about 60 pure cultures, 50 different mucors, over 20 varieties of Penicillium, 5 Aspergilli, about 1 "Die Ziichtung der Oberhautpilze," 'Monatshefte fur praktische Dermatologie,' vii, 1888, No. 10. ON THE CULTIVATION OF EPIDERMIC EUNGI. 133 a dozen belonging to the Oidium and Saccharomyces group, 3 common yeast fungi, and a considerable number of cocci and bacilli — some known and otters unknown. All these were ob- tained with weak alkaline media — viz. the ordinary peptone- gelatine and agar — and at the temperature of the room. There is no doubt indeed that other conditions, acid media, growth upon potato, apple, vegetable decoctions, &c, and higher tem- peratures, would have brought into development, and therefore to our knowledge, a fresh multitude of plant germs. Similar conditions were employedin these experiments because we know botanically that certain fungi have been formerly taken to be of distinct kinds, while only differing in consequence of vary- ing surroundings. Fungi, macroscopically and microscopi- cally distinct, systematically cultivated alongside of one another for a considerable period (six to eighteen months) on the same media, and at the same temperature, and always presenting the same characteristic, must represent distinct kinds. Not until these have been definitely identified, is it worth while mycologically analysing further cases of the same skin disease with other media and higher temperatures, &c. But what purpose, it may be asked, does the investi- gation of this legion of fungi serve, where it is a priori certain that only a twentieth or perhaps fiftieth part of them produce a really pathological action, the rest being harmless accidental parasites ? Is it not enough to test all pure cul- ' tures by inoculation, and to direct attention only to those which show positive results ? In point of fact, the first pure cultures were inoculated in the skin of three healthy medical men ; and these experiments showed that it would be an error to rely on the simple requirements of modern bacterio- logy, without modification, when dealing with the etiological meaning of a schizomycete in reference to an epidermic disease. Most parasitic epidermic affections (Parakeratoses) injure the general health but little ; and then only through acompanying nerve irritation. The fungi find an insurmount- able wall in the normal vascular connective tissue, and they cannot — as the laity and alas ! many physicians still believe — " Strike in/' overflow into the circulation, and thereby endanger the general health. Those skin fungi which can do this — like the streptococci of erysipelas, the pus-forming 134 unna's deematological papers. staphylococci, the bacilli of lupus, lepra, syphilis, the para- sites of smallpox, scarlatina, measles, rotheln, &c. — are at pre- sent out of consideration. The ordinary method of investi- gation being here inapplicable, viz. the injection of pure cultures into the blood, subcutaneous tissue, anterior chamber of the eye, and peritoneum, we are led to inoculate the epi- dermis directly. Negative results, however, with this method can have but little value. There is no certainty of being able to induce the epidermic fungi to grow in the skin, and we do not even know the principles of the methods which should be used. An incision into the vascular connective tissue, as in the case of inoculation with vaccine, cannot be requisite, but, on the contrary, may even hinder the growth. Is it possible that a stronger hyperemia is necessary for the fixation of the spores ? Should the skin be kept dry or damp, covered or uncovered, in the light or in the dark ? What parts of the surface, and what reactions and other conditions of the skin are requisite ? On the whole, we can now only give the unsatisfactory answer to these questions that these conditions vary with the fungi, and according to the kind and locality of the dermatoses generated. We may inoculate fungi which are found in Eczema seborrhoicum in the flexures, which have many coiled glands ; the fungus of Pityriasis versicolor in dark places, and so on ; and we shall find as a result at least that many fungi vegetate on some parts of the epidermis luxuriantly, and not at all on others. Individuality certainly plays nowhere a greater role than with the parasitic keratoses. If this were not so, they would be contagious, in the common sense of the word. In these inoculation experiments pure cultures contain- ing the spores were gently rubbed in over the skin (pre- viously cleansed with soap and water, and alcohol — not sublimate), which was not irritated or scratched. The left upper arm was generally used, and the spot covered with sterilized gutta-percha tissue glued down. The supposition was that any fungus which could grow at all in the horny layer, would also be able to make its way in without the latter being broken. The impermeable covering produced sufficient dampness and swelling of the horny layer, and sometimes even an erythema or a circumscribed miliaria ON THE CULTIVATION OF EPIDElffllO FUNGI. 135 rubra. After three or four days the glued bandage was removed, and the place left to itself. Negative results from this, or from any other method of inoculation, are not conclusive. The rarer a parasitic derma- tosis may be, the greater must be the effect of individuality —physical and chemical constitution of the epidermis, and so much the less value must we assign to negative inocula- tion experiments. The relative slight inoculation power of the Trichophyton and Achorion must not lead us to assume the same for all the higher Dermatophytes. The instance of the Trichophyton teaches us what fine differences the medium produces. In one family, where all the members are subjects of this fungus, we regularly find that the younger children carry it on the scalp ; the elder ones on other parts, and but seldom on the scalp ; the adults never on the scailp — the men on the beard, and perhaps on other parts of the body. Inoculation with Trichophyton on an adult's head would almost certainly fail. The above considerations as to the relatively small power of proof of negative results^ together with the constantly increasing number of Dermatophytes, determined the author to neglect for the present the distinction of pathogenic and non-pathogenic species, but to study minutely each fungus for its own sake. The various kinds were all found in the skin scales and secretions, and were able, under certain conditions, to vege- tate in the nutrient soil, or at least to retain life. Apart from the botanical and general biological interest of this common source, this knowledge is important for every dei*- matologteal inquirer. The plan, was therefore adopted, as a preliminary research, to work out a " Flora dermatologica," or rather, with the material of Eczema seborrhoicutn, to commence the working out of such a Flora. This Flora includes all mould 1 - and fission-fungi which eari be cultivated from healthy Or diseased skin, and the products thereof — whether they are serologically connected with certain dermatoses, or originate without any real appearance of disease, or able to vegetate in the skin, or can temporarily maintain themselves there in a living state. To attempt a systematic arrangement of these lower fungi 136 cnna's dermatological papers. is just as unnecessary as impossible. On the one hand, we nave at present no system for the lower fungi which could satisfy the botanists. For several — Penicillium, Oidium, Saccharomyces, allied to Trichophyton and Achorion, which we have good reason to consider true skin parasites — are now regarded in a totally different light to what they were a few years ago, and are even to some extent looked upon as lower growth forms of higher fungi. On the other hand, we medical men, with the information we have from Koch's methods of pure cultures, cannot blindly accept the system of postponement introduced in Botany in the last decade. From our standpoint, a doubt as to the certainty of the transformation by cultivation is quite justified. The correct course, therefore, appears to be to give an unprejudiced account, macroscopically and microscopi- cally, of each separate fungus, as chance brings it to light in plate cultures. The naked-eye characters are most important ; for fungi in a large group, can be easily distin- guished, whilst under the microscope they may separately appear very similar, and at first sight difficult to differen- tiate according to their mycelium or spore formation. The macroscopical differences are, therefore, to be preferred by the dermatologist as a temporary practical key to identifica- tion, after a cursory microscopical examination of the fructification has shown to which group — Mucor, Penicillium, &c. — the fungus may belong. The important differences in the macroscopic appearances are as follows : i. The colour of the fungus. — This may be in reference to the upper surface of the fungus plot, or to the lower surface, or to the deeper layer of old cultures, a white stratum of aerial mycelium partly obscuring the tint ; or the colour may appear in several layers. Moreover, it may occupy in some clusters only the centre, leaving the periphery white ; in others, the outlying prolongations are likewise coloured ; and some, again, show rings of different colours. With the age of the culture the tint generally changes ; and many fungi communicate to the medium a special colour. 2. The- extension of the plot. — Two characteristic types can be distinguished, showing an " unlimited " and a " limited " growth. Some fungi grow from the inoculation ON THE CULTIVATION OF EPIDERMIC EUNGI. 137 streak, on both sides, or in a circular manner, over the whole surface as far as the nutrient material will allow. Others, after assuming from the point of inoculation a gene- rally circular shape, do not grow further ; and the small circumscribed plaques enter into their changes of age independently, and do not fuse together. This difference is possibly not without importance, for many suspected para- sitic dermatoses can also be distinguished by their limited or unlimited method of growth. 3. Growth in the inoculation puncture and into the nutrient medium. — The diminishing amount of air in the inoculative puncture and in the deeper layers of the nutrient material will, obviously, cause just as many differences of growth with the mould fungi as with the Schizomycetes ; and these can be used as macroscopic differentiating characters. Fructifi- cation probably never takes place inside the nutrient medium, but a hypha-formation may grow in as a downy mass, or thick bush, or a hollow cup, and show, besides the intensity of the growth, characteristics of great service. 4. Peptonisation of the gelatine. — Like the bacteria, the mould-fungi form two large groups, according to their lique- fying the gelatine or not. Some impart to the liquid gelatine a characteristic colour ; and the plot of fungus may float as a compact mass in the liquid, or portions may sink to the bottom. For the final systematic classification of the fungi, micro- scopic observation is naturally of more importance. Medium powers, e. g. Hartnack's objective (Nos. 4 and 5), permit the examination of plate cultures without the assistance of a covering glass. We can easily distinguish in this way the form of the first body, the kind of hyphse branches, and the fruit-bearers. Unfortunately, these are necessarily broken in order to examine them accurately with high powers ; and many characters consequently are lost to us, especially the observation of living fungi. The difficulty just alluded to, Dr. Unna has endeavoured to overcome by using a slide with a circular hole in the centre, in the following way : The slide is sterilised and tem- porarily closed on one side by means of a sterilised cover- glass, cemented on with vaseline. The slide with the cover- 138 UNNA'S DEEMAT0LOG10AL PAPERS. glass beneath it is placed on a glass plate kept cool with ice, and the hollow thus formed in it is filled up with a mixture of peptone, gelatine, and peptone agar. As soon as the film of nutrient medium is solidified and adherent all round, the cover-glass is taken off, and about half of the jelly is easily removed by means of a heated platinum wire, a half-ntoon being allowed to remain on that side of the hole which, later on, is towards the lower edge of the slide, which is to be kept in a perpendicular position. The fungus is to be ino- culated on the free edge of this half-moon, and the aerial portions naturally grow up into the upper empty half of the hole, parallel to the surfaces of the slide ; i. e. the fungus grows in the plane of the latter. A series, twenty or more, of such slides, can be arranged, radiating from the centre, in a glass vessel lined with blotting paper, the inner lower corners resting on the centre of the bottom of the vessel, and the outer lower corners fixed in slits in pieces of cork, which are placed all round. The corks and papers must be pre- viously soaked in sublimate solution. It is advisable to let the growth of the fungus proceed for some time before com- mencing the examination. A sterilised cover-glass is applied on one side, and in order not to contaminate the lower stir- face, it is as well to fix laterally on the stage of the mierO- scope slips of cardboard, upon which the perforated slide can rest. We can now observe, with the highest powers, the fruit-bearers projecting free in the air, and uninterrupt- edly giving off spores or forming fruit-bodies ; we can accu- rately see the form and budding of the hyphse, partly in the air and partly in the nutrient substance ; and, finally, we can use the hyphae and fruit-bearers which have been accident ally pressed between the cover-glass" and the nutrient disc for detailed observations and measurements. While the ordinary plate cultivations are usually suitable for the flat growing fungi, these hole cultivations are especi- ally useful for the upright growing forms^such as mucor. For those of medium growth a hole of sufficient size can be made with a platinum needle in the middle of the nutrient disc. This method is communicated in detail, as, according to the assurances of botanical authorities, no simple way of observing the growth of mould fungi has hitherto been ON THE CULTIVATION OP EPIDERMIC EUNGI. 139 brought forward. It is hoped that it will prove useful to other workers. With reference to the staining of the mould fungi, the author states that he does not at present possess sufficient experience to discuss the methods generally ; there is no question that here, also, a rich harvest can be reaped by the earnest inquirer. Dr. Unna promises to commence shortly, in conjunction with Dr. Taenzer, the publication of a " Mora Dermato- logica." THE STAINING OE MICBO-OBGANISMS IN THE HOBNY TISSUES. 1 In order to study the harmful micro-organisms of the epidermis, we must have some reliable methods of isolating them by staining. This proof of the existence of the epidermic fungi has been neglected, and most bacteriological text- books are silent on the subject. Von Sehlen was the first who succeeded in clearly dif- ferentiating between bacteria and epidermic cells by staining, and he was followed by Bizzozero, who published a method of double-staining and differentiation of the fungi from the cells. These methods were, however, very tedious and some- what clumsy. In 1885, Boeck by using a borax-methyl- blue stain demonstrated fungi in the skin, and he had, by the help of resorcin, finally improved our means of decolorising sections. At a meeting of the Medical Society of Christiania in 1887 he showed specimens of favus, microsporon, furfur, &c, stained with these dyes. The author made a large number of experiments with various dyes, &c, and he states that we possess numerous methods which enable us to isolate by staining micro-organ- isms in the horny epidermis, nails, scales, crusts and come- dones. These methods are not all equally useful, but are of different value for different micro-organisms. To stain these micro-organisms, one proceeds as follows : The epidermic scale (crust, comedo, &c.) is placed upon 1 " Die Farlrang der Mikro-organismen im Horngewebe," * Monatsh. f . prakt. Derm.,' xiii Bd., 1891. STAINING OF MICRO-ORGANISMS IN HORNY TISSUES. 141 a glass slide and moistened with acetic acid. Another slide is placed crosswise oyer this one, and both are rubbed together until the epidermic scale is broken up into a sort of pulp. The two slides are then separated and rapidly dried over a spirit lamp, by which means the acetic acid is evapo rated. The slides must be lifted, not drawn apart. Bach slide is then seized by the thumb and forefinger of the left hand, which is covered with a cloth, and is held obliquely upwards, while a few drops of ether-alcohol are poured over it. The fat, which had become liquified by the heat, is thus washed away, and absorbed by the cloth. Two drops of methyl-blue solution are then placed on one of the slides, which is then placed crosswise upon the other, and the two are held over the flame for ten to twenty seconds. The specimens can then be either decolourised at once or dried over the flame, and kept for further observation. In all cases, the author recommends borax-methyl-blue (i per cent.) as the best staining medium. Indirect decolorisation by alcohol and anilin oil, is much used in the preparation of sections containing epidermic bac- teria ; but the author prefers especially peroxide of hydro- gen in combination with alcohol. Simple alcohol (80 to 96 per cent.) does not differentiate sufficiently ; fungi and epi- dermis are decolourised too evenly. The successive employment of peroxide of hydrogen and alcohol seems, however, especially useful for epidermic bac- teria ; for the epidermis is strongly acted upon by oxidising agents, and is always much more strongly decolourised than the micro-organisms. Among a large number of reagents which dissolve anilin dyes, there are three which decolourise the epidermis quicker than the bacteria present in it, namely, styron, glycol, and glycerine-ether. In the preparation of epidermic bacteria, indirect chemical decolourising agents are much used, especially acids. The chemistry of this method depends upon the fact that the basic anilin salts form soluble salts with the acids. The mineral acids proved to be of little use in this respect, but among the organic acids excellent decolourisers were found. 142 tjnna's dermatological papers. Formic acid and lactic acid gave good results ; but citric and oxalic acids gave the best. Arsenious, osmic, sulphurous, and picric acids are also useful. Nearly all of them have a direct effect upon the epidermis, and some of them (chromic, osmic, and picric acids) stain it. As decolourisers of the epidermis, the salts perchloride of mercury, ferrous sulphate, acetate of potash, &c, were found of service. They act mostly by directly affecting the horny layer. The alkaline salts (carbonates of soda and potash, &c.) were found to be useless. The acid salts act much in the same way as acids, though in some cases they are more useful. When they are used, the specimens must be well washed before being placed in alcohol. Treatment with iodine, and subsequent decolorisation by alcohol, which is so commonly used in preparations of bac- teria, is almost useless in the case of the epidermis. On the one hand the iodine colour sticks so fast to tihe epider- mis that subsequent decolorisation is almost impossible, and, on the other, minute particles of the colouring matter are deposited on the surface of the horny cells, which have very much the appearance of cocci and bacilli. Reducing agents, which have so far only played a small part in bacteriology, seem especially useful in the prepara- tion of epidermic bacteria. They act either upon the horny substance itself, as a consequence of which the staining mate- rial is loosened and more easily dissolved, or they exert a chemical action upon the anilin dye. The process is too quick to be a reduction in the chemical sense. Boeck found in resorcin an excellent agent. It has two properties through which epidermis is affected, and both of them may account for its decolourising power. Besides its reducing properties, resorcin, like all phenols, has the power of converting keratin into a swollen, white amorphous mass, in consequence, we may suppose, of taking up water. Permanganate of potash alone did not act well ; but, in combination with H 3 3 , it gave excellent results. The epi- dermis is almost entirely decolourised, and the bacteria show up well. Chlorate of potash and H 2 3 gave equally good STAINING OF MICRO-ORGANISMS IN HORNY TISSUES. 143 results, The author then made some further experiments and found, if the specimens were dipped in a solution of common salt and then in H 2 2 , that, after decolourising with alcohol, the epidermic bacteria were well brought into view. He got equally good effects with ammonium chloride, and potassium iodide. "We may lay it down as a general rule that the stained epidermis is not quickly decolourised by salts and alcohol alone, or by H 2 2 and alcohol alone j the successive use of these agents, however, gives excellent results. For double- staining the epidermic fungi we possess von Sehlen's method, which consists in first staining with fuchsin, then decolouris- ing the bacteria with acids and alcohol, and staining them with methyl-blue or gentian violets. According to the author this method is not very satisfac- tory, for different parts of the sections are often differently stained, and, what is more important, some kinds of fungi are not stained at all, and consequently escape detection. The author then goes on to give an account of twenty-four methods of decolourising preparations stained with methyl- blue, of which we may mention a few. (16). Sodium chloride-peroxide of hydrogen method. — The specimens should be somewhat more deeply stained by methyl-blue than usual ; they are then placed in the salt solution (i to 10 per cent.) for a few seconds, washed in water, passed through alcohol, placed in the H 2 2 solution for five seconds, and then decolourised with absolute alcohol. They can be either mounted dry, or in oil or Canada balsam. To show the small epidermic bacilli well, it is as well to neutralise the H 2 2 solution. (20). Besorcin method. — A 5 per cent, aqueous solution of resorcin is the best. The somewhat overstained speci- mens are left in this solution for a few seconds, and are then placed in alcohol, oil, and Canada balsam. (18). Permanganate of potash and peroxide of hydrogen method. — The specimens are placed in a 1 per cent, solution of permanganate of potash, washed in water and then treated with the acid H 2 2 solution of commerce. The specimens lose much of their colour, and the decolorisation is completed 144 UNNA S DERMATOLOGIOAL PAPERS. with alcohol and anilin oil ; then oil and Canada balsam. This method shows the large and small bacilli sharply de- fined and clearly. The author gives a list of some of the best methods of staining these bacilli in a tabular series. All specimens are first stained in the solution borax- methyl-blue aa i, Aq. destill. ioo. This he designates as B.m.b. He gives two tables ; one for sections, and one for specimens obtained by pressing a small amount of the sub- stance to be examined between two slides, much in the same way as sputum is prepared for staining. Styron Method. Pressed preparations. (i) Bmb., i minute. (2) Wash in spirit, 10 seconds. (3) Deoolourise in styron, 2 minutes. (4) Wash in xylol. (5) Canada balsam. Sections. (1) Bmb., 1 minute. (2) Spirit, 10 seconds. (3) Styron, 4 — 5 minutes. (4) Xylol. (5) Balsam. Acetic Acid Method. Preparations. (1) Bmb., 2 minutes. (2) Wash in 1 per cent, acetic acid. (3) Wash in water. (4) Wash in alcohol. (5) Dry over a flame. (6) Balsam. Sections. (1) Bmb., 5 minutes. (2) 1 per cent, acetic acid, 10 seconds. (3) Alcohol absolute. (4) Oil. (5) Balsam. Sodium Chloride H„0„ Method. Preparations. Sections. (i)"Bmb., 5 minutes. (2) 1 per cent. Sod. Chlor. Sol., 5 seconds. (3) Wash in water. (4) Wash in alcohol. (5) 3a P er cent - H s 2 solution, 5 seconds. (1) Bmb., 2 minutes. (2) NaCl solution, £ minute. (3) H 2 2 solution, 10 seconds. (4) Alcohol, absolute, 10 — 20 seconds, (5) Oil. (6) Balsam. (6) Wash in alcohol. (7) Dry over flame. (8) Balsam. ON PLASMA-CELLS, ESPECIALLY IN LUPUS. 1 The staining methods in use for the last twenty years have almost solely demonstrated the nuclei of cells, and have left horny substance, fat, mucus, and some intercellular substances almost untouched. All those problems which concern the life of protoplasm and of the intercellular substance are still the subject of discussion, and science here comes to a full stop. Three problems seem to block the way to further investi- gation. i. ''Where do the connective-tissue cells begin and where do they end V' In this question lie the boundaries of cellular pathology, and the beginning of an intercellular one. 2. The question of animal parasites in animal tissues. 3. The differentiation between protoplasm on the one hand, and the slimy material of plants on the other. The author gives an account of various methods of stain- ing tried by him since 1875, and then proceeds to discuss the histology of lupus. By his methods of staining proto- plasm the author believes that he has settled the questions of the part that the leucocytes play in lupus, and of the origin of the epithelioid and giant-cells. In sections of lupus large deeply-stained cells are seen, which have very much the appearance of Bhrlich's fatty granular cells. They are granular and of cubical or rhom- boidal shape, but the granules are stained blue, and not 1 "TJeber Plasmazellen, insbesondere beim Lupus." — Arztlicbe Verein xa Hamburg, Marz, 1891 ; 'Monatsb. f. prakt. Derm.,' Bd. xii, 1891, p. 296. 10 146 unna's dermatological papers. violet or reddish blue, but the nucleus is also stained, thus differing from Ehrlich's cells. There is no transition from these albuminous, granular lupus-cells to the mucin-holding granular fatty cells of the same tissues. These cells are identical with Waldeyer's plasma-cells, and Waldeyer re- cognised them as such in some lupus sections submitted to' him by the author. These cells are the same large cells which have been recognised in lupus and tubercle and called epitheloid cells, a name which to-day is quite out of place and entirely wrong. They are found in the same situations as the epitheloid cells ; they are exceedingly numerous in the most recent tubercles, and much less so in the periphery of the older- ones. The plasma-cells are the most important, as well as the- earliest, part of a lupus nodule. Their formation represents the first stage of tuberculosis of the skin, and is associated with the disappearance of the collagenous and elastic tissues. It is not the endothelial cells of the capillaries, especially, which are transformed into plasma-cells ; all connective- tissue cells, which are exposed to the infective virus, go through this progressive change. Nowhere do we see a transformation of leucocytes into plasma-cells. The fate of these plasma-cells is of two kinds. They either degenerate to the central cells of the lupus nodule at once, or they undergo, before this, active proliferation. In either case they eventually become degenerated. The large giant-cells result from the degeneration of plasma-cells. To speak accurately they are not cells at all. They consist of two parts, a degenerating and a proliferating portion. The degenerated cells enclosing degenerating collagenous or elastic fibres, and perhaps bacilli, are enclosed, as a whole by neighbouring proliferating cells. The author then goes on to speak of lupus cicatrices and states that they are not, as has been generally supposed,, indifferent cicatricial tissue such as results when a simple ulcer heals. A lupus cicatrix never produces elastic tissue, and the collagenous tissues are not arranged in crossing bundles, but lie parallel to the surface of the skin. The lupus cicatrix is histologically different from other ON PLASMA-CELLS, ESPECIALLY IN LUPUS. 147, cicatrices, and is, in fact, lupoid tissue of remarkable dura- bility. If one examines the transitional stages between the tumour; consisting of plasma-cells, and the lupoid cicataix, one notices that they both pass directly into each other. The beginning as well as the end of the life of a lupus nodule (that runs a normal course) is characterised by very durable tissue, at first of an entirely cellular structure, later of a fibro-cellular one. Both, though not of the recognised structure of tubercle, in the narrower sense, are yet not less lupoid or rather tubercular than it. To many it will be a matter of opinion which tissue should be looked upon as especially tubercular. "We must expect the acutest process when numerous bacilli and a rich blood- supply are present ; a more chronic one with few bacilli and a meagre supply of vessels. Except in the last stages of phthisis the skin affords but a poor nidus for bacilli, and gives us in lupus an excellent picture of the primary changes of the tisrmes in tuberculosis. Lupus often heals without necrosis of the tissues, and gives us a very instructive, if somewhat one- sided picture of tuberculosis, and is an instance of the various effects of the tubercular poison. In the so-called surgical tuberculosis of the skin (secondary infection from underlying organs, &c.) the appearances are different — true caseation of the skin takes place from the eruption into it of a material rich in bacilli. In such cases one finds lupus tissue, but only at the edges ; one finds remnants of it, or rather of the plasma-cells (the mother-tissue of every tubercle), in the surroundings of the necrotic foci in internal organs. Koch's tuberculin acts only upon the plasma-cells ; with the absorption of the plasma-cell tumour and the lupoid fibroma the action of tuberculin ceases. The degenerated, but not yet necrotic, plasma-cells are hardly affected by it. Tuberculin has chemical affinities for the tubercular plasmoma and fibroma; it acts upon these two portions of lupus, and perhaps of all tubercle, and causes their destruc- tion and absorption. In conclusion, the author gives an account of some ex- periments he made by treating freshly excised portions of 148 unna's dermatologioal papers. lupus with tuberculin. He states that it does not cause necrosis of protoplasm, nor are the nuclei destroyed. Its chief action takes place in the neighbourhood of the bacilli where the giant-cells are formed. ON WALDEYER'S PLASMA-CELLS AND EHRLICH'S MAST-CELLS. 1 It appeared to be necessary from the importance of the plasma-cells in progressive disturbances of nutrition, espe- cially in the infective granulomata, to multiply the methods of demonstrating them. Up till now the only method in use was to stain the sections (e.g. of lupus) in alkaline methyl-blue (methyl-blue i, caustic potash 0*05, water 100), and to decolourise with creosol or styron. For general use, decolorisation by glycol is the best and most practical, as it takes place slowly. The successive use of H 2 3 and alcohol decolourises better than alcohol alone ; for this purpose, however, the H 3 3 solu- tion must be neutralised. By treating the sections with very weak alkaline solutions and then with alcohol no good results were obtained — decolourising with sodium sulpho-ichthyolicum and hydroxy- laminum gave good results ; the protoplasm appeared deeply stained, and the nuclei only slightly tinted. The authors then go on to give an account of experi- ments they made with numerous salts, with arsenical salts, iodine, resorcin, pyrogallol, &c. They obtained the best results with resorcin, hydrochinon, and phenylhydrazin. They draw up the following scheme for the demonstration of the plasma-cells after staining with alkaline methyl-blue : 1 "Zur Kenntniss der Waldeyerschen Plasmazellen und Ehrlichschen Mastzellen," 'Monatsh. f. prakt. Derm.,' Bd. xiii, 1891, p. 364, Dr. J. van Spek (Amsterdam) and Dr. Unna. 150 unna's dermatological papers. Decolorisation by (1) Glycol, ,„ 2 Greosol, . ., . . fg 6 ™'- 3 Styron, or h ? M ? o}l01 \ ^luT' ■ 4) HO, (neutral) and / Phenylhydrazm, and Alcohol, V.Amhn, or by acids (arsenious and osmic acids) and alcohol, or by salts (sod. chloride, soap, ichthyol, &c.) and alcohol. These methods also demonstrate Ehrlich's mast-cells very well ; they are distinguishable from the plasma-cells by their red- dish colour, not to mention their granular appearance, their irregular form, and their solitary position. Sulphate of copper, carbonate of soda, arsenious acid, chrysarobin and almost all acids bring the fatty granular cells well into view. If, therefore, any doubt exists as to the nature of cells in a specimen, one has only to treat it with a dilute acid, by which procedure the plasma-cells disappear at once, while the fatty cells withstand the action of the acid for some time. , In conclusion, the authors state that they have tried a large number of combinations of decolourising methods, and can only recommend two, namely, arsenite of potash, resorcin, , alcohol ; and resorcin, chloride of gold (0^05 per cent.), and alcohol. SOME OBSERVATIONS ON RODENT ULCER. 1 When extirpation of rodent ulcer is impracticable, the treatment recommended by Boeck with resorcin plasters gives excellent results. The author treated a case of this disease on the lower eyelid with a 10 per cent, resorcin solution and resorcin plasters, and was astonished to find that in six months the ulcer was almost entirely healed. He states that German medical men do not seem to be able to recognise cases of this disease, for in all the cases he has seen a correct diagnosis had never been made ; it is often mistaken for lupus. He considers that the disease is espe- cially an English one ; it was first described by the Irish oculist, Jacob. Histologically and clinically, it is a typical carcinoma. The author's cases occurred for the most part in sailors, or in people who had crossed the seas. In three cases he found it in conjunction with another skin disease peculiar to sailors, viz. "sailors' -skin." In this disease the epidermis covering the backs of the hands, the face, and ears becomes thickened, rough, cracked, and desqua- mating j and excoriations may occur and crusts form. On the face and ears localised enlargements of blood-vessels occur. The author thinks that this affection favours the development of rodent ulcer. He has found that 2 per cent, resorcin vaseline cures the " sailors'-skin." 1 " Bermerkungen fiber Ulcus Eodens," 'Monatsh. f.. prakt. Derm.,' Bd. xii, 1891, p. 17S. CONTBIBTJTIONS TO DEBMATOLOGY By De. P. G. UNNA. Anatomical and Physiological. Die Lymphbahnen der menschlichen (imd tierischen) Haut. (The Lymph-paths in Human [and Animal] Skin.) 'Monatsh. f. prakt. Derm./ Bd. i, 1882, p. 19. Das subkutane Fettgewebe. (The Subcutaneous Adipose Tissue.) lb., Bd. i, 1882, pp. 81 and 139. Das elastische und glatte Muskelgewebe der Haufc. (The Elastic and Smooth Muscle-tissue of the Skin.) lb., Bd. i, 1882, p. 341. Beitrage zur Histologic und Entwickelungsgeschichte der menschlichen Oberhaut und ihre Anhangsgebilde. (Con- tributions to the Histology and Development of the Human Epidermis and its Appendages.) ' Archiv f . mikr. Anat./ Bd. xii, 665. Ueber das Keratohyalin und seine Bedeutung fur den Prozess der Verhornung. (On Kerato-hyalin and its Signification in the Process of Cornification.) ' Monatsh. f. prakt. Derm.,' Bd. i, 1882, p. 307. Die Nervenendigung in der menschlichen Haut. (The Nerve-endings in the Human Skin.) lb., Bd. i, 1882, No. 8. Neue Beitrage zur Anatomie der Haut. (New Contribu- tions to the Anatomy 'of the Skin.) lb., Bd. ii, 1883, Nos. 7 and 8. Entwickelungsgesch. u. Anatom. der menschl. Haut. (Development and Anatomy of the Human Skin.) ' Handb. der spec. Path. u. Ther./ Bd. xiv. CONTRIBUTIONS TO DERMATOLOGY. 153 Die Fortschritte der Hautanatomie in den letzten fiinf Jahren. (Advances in the Anatomy of the Skin during the last Five Years.) lb., Bd. vii, 1888, and Bd. viii, 1889 : I. Die Architektur der Oberhaut und des Papillar- korpers. (The Construction of the Epidermis and Papillary Body.) lb., Bd. vii, 1888, Nos. 15 and 16. II. Die Struktur der unverhornten Oberhautzellen. (The Structure of the Non-corneous Epidermic Cells.) a. Die fibrillare Struktur der Stachelzellen und ihre Verbindungsbriicken. (The Fibrillar Structure of the Prickle-cells and their Com- municating Processes.) lb., Bd. vii, 1888, No. 17. B. Kernteilungsbilder und Begeneration der Stachelschicht. (Nucleus Division and Re- generation of the Prickle Coat.) lb., No. 18. C. Keratohyalin, Eleidin, und Beginn der Verhornung. (Kerato-hyalin, Eleidin, and commencing Cornification.) lb., No. 18. D. HornschichtundVerhornung. (The Horny Layer and Cornification.) lb., No. 19. III. Das Haar. (The Hair.) lb., Bd. vii, 1888, No. 21. IV. Der Nagel. (The Nail.) lb., Bd. viii, 1889, No. 2. V. Die Nerven der Haut. (The Nerves of the Skin.) lb., Bd. viii, 1889, No. 5. VI. Das Pigment der Haut. (The Pigment of the Skin.) lb., Bd. viii, 1889, No. 8. Ueberhautung und Ueberhornung. (The Formation of New Skin and Epidermis.) ' Berl. klin. Wochen./ Aug. 27, 1883. Zwei vergessene Arbeiten aus der klassischen Periode der Hautanatomie. (Two Forgotten Works of the Classical Period on the Anatomy of the Skin.) ' Dermatolog. Studien/ Bd. ii, 1889 (Hamburg). Ueber die insensible Perspiration der Haut. (On the Insen- sible Perspiration of the Skin.) " Vortrag gehalten am IX; Congresse fur innere Medicin," ' Med. Rev. fur Bain.,' &c. 154 UNNA ? S DERMATOLOGICAL PAPERS. A Critical and Historical Essay on the Sweat. Intern. Medical Congress, London, 1881. Ueber die normale Zungenoberflache und den normalen Zungenbelag. (On the Normal Upper Surface and Coating of the Tongue.) ' Vierteljahresschrift fur Dermatologie und Syphilis,' 1 88 1. Neuere Arbeiten iiber Kern- und Zellteilung. (Eecent Papers on Nucleus and Cell Division.) ' Monatsh.,' Bd. iii, 1884, p. 17. Zur Kenntniss des elastischen Gewebes der Haut. (Con- tribution to our Knowledge of the Elastic Tissue of the Skin.) ' Dermatolog. Studien/ iii, 1887 (Hamburg u. Leipzig). Zur Kenntniss der Waldeyerschen Plasmazellen und Ehrlichschen Mastzellen. (Contributions to our Knowledge of Waldeyer's Plasma-cells and Ehrlich's "Mast-cells.") 'Monatsh./ Bd. xiii, 1891, p. 364 (I. van der Spek, and P. G. U.). Pathological. Zur Pathologie der Syphil. Initial-sclerose. (On the Patho- logy of Syphilitic Initial Sclerosis.) By Prof. Auspitz and Dr. P. Unna. ' Viertelj. fur Derm, und Syph.,' 1877, p. 107. , Ueber ein papulo-pustuloses Exanthem in einem Palle v. Diphtheria septica. (On a Papulo-pustular Exanthem in a Case of Septic Diphtheria.) lb., 1878, p. 193. Zur Anatomie der Blasenbildung an der menschl. Haut. (On the Anatomy of Vesication in the Human Skin.) lb., 1878, p. 3. Ein weiterer Beitrag zur Anatomie der syphilit. Initial- sclerose. (A Further Contribution to the Anatomy of Sy- philitic Initial Sclerosis.) ' Viertelj. f. Derm, u, Syph.,' 1878, P- 543- Das Fibrokeratoma nebst Bemerkungen iiber die Classifi- cation und Nomenclatur homoo-plastischer Hautgeschwulste. (Fibro-keratoma, together with Remarks on the Classifica- tion and Nomenclature of Homeoplastic Tumours of the Skin.) 'Deutsche Zeitschr. f Chirurg.,' Bd. xii, p. 267. Ueber die Impetigo contagiosa (Fox), nebst Bemerkungen CONTRIBUTIONS TO DEEMATOtOGT. 155 iiber pustulose u. bullqse Hautaffectionen. (On Impetigo con- tagiosa [Fox] , with Remarks on Pustular and Bullous Affec- tions of the Skin.) ' Viertelj. f. Derm. u. Syph., 1880, p. 13. Woraus besteht der schwarze Punkt der Comedonen ? (What constitutes the Black Point of. the Comedone ?) . Ueber Ultramarin in den Talgdriisen. (On Ultramarine in the Sebaceous Glands.) ' Cemtralbl. f. d. Med. Wissensch., 1880, No. 50. Anatomisch-physiologische Vorstudien zu einer kiinftigen Onychopathologie. (Preliminary Anatomico-physiological Stu- dies for a Future Onycho-pathology.) 'Viertelj. f. Derm, u. Syph./ 1881, p. 3. Beifcrage zur Onychopathologie. (Contributions to Onycho-pathology.) lb., 1882, p. 3. Eczem im Kindesalter. (Eczema in Childhood.) ' Deutsch. med. Zeitschr./ 1884, Nos. 43 to 47. Ueber kreisfleckige Exfoliation der Hohlhand und der Zunge (exfoliatio areata palmse manus und exfoliatio areata linguie) . (On Circular Exfoliations of the Palm and Tongue.) ' Vierteljahresschrift fur Dermatologie und Syphilis/ 188 1. Die Stauungsdermatosen des Unterschenkels und ihre Behandlung. (The Congestion Dermatoses of the Leg and their Treatment.) ' Deutsche med. Zeitung/ Jahr. vi, Nos. 1 and 2, 1885. Zur Histologic und Therapie der Lepra. (On the Histo- logy and Therapeutics of Leprosy.) ' Verhandlungen des V Congresses fur innere Medicin/ 1886. Syphilis und Ekzema Seborrhoicum. (Syphilis and Sebor- rheic Eczema.) " Vortrag gehalten in der Sekt. f. Derm. u. Syph. auf d. 61 Naturforscherversammlung in Koln," ' Mo- natsh. f. prakt. Derm./ vii, 1888, No. 21. Vorlesungen iiber allgemeine Pathologie der Haut, gehalten im Wintersemester, 1888— 9. (Lectures on the General- Pathology of the Skin, delivered in the Winter Session, 1888-9.) 'Monatsh. f. prakt. Derm./ Bd. ix, 1889, Nos. 1, 2, 6, and 8; Bd. x, 1890, Nos. 3, 4, 6, and 7; and Bd. xi, 1890, pp. 417. 488, and 528: I. Anamie. (Anaemia.) II. Allgemeines iiber Hyperamien der Haut. (General- ities concerning the Hypersemias of the Skin.) 156 tjnna's dermatological papers. III. Wallungshyperamie. (Relaxive Hyperemia.) IV. Stauungshyperamie. (Congestive Hypersemia.) V. Oedem. (CEdema.) VI. Blutung. (Haemorrhage.) VII. Angioneurosen. (Angioneuroses.) Die nicht-endziindlichen Oedeme der Haut. (The Non- inflammatory CEdema of the Skin.) 'Monatsh. f. prakt. Derm./ Bd. vii, 1889, Nos. 10 and 11. Hyphogenic, Coccogenic, and Bacillogenic Sycosis. ' St. Louis Med. and Surg. Journ.,' August, 1888. Ueber die Parakeratosen im allgemeinen und ein neue Form derselben (Parakeratosis variegata). (On the Para- keratoses in General, and on a New Form.) In conjunction with Dr. Santi (Berne) and Dr. Pollitzer (New York). ' Mo- natsh. f. prakt. Derm./ Bd. x, 1890, Nos. 9 and 10. TJeber die MundafEektion bei Lichen ruber. (On the Mouth Affection in Lichen ruber.) lb., Bd. i, 1882, p. 257. On Herpes Progenitalis, especially in Women. ' Journ. Outan. and Ven. Diseases,' i, No. 11, New York, 1883. Das Keratoma plantare und palmare hereditarium. (Here-' ditary Keratoma Plantare and Palmare.) lb., Bd. ii, 1883, p. 324. Filaria sanguinis undihr Zusammenhaug mit der Elephan- tiasis Arabum. (Filaria sanguinis and its Connection with Elephantiasis Arabum.) 'Monatsh. f. prakt. Derm., 5 Bd. i, 1882, p. 38. Neuere Arbeiten zur Pockenhistologie. (Recent Works on the Histology of Smallpox.) ' Monatsh. fur prakt. Derm.,' Bd. i, 1882, p. 345, and Bd. ii, 1883, p. 271. Neuere Amerikanische Arbeiten iiber Akne. (Recent American Papers on Acne.) lb., Bd. ii, 1883, p. 367. Beitrage zur Anatomie und Pathogenese der Urticaria simplex und pigmentosa. (Observations on the Anatomy and Pathology of Urticaria Simplex and Pigmentosa.) ' Dermat. Studien,' Heft 3, 1887. Zur Lichenfrage. (On the Lichen Question.) ' Monatsh. f. prakt. Derm.,' 1886, p. 554. Die postekzematose Furunkulose. (Post-eczematous Furunculosis.) 'Monatsh. f. prakt. Derm.,' Bd. vii, 1887, p. 147. CONTRIBUTIONS TO DERMATOLOGY. 157 Ueber Sycosis. (On Sycosis.) ' Monatsh. f. prakt. Derm.,' Bd. vii, 1887, p. 247. Was wissen wir von der Seborrhoe ? (What do we know of Seborrhcea ?) ' Monatsh. f. prakt. Derm.,' Bd. vi, 1887, pp. 698 and 739. DasseborrhoischeEkzem. (Seborrheic Eczema.) 'Monatsh. f. prakt. Derm.,' Bd. vi. 1887, p. 827. Das Wesen der Arzneiexantheme. (The Existence of Drug Rashes.) 'Monatsh. f. prakt. Derm.,' Bd. xi, 1890, p. 213. Ein Fall von Hautsyphilis des Gesichts. (A Case of Dermal Syphilis of the Pace.) 'Deutsch. med. Wochenschr.,' 1890, No. 37. Ein Fall von multiplen Granulomen der Haut. (A Case of Multiple Granulomata of the Skin.) ' Deutsch. med. Wochenschr./ 1890, No. 37. Ueber Erkrankungen der Schleimdriisen des Mundes. (On Diseases of the Mucous Glands of the Mouth.) ' Monatsh. f. p. Derm.,' Bd. xi, 1890, p. 317. Parakeratosis scutularis. ' Internat. Atlas selt. Haut- krankheiten,' Heft 3, No. 8, 1890. Ulerythema akneiforme. 'Internat. Atl. selt. Hautk.,' Heft 2, 1890. Ueber Plasmazellen, insbesondere beim Lupus. (Plasma- cells, especially in Lupus.) ' Monatsh. f . p. Derm.,' Bd. xii, 1891, p. 296. Bemerkungen zur vorhergehenden Notiz iiber Ulcus rodens. (Remarks on a Preceding Notice on Rodent Ulcer.) 'Monatsh. f. prakt. Derm.,' Bd. xii, 1891, p. 175. Ueber Autotuberculinisation beim Lupus. (On Auto- tuberculinisation in Lupus.) ' Berlin, klin. Wochenschr.,' 1891, No. 25. Neurosyphilide und Neurolepride. (The Eruption in Nerve Syphilis and Nerve Leprosy.) ' Dermat. Studien,' Reihe 2, Heft 3, 1890. Ueber die Duhring'sche Krankheit u. eine neue Form derselben. (On Duhring's Disease, and on a New Form of it.) 'Monatsh. f. prakt. Derm.' Bd. ix, No. 3, 1889. Ueber Ulerythema sycosiforme. (On Sycosiform Ulery- thema.) lb., Bd. xii, No. 2, 1891. 158 unna's dermatological papers. Impetigo (Boekhart) der durch , Eiterkokken verursachte Oberhaut Abscess. (Impetigo [Bockbart] an Abscess of tbe Epidermis caused by Pus Cocci.) ' Berl. klin. Samml. herausg. v. Prof. Habn u." Prof . Fiirbringer/ Heft 46, 1892. Sitz der Pocke in der Epidermis. (On tbe Situation of tbe Small Pock in tbe Epidermis.) ' Vircb. Arch./ 1877. Leukonychie und Leukotbricbie. (Leuconycbia and Leuco- trichia.) f Int. Alt. Selt. Haut krank.," vi, 1891. Der Streptobacillus des weichen Scbankers. (Tbe Strepto- bacillus of Soft Cbancre.) ' Monatsh. f. prakt. Derm;/ 1892, Juni Heft. Therapeutical. Der Salbenmullenband : ein Beitrag zur Bebandlung des Eczems. (Tbe Salve mull Bandage : a Contribution to tbe ■Treatment of Eczema.) f Berl. klin. Woch./ 1880, No. 35, p. 1. Der medicamentose Aether- und Alcobol-Spray. (Medica- tion by Etber and Alcobol Spray.) lb., 1882, No. 20. Die Mullscbarpe, ein Universal Suspensorium. (The Mull Material, a Universal Suspensory Bandage.) ' Deutsch. med. Woch./ 1882, No. 17. Zur Klinik und Therapie des Lichen ruber. (On the Clinical Characters and Therapeutics of Lichen ruber.) 'St. Petersburger medicin. Wochenschrift/ No. 45, u. s. f., 1 884. (Translated in the ' Medical Bulletin/ Philadelphia, 1885.) Die Neueren Fortschritte in der Therapie der Haut- krankheiten. (Eecent Advances in the Therapeutics of the Skin.) ' Separat-abdruck aus dem Aerztlichen Vereinsblatt fur Deutscbland/ 1885, No. 158. Ueber einen Pall geheilter Lepra tuberosa. (On a Case of Cured Tuberous Leprosy.) ' Separat-abdruck aus den Verhandlungen des Congresses fur innere Medicin,' iv, 1885. Untersuchungs-Stublund Albokarbon-Lampe zu endoskopi Zwecken. (Surgical Chair and Albo-carbon Lamp for Endo- scopical Examinations.) ' Monatsh. f . prakt. Derm./ Bd. iv, 1885, No. 2. CONTRIBUTIONS TO DERMATOLOGY. 159 Ueber Suspensorien. (On Suspensory Bandages.) lb., Bd. iv, 1885, No. 4. Zur Histologie und Therapie der Lepra. (On the His- tology and Therapeutics of Leprosy.) ' Verhandlung der V Congresse f. innere Med./ 1886 (Wiesbaden). Salbensonde bei Behandlung der chronischen Gonorrhoe. (Salve-sounds in the Treatment of Chronic Gonorrhoea.) ' Therap. Monatsh./ 1887, Juni. On Becent Advances in the Treatment of Diseases of the Skin. Therapeutical Section, British Medical Association, August, 1887, 'Brit. Med. Journ./ and ' Sammlung klinischer Vortrage/ von R. v. Yolkmann, No. 300, Nov., 1887 (Leipzig). Das Ichthyol bei inneren Krankheiten. (The Use of Ichthyol in Internal Medicine.) ' Deutsch. medicinisch Zeit./ Nov. 17, 1883. Ueber Seifengeist. (On Soap Spirit.) In conjunction with W. H. Mielck, 'Monatsh. f. prakt. Derm./ Bd. vi, 1887, No. 11. Zur Behandlung der Trichophytia Capitis. (On the Treatment of Ringworm of the Head.) " Vortrag gehalten in der Sekt. f. Derm. u. Syph. auf der 62 VersammL deutscher Naturforscher u. Aerzte in Heidelberg," ' Mo- natsh. f. prakt. Derm./ Bd. ix, 1889, No. 12. Zur Kenntniss des Lanolins. (Contributions to our Knowledge of Lanolin.) ' Therapeutische Monatsh./ 1890. Ueber einen neuen Microbrenner, und seine Anwendung bei der Rosacea und anderen Hautkrankheiten. (On a New Microburner, and its Application in Rosacea, and other Dis- eases of the Skin.) " 62 VersammL deutscher Naturforscher u. Aerzte in Heidelberg," ' Monatsh. f. prakt. Derm, und Syph./ Bd. x, 1890, No. 1. Ueber Ichthyolfirnisse. (On Ichthyol Varnishes.) 'Monatsh. f. prakt. Derm./ Bd. xii, 1891, No. 2. Medicinische iiberfettete Kaliseifen (Salbenseifen). (Me- dicated Over-fatted Potash Soaps [Ointment Soaps].) 'Monatsh. f. prakt. Derm./ Bd. v, 1886, p. 348. Guttaperchapflastermulle. (Gutta-percha Plaster-mulls.)- ' Monatsh. f. prakt. Derm./ Bd. i, 1882, p. 32. Ueber Heilung der Lichen ruber ohne Arsenik. (On the 160 unna's deematological papbes. Cure of Lichen ruber without Arsenic.) 'Monatsh. f. prakt. Derm./ Bd. i, 1882, p. 5. Behandlung der Gesichtsrose mit inneren Mitteln. (The Treatment of Erysipelas of the Face with Internal Medicines.) ' Monatsh. f. prakt. Derm.,' Bd. i, 1882, p. 256. Eine besondere Eigenschaft der Salicylsaure. (A Special Property of Salicylic Acid.) ' Monatsh. f. prakt. Derm.,' Bd. i, 1882, p. 128. Chrysarobin und Pyrogallussaure in der Praxis. (Chry- sarobin and Pyrogallic Acid in Practice.) lb., Bd. ii, 1883, p. 71. Leimglycerin als Konstituens in der Dermatotherapie (gelatinse glycerinatae medicatas) . (Glycerine Jelly as a Basis in Dermato-therapeutics.) lb., Bd. ii, 1883, p. 37. Schwefelcalcium in der Dermatotherapie. (Calcium Sul- phide in Dermato-therapeutics.) lb., Bd. ii, 1883, p. 103. Aphorismen iiber S ch wef either apie und Schwefelpraparate. (On the Therapeutics of Sulphur and Sulphur Preparations.) 'Monatsh. f. prakt. Derm.,' Bd. i, 1882, pp. 289 and 325; andBd. ii, 1883, pp. 197 and 329. Die Pastenbehandlung der entziindlichen Hautkrankheiten, insbesondere des Ekzems. (The Paste Treatment of Diseases of the Skin, especially Eczema.) lb., Bd. iii, 1884, p. 38. Die Ziele und Resultate der neueren Lupusbehandlung. (The Objects and Results of the Later Treatment of Lupus.) lb., Bd. iii, 1884, p. 50. Pettsalben und Kiihlsalben. (Patty Ointments and Cool- ing Ointments.) lb., Bd. iii, 1884, p. 168. Zur Iodoformbehandlung des Ulcus molle. (On the I'odoform Treatment of the Soft Sore.) lb., Bd. iii, 1884, p. 242. Komedonenquetscher. (Comedo Extractors.) lb., Bd. iii, 1884, p. 332. Kokain gegen wunde Brustwarzen. (Cocain for Fissures of the Nipple.) lb., Bd. iv, 1885, p. 71. Nadelhalter zur electrolytischen Behandlung der Haar- balge. (Needle-holders for the Electrolytic Treatment of Hair Follicles.) lb., Bd. iv, 1885, p. 335. Saponimente. (Soap Liniments.) lb., Bd. iv, 1885, P- 3i5- CONTRIBUTIONS TO DERMATOLOGY. 161 Ueber medicinische Seifen. (On Medicinal Soaps.) Volkmann's 'Klin. Vortr./ 252. Ueber Sphacelinsaure bei Rosacea. (On Sphacelinic Acid in Rosacea.) lb., Bd. iv, 1885, p. 406. Icbtbyol. ' Monatsh. f. prakt. Derm./ Bd. v, 1886, p. 544. Ichthyol und Resorcin als Reprasentanten der Gruppe reduzierender Heilmittel. (Ichthyol and Resorcin as Re- presentives of the Group of Reducing Remedies.) ' Derma- tolog. Studien, Hamburg und Leipzig/ 1 886. Mineralsauren als Prophylaktikum bei Applikation von reduzierenden Substanzen. (Mineral Acids as Prophylactics in the Application of Reducing Substances.) c Monatsh. f. prakt. Derm./ v, 1886, p. 281. Ueber Salben- und Pastenstifte. (On Salve- and Paste- pencils.) 'Monatsh. f. prakt. Derm./ v, ,1886, p. 157. Behandlung von Pigmentflecken der Haut. (The Treat- ment of Pigment Spots on the Skin.) ' Monatsh. f. prakt. Derm.,' Bd. vi, 1887, p. 576. Die medikamentosen Leime. (The Medicated Gelatines.) ' Aerztl. Vereinsblatt./ 1886, No. 176. Konstituenten fur Pasten. (Constituents for Pastes.) 'Monatsh. f. prakt. Derm./ Bd. vi, 1887, p. 94. Der Behandlung der Akne. (The Treatment of Acne.) 'Monatsh. f. prakt. Derm./ Bd. vii, 1887, p. 54. Die Lupus Behandlung. (The Treatment of Lupus.) 'Monatsh. f. prakt. Derm./ Bd. vii, 1887, p. 195. Die Therapie der "roten Nase." (The Therapeutics of " Red Nose.") ' Monatsh. f. prakt. Derm./ Bd. vii, 1887, p. 1 162. Die Behandlung der Leuplakia Oris. (The Treatment of Leucoplakia Oris.) ' Monatsh. f . prakt. Derm./ Bd. vii, 1887, p. 706. Behandlung der hyphogenen Sycosis. (The Treatment of Hyphogenous Sycosis.) ' Monatsh. f. prakt. Derm./ Bd. vii, 1887, p. 345. Therapie der kokkogenen Sycosis. (The Therapeutics of Coccogenous Sycosis.) ' Monatsh. f . prakt. Derm./ Bd. vii, 1887, p. 555. Ueber Hautklemmen. (On Skin Clamps.) ' Monatsh. f . prakt. Derm./ Bd. vi, 1887, p. 359. 11 162 tona's dermatological papers. Ein regulierbarer Zerstauber. (A Regulating Spray- producer.) 'Monatsh. f. prakt. Derm./ Bd. vii, 1888, No. 1. Natur und Behandlung des Ekzems. (The Nature and Treatment of Eczema.) 'Berliner Klinik/ 1890, Heft 27. Lupus Behandlung. (The Treatment of Lupus.) ' Mo- natsh. f. prakt. Derm./ Bd. xii, 1891, p. 74. Zur Kenntniss der Hautfirnisse. (Contributions to our Knowledge of Skin Varnishes.) "Versamml. deutsch. NaturL und Aerzte in Halle," 'Therapeut. Monatsh./ 1891, No- vember. Ueber die Verwendung des Tuberculins bei der Lupus- behandlung, und einige neue Mittel gegen Lupus. (On the Action of Tuberculin in the Treatment of Lupus, and some New Remedies for Lupus.) " Aerztlichen Verein zu Hamburg, Marz, 1891/' 'Monatsh. f. prakt. Derm./ Bd. xii, 1891, p. 341 ; and Translation in ' British Journ. of Dermatology/ vol. iii, Nos. 32 and 33, 1891. Die Einwirkung von Karbolsaure und Nelkenol auf Lupus- gewebe. (The Action of Carbolic Acid and Oil of Cloves on Lupus Tissue.) 'Monatsh. f. prakt. Derm./ xiii, 1891, p. 463. Histological and Bacteriological Technique. Mykologische Beitrage. (Mycological Contributions.) ' Viertelj. f. Derm. u. Syph./ 1880, p. 165. Eine neue Darstellungsmethode des elastischen Gewebes der Haut. (A New Method of demonstrating the Elastic Tissue of the Skin.) 'Monatsh. fur prakt. Derm./ Bd. v,. 1886, p. 243. Ueber eine neue Art erstarrten Blutserums, und iiber Blut- serumplatten. (On a New Kind of Solidified Blood-serum, and on Blood-serum Plates.) ' Monatsh. f . prakt. Derm./ Bd. v„ 1886, No. 9. Zur Histotechnik. (On Histological Technicalities.) ' Mo- natsh. f. prakt. Derm./ Bd. v, 1886, Nos. 3, 4, and 7. Ueber Erzeugung von Vesuvin in G-ewebe, und iiber Meta- phenylendiamin als Kernfarbemittel. (On the Production of Vesuvin in the Tissue, and on Metaphenyl-diamine as a. I CONTRIBUTIONS TO DERMATOLOGY. 163 Nucleus-staining Agent.) 'Monatsh. f. prakt. Derm.,' Bd. vi, 1887, No. 2. Ueber weitere Versuche, Farben auf dem Gewebe zu erzeugen, und die chemische Theorie der Farbung. (On Further Experiments in staining Tissues, and on the Chemical Theory of Staining.) ' Separatabbruck aus dem Archiv fur microskop. Anatomie/ Bd. xxx. Die Ziichtung der Oberhautpilze. (The Cultivation of Epidermic Fungi.) ' Monatsh. f. prakt. Derm./ Bd. vii, 1888, No. 10. Zur Histologic der leprosen Haut. (On the Histology of the Leprous Skin.) ' Leprastudien/ Hamburg and Leip- zig, 1886, p. 65. Zur Farbung der Leprabacillen. (On the Staining of Lepra Bacilli.) ' Leprastudien,' Hamburg and Leipzig, 1886, p. 47. Die Leprabacillen in ihrem Verhaltniss zum Hautgewebe. (Lepra Bacilli and their Belation to the Skin Tissue.) ' Der- matolog. Studien,' i, Hamburg and Leipzig, 1886. Die Bacillenklumpen der Leprahaut sind keine Zellen. (The Bacilli Collections in the Leprous Skin are not Cells.) ' Virchow's Archiv,' Bd. ciii, No. 8 ; and ' Monatsh. f . prakt. Derm.,' Bd. v, 1886, p. 320. Wo liegen die Leprabacillen ? (Where are the Leprosy Bacilli situated?) 'Deutsche med. Wochenschr.,' 1886, No. 8. Histologische Verwendung des Wasserstoffsuperoxyds. (Histological Action of Hydrogen Peroxide.) ' Monatsh. f . prakt. Derm.,' Bd. ii, 1883, p. 31. Die feinere Struktur des Leprabacillus. (The Minute Structure of the Lepra Bacillus.) " Hamburger Aerztlicher Verein, Juli, 1886," 'Monatsh. f. prakt. Derm.,' v, 1886, p. 404. Die Bosaniline und Pararosaniline : eine bakteriologische Farbenstudie. (Bosaniline and Pararosaniline : a Study in Bacterial Staining.) ' Dermatolog. Studien/ iv, 1887, Ham- burg u. Leipzig. Flora Dermatologica ; unter Mitwirkung von H. Griindler und P. Taenzer. ' Monatsh. f . prakt. Derm./ Bd. vii, 1 1 p. 817. 164 TTNNA'S DERMATOLOGICAL PAPERS. Flora Dermatologica, vi (von Sehlen und P. G-. U.). lb., Bd. x, 1890, p. 485. Flora Dermatologica, vii. lb., Bd. xii, 1891, p. 249. Notiz betreffend die Taenzersche Orceinfarbung des elasti- schen Gewebes. (Note relating to Taenzer's Orcein Stain for Elastic Tissue.) ' Monatsh. f . prakt. Derm.,' Bd. xii, 1 89 1, p. 394. Eine neue Farbemethode fiir Lepra- und Tuberkel- bacillen. (A New Mode of staining Leprosy and Tubercle Bacilli.) 'Monatsh. f. prakt. Derm.,' Bd. xii, 1891, p. 477. Die Farbung der Microorganismen im Horngewebe. (The Staining of Micro-organisms in Horny Tissue.) ' Monatsb. f. prakt. Derm../ lb., Bd. xiii, 1891. Einige neue Metboden zur tinctoriellen Isolirung von Bak- terien. (Some New Methods for the Tinctorial Isolation of Bacilli.) 'Berliner klin. Wochenschr./ 1891, p. 31. Zur Untersuchungstechnik der Hyphomyceten. (On the Technical Examination for Hyphomycetes.) ' Centralbl. f. Bakt. u. Parasitienk./ Bd. xi, 1892, No. 1. Drei Favusarten. (Three Kinds of Favus.) " 64 Ver- samml. deutscher Naturf. u. Aerzte zu Halle, 1891," * Monatsh. f. prakt. Derm.,' Bd. xiv, 1892, No. 1. Bakterienharpune. (Bacterial Harpoon.) ' Centralb. f. Bakt. u. Parasitenk.,' xi, 1892, Nos. 9 and 10. Ueber die Reifung unserer Farbstoffe. (On the Matur- ing of our Staining Materials.) ' Zeitschr. f . wiss. Mikroski u. Technik/ Bd. viii, 1892, p. 425. Der Entwickelung der Bakterienfarbung. (The Develop- ment of Bacterial Staining.) " Histor. kritische Uebersicht," ' Centralb. f. Bakterien u. Parasitenk., J Bd. iii, 1888. Miscellaneous. Ein neues Laryngoskop zur Untersuchung der hinteren Kehlkopfflache. (A New Laryngoscope for the Investiga- tion of the Posterior Surface of the Larynx.) ' Monatsch. f. Ohrenhoilk./ 1878, No. 4. Albuminurie wahrend der Styraxein reibung Kratziger. (Albuminuria during the Inunction of Styrax in Scabies** 'Yirch. Arch./ 1878, Bd. lxxiv, p. \. CONTRIBUTIONS TO DERMATOLOGY. 165 Die missbrauchliche Bezeichnung des Chrysarobins als " Chrysophansaure." (The Misnomer of Chrysarobin as Chrysophanic Acid.) 'Monatsh. f. prakt. Derm./ Bd. i, 1882, p. 254. Die Dermatologie an dendeutschen Hochschulen. (Derma- tology in the German High Schools.) ' Monatsh. f. prakt. Derm./ Bd. iv, 1885, No. 1. Ueber Diinndarmpillen. (On " Small-intestine Pills.") ' Pharmaceutischen Centralhalle/ 1885, Nos. 45 and 46. Die Dermatologie in ihrem Verhaltniss zur Gesammfc- medicin. (Dermatology and its Relation to General Medi- cine.) Address given in September, 1887, at the Inter- national Medical Congress in Washington. Die Anwendung des Chloroformwassers zur Losung von Medikamenten. (The Use of Chloroform Water as a Solvent for Drugs.) 'Monatsh. f. prakt. Derm./ Bd. vii, 1 888, No. 9. Internationale Spezialistenkongresse, und der Pariser Kongress fur Dermatologie und Syphilographie im Jahre 1889. (International Specialist Congresses, and on the Paris Congress for Dermatology and Syphilography of the Tear 1889.) 'Monatsh. f. prakt. Derm./ Bd. vii, 1888, No. 23. Ueber Atlanten der Hautkrankheiten im allgemeinen, und iiber einen internationalen Atlas seltener Hautkrankheiten im besondern. 'Monatsh. f. prakt. Derm./ Bd. viii, 1889, No. 7. Papuloses Syphilid der Handteller und gynakologische Praxis. (Papular Syphilide of the Palm and Gynaecological Practice.) ' Monatsh. f. prakt. Derm./ Bd. ix, 1889, No. 10. Der Dampftrichter. (The Steam Funnel.) ' Centralbl. f . Bakt. u. Parasitenk./ Bd. ix, No. 23. Ueber das Mikrokauterium. (On the Microcauteriser.) 'Deutsch. med. Wochenschr./ 1890, No. 29. Dr. Unna is the editor of the ' Monatshefte f iir praktische Dermatologie,' Hamburg and Leipzig ; joint editor of the ' Atlas seltener Hautkrankheiten ' (Atlas of Rare Diseases of the Skin), and of the ' Flora Dermatologica.' ON THE APPEARANCE OF HERPES ZOSTER DURING THE ADMINISTRATION OF ARSENIC. By LUDWIG NIELSEN, SECUNDAP.AEZT TO THE GENERAL HOSPITAL. COPENHAGEN. Evert now and then herpes zoster appears in patients while under a longer or shorter course of treatment with arsenic. In some of the published cases zoster has appeared during the administration of arsenic in lichen ruber : thus Hans v. Hebra 1 has noted two ; Kaposi/ three. There are, however, other diseases where arsenic has been given and herpes zoster has made its appearance ; psoriasis (Julius- burger, 3 and also two cases of lichen ruber), chorea (Bokai,* three cases), and nervous debility in consequence of sperma- torrhoea (Epstein, 5 one case). . 1 H. v. Hebra, ' Morbid Affections of the Skin,' 1884, p. 204. 2 Kaposi, "Eemarks upon the recent outbreak of Herpes Zoster, and upon its aetiology," 'Supplement to the Archives of Dermatology and Syphilis,' 21st year, 1889, pp. 57 — 72 ('Transactions of the Dermatological Congress in Prague '). 3 Juliusburger, "The Appearance of Herpes Zoster during the Use of Arsenic" ('Quarterly Journal of Dermatology and Syphilis,' 1884, pp. 97 — 104, containing also an index of the literature on the subject). 4 G. Bokai, jun., " Three Cases of Chorea Minor treated with arsenic ; eruption of Herpes Zoster," ' Monthly Journal of Practical Dermatology,' 1889, vol. viii, p. 39. 5 E. Epstein, " Herpes zoster, H. facialis, and H. genitalis," ' Quarterly Journal of Dermatology and Syphilis,' 1886, pp. 787, 788. 168 NIELSEN ON HERPES ZOSTER DURING In accordance with the statements of various writers the eruption runs the usual course, it gets well, no relapse occurs in spite of the continued use of the drug, and the patients show otherwise no sign of intolerance. The opinions of these writers as to the relation between arsenic and herpes zoster are very diverse, based as they are upon their relatively frequent coincidence. Several (Kaposi, James White, and others) regard it as accidental ; so does Juliusburger, who mentions it, however, as remark- able that the patients have often been in the hospital for some months, and consequently the possibility of infection, as suggested by some, is excluded. Kopp 1 also regards it rather as an accidental coincidence, since no real proof of an interrelationship has been adduced. Neisser, 3 who has seen a far greater number of cases of herpes zoster after the free administration of arsenic than Kaposi, is still uncertain whether any relationship subsists between the two. Lastly, some writers (H. v. Hebra, Epstein, Bokai, Hutchinson, 3 and others) admit a causal re- lationship between the use of arsenic and herpes zoster. While referring to the hospital reports of the cases of psoriasis from 1864 to 1889 inclusive, we were struck by the not inconsiderable number of patients suffering from psoriasis who were attacked by herpes zoster while under the usual treatment with arsenic. We shall now give some further particulars about these cases. Of 777 cases of psoriasis (5 14 patients) observed during the above-mentioned period, 4 557 cases (319 patients) were 1 Kopp, ' Trophoneuroses of the Skin,' Vienna, 1886, p. 103. 2 Neisser, ' Discussion upon Kaposi's Address,' p. 67. 3 J. Hutchinson, " The Study of Skin Diseases as illustrating the doctrines of General Pathology," ' Brit. Med. Journal,' 1887, 23rd and 30th July, Nos. 1386 and 1387. Hutchinson's first assertion that arsenic could cause herpes was published in the 'Medical Times and Gazette ' for 1868, vol. ii, p. 722, hut I have not been able to refer to the volume. This was probably the earliest mention of the subject. 4 During the period, 150 patients suffering from psoriasis were admitted in addition : these were, however, not detained more than one or two days in the skin wards. Delirium tremens developed in a few ; the majority, however, were suffering from venereal disease, with which psoriasis happened THE ADMINISTRATION OP ARSENIC. 169 under treatment with arsenic 1 for varying duration ; external treatment was also prescribed. In the remaining 220 cases iodide of potassium in large doses was administered, or external treatment alone was employed. In a very few cases other remedies (carbolic acid in pill form) were given. In ten of the total number of cases herpes zoster appeared after a longer or shorter course of treatment, and only in those patients who were being treated with arsenic. More- over a female patient stated that before admission to the hospital she had, while taking arsenic, just had an attack of zoster. If this case be excluded as not coming under direct ob- servation, i '8 per cent, of 557 cases of psoriasis treated with arsenic suffered from an attack of zoster. Moreover it did not appear in a single one of the remaining 220 cases that were differently treated. Again, just as herpes zoster under ordinary circumstances only very seldom attacks the same patient again, so also in these patients it appeared but once. The 557 cases represent 390 patients, therefore one in every thirty -nine patients was attacked by herpes zoster while under the in- fluence of arsenic (2 '6 per cent.). In two patients only (v. Synopsis of cases, Nos. 8 and 10) the arsenic treatment was interrupted, viz. on the third and second day respectively before the appearance of the erup- tion. In the remaining eight it was continued during the eruption as well as after its disappearance. The duration of the treatment with arsenic before the eruption of herpes zoster differed considerably in the ten patients. In seven the interval that elapsed was one month or more (in No. 3, three and a half months) ; in the remaining three, from nine (No. 9) to twenty-five days. to be associated as a trivial complication, and it was for the former disease they sought hospital treatment. Herpes zoster appeared only in one of the Igo, shortly before admission of the patient, who was suffering from chronic syphilitic disease of the brain. In none of these cases did herpes zoster appear while actually in the hospital. 1 As arsenious acid, or as its potassium or sodium salts administered in pill form or in solution. Arsenic was only administered subcutaneously quite recently and in a small number of cases. 170 NIELSEN ON HERPES ZOSTER DURING Unfortunately, the amount of arsenic administered cannot be stated, except in case No. 10, where 14 J milligrams of sodium arseniate were given (about quarter of a grain). In this case (No. 10) epigastric oppression and an urticaria-, like exanthem preceded the eruption of the herpes zoster; in another (No. 3), transient diarrhoea was present; in all the rest, however, no toxic symptoms were manifest. In spite of the continued administration of the drug in the majority (8) of the patients after the eruption of herpes zoster, not one had a second attack. The same remark holds good with those patients (Nos. 1, 2, 8, and 9) who were admitted again later on (No. 1 on no less than three different occasions), and subjected again to a course of ar- senic. The cases of herpes zoster are distributed fairly evenly over this period of twenty-five years — an interval of one or two years has generally elapsed. In 1877, however, two cases appeared. Twice the interval was longer, and from November, 1869, to February, 1875 (a little over five years), no case of zoster occurred. During that time, but chiefly in 1870, a small number of patients were treated internally with carbolic acid instead of arsenic. The second long in- terval occurred from 1880 to 1889, when no case of zoster was seen. But from the end of 1882 to the end of 1888, of internal remedies used in the treatment of psoriasis, potas- sium iodide in large doses was most frequently prescribed, and only in a very small number of cases was arsenic used. At the end of 1888 arsenic was again resumed and given hypodermically, and in the following year a case of zoster appeared amongst the patients under this treatment. Two cases occurred in each of the months of February, March, and October, one only in April, May, September, and November. The eruption attacked 4 males, 6 females. Bight patients were between eight and twenty-two years, 2 between forty and forty-six. As regards locality, herpes zoster dorso-pectoralis occurred seven times, herpes zoster dorso-abdominalis twice, herpes zoster lumbo-femoralis once. The rash was always confined to one side in a few cases but slightly developed, in others fairly extensive. THE ADMINISTRATION OF ARSENIC. 171 On several occasions " points douloureux " were noted, but in one case only (No. 8) is general malaise stated to have been present. With all the patients the course of the affection was the usual one, as in ordinary uncomplicated cases of herpes zoster. The psoriasis was in some cases slight, in others exten- sive ; in one patient (No. 8) patches of psoriasis developed in the herpetic region shortly after the disappearance of the herpes zoster. One only of the ten patients (No. 8), who had old-standing kypho-scoliosis, was being treated with wet compresses and subsequent wet rubbing. It is possible that in this case the treatment may bear an etiological relationship to herpes zoster, for the rash showed itself immediately after the wet rubbing. Moreover this was one of the patients alluded to above, where arsenic was stopped three days before the eruption appeared. In none of the other patients were we able to demonstrate any possible aetiological factor. Psoriasis is not considered to bear any nearer relation to herpes zoster, even by those writers who, on doubtful grounds, regard the former as nervous in origin. Just as little, so far as we know, has it ever been maintained that herpes zoster appears frequently with, or as a complication of, psoriasis. On the contrary, no herpes zoster was seen in the 220 cases which were not under arsenic treatment. Further, clinical observers have not noticed it in connection with any particular disease, and certainly not with psoriasis, but rather as a sequela of arsenic administered in very different diseases. The relatively large number of herpes zoster cases we have brought forward — r8 per cent, of cases, 2"6 per cent, of patients arising during the administration of arsenic, but not in any of those under different treatment (220) ; — in con- junction with the fact of the tolerably even distribution of the cases over twenty-five years, where the longest interval during which no zoster was seen coincided with the much less fre- quent use of the drug, is all the more striking, as herpes zoster is seldom seen in hospital. Should, however, doubt be entertained in the two cases in 172 NIELSEN ON HERPES ZOSTER DURING which arsenic was withheld two and three days respectively before the appearance of zoster — especially in the case where the rash showed itself after the cold pack — the number is still considerable. Furthermore this number does not in- clude the case mentioned above, where the patient had just passed through an attack while taking arsenic before admission to the hospital. Again, no comparison can be instituted between the rela- tive frequency of the eruption after arsenic and its appear- ance after different treatment among hospital patients. Lastly, the percentage of these herpes zoster cases arising in the course of arsenic treatment exceeds by far the number of patients who come to the hospital solely on account of this affection. To illustrate this point we shall give the number of patients suffering from herpes zoster from January, 1888, to July, 1 89 1, inclusive (my tenure of office as Secundararzt), who were treated in the skin department. Of 5267 cases of skin and venereal disease during these years herpes zoster occurred only in 14 cases ("27 per cent.). Of these, two only developed in the hospital during treatment of other diseases. In one the eruption was distributed on the nates, the patient was suffering from syphilitic paraplegia, and the eruption was regarded as the result of the spinal cord affec- tion. The case (No. 10) was that in which the eruption occurred after hypodermic injection of arsenic. We should also remark that arsenic was not much used during this period in other skin affections. For instance, eczema, the most frequent skin disease, was only exception- ally treated with arsenic. Pemphigus, lichen ruber, and others which are usually treated with this drug, were seldom seen here, as is the case everywhere. The above-stated conditions admit of an overwhelming probability — in fact, prove to us — that a real relationship does subsist between arsenic and herpes zoster, although questioned and even denied by several writers. In fact, under certain though not well-known circumstances herpes zoster may make its appearance, generally after a longer rather than after a shorter period of arsenic treatment. In other words, herpes zoster must be looked upon in THE ADMINISTRATION OF ARSENIC. 173 these cases as a drug-rash, although without interrupting the use of arsenic it disappears in the usual manner, and does not recur, as far as observation goes, even under a renewal of the treatment on later occasions. In contrast to local causes (traumatism, vertebral caries, &c.) of herpes zoster, arsenic may be mentioned in setio- logical connection with carbon monoxide, which has pro- duced in certain cases of poisoning herpes zoster (Leudet, Sattler). Again, in the epidemic of herpes zoster men- tioned by several writers, and especially by Kaposi, it is maintained by the latter (Weiss 1 and others) that some infective source is at work, as well as some general disturb- ing influence. Kaposi himself draws a parallel between herpes zoster aris- ing during the administration of arsenic and that seen in cases of carbon monoxide. But though he recognises this as in a measure supporting the distribution of herpes zoster on only one or a few corresponding nerve territories, and therefore as hardly harmonising with his infective theory, he nevertheless maintains it to be an accidental coincidence. Although we believe it is as good as demonstrated from our researches that arsenic can give rise to herpes zoster, yet this does not seem to conflict with the theory of infection. The following is a synopsis of the ten cases on which the above statements are based. 3 1 E. Weiss, "Epidemic Zoster," 'Archives of Dermatology and Syphilis,' 1890, p. 629. 3 I have to thank Primararzt Professor Haslund for the patients' cases, which are considerahly abbreviated, partly for want of space and partly for convenience of reference. 174 NIELSEN ON HERPES ZOSTER DURING Synopsis of cases given by the Author No. Sex, age, occupation, previous history. Description of psoriasis. Number of days under treatment. Preparation of arsenic used and other treatment. II III IV V VI VII VIII IX Boy, set. 1 1 ; psoriasis from 4 years old. Female, set. 15, domestic servant. Girl, set. 13. Boy, set. 8. Female, set. 15. Female, set. 19, domestic servant. Girl, set. 13. Male, set. 22; several times treated; kypho- scoliosis (since set. 10). Male, set. 40; psoriasis from childhood; several times treated with arsenic. Female, set. 46, ship's stewardess psoriasis from childhood. Nummularis and annularis on scalp, body, and extremi- ties; extensive. Guttata and diffusa on scalp and body; fairly extensive. Punctata and diffusa on body and extremities; fairly extensive. Papularis on ex- tremities and left ear; slight. Guttata, nummu- laris, and annularis on body and ex- tremities; fairly extensive. Very extensive patches on scalp, face, body, and extremities. Punctata and guttata on body, extremities, and face; strongly marked. Guttata, nummu- laris, and diffusa on scalp, face, body, and extre- mities; strongly developed. Nummularis and diffusa on hairy scalp and extre- mities; fairly well developed. Patches extensive and well marked. From March 2 1 st to July 7th, 1864; about 3 j months, From Jan. 19th to May 29th, 1866 ; about 43 months. From June 22nd to Oct. 31st, 1868; about 4j months. From Nov. 1st to Dec. 27th, 1869; nearly 2 months. From Jan. Jth to March 18th, 1875 ; about 2\ months. From July 31st to Oct. 12th, 1877; about 2>j months. From Aug. 9th to Oct. jth, 1877; nearly 2 months. From Jan. 14th to June 18th, 1878 ; 5 months. From April 1 3th to June 10th, 1880; nearly 2 months. From Feb. 13th to March 19th, 1889; i-'; months. Liquor Sodii Arseniatis in increasing doses; laths and ointments. Liquor Sodii Arseniatis in increasing doses; baths and tar preparations. Liquor Sodii Arseniatis in increasing doses; bathe and tar preparations. Liquor Sodii Arseniatis baths and tar prepara< tions. Mistura Arsenicalis (ctgrms. 10 to grms. 3ooliquoris); baths and various oint- ments. Mistura Arsenicalis (ctgrms, 10 to grms. 300 liquoris); baths and various oint- ments. Mistura Arsenicalis (same strength as above); baths and tar ointments. Mistura Arsenicalis (as above). On Jan. 24th Liq. Arsenicalis cTinctura Ferri Pomati; baths and tar remedies. On Feb. 29th arsenic stopped and wet pack ordered. Mistura Arsenicalis (si above) ; baths and tar preparations. Sol. of Sodium Arsenial (ctgrms. 2 to grms. 20 •5 c.c, about 9*1, inji hypodermically; st on March 10th. 23 tions given — 14J mgrmJ. =i grain of the salt. THE ADMINISTRATION OP ARSENIC. 175 [tabulated by the Translator] . Bate of appearance of herpes zoster. May 28th, i. e. 68 days after commencement of arsenic. Feb. 6th, i.e. 22 days after commencement of arsenic. Oct. 13th, i.e. 114 days after commencement of arsenic. Might side. — Sacral re- gion, inner side of thigh, outer side of knee. Left side. — From hack to umbilicus. Left side. — Over angle of scapula and side of thorax. Nov. 26th, i.e. 25 days after commencement of arsenic. Feb. Jth, i.e. 34 days afte commencement of arsenic. Oct. 7th, i. e. 68 days after commencement of arsenic. Sept. Jth, i. e. 29 days after commencement of arsenic. On March 4th, i. e. 3 days after stopping arsenic, and after using the wet pack. On April 22nd, i. e. 9 days after commencement of arsenic. On March 9th papules, s: of pea, resembling urticaria, scattered in groups of two and three over the body. On March 12th, 2 days after arsenic was stopped, zona appeared. Description of site. Left side.- of ilium. -Over crest Under treatment 4 years pre. viously. Arsenic also given on three distinct subsequent admissions. No zona. No recurrence of zona on treat ment with arsenic on a subse quent admission. Arsenic stopped two days on account of diarrhoea (2nd to 4th July). No recurrence of zona. No recurrence of zona. Might side. — 3rd and 4th intercostal spaces from spine to sternum. Left side- mamma. ■Under the Might side. — Over shoulder - blade, in axilla, and nipple. side. — Prom mid- dorsal spine, round the thorax, to ensi- form cartilage. Might side. — Over 6th intercostal space. Left side. — Outside angle of scapula and below ensiform carti lage. General remarks. ' Points douloureux " in axilla and 2nd intercostal space. No recurrence of zona. No painful spots and no recur- rence of zona while in hos- pital. General malaise, painful area? over the spine and angle of scapula. On March 13th, i. e. 9 days later, psoriasis in her- petic region. No recurrence of zona on a subsequent admis- sion during arsenic treatment Painful area in dorsal region. Zona was not present on a pre- vious occasion, nor any recur- rence on a subsequent occasion, with arsenic treatment. Epigastric oppression on day of urticaria-like eruption. Pain- ful areae in herpetic region No recurrence of zoster while in the hospital. A COLLECTION DE. DUHEING-'S PAPERS DERMATITIS HERPETIFORMIS. 12 CONTENTS. PAGE 1. Case of Impetigo Herpetiformis. June 2nd, 1883 . • 179 2. Dermatitis Herpetiformis. August 30th, 1884 . . 182 3. Notes of a Case of Dermatitis Herpetiformis extending over Eleven Tears. July 12th, 1884 . . . .196 4. A Case of Dermatitis Herpetiformis (Bullosa). July 19th, 1884 201 S- Case of Dermatitis Herpetiformis (Multiformis), aggravated by Pregnancy and Irregular Menstruation. July 19th, 1884 . 205 6. Case of Dermatitis Herpetiformis, illustrating in particular the Pustular Variety (Impetigo Herpetiformis of Hebra). August, 1884 . . . . . .210 7. Dermatitis Herpetiformis : its Relation to so-called Impetigo Herpetiformis. October, 1884 .... 217 8. Notes of a Case of Dermatitis Herpetiformis during Thirteen Tears. November 15th. 1884 . . . .231 9. Preliminary Note on the Relation of Dermatitis Herpetiformis to Herpes Gestationis and other similar Forms of Disease. Novem- ber 22nd, 1884 ..... 239 10. Case of Dermatitis Herpetiformis, with peculiar Gelatinous Lesions. March 7th, 1885 .... 241 11. Case of Dermatitis Herpetiformis of the Pustular Variety. March gth, 1887 ...... 249 12. Case of Dermatitis Herpetiformis resembling Erythema Multi- forme. April 2nd, 1887 .... 233 13. Uber die Diagnose der Dermatitis Herpetiformis. September 1st, 1887 . . . . .256 14. Case of Dermatitis Herpetiformis caused by Nervous Shock. January, 1885 ..... 271 15. On the Relation of Impetigo Herpetiformis (Hebra and Kaposi) to Dermatitis Herpetiformis (Duhring). March, 1890 . 278 16. Case of Typical Dermatitis Herpetiformis. June, 1890 . 287 17. The Treatment of Dermatitis Herpetiformis. February, 1891 . 291 CASE OF IMPETIGO HERPETIFORMIS. 1 RECOVERY. Impetigo herpetiformis, first described and so named by Hebra, is a rare disease of the skin, about which but little has been written either abroad or in this country. As I have stated in the third edition of my treatise on skin diseases, it may manifest itself in a variety of forms, all having, however, certain features in common. Cases showing the several varieties of the disease have, from time to time, presented themselves to me, one of which I shall briefly describe with the following case : Mrs. Naomi P — , aged 24, applied for advice at University Hospital, December 26th, 1882, suffering with a mixed vesicular, bullous, and pustular disease of the skin, occupy- ing the greater portion of the general surface. The following history was obtained. She had enjoyed good health until seven months ago, when the disease of the skin made its appearance. At the time she was six months pregnant, and in average health. The eruption began upon the abdomen, but within a week the whole surface, including the hands and feet and fingers and toes, was invaded. The first lesions were wheals, which in a few days passed into vesicles and small blebs, accompanied with violent itching. The urticarial lesions soon ceased, vesicles, blebs, and pustules now appear- ing from day to day. The blebs possessed the peculiarity of refilling upon being opened. Many of the lesions came out as "water-blisters," and later became whitish pustules. This change was often noticeable when they refilled a second or a third time after being evacuated. The disease increased steadily in severity up to within a week of confinement. At 1 Reprinted from the ' Medical News,' June 2nd, 1883. 180 DE. DTTHEING's PAPERS ON times the whole surface, including even the mucous membrane of the mouth and vagina, was literally covered with lesions. They made their appearance in the form of crops every few weeks, at one time vesicles and blebs predominating, at another time vesicles and pustules, or a mixture of all three lesions. They varied in size from a pin-head to a pea, or even a walnut, and were of different shapes, most being very irregular in outline. Some were flat, others were raised, the vesicles being generally flat. Each attack lasted about a fortnight. The distress from the itching was almost unendurable. None of the many applications used afforded any relief, and anodynes were resorted to nightly. Early in the course of the disease the nails of the fingers and toes became affected, and the hair fell out to a considerable extent. The child was born healthy at full term, four months ago. After delivery the eruption began to decrease somewhat in severity, but it has never- theless persisted, and now presents the same general characters as at first. In fact, at no time has the type of the eruption materially changed. The following notes were recorded at the time of the exa- mination : — The patient is a blonde. She is tall and spare, and is evidently in poor general health ; the expression is anxious, and she is both nervous and despondent, fearing that she will never recover. She has lost weight of late. The whole surface, especially the trunk and upper extremities, is the seat of a profuse multiform eruption, characterised by vesicles, vesico-pustules, pustules, and blebs, of the most varied sizes and shapes. Many of the vesicles are extremely small — pin-point and pin-head sized. All are tense, and have a glistening glazed look. The small lesions are, as a rule, flat, and but little raised. The pustules are more vari- able in size, some being as large as peas, or even cherries; the blebs are in some instances as large as cherries, or even walnuts. None of the lesions show any disposition to rupture, and are in this respect distinctly herpetic. As a rule, they are not accompanied by redness of the skin, nor by marked areolae ; often they rise from apparently sound skin. Many of the larger ones have an irregular, jagged, or stellate out- line, which gives them a "puckered" appearance, similar to DERMATITIS HERPETIFORMIS. 181 that we sometimes see in herpes zoster. This peculiarity is particularly noticeable with the pustules. Vesicles, pustules, and blebs exist in all stages of evolution ; vesicles are observed passing into pustules and also into blebs. Here and there vesicles and pustules are developed side by side, and owing to the fact that the latter are whitish rather than yellowish the contrast is marked. Another peculiarity to be mentioned is the tendency all the lesions evince to group — to occur in more or less well- defined clusters. At the same time it must be stated that this does not exist in so marked a manner as in herpes zoster. For example, here and there two or three pustules are grouped, but of tener a number of vesicles are irregularly clustered, forming a patch the size of a dime or a quarter- dollar. The eruption in no instance follows the course of nerve-tracts. The extensor surfaces are more affected than the flexor. The finger-nails show two distinct transverse ridges, indicating attacks of cutaneous outbreak. The patient was placed upon full doses of arsenical solu- tion and wine of iron, and used locally an ointment of oleate of bismuth. The following week, new lesions still appearing, one half of the general surface was anointed three times daily with precipitated sulphur, two drachms ; olive oil, two drachms ; lard, one ounce. Upon the other half of the body the " liquor carbonis detergens " (an alcoholic solution of coal-tar), one part to four of water, was applied freely. Under these local remedies improvement set in at once, both seeming to act beneficially. The tarry preparation was sub- sequently used (full strength) upon the whole surface. A tonic saline aperient was also prescribed for daily use in con- nection with the iron and arsenical mixture, and under these remedies the patient made a very satisfactory recovery. Six weeks ago she regarded herself as cured, and a few weeks later passed from under observation. 182 DR. DUHEING's PAPEKS ON DERMATITIS HERPETIFORMIS. 1 Undee the name Dermatitis Herpetiformis I propose to place a number of cases of skin disease that I have encoun- tered from time to time. These cases at present are for the most part nameless, having been regarded and diagnosed either as peculiar manifestations of one or another of the commoner and well-known diseases, as eczema, herpes, or pemphigus, or in some cases as undescribed diseases. Prom these remarks it will be inferred that the disease is rare, and such in a measure is the fact. At the same time I have met with a sufficient number of cases during the last fifteen years to warrant the view that the disease is worthy of a special description and a name. I first recognised the affection as being peculiar as far back as 1871, but with the few cases observed at that time was at a loss to classify or to treat them satisfactorily. Since this date I have encountered a number of other cases illustrating the same and other varieties of the disease. In the first edition (1877) of my ' Treatise on Skin Diseases ' I made no allusion to the subject, for the reason that my mind was not clear as to the relation that the several cases I had encountered bore one to another, nor that they were really all merely different manifestations of the same pathological process. In the light, however, of a number of marked cases that have now been under observation for a period of years, and of others that have been more recently noted, the statement may be made that, dissimilar as they may in some cases at first sight appear, they all represent varieties of one and the same 1 Eeprinted from the 'Journal of the American Medical Association,' August 30th, 1884. DERMATITIS HERPETIFORMIS. 183 disease, for which I propose the name dermatitis herpeti- formis. In the present communication attention will he directed to the principal features of the disease, describing more par- ticularly its symptoms and natural course. On another occa- sion cases illustrating the several varieties will be brought ' forward. It may be premised here that dermatitis herpetiformis in- cludes what Hebra 1 designated first " herpes impetigini- formis," and afterwards " impetigo herpetiformis ;" that is to say, that the cases of Hebra constitute one of the varieties of the disease it is proposed to call dermatitis herpetiformis. And here it may be remarked that this name must not be confounded with the "dermatitis circumscripta herpetiformis " of Neumann, a term introduced by this author a few years ago to designate lichen planus, which at that time he sup- posed to be an undescribed disease. It may be added that this term is now no longer used by Neumann. In the second edition of my ' Treatise on Skin Diseases * (1881), p. 276, under the title impetigo herpetiformis, will be found an abstract of Hebra's description of the disease he so named. His account may be summarised as follows. It is a rare and grave form of skin disease, of which at the date of his report he had seen but five examples, four of which termi- nated fatally. The disease is characterised by the formation of yellowish pustules, arranged in groups or in an annular form, which tend to run together and to dry into yellowish, greenish, or brownish crusts, beneath which a red, excoriated, moist surface exists. On the periphery of the lesions and patches new groups and rings of pustules form. The course of the disease was similar in every case. Bach outbreak of pustules was preceded by malaise, chills, fever, and systemic disturbance. The disease occupied all regions, with pre- ference for the anterior surface of the trunk and the flexor surfaces of the thighs. Single cases under different names 2 were before this date 1 ' Wiener med. Wochensch.,' No. 48, 1872 ; see also ' Lancet,' March 23rd, 1872. 2 'Wiener med. Wochensch.,' No. 48, 1872; the 'Lancet,' March 23rd, 184 DE. DOHBING-'S PAPERS ON reported by Baerensprung, 1 Neumann, 2 Auspitz, 3 and Geber.* Heitzmann 5 has more recently also reported a case with the name impetigo herpetiformis. As supplementary to Hebra's description, I gave my own experience with hitherto un- described varieties of the disease in the following language: — " Within the last ten years I have from time to time met mitk cases, occurring in both sexes, representing other phases of the disease than heretofore described. In some cases the lesions were vesicular and bullous, 6 in others pustular ; in still others, . and in the majority of cases, bullous and pustular combined, or these lesions appearing alternately, — the disease being at one time vesicular and bullous, at another time pustular. In all instances the disposition to group or to extend about the periphery was more or less marked. A varied amount of con- stitutional disturbance with violent itching was always present. The disease manifested a disposition to constant recurrence, in the form of repeated attacks, extending in the majority of cases over years, and was but little influenced by treatment. None of the cases occurred in pregnant women, nor in any case has the disease proved fatal. The disease is liable to be confounded with eczema, ecthyma, and pemphigus, according as the lesions happen to be vesicles, pustules, or blebs. The setiology and pathology of the disease are both obscure. In some cases it possesses many features in common with pem- phigus ; other cases, however, manifest but little dis- position to the formation of blebs. It is therefore evident that the process is capable of appearing in the form of various lesions, and that the true impetigo herpetiformis represents but one variety of the disease. More information is needed before the disease can be assigned its proper place in classification." 1872; 'Atlas der Hautkrankheiten,' Heft 9, Tafeln ix und x, "Wien, 1876. 1 'Atlas del: Hautkrankheiten,' Tafel viii, Berlin, 1867. 3 'Lehrbuch der Hautkrankheiten,' Auflage iii, Wien, 1873, p. 173. 3 ' Archiv fur Derm, und Syph.,' Heft 2, 1869, p. 246. 4 ' Jahresb. des K. K. allg. Krankenhauses zu "Wien, Jahrg. 1871. 6 'Archives of Dermatology,' January, 1878. 6 In Hebra's fifth case the disease was characterised by vesicles and blebs, from which circumstance he was inclined to regard the disease as a variety of herpes, and designated it "herpes impetiginiformis " ('Lancet,' March 23rd, 1872). DERMATITIS HERPETIFORMIS. 185 These words, written four years ago, give a brief account of the disease which, is the subject of this communication, and portray its important features. The description is succinct, but it embraces the leading points, and, it may be added, agrees with the views I hold at the present time. It will be seen from this description that the name impetigo herpetiformis is altogether inappropriate to express the con- dition in other and equally important varieties of the disease. The cases that fell under Hebra's observation were for the most part instances of the pustular variety, and he therefore regarded the name he selected as proper ; but to call a vesicular or bullous disease " impetigo," with our present ideas of nomenclature, is of course most confusing. Because of the multiformity of the lesions manifested in the several varieties which will be shown may exist, therefore I think the term dermatitis more suitable, allowing as it does all varieties of this most protean affection to come under its title. The adjective herpetiformis expresses the chief characteristic of the disease, and, as in Hebra's cases of the pustular variety, has been present in all of my cases. The disease is unquestionably herpetic, especially in its typical and commonest manifestation ; that is, the lesions tend to be vesicular, and to occur in small groups or clusters. And for this reason it has on several occasions occurred to me that the affection might be regarded as a herpes, an observation that was also made by Hebra, and by the other reporters of cases mentioned. All of these observers recognised its herpetic character. The name herpes pruriginosus, it might be suggested, would seem suitable, and would answer well for most of the cases observed, itching being almost always a marked and constant symptom. At the same time if this term were adopted our present definition of herpes would require to be changed, and we should be obliged to regard pus- tular and bullous lesions as manifestations of herpes, an admission which would be confusing or even disastrous in its results. For these reasons I think the name now introduced preferable. That such a protean disease as I have inti- mated exists, and that these varied cutaneous manifestations 186 de. duhbing's papers on are all but forms of one pathological process, there can be no doubt j and I shall elucidate this point by describing the ' several important varieties, which, as in the case of eczema, are based upon the predominance of certain lesions. Before ' doing this, however, I may refer to certain symptoms common to all forms of the disease, to which no particular allusion has as yet been made. In severe cases prodromata are usually present for several days preceding the cutaneous outbreak, consisting of malaise, constipation, febrile disturb- ance, chilliness, heat, or alternate hot and cold sensations. Itching is also generally present for several days before any sign of efflorescence. Even in mild cases slight systemic disorder may precede or exist with the outbreak. This latter may be gradual or sudden in its advent and development. Not infrequently it is sudden, one or another manifestation ~ breaking out over the greater part of the general surface diffusely or in patches in the course of a few days, accom- panied by severe itching or burning. A single variety — as, for example, the erythematous or the vesicular — may appear, or several forms of lesion may exist < simultaneously, constituting what may very properly be designated the multiform variety. The tendency is, in almost every instance that I have observed, to multiformity. There is, moreover, in almost every case a distinct disposi- tion for one variety, sooner or later, to pass into some other variety ; thus for the vesicular or pustular to become bullous, or vice versa. This change of type may take place during the course of one attack or on the occasion of a re- ■ lapse ; or, as is often the case, it may not show itself until months or years afterwards. I have notes of several cases where, during a period of from two to five years, the ery- thematous, vesicular, and bullous varieties were all' in turn manifested. Permit me, however, to state again that not only multiformity of lesion, but irregularity in the order of development, is the rule, whether during an attack or later in the course of the disease. Itching, burning, or pricking sensations almost always exist. When the eruption is profuse they are intense, and cause the greatest suffering. As in the case of eczema, before and with each outbreak they become most violent, DERMATITIS HERPETIFORMIS. 187 abating in a measure only with the laceration or rupture of the lesions. The disease is rare, but is of more frequent occurrence than I formerly supposed. I have encountered fifteen cases during a period of as many years, drawn from hospital, dis- pensary, and private practice. All, with one exception, were adults, including both sexes in about equal proportion. The natural history is interesting. The process is in almost all instances chronic, and is characterised by more or less distinctly marked exacerbations or relapses, occurring at intervals of weeks or months. The disposition to appear in successive crops, sometimes slight, at other times severe, is peculiar. Relapses are the rule, the disease in most cases extending over- years, pursuing an obstinate, emphatically chronic course. All regions are liable to invasion, includ- ing both flexor and extensor surfaces, the face and scalp, elbows and knees, and palms and soles. Excoriations and pigmentation, diffuse and in localised areas, are in old cases always at hand in a marked degree. The pigmentation is usually of a mottled, dirty yellowish or brownish hue, and is persistent. I have seen it as pronounced as in chronic pediculosis corporis. The more important forms of the disease may now be considered. Dermatitis Herpetiformis (Erythematosa). The erythematous variety manifests itself in patches or as a diffuse efflorescence, as an erythema or superficial inflammation, usually of an urticarial or erythema-multi- forme-like type. The urticarial element may be marked, the skin showing a disposition to acute cedematous infiltra- tion in a diffuse form. Urticarial complication, rather than urticaria, is suggested by the condition of the skin ; in like manner, a resemblance to diffuse erythema multiforme may be noted. At times the patches, whether discrete or con- fluent, are circumscribed ; and later, by their coalition, show irregularly-shaped, marginate outlines, as in erythema multi- forme. The colour varies with the shape, being at first 188 DE. DUHEING'S PAPERS ON bright red, but soon becoming deep red or violaceous, mottled, and tinged with yellowish hues. The variegation is usually pronounced in the later stages of the process, at which period more or less diffuse pigmentation is also pre- sent. Together with the erythematous inflammation there may form maculo-papules, or circumscribed or diffuse flat infiltrations, variable as to size and shape ; also vesico- papules, the process now bearing a resemblance to the first stage pf herpes iris. It will thus be noted that the erup- tion, in its general aspect and course, is much like that of erythema multiforme. In severe cases the outbreak is preceded by and accompanied with malaise, chilliness, or slight febrile disturbance. The itching is generally violent, the disease differing in this respect from erythema multi- forme. Its course is variable. It may continue for days or weeks, or, as is usually the case, it may pass into the multiform variety, to be described later. It may be the first manifes- tation, or it may follow other varieties as a relapse. As a variety it is not as clearly defined as the vesicular^ bullous, or pustular, in some cases it appearing to be but the first manifestation of one of the first-mentioned forms. But it is important that its features be described, for the reason that it is liable to be met with as a clinical picture, and may readily be confounded with other diseases, notably urticaria, erythema multiforme, and eczema. I recall two cases where the diagnosis was at first difficult, and it was not until other manifestations appeared on the skin that the true nature of the process became evident. Dermatitis Heepetifoemis (Vesiculosa). The vesicular variety is that most frequently met with. It is characterised by variously sized, varying from a pin- head to a pea, flat or raised, irregularly shaped or stellate, glistening) pale yellowish or pearly, usually firm or tensely distended vesicles, as a rule unaccompanied by areolae. In their early stages they can be seen only with difficulty, and are liable to be overlooked in the examination. Some- DERMATITIS HERPETIFORMIS. 189 times they can only be detected or seen to advantage in an oblique light. This observation I have repeatedly noted, and it arises from the fact of the lesions being flat, translu- cent, and without areolae. In size they vary extremely, large and small being formed side by side, and in this respect they differ from the vesicles of eczema. Here and there papules, papulo-vesicles, vesico-pustules, and small blebs will sometimes be encountered. Concerning their distribution, the eruption as a whole is disseminate, the lesions existing scattered more or less profusely over a given region, as, for example, the neck or the back, but they are for the most part aggregated in the form "of small clusters or groups of two, three, or more ; or there may be patches here and there as large as a silver dollar, upon which a number will be seated. When in close proximity they incline to coalesce, as in herpes zoster, forming multilocular vesicles or small blebs. Where this occurs they are generally slightly raised, and are surrounded with a pale or distinctly reddish areola, which shows forth the irregular, angular, or stellate outline of the lesion. At this stage, moreover, the little cluster will generally present a " puckered " or " drawn-up " appearance, indicative of its herpetic nature. The eruption is usually profuse, sometimes to the extent of the upper extremities, trunk, and thighs being well covered. It may attack any region, the neck, chest, back, abdomen, upper extremities, and thighs, all being especially liable to invasion. The most striking symptom is the itching. Not infre- quently burning is also complained of. Itching, however, predominates, and is in all cases violent or even intense. Patients state that it is altogether disproportionately in excess of the amount of eruption. It is, moreover, a persistent itching, causing the sufferer to scratch constantly. It generally precedes the outbreak, and does not abate until the lesions have been ruptured. Old sufferers, familiar with the natural course of the process, have informed me that they can obtain no relief until the lesions have been ruptured. Prom my observation I should say that the itching was both more severe and more lasting than in vesicular eczema. The vesicles make their appearance slowly, so that several 190 DR. DUHRING's PAPERS ON days or a week may be required for their complete develop- ment. Notwithstanding that scratching is indulged in in the early stages of the disease, excoriations are not promi- nent, owing to the fact that the walls of the lesions are tough, and do not rupture, and that they incline to refill immediately on being evacuated. The diagnosis in some cases is attended with difficulty, on account of the resemblance to vesicular eczema. I recall the embarrassment experienced in the classification of the earlier cases encountered, and the provisional diagnoses of " vesicular eczema ?" made at the time. But the irregu- larity in the size and form of 'the vesicles ; their angular or stellate outline ; their firm, tense walls, with no disposition to rupture, and their herpetic character, will all serve to aid in the diagnosis. In some cases the constitutional dis- turbance and the magnitude of the eruption, as regards profusion, distribution, and multiformity, showing a more formidable disease than eczema, will also be striking. The itching and burning will usually be found to be more con- tinuous and intenser than in eczema. The obstinacy of the disease to the ordinary treatment of eczema, moreover, must also soon become apparent, the usual milder remedies so fre- quently of service in acute vesicular eczema being of little or no benefit in this disease. Finally, the tendency to repeated relapses, and the chronicity of the affection, must strike the observer as peculiar. This variety cannot be con- founded with herpes zoster, herpes iris, or pemphigus. Its relations to the " herpes gestationis " of some authors will not be considered in this paper, further than to state that in my opinion they are probably one and the same disease. On a future occasion I shall deal more at length with this point. Dermatitis Herpetiformis (Bullosa). In the bullous variety the lesions are more or less typical blebs, tense or flaccid, rounded or flat, usually the former, filled with a serous or cloudy fluid, seated upon a non- inflammatory or slightly inflamed base. In size they vary DERMATITIS HERPETIFORMIS. 191 from a pea to a cherry or walnut, and are for the most part irregular or angular in outline. They incline to group in clusters of two or three, the skin between them in this event being reddish and puckered. Sometimes in. imme- .diate proximity — almost contiguous — will exist one, two, or three, or a part of a circle of small, pin-head sized, flat, whitish pustules. Vesicles of all sizes, flat or raised, are also generally found near by, or disseminated over the affected surface. As in the other varieties, all regions may be attacked, especially the trunk, upper extremities, and thighs. In several cases I have seen the greater part of the general surface invaded most profusely, in which event the lesions are usually smaller than where comparatively few exist. They incline to appear in crops at irregular intervals, as in the other varieties. The lesions are generally ruptured in the course of a few days, and then crust over with a yellow- ish, greenish, or brownish crust. They are accompanied by burning and itching, which may be very severe. They bear resemblance to those of pemphigus vulgaris, with which of course they may be readily confounded, but they are more herpetic in character. They differ in that they incline to group, and have a more inflammatory herpetic aspect, the type of which picture is seen in herpes zoster. Moreover around and near the bleb will usually be found vesicles and pustules, the latter often in close proximity, the whole manifestation being quite different from that of pemphigus. Dermatitis Herpetiformis (Pustulosa). The pustular variety is generally less clearly defined than the vesicular, because the lesions are often intermingled with vesicles, vesico-pustules, and blebs. In typical cases the pustules are acuminate, rounded or flat, tense or flaccid, usually the former, and vary in size from a pin-point to a pea or silver quarter-dollar. Vesicles and blebs in some cases precede the pustules. The smallest lesions are gene- rally flat, or on a level with the surrounding skin, and, as stated, are frequently not larger than a pin-point or pin- head. Larger pustules, the size of a pea, are generally 192 DE. DUHEING's PAPEES ON rounded or acuminate, and are surrounded by a reddish inflammatory areola. Later .they incline to flatten, and to increase in size by spreading peripherally, and drying in the centre. Sometimes they are seated on a slightly raised base. When fully matured they generally present an " angry " ap- pearance, the skin immediately around them having a " puckered " look, from the fact that the pustule itself is irregular in outline, as sometimes is the case in herpes zoster. They incline to form in groups of two, three, or more, and, moreover, often appear in patches of two or more groups. Such an arrangement is generally met with on the trunk. The grouping is further peculiar in that a central pustule will often be immediately surrounded by a variable number of smaller pustules, sometimes in a circinate form, as in herpes iris. In other localities, however, no such peculiarity occurs, the lesions being discrete, and even disseminate. The pustules are usually opaque, and of a whitish colour ; some- times they are yellowish, though they are seldom so yellow as in pustular eczema. Not infrequently slight haemor- rhagic exudation occurs, as in the later stages of herpes zoster, giving them a reddish, bluish, or brownish hue. They are generally accompanied by sensations of heat, pricking, or itching ; in some cases these symptoms precede for several days the eruption. They pursue a slow course, from one to two weeks being usually necessary for their full development ; in other cases their maturation occurs more rapidly. In some cases, together with the pustules are found vesicles and blebs of various shapes and sizes, and these often form immediately by the side of, or in close proximity to, the pustules. Papules and papulo-vesicles may also be present. In a given area, say of a few square inches — as, for example, upon the abdomen — there may exist all of these lesions in various stages of evolution. This multiformity is striking, and presents a curious and peculiar mixture of lesions. The attacks last from two to four weeks, after which there generally follows a comparative respite of from one to six weeks. The disease may thus be DERMATITIS HERPETIFORMIS. 193 kept up indefinitely, the outbreaks being at one time slight, at another time severe. Sometimes it has preceded other varieties ; in other cases it has followed the bullous variety ; while in some instances that have been under observation for a long period it has at intervals of months alternated between the vesicular and bullous varieties. After what has been previously said, it need scarcely be stated that this variety is identical with the " impetigo herpetiformis " of Hebra, although in but few of the cases observed by me have the symptoms been so pronounced as in Hebra' s experience, if I may judge from the portraits in his Atlas of Skin Diseases. The account given by me relates to the disease as I have encountered it. Hebra's account has been already given, and need not be repeated here. The difference of experience concerns chiefly the severity of the process. Thus in none ,of my cases has it proved fatal, while it will be remembered four out of five of Hebra's cases died, and, according to Kaposi 1 (Hebra's successor), ten out of eleven cases observed by him have perished. Finally, I have observed it to occur about as often in men as in women, and also in the latter apart from pregnancy. Hebra, on the other hand, met with it only in women, and, moreover, only during the par- turient state. Concerning the constitutional symptoms, they may be stated to vary with the gravity of the attack. Usually, however, they are more marked than in the other varieties, rigors and alternate paroxysms of heat and cold being especially noticeable. It is the most serious phase of the disease. Dermatitis Heepetipoemis (Papulosa). The papular variety is in my experience rarer than any other form. I have met with only two cases, one in an adult, the other in a boy, and in both of these the eruption was scanty. It is characterised by the formation ,of small or large pea-sized, irregularly-shaped, usually firm, reddish 1 'Pathologie und Therapie der Hautkrankheiten,' 2te Auflage, Wien, 1883. 13 194 DE. DUHEING'S PAPERS ON or violaceous papular lesions, occurring for the most part in groups of two or three, scattered here and there over the affected surface. They are of variable size, large and small ones not infrequently existing side by side, and are as a rule ill-defined, being neither acuminate nor flat, but resemble the papular infiltrations sometimes met with in abortive herpes zoster. They are of an acute or subacute inflamma- tory type, and, as stated, bear resemblance to abortive herpetic lesions, and also to certain phases of chronic re- lapsing papular eczema. Their surfaces are generally excoriated from scratching, and may be covered with blood- crusts, or with slight, adherent, thin epidermic scales. The itching is severe, so much so that comparatively few lesions may so torment the patient as to interfere with the night's rest. Ill-defined papulo-vesicles are also met with here and there, as in the case sometimes of papular eczema. The lesions pursue a slow, chronic course, lasting from one to two or four weeks, when they gradually disappear, leaving more or less pigmentation. Relapses are the rule at longer or shorter intervals. As I have intimated, this variety bears a close resemblance to chronic papular eczema, and the earlier cases encountered by me were so diagnosed ; but the irregularity in the size and form of the lesions, the disposition to group, the usually slow evolution of the lesions, the tendency to appear in crops at irregular intervals, the chronicity of the process, and the extreme obstinacy to local and internal treatment are all peculiar. It is the mildest phase of the disease. Dermatitis Herpetiformis (Multiformis). This may be regarded in the light of clinical variety, one that is eminently useful from a practical standpoint. It is a variety of the disease in the same sense that eczema rubrum is a variety of eczema. It is important to consider it for the reason that it is a picture which may at any time show itself in the course of the disease. It is a phase not infrequently met with, and on account of the great mixture DERMATITIS HERPETIFORMIS. 195 of lesions, and the difficulties presented in diagnosis, is worthy of special description. The multiform variety con- sists of erythematous, sometimes slightly raised, urticarial patches of variable size and outline, often confluent, of a reddish or violaceous, yellowish, dusky, sometimes variegated colour, not unlike that of erythema multiforme. In addition there often exist more or less well-defined, irregularly-shaped or rounded maculo-papules and flat infiltrations, papules and vesico-papules, all in various stages of evolution. Small blebs and pustules, pin-point sized or larger, may also be present, though with the vesicular element predominating it is not usual to meet blebs or pustules of large size nor in numbers. As the disease is in an early or late stage of its existence will pigmentation and excoriations be slight or marked. Briefly, then, to recapitulate, there exists a mix- ture of lesions, with no single type predominating, calling to mind in its behaviour eczema, although it is far more capricious and protean. It must also be remembered that the process may at any period change its type, such an occurrence usually taking place with an exacerbation or a relapse. Thus the vesicular variety may exist for a vari- able period, to be followed in a few weeks or months by an attack of blebs, or it may be pustules, or by a mixture of the blebs and pustules. This mingling of several varieties is a marked and peculiar feature of the disease, giving a very striking dermatological picture, different from that seen in any other disease of the skin. In conclusion, permit me to summarise by saying that I have endeavoured to show — i. The existence of a distinct, well-defined, rare, serious, inflammatory disease of the skin, manifestly of an herpetic nature, characterised by systemic disturbance, a great variety of primary lesions, by severe itching and burning, and by a disposition to appear in repeated successive outbreaks. 2. That the disease is capable of exhibiting itself in many forms, all having a tendency to run into or to succeed one another irregularly in the natural course of the process. 3. The principal varieties are the erythematous, papular, vesicular, bullous, and pustular, which may occur singly or in various combinations. 196 DR. DUHRING's PAPERS ON 4. That it is a remarkably protean disease. 5. That the pustular variety is the same manifestation as the disease described by Hebra under the name " impetigo herpetiformis," this being the only form hitherto described. 6. That the several other and equally important forms are worthy of special remark. 7. That the term " dermatitis herpetiformis " is suffi- ciently comprehensive and appropriate to include all varieties of the process. 8. That it may occur in both sexes, and in women inde- pendent of pregnancy. 9. That it usually pursues a chronic, variable course, often lasting years, and is exceedingly rebellious to treatment. NOTES or a CASE OF DERMATITIS HERPETIFORMIS, EXTENDING OVEE ELEVEN YEAKS, Illustrating the Several Varieties of the Disease. 1 In the following case the pustular, vesicular, bullous, and papular manifestations of the disease 2 were all developed on one or on several occasions during the long period the patient was under my observation. The characteristic fea- 1 Reprinted from the ' Philadelphia Medical Times ' for July 12th, 1884. 2 For an aoconnt of dermatitis herpetiformis the reader is referred to my paper read before the American Medical Association, May 6th, 1884, abstracts of which may be found in ' New York Medical Journal,' p. 562, May 17th, 1884, and in ' Philadelphia Medical Times,' p. 603, May 17th, DEEMATITIS HERPETIFORMIS. 197 tures of the affection are clearly defined in the history, the notes of which, it may be remarked, were recorded at the time of each examination. James W — , set. 38, a native of Philadelphia, and a wood- carver by occupation, was admitted to the Philadelphia Dispensary for Skin Diseases, January 16th, 1873. Ac- cording to the notes in the record-book, he was suffering from an imperfectly defined inflammatory, multiform erup- tion, composed of erythematous spots and patches which had evidently been the seat of previous disease, papulo-vesicles, pustules, and excoriations. It occupied the general surface, with preference for the arms and forearms, sacral region, buttocks, and thighs. The lesions were not very numerous, and were disseminated, except over the sacral region, where a dozen or more formed a conspicuous patch. The disease appeared to be fading away, and, inasmuch as the patient gave a history of having recently had quite active treatment, internal as well as external, and that he had been treated for supposed " secondary syphilis," the diagnosis was for the time being withheld. According to a note, the eruption resembled that resulting from the internal use of the iodide or the bromide of potassium. He stated that he had been suffering from the disease for five years, and that while better, and even nearly well at times, it had never entirely left him ; it was the source of great annoyance to him, itched considerably, mani- fested itself in different forms from time to time, and was apt to appear in distinct crops from week to week or month to month. He was not aware that he had ever contracted syphilis, but several physicians had assured him that the present eruption was a manifestation of this malady. He was placed upon a simple tonic treatment until the diagnosis might be more definitely ascertained. January 25th. — New pustular lesions have appeared on the buttocks and on the thighs. These are highly inflam- matory, flat, and incline to crust in the centre and to spread on the circumference. Alkaline lotions and baths were ordered ; also a saline aperient. February 8th. — Considerable improvement, the disease 198 dr. dtjheing's papers on being in about the same state as when the patient first came under observation. 1 2th. — New lesions are appearing. 19th. — The disease has been manifesting itself chiefly on the arms and on the buttocks, new pustules making their appearance from day to day. 24th. — No new lesions ; condition decidedly better. March 19th. — There has been steady improvement since last note. The remedies used during the past two months have been syrup of the iodide of iron, bitartrate of potas- sium from time to time, and a carbolic acid lotion. May 12th. — ; The disease continued improving during the last two months until within the present week, when a crop of new pustular lesions began to appear, scattered here and there over the general surface, especially upon the arms, buttocks, and thighs. The patient enjoys average general health notwithstanding the eruption, which now is abundant, and is unusually active. It may be described in its present state as a pustular form of disease, the lesions beginning as pin-head and split-pea sized, flat pustules, with extensive bright red areolae. They increase rather slowly in size, and soon begin to crust over with a yellowish-brown crust, after which they continue to in- crease in size by new, small, flat, pin-head sized pustules forming on the periphery. This process goes on until the lesions assume the size of a dime or quarter-dollar, when it ceases, and a crust covering the whole remains. The crust is adherent from the beginning ; if detached, it shows a circumscribed, superficially excoriated surface, covered with a puriform fluid. Later, at the end of two or three weeks, the crust drops off, leaving a dark red infiltrated spot, but no scar. These inflammatory infiltrations are slow to disappear, weeks being necessary for the larger ones to become effaced. About the buttocks and sacral region and on the thighs the lesions show a disposition to occur in patches, and, moreover, to group, two or three not infrequently existing in such close proximity as ultimately to run together. Over the arms and elsewhere this tendency is not so notice- able j nor are the lesions here so well defined and large as on the back and thighs. DERMATITIS HERPETIFORMIS. 199 26th. — The outbreak was at its height when the last note; was recorded, since which date the eruption has been steadily declining. November 3rd. — The patient has absented himself for six months. He states that he continued to improve through the summer, and that only within the last two months has the disease again become annoying. He was almost free from eruption at one period during the summer. Lately th& disease has manifested itself in another form, the lesions being decidedly papular rather than pustular, and in distri- bution more scattered than formerly, and also much more itchy. Upon examination the eruption was seen to have changed its character completely, and to consist of dissemi- nated, here and there distinctly grouped, variously sized and shaped, imperfectly formed papules and papulo-vesicles , which closely resembled eczema. He was again placed upon a preparation of iron and a saline aperient, the bowels being habitually constipated. 1 8th. — The eruption has entirely disappeared, leaving the skin pigmented in dirty yellowish-brownish spots and patches, and in some places deprived of the normal pig- ment, dirty whitish patches existing. March 3rd, 1874. — Four months have elapsed since the last note. The disease has during this period been " better and worse." There have been several relapses, which have continued a fortnight or longer and have disappeared as before. The patient has taken arsenic in the form of Liq. Potass. Arsenit. in from two- to four-minim doses, but without benefit. Of late he has been using strong drink in excess, which, he states, is pretty sure to cause an exacerba- tion of the eruption. A new crop of lesions is to-day making its appearance. The character of the disease has again changed, the lesions now being vesicular and pustular, especially the latter, similar to the form of eruption that existed a year ago. The single lesions resemble ecthyma, while those in groups or patches bear a close resemblance to pustular eczema. 13th. — New lesions are here and there manifesting them- selves, the neck, lower portion of the back, buttocks, thighs, and arms being the regions chiefly invaded. Iron and 200 dr. duhring's papers on arsenic are still being taken, and various antipruritic lotions and ointments have been employed, with, however, but little benefit. April 3rd. — The pustular character of the eruption has ceased, and variously sized herpetic vesicles and small blebs have lately developed. Many of them are as large as split peas. They appear quite suddenly and are very itchy. The disease has lately attacked the folds of the axilla and the pubes, which regions have become extensively crusted. 24th. — The surface has again cleared off, only a trace of the former eruption remaining in the form of primary lesions ; but scratch-marks and pigmentation are everywhere present, the whole integument having a dirty, muddy, mottled look. Has been taking arsenic steadily ; general health has remained good. April 30th, 1877. — Three years have elapsed since last note, and since the patient has been seen. The disease still exists, with the same history as formerly, the lesions being variable, papules, pustules, and vesicles occurring from time to time. During the past six weeks there have been several slight relapses, and again a change in the character of the lesions, indistinctly defined, flat, variously sized and shaped papules appearing together, with here and there ill- defined abortive pustules and papulo-pustules. These lesions now exist. The patient considers himself, upon the whole, considerably improved. He has been taking the arsenic from time to time, in varying quantity, from one to five minims thrice daily. January 15th, 1879. — A year and a half has passed since the patient was last examined. He states that he has but little change to report. He has not been free of the erup- tion, and has had two very severe attacks and many slight ones. The severer attacks have continued three or four weeks, while the lighter ones come and go from week to week. He has had the eruption so constantly of late that no particular note has been made as to the occurrence of distinct outbreaks. The lesions have been coming and going without intermission. Within the year the lesions have been for the most part vesicular and bullous ; or, as he expresses it, " they have been blisters of various sizes, con- DERMATITIS HERPETIFORMIS. 201 taming a clear fluid." They have had a disposition to cluster, but there have also been many isolated single lesions. They have been very itchy, so much so that he lost no time in scratching and rupturing them. He does not know whether they ever ruptured spontaneously, for he has in- variably opened them as soon as they appeared. Lately all regions of the surface, except the palms and soles, have been attacked, the scalp even being the seat of numerous lesions, but preference is still shown for the regions before invaded. March 2nd, 1879. — During the past two months he has been better than usual, the most annoyance being due to considerable eruption, vesico-pustular in character, about the scrotum. He has been drinking of late, with the hope, he states, of " bringing out the disease," but thus far with- out success. He has been better this winter than during any period within the past ten years. He is positive that the various forms of treatment employed have had little or no influence in controlling the disease. He is about as free of the eruption in summer as in winter, the seasons exerting no special influence upon his condition. His general health remains fair, although, owing to his irregular mode of life, he is dyspeptic, and, as a rule, is constipated. A CASE OF DERMATITIS HERPETIFORMIS (BULLOSA): On February 3rd, 1879, the patient, the notes of whose case are about to be given, was sent to me by Dr. H. Gr. M. Kollock, of Newark, Del., who in his letter stated that the disease was regarded as pemphigus. The man had been under treatment for some months, during which period he had taken quinine, iron, and arsenic, and had used varied remedies locally, all without relief. Dr. Kollock's letter 1 Keprinted from the 'New York Medical Journal ' for July 19th, 1884. 202 de. duhrtng's papers on states : " He has not had a full crop of bullae for about two weeks, prior to which they would appear in great numbers every two or three days. He has never been entirely free from them." The patient, Newton B. E — by name, was admitted to the University Hospital, at which date the following record was made : — He is sixty years of age, tall and slender, some- what emaciated, debilitated, and nervous ; he is a native of Delaware, a shoemaker by occupation, and is married. There is no special family history. He never suffered any disease of the skin, except occasional attacks of inflammation from poison ivy, until eight months ago, when the present disease appeared. He was at the time in average health, and could attribute the outbreak to no cause. It began about the ankles and feet with swelling, heat, and violent itching ; the following day eruption manifested itself on the arms and around the neck, and later on the trunk. Several household remedies were applied, but the disease spread until at the end of a week he was well covered with a mixed eruption consisting of papules, vesicles, and blebs, the latter pre- dominating, and some being as large as a walnut. Upon bursting or being ruptured, the walls adhered to the skin and formed crusts. Successive crops of blebs continued to appear until a fortnight ago — in all, during a period of eight months. He has lost flesh — as much, he thinks, as fifty pounds. A new outbreak of eruption is now manifesting itself. Present condition. — The disease of the skin is almost uni- versal, involving the greater part of the general surface from the scalp to the soles of the feet. It is made up of variously sized and shaped vesicles, blebs, and pustules, in all stages of evolution. The vesicles predominate, and vary in size from a pin-head to a pea, the majority being as large as small peas. They are notable for their irregularity of shape, being for the, most part very irregular, and in many instances angular in out- line. Some are raised to the height of a line, others are flat. They are distended, and have a glistening, glazed look, and, as a rule, are not surrounded by any areola, rising abruptly from the surrounding healthy skin. They are DERMATITIS HERPETIFORMIS. 203 yellowish and contain serous contents, as in the case of the early stage of herpes zoster. The blebs, some raised, others inclining to flatten, are met with here and there on the neck, arms, thorax, abdomen, thighs, legs, feet, and hands. Some are as large as a pigeon's egg. They are manifestly advanced stages of the vesicles, or at least often grow from these lesions. They are as a rule tensely distended, and have clear contents ; some show cloudy contents and are flaccid. They do not rupture spontaneously. Their contents are alkaline. The pustules are present in like manner here and there, distributed over the same regions. They are distinctly pustular, having whitish contents and more or less inflam- matory areolae ; are small, raised, irregular in outline, though less so than in the case of the vesicles, and have a "puckered" or "drawn-up" appearance. Excoriations and blood-crusts are conspicuous, and are plainly the result of prolonged scratching. Yellowish, brownish, "dirty-looking" patches of pigmentation, giving the skin the appearance of chronic pediculosis corporis, are also prominent symptoms. The itching and burning are most distressing . They inter- fere with sleep at night. New lesions in great numbers are beginning to form. Some of the earliest are flat papulo- vesicles. They can be felt with the finger as small circum- scribed infiltrations even before they become visible. In some localities there is a marked tendency for all the lesions to group, two, three, or four being crowded together into a cluster ; in other places they are disseminated. Here and there blebs are surrounded concentrically by a variable number of small, flat, whitish pustules of the size of pin- heads, making a striking combination. February 7th. — During the last three days lesions of all kinds have appeared, accompanied by intense itching and burning. Some of the blebs have attained the size of walnuts. On the forehead an abundant crop of variously sized and shaped herpetic vesicles are present. 28th. — A fortnight ago the attack was at its height, vesicles, blebs, and pustules, as well as intermediate forms, existing in profusion. Almost the whole integument was invaded, scarcely a square inch being exempt. The blebs 204 dr. duheing's papises on frequently reached the size of a hen's egg; the pustules flattened, seldom exceeding the size of a dime or a quarter- dollar. They spread peripherally, inclining to dry and crust in the centre. The course of both these lesions was rapid, disappearing in four or eight days, followed by crusting and pigmentation. The general condition remained fair, there being no marked febrile disturbance, although the appetite was im- paired, and the patient was weak, nervous, and much dis- tressed in mind and body. With the cessation of new lesions the itching and burning declined, but did not leave entirely. The treatment consisted of a generous diet, with saline laxatives and small doses of arsenic and strychnia, together with antipruritic lotions of carbolic acid and tar. The man remained in the hospital several weeks longer, during which time he improved with remarkable rapidity. I cannot, however, attribute the recovery altogether to the remedies used, knowing well as we do the singularly arbitrary course the disease usually pursues. About three years afterward (December 20th, 1882) I re- ceived a letter from Dr. Kollock (under whose care the patient had since been), stating that he had not seen the man for a year, but that, " according to last accounts, he had improved markedly in general health as well as locally under a tonic treatment. The eruption has appeared at longer intervals, and is confined to smaller areas. He seemed to derive great relief from the application of a lotion containing corrosive sublimate and alcohol." Since this date I have heard nothing. The case represents more particularly the bullous variety of the disease, although its multiformity, as in almost all instances, was repeatedly shown. As I have so recently described this remarkable disease in a paper 1 read before the American Medical Association, comment here is scarcely necessary. It may be stated, however, that the case illus- trates the vesicular and bullous lesions as they usually occur in the course of the disease, the latter predominating. The 1 Abstracts may be found in the ' N. Y. Med. Journ.,' May 17th, 1884, p. 562, and in the ' Philad. Med. Times,' May 17th, 1884, p. 603. DERMATITIS HERPETIFORMIS. 205 resemblance to pemphigus is obvious, but I think it will be seen that the process is different, and that it cannot be viewed as a variety of this disease. CASE OF DERMATITIS HERPETIFORMIS {MULTIFORMIS), AGGRAVATED BY PREGNANCY AND IRREGULAR MENSTRUATION. 1 Mes. M — , set. 28, a resident of St. Paul, Minn., con- sulted me February 3rd, 1883, for a chronic inflammatory disease of the skin, involving the entire surface. She was of spare frame, with brown hair, and of a nervous temperament. She gave the following clear and interesting history of her case : — Her ill-health began three and a half years ago, up to which date she had been in good general health ; had menstruated regularly and normally, and had weighed one hundred and thirty-five pounds. She had borne a healthy child three years before, without difficulty. • The first manifestations were upon the tongue and in the throat, in the form of whitish spots, similar to so-called " canker-sores," which continued for six months, desqua- mating from time to time, the mouth being so sore and sensi- tive as to render eating painful. She was in the third month of her second pregnancy when the first sign of cutaneous disease appeared on the flexor surfaces of the right arm and thigh, and on the abdomen, in the form of small annular clusters of vesicles, occupying the space of a five-cent silver piece. The lesions were itchy from the beginning. They spread slowly, new " little water-blisters " coming out from day to day. This process progressed for six weeks, when the body was well covered with eruption, and she was com- 1 Reprinted from the ' Medical News,' July 19th, 1884. 206 DE. DUflEING's PAPERS ON pelled to remain in bed. Three weeks after the attack began blebs appeared, accompanied by comparatively slight itching, They ruptured easily and left excoriated surfaces. As gestation proceeded the disease became steadily worse, being at its height during the fourth and fifth months, at which date vesicles and blebs of all sizes were very numerous, and the itching intense, accompanied by extensive excoriations and scratch-marks, with more or less oozing and crusting. No treatment used seemed to have any effect in relieving the symptoms. At this date very curious lesions were noticed on the wrists and on the palms and soles. They were elongate (about an inch in length), rounded (about an eighth of an inch in thickness), firm, whitish, striated elevations, situated transversely on the wrists, the same condition existing on the palms and soles. When opened a non-offensive, cheesy mass " popped out," to use the words of the patient. The contents were not expressed, but were forced out naturally. The lesions were opened every day for several weeks, when they ceased appearing. At the sixth month of pregnancy the skin cleared off, the lesions disappearing except a large bedsore, which did not heal until a month after delivery. The skin remained comparatively clear about one week, when small pin-head sized vesicles, soon followed by large hazel-nut sized blebs, again appeared. This crop also manifested itself on the legs and feet, regions hitherto exempt. The blebs were all large, very abundant, crowded one another, and were very itchy. Some of the lesions became pustular. Three or four weeks before delivery the whole integument became oedema- tous, swelled, or " puffed up," as she expressed it. This condition gradually subsided a week or ten days after the birth of the child, which was born healthy at full term, but lived only four days. After delivery, and for three weeks following, the vesicles and blebs became fewer, the skin becoming again entirely clear of eruption, and she regarded herself as cured. She remained free, however, only a few days, when small pustules, pin-point in size, appeared in abundance ; these disappeared and were followed by a crop of mixed lesions — of pustules DERMATITIS HERPETIFORMIS. 207 and blebs. This condition continued better and worse during the winter, the disease towards summer locating itself chiefly about the axillse and groins, characterised now by an offensive, excoriated, at times weeping, crusted surface, with itching. Through the summer the skin of the palms and soles thickened, beneath which pus formed, undermining it. This continued for three or four months. In August, 1 88 1, she indulged in a bath, just before the menstrual epoch, after which the face became blotchy, bluish, and swollen, giving her " a dissipated look." Vapour-baths taken repeatedly for one month completely exhausted her. September ist the menses failed to appear, and October ist there was a slight discharge, at which date she again broke out with Variously sized vesicles and blebs, the latter for the most part as large as a hazel-nut, many of them having puriform contents. There was now much excoriation and crusting, the bed-linen everywhere adhering to the raw skin. Numerous small, pin-point sized vesicles, closely crowding one another, again came out over the whole surface. They were so abundant that a pin-point could scarcely be put down between them. She was " literally covered with them," and this condition, in the form of crops, lasted all winter. The skin disease later again changed its character, large blebs and pustules appearing, especially upon the face, which was much swollen. The menstrual flow remained absent five months (from October, 1881, to February, 1882). Arsenic in large doses, and later electricity were used, and it was thought that she was benefited by the latter. Improvement continued slowly but steadily up to July, 1882, when suddenly, and without apparent cause, violent inflammation of the hands and feet, with large pustules on the palms and soles and on the face, manifested itself. These continued to appear and to dis- appear in crops through the summer and autumn up to the present date ; the lesions being as a rule shot-sized, whitish pustules and vesicles, closely crowded together over almost the entire cutaneous surface. Her general condition has been variable. On many occasions she has felt ill, weak, very nervous, depressed, with chilly or heated sensations or rigors. On one occasion the tongue swelled and became coated with 208 DR. DUHRING's PAPERS ON a puriforin exudation with profuse salivation. Menstruation when present is usually normal. Her weight now is about ninety-five pounds (forty pounds below her former average). The appetite has always remained good. She has been under the care of a skilful specialist in skin diseases for six months, but has failed to receive any benefit. The present condition (February 3rd, 1 883) is as follows : — The whole general surface is the seat of a subacute and chronic inflammatory erythematous (somewhat urticarial), papular, papulo-vesicular, vesicular, and pustular eruption, the lesions being very markedly multiform. They are pin-point, pin-head, and pea sized ; are thickly studded ; are firm and have a shotty feel, as in the early stage of variola. The skin is everywhere much thickened, and is even tough and leathery, and is markedly pigmented, being of a mottled, reddish, dirty yellowish-brownish hue. The eruption is intensely itchy. The face and scalp are least affected, but, as stated, the rest of the general surface, in- cluding the palms and soles, is well covered with primary and secondary lesions. The patient was ordered for local use an ointment of pre- cipitated sulphur, two drachms to the ounce, to be applied to the right half of the body ; to the left half, an alcoholic solution of coal-tar, diluted one by four or eight parts of water. Internally, a mixture containing sulphate of mag- nesium, three ounces ; bitartrate of potassium, six drachms ; precipitated sulphur, one drachm ; glycerine, four fluid drachms ; peppermint water, four fluid ounces. Dose, a half fluid ounce with a gobletful of water before break- fast. Also a preparation of iron, bark, and arsenic (one- minim dose), to be taken thrice daily. At night a mixture of chloral and bromide of potassium. Both local remedies acted happily, and for five days no preference for one or the other was expressed by the patient. A few days later more improvement was observed upon the side where the tarry solution had been used, and this was then applied, fulk strength, to the whole surface. Both remedies also had immediate and positive effect in relieving the distressing itching. The skin began to improve and the eruption to decrease within several days after the treatment was insti- DERMATITIS HERPETIFORMIS. 209 tuted, and at the end of a fortnight very decided benefit was noticeable in the condition of both the general health and the skin. She was well enough a month later to return home, since which time I have heard nothing from her. The history of the case, extending over three years, shows well the protean character and the multiformity of the disease. It shows the simultaneous occurrence at several periods in the course of the process of erythematous patches, maculo -papules, papular infiltrations', vesico-papules, vesicles, blebs, and pustules. At other periods vesicles and blebs prevailed ; sometimes vesicles and pustules ; and occasion- ally vesicles, blebs, and pustules. The lesions were always accompanied by severe itching and more or less burning. Constitutional symptoms at times were marked, consisting of rigors, sensations of alternate heat and cold, and febrile and nervous symptoms. The latter were especially pro- minent. The disease of the skin was unquestionably due partly to the depraved condition of general health preceding preg- nancy, but more particularly to this latter state itself. It will be remembered that the cutaneous manifestations ap- peared in the third month of gestation. It was without doubt subsequently kept up by the disordered condition of the menstrual function and the accompanying disturbed nervous system. At present I shall not consider the disease further than to say that the case may be regarded as representing the mul- tiform variety of dermatitis herpetiformis. Noted at one period, it would have illustrated the vesicular or the papular variety ; at another time, the bullous variety ; again, the erythematous ; while more often, however, the condition was one of multiformity of lesion, including at times the abun- dant development of peculiar pustules. The latter phase is that which was first described by Hebra as " impetigo her- petiformis." The vesicular variety has figured conspicuously of late years under the head of "herpes gestationis." In a paper recently read before the American Medical Associa- tion I have described dermatitis herpetiformis at length, giving its characteristic features, together with its more pro- minent varieties or phases. I think both the impetigo 14 210 t DR. duhring's papers on herpetiformis of Hebra, and the herpes gestationis of authors, should he placed under dermatitis herpetiformis, both being mere varieties of one pathological process. The case just considered shows the disease in a severe form, characterised by marked constitutional symptoms ; profuse eruption, multiform in character, and appearing in crops ; extensive secondary changes in the skin ; and itching and burning of the most distressing kind. The patient suffered greatly, the disease for a long period being most rebellious to treatment. Concerning the diagnosis, I may add that as the eruption was noted as one or another set of lesions was out, the disease might easily have been con- founded with eczema, herpes, or pemphigus ; but keeping the history in mind, and observing the course of the process for some time, the individuality of the disease always asserted itself. It is a distinct and clearly defined disease, which, when once recognised, cannot be confounded with any of the well-known skin diseases. CASE OF DERMATITIS HERPETIFORMIS, • Illustrating in particular the Pustular Variety (Impetigo Herpetiformis of Hebra). 1 The following case of this rare disease was brought to my notice by Dr. J. H. Stubbs, of London Grove, Pa., September 28th, 1878. The patient was suffering grievously, and was admitted to the hospital of the University of Pennsylvania. The notes were taken at the date of her admission. Annie McC — , American by birth, a brunette, aet. 27, single, a domestic, living in London Grove, Chester Co., Pa. There is no family history bearing on the case. She is strong and 1 Eeprinted from the ' Journal of Cutaneous and Venereal Diseases,' vol. ii, No. 8, August, 1884 DERMATITIS HERPETIFORMIS. 211 robust, and has always enjoyed good general health. The disease of the skin from which she is now suffering first made its appearance two years ago, previous to which time she had never experienced any cutaneous disease. It began suddenly on the flexor surfaces of the forearms in the form of a violent attack of itching unaccompanied by eruption. The following day " small water-blisters/' the size of pin- heads, appeared in clusters on either elbow. They were very itchy, and were soon ruptured by scratching. In the course of a few days they made their appearance upon the hips, thighs, and knees, while new ones continued to appear about the elbows. Within three or four weeks the other regions of the body, especially the neck, shoulders, back, and buttocks, were invaded. The scalp, ears, chest, mammae, hands, and feet remained free. The lesions she describes as having been small, variously sized vesicles, or " small water- blisters, containing a clear watery fluid.". They varied in size from a pin-head to a split pea, the majority being the size of pin-heads. They were irregular in outline, some being rounded, others quite angular, and were considerably raised above the level of the surrounding skin. They mani- fested no disposition to rupture spontaneously, but were in every instance scratched open, for they itched intensely. As stated, they were in clusters or groups, from three or four to a dozen or more lesions occurring together upon an area the size of a silver dollar. The grouping was irregular, the lesions showing no disposition to form into circles or other peculiar configuration ; four or five would frequently be found clustered together. The eruption continued in this form for a year, manifest- ing itself from time to time in distinct outbreaks, or crops of lesions, which would appear gradually or suddenly at variable intervals. At times the disease would disappear, when in the course of a week or two a new outbreak would occur, lasting days or weeks, to be again followed by another slight or severe attack, and thus the skin remained in an almost constant state of eruption. At no time was it entirely free of disease for longer than a fortnight. About a year ago an outbreak manifested itself in which the lesions assumed a distinctly pustular character; the attack 212 dr. duheing's papers on was of short duration, lasting only a week or ten days, and the next outbreak was vesicular and hullous. Within the past year the lesions have not been so numerous, but they have been larger, and the distress accompanying them greater. Not until within the present month has the disease again assumed the pustular phase. In place of the vesicular and bullous lesions which have existed almost constantly for nearly two years, distinct pustules have appeared, which will be presently considered. The seasons have in no way influenced the disease, the eruption being quite as annoying in summer as in winter. The itching has been constant and very distressing, and at times has been almost unbearable. She states that it is impossible to describe the intensity and violence of this sym- ptom ; that were she debarred from scratching it would be altogether unendurable, for until the vesicular and bullous lesions are ruptured she cannot refrain from scratching ; after they are broken down a certain amount of relief is ex- perienced, which lasts until a fresh outbreak threatens. The recent pustules, she states, are much less itchy than the usual vesicular form of eruption. Present condition. — .The patient is suffering with a general copious eruption, occupying the greater portion of the trunk and extremities. It manifested itself, it will be remembered, about three weeks ago, and was at its height four or five days since. It consists of numerous, variously sized, rounded or irregularly shaped pustules in all stages of evolution. They are typical pustules, the smallest of them exhibiting a distinctly pustular state. They vary in size from a pin-head to a large pea, the greater number being of the size of small peas ; when two or more have coalesced, however, a small or large finger-nail sized lesion exists. In shape, when small, they incline to be acuminated, but as they increase in size they become decidedly flat, with an irregularly rounded or angular outline. They incline to crust in the centre, and to spread in a creeping manner on the periphery, a ring of small flat pustules, isolated or confluent, being frequently present ; and where two or more are in close proximity thus almost invariably run together, forming flat broad lesions as large as a quarter- dollar, and sometimes even larger, the DERMATITIS HERPETIFORMIS. 218 crusting being more or less complete. A bright or deep red areola of considerable size surrounds all of the lesions. In colour the pustules are whitish and opaque, and contain a thin, puriform, pale yellowish or whitish fluid. The walls of the young lesions are distended, but those of the older ones are more or less flaccid, and in many instances are rup- tured, the fluid oozing forth, and drying into flat, uneven crusts of a greenish or brownish colour. Here and there are patches of disease, made up not only of confluent lesions, but of two or more distinct groups of lesions. These areas of disease, several inches in diameter, are striking upon the arms and upon the thighs. The distribution of the lesions is, for the most part, in the form of more or less distinct groups, but there are also disseminated lesions. The groups are irregularly formed, and are, as a rule, composed of from two to four pustules. Clusters of two and three lesions situated in close proximity, within an area of an inch in diameter, are not uncommon, while in some places as many as a half-dozen or more of various sizes may be found. On the anterior aspect of the middle of the thigh is a conspicuous group, composed of a central, unbroken, tensely distended, somewhat acuminated, pea-sized, irregularly shaped pustule, with a vivid, deep red, " puckered " areola, around which are three similar but smaller lesions, the whole occupying an area the size of a quarter-dollar. The grouping, however, viewing it as a feature of the disease, is much less marked than in herpes zoster. In addition to the pustules there are numerous ex- coriations, blood-crusts, scratch-marks, deeply stained spots, with or without old crusts, and general pigmentation of a dirty yellowish-brownish hue. The disease is the impetigo herpetiformis of Hebra. October 12th. — The patient stated, upon her admission to the hospital, that the disease had, she thought, passed the height of the attack, and would soon begin to subside ; and so the events have proved, but there have been, notwith- standing, sufficient typical new lesions for purposes of study. They have appeared as distinct pustules, usually the size of pin-heads, preceded by and accompanied with violent itching. Their areolas at first are insignificant, but in the 214 de. dtjheing's papees on course of from twelve to forty- eight hours both areolae and pustules assume, considerable size, the latter flattening out and crusting in the centre, with a somewhat depressed, greenish-yellow, uneven crust. As the crust grows, new, small, flat, frequently indistinctly defined, whitish pustules, pin-head in size, appear in the form of an irregular broken ring just beyond the line of the crust. In the case of large lesions this process is observed to repeat itself several times, or, indeed, until the pustule ceases growing. This concentric arrangement of the lesions, while not conspicuous — not as much so, for example, as in herpes iris — is readily noticeable, and is more marked in some lesions than in others. The itching has been exceedingly violent, and has been only partially controlled by antipruritic lotions. The patient has scratched incessantly by day and night, without which, she adds, the disease could not be tolerated. November ist. — At the present date the attack has almost subsided, and the patient feels that in all probability she will be comparatively well for a brief period until the next outbreak, which she confidently looks for, and which, accord- ing to her experience, may announce itself within a week, or perhaps not for a month. The treatment has been directed with the view of better- ing her general condition, although, as has been stated, no marked impairment of general health seems to exist. Saline laxatives, bromide of potassium, and chloral were ordered ; locally, lotions of carbolic acid and tar in various combina- tions were relied upon. While a certain amount of relief was obtained from the lotions, the itching still persisted, and recurred from time to time with all its former violence. No benefit worthy of mention was obtained from the internal remedies. January 22nd, 1879. — The patient left the hospital shortly after the last note, and for the past three months has been taking a course of arsenic. Dr. Stubbs writes that the character of the eruption has changed since I last saw her, having been lately papular and vesico-papular, with violent itching. A fortnight ago, while undressing one evening, she was seized with severe itching, and in the course of a alf-hour was well covered with an eruption similar to that DERMATITIS HERPETIFORMIS. 215 which she now shows. It occupies the entire general sur- face, and consists of flat, irregularly shaped and sized, in- distinctly defined herpetic p apules and papulo-vesicles, seated upon considerably infiltrated reddened skin, which is every- where so excoriated that it is difficult to find lesions that have not been scratched. Excoriations and blood-crusts are conspicuous. Here and there upon the trunk and extre- mities, especially upon the back, arms, buttocks, and thighs, there are distinct patches of pin-head sized, mostly flat vesicles. They are small and are ill defined, so much so that at a distance they would scarcely be detected. Some of the patches contain as many as a dozen or more, other groups not more than three or four. Smaller and disseminated lesions of the same kind exist on the forehead and neck. There are no pustules ; none have formed since last October. She states that the eruption comes out and disappears every few days, the itching being most severe in the interim. She- is kept awake the greater part of the night, and is exhausted from the long-continued itching. May 1 6th. — She recovered from the attack in January, in February, and remained comparatively well about ten days, when a new outbreak was announced, which appeared very gradually in the same form as before, namely, as small, flat, grouped, abortive papules and vesico -papules. She has suf- fered two like attacks since, from the last of which she is just recovering. Under date of August 18th, 1879, Dr. Stubbs writes that the patient is again suffering greatly from an outbreak, and that no relief is afforded by any of the remedies used. He further adds, " I do not know what to call the disease ; sometimes it is pustular, at other times it is vesicular or papular, while sometimes wheals and boil-like lesions form. It is now vesicular." Two months later (October 16th, 1879) the doctor writes, " Her condition now is the same as when I first sent her to you one year ago ; the lesions are pustular. We have not had this condition from that time until now. On the 5th of this month three pustules came on her knees ; others rapidly followed on other parts. She can get scarcely any sleep. She has had no appetite for two or three weeks." I subsequently saw the patient again during an 216 de. duheing's papees on attack, her condition being about the same as the last note. Early in 1883 (January 17th) I received a communication from Dr. Stubbs stating that the patient was still afflicted, although she now suffered less severely than formerly. " She has since been married, and has had one child. During pregnancy the disease of the shin gave her no trouble, and most of that period she was quite clear. 1 Last summer the mucous mem- brane of the mouth, throat, and eyes became inflamed, dry, and hot, and finally an eruption, which was the same as that on the skin, appeared. The labia and vagina have never been affected. She has not been under treatment of late for the cutaneous disease. The eruption, as before, is still confined chiefly to the back and flexor surfaces of the ex- tremities." I would add that no treatment used in this case seemed to exert any beneficial effect, the internal remedies prescribed including arsenic in small and large doses, quinia, iron, sul- phur, saline laxatives, and alkalies. Externally, weak and strong ointments and lotions of carbolic acid, tar, and mercurials were all tried on different occasions, affording only temporary relief. The case illustrates several varieties of the disease, but more particularly the pustular (the "impetigo herpetiformis" of Hebra), which condition ex- isted when she first came under my observation. For an account of dermatitis herpetiformis I must refer to abstracts 3 of my communication recently presented to the American Medical Association. 1 The italics are mine. 3 ' Philad. Med. Times,' May 17th, 1884, p. 603, and 'New York Med. Journ.,' May 17th, 1884, p. 562. DERMATITIS HERPETIFORMIS. 217 DERMATITIS HERPETIFORMIS : ITS RELATION TO SO-CALLED IMPETIGO HERPETIFORMIS. 1 In a recent communication made before the American Medical Association I described a remarkable disease of the skin under the name dermatitis herpetiformis. The observa- tions there recorded are the result of many years' study upon this subject, several of the cases from which my data were derived having been under surveillance for a number of years ; and it is this fact, in my opinion, which makes the notes especially valuable. Had the notes of any one of these cases been confined to the condition as shown by a single attack, we certainly should have had a very different idea of the process as a whole from that which is now held. In the study of diseases of the skin the natural course of the process must not be lost sight of. We cannot make the diagnosis in all cases from the presence of the lesion alone ; we must note further its evolution and general characteris- tics. This remark is especially applicable to multiform or protean diseases — such, for example, as the affection under consideration. Permit me first to state briefly what dermatitis herpeti- formis stands for, according to my definition. It is a well- defined disease, characterised by a variety of symptoms, which, although they appear dissimilar, and perhaps in no way related at first sight, will sooner or later be found to be but different expressions of one process. It is one of the s • ' Read before the American Dermatologieal Association, at its eighth annual meeting, August 27th, 1884. Reprinted from the 'American Journal of the Medical Sciences,' October, 1884. 218 de. duhring's papers on rarer cutaneous manifestations, only one variety of which has been heretofore carefully described, namely, the pus- tular, by Hebra, under the name of impetigo herpetiformis. The disease in severe cases is ushered in with more or less constitutional and febrile disturbance, characterised by malaise, shiveriugs, alternate hot and cold sensations, or fever. Itching or burning is early announced, followed in the course of from twelve to forty-eight hours by more or less eruption, consisting of erythematous, maculo-papular, papular, tubercular, vesico-papular, vesicular, vesico-bullous, bullous, or pustular lesions — as a rule all having peculiarities which distinguish them from the manifestations characteris- ing other well-known diseases. The erythematous lesions are usually in the form of patches of an erythema multiforme-like or urticarial kind, varying in size from a small coin to the palm of the hand, and of an irregularly rounded shape, tending, when in proximity, to coalesce. Some are ill-defined ; others have a sharp, somewhat marginate outline. They are usually more or less raised, somewhat less in the cases I have met with than in either erythema multiforme or urticaria. They re- semble especially the lesions of the former of these diseases. They are not so fugitive as in urticaria. I may even say that they bear more resemblance to ill-defined patches of erythema multiforme than to any other disease. These remarks may be taken to apply in part also to the maculo- papular lesions, but the papules and tubercles are different, being imperfectly defined inflammatory elevations, variable in size, shape, and consistence. The vesico-papules are similar to those encountered in erythema multiforme or in the early stages of herpes iris, and where numerous and close together, occurring upon thickened pigmented skin, may re- semble the first stages of confluent variola. The vesicular lesions vary in size from a pin-head to a pea ; are flat or slightly raised, broad, angular or irregular in outline ; of a pale yellow, straw-coloured hue, tensely, distended ; glistening, and without areolae unless closely grouped. The blebs vary in size from a pea to a pigeon's egg or even a hen's egg, and possess most of the features enumerated in speaking of the vesicles. They are, however, DERMATITIS HERPETIFORMIS. 21& raised, as in the case of most other blebs, as of pemphigus, and may have opalescent, cloudy, hsemorrhagic, or even pus- tular contents, although the pustules to be presently de- scribed do not pass through stages of evolution from the bleb, but begin usually as clearly defined small pustules. The pustules are peculiar. They begin as small, flat, pin-bead sized, whitish lesions, which grow, as a rule, to the size of a small pea, when they are surrounded by a deep red, " angry-looking," more or less raised areola. Their course up to this point occupies from two to six days. Sometimes two or three small pustules appear as a little cluster ; as they grow they run together, forming a large pustule. About the time the lesion is at fts height, one, two, four, or more new, small, flat pustular points or distinct pustules begin to appear in the form of a ring, or as a segment of a circle, immediately around the original lesion, which by this time is somewhat crusted. As these increase in size they are absorbed into the first pustules, the whole being covered with a yellowish, greenish, or brownish, flat, adherent crust. New small pustules may still continue to form around this lesion as before, or the process may be arrested. The number of pustules varies ; there may be half a dozen scattered about, or hundreds, some the size of a pin-head or of a pea, others as large as a quarter-dollar. When they are in close proximity and have run together, large patches may form. I may now direct attention to a peculiarity of the several lesions of the disease, and this is the tendency for two or more kinds to exist simultaneously — as, for example, vesicles, vesico-blebs, and blebs ; or it may be vesicles, blebs, and pustules — both rare combinations in the list of cutaneous diseases. The order of manifestation is variable. There is no definite order in the evolution of the lesions during an attack, nor even in relapses or in recurrences of the disease. This irregularity in the evolution of the process is peculiar, and must be regarded as one of the marked features of the disease. It has been present in almost all of the cases that have been under my observation. The longer the patient has been under observation the more frequently has this feature asserted itself. An attack beginning as an erythema 220 J)R. duhjjing's papees on may pass rapidly into the vesicular or bullous variety, to be in a few weeks succeeded by the pustular variety, this again by the vesicular or bullous variety, followed by perhaps the pustular for the second time, these several changes or varieties of the disease appearing, it may be, in the course of a month or a year. The mixture or commingling of the several lesions, two or more kinds often showing themselves during an attack of any one variety, certain lesions deci- dedly predominating and giving the type to the eruption, is striking. Thus in the pustular variety it is not uncommon to note vesicles, vesico-blebs, and blebs seated in close proximity to the pustules ; and in the bullous variety to observe pustules almost contiguous to the blebs. Multiformity, therefore, is the rule ; and where cases re- main under notice for a period of years, and repeated recurrences are recorded, this feature is in almost all in- stances one which impresses itself alike on patient and physician. Eczema, as we all well know, is often multi- form, but surely this disease far exceeds eczema in the extent to which this character may go. It is not only multiform, but is capriciously so, the various manifestations often taking place in rapid succession, but especially in the case of new crops of lesions and relapses. At one period it is strictly vesicular, this variety continuing it may be several weeks or mouths, several attacks of the same kind appear- ing during this time ; on another occasion it will be vesicu- lar and bullous,- or alternately vesicular and pustular. The tendency is to be vesicular and bullous, the erythematous and pustular manifestations being rarer. The general character of the eruption is herpetic, in the sense that the lesions incline to group or to appear in small or large patches, and further that where they form in proximity they tend to coalesce. This feature, however, is variable. The arrangement may be in little groups of two or three or four lesions, or, as in the case of the pustules, they may form in circles or segments of circles around the original lesion. In both the erythematous and pustular varieties there is a marked disposition to spread on the periphery, and in the former variety a disposition to creep, causing at times marginate patches. In the vesicular and DERMATITIS HERPETIFORMIS. 221 bullous varieties there is less tendency to group, and the vesicles and blebs may even be disseminated. In the same patient with different attacks I have noted the lesions dis- seminated and grouped. It frequently happens when the eruption is abundant that grouping will occur here and there, while in between the groups and elsewhere the vesicles and blebs will be disseminated. Another evidence of the her- petic nature of the disease is noted in the irregularity of the lesions, especially in the case of the papules, vesicles, blebs, and pustules. The irregular, angular, or stellate outlines of vesicles and blebs, as a rule without marked areolas, are strongly suggestive of the nature of the process. Pigmentation must also be mentioned as a symptom com- mon to all varieties, and in chronic cases is usually pro- nounced. Considerable thickening of the skin is also marked in such cases. In almost all instances, at all periods of the eruption, an irritable state of the skin, comprising itching, pricking sensations, heat and burning, is a prominent sym- ptom. In most cases it precedes the outbreak for several days, becoming more pronounced as the eruption reaches its height, then declining and again asserting itself with a new crop of lesions. Itching is the sensation generally com- plained of. It is usually severe, causing great distress of mind and body. In most of the cases that I have en- countered it has shown itself intense, and to be far more formidable than in an eczema of like grade. Burning sen- sations also are frequently described, especially in connec- tion with the pustular variety ; and when the varieties have changed from one to another, as the vesicular to the pus- tular and back again, itching and burning will exist alter- nately or be present together, constituting a sensation said to be much the most trying to bear. Sometimes it happens that an attack of the pustular manifestation, especially when the lesions remain small, is unaccompanied by subjective symptoms. I recall one such case in a man where the pus- tules were abundant, the patient stating that at the time he suffered but little inconvenience from the eruption ; but in a subsequent attack, of the vesicular and pustular varie- ties combined, he was greatly distressed with itching and burning. 222 dr. duhring's papers on The disease usually runs a chronic course, extending over years, repeated attacks appearing from time to time at in- tervals of months or years. I have known cases where it has continued, most rebellious to treatment, for five, ten, and fifteen years. During these long periods the patient has suffered more or less continuously, sometimes with periods of months of comparative or entire freedom from the disease ; but the tendency is to persist, frequently in a milder form as time rolls on. In some cases I believe com- plete recovery has taken place, but with the histories at hand I cannot speak positively on this point. In chronic cases the process often takes on a subacute form. The disease attacks both sexes, and usually in early or middle adult life. It occurs in single as well as in married women, though more frequently in the latter, especially during preg- nancy and in the parturient state. For its cause we must look to the nervous system. It is without question a neu- rotic disease, in some cases being manifestly under the con- trol of the nervous system. This statement need excite no surprise when we consider the large number of similar cuta- neous diseases traceable directly to impaired nerve-force, a list which is yearly being enlarged. With these introductory remarks upon the disease I shall proceed to consider the subject of its relation to the impe- tigo herpetiformis of Hebra. I have already (in a paper read before the American Medical Association at its last meeting 1 ) expressed the opinion that the form of disease de- scribed by Hebra was the same as the pustular variety of dermatitis herpetiformis, and that it constituted merely one variety of an extensive multiform disease, and that there- fore the term " impetigo " was inappropriate. I also made the statement that the so-called impetigo herpetiformis, in opposition to the views of Hebra, Kaposi, Neumann, and other dermatologists, occurred in men as well as in women, and in women independent of pregnancy. If we look into the history of impetigo herpetiformis we shall find that the name dates back to 1872, when Hebra first described the disease in a paper entitled " On some 1 May 6th, 1884. For abstract see ' Philad. Med. Times,' May 17th, 1884, p. 603, and 'New York Med. Journ.,' May 17th, 1884, p. 562. DERMATITIS HERPETIFORMIS. 223 Affections of the Skin occurring in Pregnant and Puerperal Women," 1 his remarks being based upon five cases ob- served by him. Before this, however, Barensprung had met with a striking case of the disease. In the ' Atlas of Skin Diseases/ by Hebra and Barensprung, 3 this latter author figures a case with the title " herpes circinatus," which portrays a peculiar and striking form of circinate and annular pustular disease, which Hebra subsequently stated was an example of his impetigo herpetiformis. No notes of the case accompanied the portrait, nor is any information given concerning the disease beyond the statement that it illustrates a rare form of herpes circinatus. It manifestly portrays the affection under discussion. Two years later Auspitz, 3 with the name " herpes vege- tans," reported two cases which I think without doubt re- present unusual forms of the disease we are considering. The first case (which was under the care of a " Dr. G." at the time of the outbreak, and who gave Dr. Auspitz an ac- count of the eruption) was a pregnant woman. The cuta- neous disease began as a bright red erythema upon the abdomen, which soon passed into a moist, itching, and burn- ing surface, studded here and there with vesicles. The disease at the time was regarded as an eczema. The vesi- cles, in groups, continued to appear, passing into pustules closely crowded and covered with crusts, the condition re- sembling a papillomatous vegetation (" Jleischwdrzenartigen Wucherung "). Febrile disturbance existed, and the patient suddenly collapsed with oedema of the lungs. There was no autopsy. The second case is one which was under Hebra' s care in the hospital, and was one of the five cases of Hebra. The woman was twenty-six years old, married, and in the sixth month of pregnancy. The eruption consisted of reddened skin with vesicles and pustules, varying in size from a pea to a bean, disseminated and grouped in a circular form. In the inguinal region there were dollar-sized, red, excoriated, moist patches covered with greenish crusts, with here and 1 'Wiener med. Woehensch.,' No. 48, 1872. 2 Tafel viii, Brlangen, 1867. 3 ' Archiv fur Derm. u. Syph.,' 1869, p. 247. 224 DR. DUHEING'S PAPERS ON there vesicles and pustules. On the lower extremities there were disseminated pustules and vesicles. There was burn- ing and itching, also marked febrile disturbance. Later some of the patches assumed a papillomatous or vegetating appearance, " like acuminated warts." The eruption in- creased in extent and intensity, the lesions spreading on the periphery of the patches, the patient being very ill. She was delivered of a dead child, but a week later died with symptoms of diarrhoea and delirium. The autopsy showed " endometritis, oophoritis, metrosalpingitis, and peritonitis." Dr. Auspitz sums up the characters of the disease as follows : — i. The occurrence of grouped vesicles and pustules with eczematous infiltration between the lesions. 2. Cutaneous vegetation on these patches of condyloma-like tumours. 3. The development of the disease in both cases in pregnant women. The reporter regarded the disease as new, and thought that the term " herpes vegetans " expressed the condition in both cases. We may now consider Hebra's paper. In the article above alluded to, this distinguished observer 1 called atten- tion to an eruption of which at the time he had encountered only five examples, all occurring in pregnant and puerperal women. It was characterised by pustules filled with pus at their first appearance, and by these affecting a peculiar mode of grouping and peripheric extension. In almost every case they first appeared at the inner surface of the thighs, partly in groups the size of a dime, and partly as separate pustules the size of a pin-head. Successive crops immediately fol- lowed, extending towards the periphery in a circular or iris form, so that in the course of a few days a gradual invasion took place on the thighs, abdomen, legs, arms, hands, and feet, and afterwards on the neck, face, and scalp. While at the centre of each group the pustules became covered with flat brownish scabs, at the circumference new ones filled with yellow pus were being constantly produced. In this disposition they resembled " herpes iris circinatus ;" but as from the very first, Hebra states, it was a pustular disease, it must be regarded as a form of impetigo, and 1 'Amer. Journ. of Sjph. and Derm.,' April, 1873, p. 156, translated from •Wiener med. Wochensch.,' No. 48, 1872. DERMATITIS HERPETIFORMIS. 225 might, from its circular mode of grouping, be termed " im- petigo herpetiformis." The affection throughout its whole course was attended by intense fever, a dry tongue, and great prostration. In three of these cases this reproduction of the pustules continued with more or less rapidity until the patient died ; while in the other two, after several weeks' duration, the pustules dried up, the thick scabs finally falling off and leaving the skin beneath healthy but strongly pigmented. Some of the pustules, instead of drying, especially at the bends of the joints, were converted into a greyish, stinking mass, which, lying on a red and moistened base, assumed an eczematous appearance. Only one out of the five cases finally survived. 1 Bach outbreak of pustules was preceded by shivering, which was followed by febrile action that lasted some days. Of the five women, three had been delivered from two to five weeks before admission, and two came in during the last month of pregnancy. The appearances were the same both before and after delivery. The autopsies of the four women who died revealed no certain cause of death. Neither the mode of life, employment, nor constitution of these patients threw any light upon the origin of this affection. In none of them was there any symptom of syphilis. In the absence of all other etiological data, and seeing that these cases all occurred in pregnant women, it might be stated, in connection with the cases already referred to in this paper, as most probable that these instances of herpetiform impetigo were dependent upon a diseased change in the genital apparatus. Several years later (1876) Hebra again takes up the subject in his 'Atlas of Skin Diseases/ 3 and gives two portraits. He says, in allusion to the inappropriateness of regarding it as a form of herpes, " The disease under consideration does not appear in the form of vesicles and circles of vesicles, nor does it run an acute or typical course. ... It makes its appearance in the form of pustules, resembling in the manner of spreading herpes iris and circinatus, and on this account the disease had better be termed impetigo herpetiformis." 1 In Hans Hebra's work on 'Diseases of the Skin,' Braunschweig, 1884, p. 198, it is stated that this patient also died subsequently during a relapse. 5 Heft 9, Tafeln ix and x, text, p. m. 15 226 de. dtjhring's papers on The disease, in the first article, is graphically but very briefly described. The leading features only are touched upon. There are many points of interest which barely re- ceive mention — such, for example, as the description of the lesions, their multiformity, and their evolution. These fea- tures, however, are brought out in the report of a case by Auspitz, already referred to, and also in the case reported by Greber, to be spoken of presently. This criticism is made for the reason that, I think, had Hebra's account of the disease been more complete, the affection would have re- ceived more attention at the hands of dermatologists. The description was scarcely full enough to enable observers to recognise the affection. The subject, I am sure, has been received by many with doubt as to the precise features charac- terising the disease. It may be added that all of Hebra's cases were severe, and that the two portraits given in his 'Atlas of Skin Diseases' show the disease at its height, and are sketched with a bold brush and in strong colours. One of Hebra's cases, as stated, was reported in full by Geber. 1 The patient was a woman, a dark blonde, set. 25, in the ninth month of pregnancy. The skin disease had existed four weeks. In consisted of numerous disseminated, miliary, and hempseed-sized vesicles. Here and there they occurred in groups of two, three, or more, in which event they ran together, crusted, and spread on the periphery, in the form of rings of pustules. In this manner, as in herpes iris, patches as large as a dollar or even the palm of the hand were formed, the centres being crusted with greenish- yellow crusts. The largest patches existed on the breasts, on the flexor surfaces of the thighs, on the abdomen, and about the flexures of the knees and elbows. The tongue also showed symptoms of the disease. After delivery the lesions began to desiccate, and abundant desquamation set in, which, however, was shortly afterwards followed by signs of moist eczema about the neck and under the breasts. Three days after delivery diarrhoea occurred ; the temperature and pulse both rose, and there were rigors. Later, the skin ' 'Bericht aus dem "Wiener allg. Krankenbause fur 1871,' von Hebra's Klinik, Wien, 1872; abstract in 'Archiv fur Derm. u. Syph.,' Heft 1, 1873, p. 169. DERMATITIS HERPETIFORMIS. 227 became clear of eruption, and the general symptoms ceased. Two weeks afterwards a relapse of the cutaneous lesions took place in the form of groups of vesicles involving the whole surface, pursuing the same course as before. A month later the patient was dismissed from the hospital. The description of the lesions in this case corresponds with the condition as portrayed in one of the plates in Hebra' s Atlas, and it is probable that this case was utilised for the portrait. Neumann first described the impetigo herpetiformis of Hebra in the third edition of his ' Handbook of Skin Dis- eases,' J in considering herpes zoster. A brief account of the disease, together with Auspitz's case, is given, and the titles " herpes pyaemicus " and " herpes puerperalis " sug- gested. In the fourth and fifth editions it finds a place under impetigo herpetiformis, a very brief account only being given, accompanied in the last edition with a woodcut illustrating the anatomy of the lesion. In speaking of herpes this author, in the third edition of his c Handbook of Skin Diseases/ 2 describes at length an affection which he regarded as a form of herpes, a view which, as we shall see, he subsequently retracted. The subject was later made the occasion of a paper bearing the title " Dermatitis Circum- scripta Herpetiformis/' 3 under which name the disease appears in the fourth edition of his 'Handbook' (p. 347). He regarded the disease as " herpes chronicus," and so named it. Shortly after this publication, Hebra, in the second edition of his great work on diseases of the skin (p. 311), expressed himself to the effect that this affection was probably not herpes, but rather lichen ruber occurring in groups. Neumann again described the disease in the fourth edition of his ' Handbook ' with the same name (dermatitis circumscripta herpetiformis), giving special attention to the pathological anatomy. In the fifth edition of his work, however (p. 310), we find dermatitis circumscripta herpeti- formis synonymous with lichen planus, being regarded as distinct from lichen ruber. I have felt it incumbent upon 1 Wien, 1873, p. 185. s ' Viertelj. fur Derm. u. Syph.,' 1875, Heft 1, p. 41. 3 Wien, 1873, p. 188. 228 db. duhring's papees on me, in connection with, my subject, to give this history of the dermatitis circumscripta herpetiformis of Neumann, lest it should be thought by some to be the same as my derma- titis herpetiformis. I may now refer to Heitzmann's interesting case. This author, in a paper 1 read before the American Dermatological Association, reports a case of impetigo herpetiformis under the beading " On the Relation of Impetigo Herpetiformis to Pemphigus." The patient was a well-nourished woman, set. 52, who had given birth to several healthy children. She had had eczema the previous year, whicb had been cured. The mucous membrane of the lower lip, the gum, the cheeks, and the tongue, on the lateral parts, were the seat of flat blebs, partly confluent and partly coated with a greyish-yellow epithelial layer, which on many places being torn away left an intensely red, excoriated, bleeding surface. The right auricle was the seat of an eruption, also the skin of the neck, and the folds below the mammae, the surface being dark red, infiltrated, and thickened, as if the seat of eczema rubrum. On many places the periphery showed groups of small pustules. There was no fever; menstrua- tion had ceased naturally several years before ; nor was there any uterine disease. New eruptions of blebs occurred every few days on the mucous membrane of the oral cavity, preceded by sharp pains and a severe rigor. , Pustules also appeared on the mucous mBmbrane of the nose, accompanied by nigh fever, followed by erysipelas of the face. They, moreover, appeared on the body, on the genitals, and about the umbilicus, the sites of former lesions being reddish brown, pigmented, or pale greyish blue, coated with a thick, exuberant, irregular epidermal layer. Several weeks after- wards, during which period she had partly recovered, a few flaccid blebs appeared. Two weeks later, within two or three days, there appeared a great many " pemphigus blebs " on the abdomen, the back, and the feet, accom- panied with high fever, weak pulse, signs of collapse, brain symptoms, and manifold other serious constitutional disturb- ances. The mouth and cutaneous manifestations were on several occasions repeated during the next three months, 1 'Archives of Dermatology,' Jan., 1878. DERMATITIS HERPETIFORMIS. 229' followed by emaciation, oedema, bedsores, ascites, the patient dying from oedema of the brain. Heitzmann con- cludes his remarks by stating that the disease is closely allied to pemphigus, and the diseases must be regarded as being kindred to each other. In recent English and American literature, with a few exceptions, no reference is made to impetigo herpetiformis, either as a distinctive disease or to the cases described by Hebra. Thus the books of Liveing, 1 Morris, 2 Bulkley, 8 and* Pox 4 contain no allusion to the subject, Hyde, 5 in his' 'Treatise on Diseases of the Skin,' defines impetigo herpeti- formis to be " a cutaneous disease of women, frequently complicating the puerperal state, characterised by the occurrence upon the skin and mucous membranes of con- centrically grouped pustules, and by a febrile condition' which usually terminates fatally." A description is given of the affection, mainly based upon the cases of Hebra, with an allusion to Duhring's observations. Besnier and Doyon, eminent French dermatologists, and the translators of Kaposi's ' Pathologie und Therapie der Hautkrankheiten ' (Paris, 1881, vol. ii, p. 49), in a note state that the author's description of imepetigo herpetiformis! is not sufficiently extended to base an opinion upon, and that it is necessary first to bring forward a record of the' facts. They object to the denomination impetigo herpeti- formis, first, because " la dermatite pustuleuse circinee et excentrique," of which they state the affection in question is an example, cannot be grouped with impetigo as this' term is used by French dermatologists ; secondly, because 1 the title herpetiform can be applied only to an affection truly of the form of herpes, that is to sayj resembling the' herpes type (herpes labialis, herpes zoster, &c), and not to a special eruption which does not belong exclusively to herpes. They regard' the disease as of septicsemic origin. 1 ' Handbook of the Diagnosis of Skin Diseases,' Amer. ed., New York, 1879. 2 ' Skin Diseases,' London, 1879. 3 ' Manual of Skin Diseases,' New York, 1882. 4 ' Epitome of Skin Diseases,' third Amer. ed., revised by T. C. Fox, Philad., 1883. 5 Philadelphia, 1883. 230 DR. DUHBING's PAPERS ON Barthelemy states 1 that the disease is rare in France, although it is not unknown to French accoucheurs, who regard it of septicsemic origin. G. Behrend, in his ' Lehr- buch der Hautkrankheiten/ 2 describes the disease briefly, drawing upon the Viennese observations for the account, but does not present any new facts. Kaposi, in the last edition of his work, 3 in considering " impetigo herpetiformis," states that eleven cases have been observed at the clinic of the Vienna General Hospital, all occurring in pregnant women, and for the most part in the latter months of gestation. Ten of the eleven cases ended fatally, recovery taking place in one case. In one apparent recovery occurred, which, however, in a few weeks was followed by a relapse and death. In another the disease, occurring in two rapidly succeeding pregnancies followed by cure, ended fatally in the third pregnancy. In Hans Hebra' s recent work* the subject of impetigo herpetiformis (Hebra) is considered and described, but nothing new is added, to Prof. Hebra's original account of the disease. He states that they have observed in Vienna about ten cases of the disease, all of which occurred in women towards the end of pregnancy, or in the puerperal state. In conclusion, I may say that there exists no room for doubting the relationship between the impetigo herpetiformis of Hebra and the pustular variety of dermatitis herpetiformis. The two are one and the same — are identical, as must be seen, I think, upon looking into the subject ; and if this be the case, the whole field opens, and must include a variety of other manifestations, namely, the other varieties of dermatitis herpetiformis, as I have described them briefly in the second edition of my ' Treatise on Skin Diseases ' in speaking of the impetigo herpetiformis of Hebra, and also in my paper read before the American Medical Association already alluded to. The subject, it seems to me, is most interesting. Our know- 1 French translation of the second edition of Duhring's ' Treatise on Skin Diseases,' p. 334, note, Paris, 1883. J Berlin, 1883, 2te Auflage, p. 260. * ' Path. u. Therap. der Hautkrankheiten,' Wien, 1883. 4 ' Die Krankhaften Veranderungen der Haut, &c.,' Braunschweig, 1884, p. 196. DERMATITIS HERPETIFORMIS. 231 ledge of the disease, if my views be correct, is yet in its infancy. As clinical reports and other information come to light it will be found that it will assume an important posi- tion in dermatology. Many cases that have hitherto been regarded as obscure or as difficult of classification will become plain. Cutaneous medicine covers an extended field in patho- logy, and to include the numerous manifestations now known to exist both terms and definitions must be broad. The tendency in the past has been to study symptoms rather than processes. In the future it is to be hoped we shall be able to bring symptoms together, to reduce rather than to aug- ment the number of diseases, and to classify them according to their pathology. NOTES OP A CASE OF DERMATITIS HERPETIFORMIS DURING THIRTEEN TEARS. 1 The notes here presented, portraying the disease I have named dermatitis herpetiformis, are of such interest that they are given in full, with the view of directing attention to the many and peculiar phases this remarkable disease may assume. The long period the disease was under obser- vation, and the extended notes which were made at the time, give us valuable information on the natural course of the disease — a point always of importance in the study of cuta- neous affections. H. H. McK — , set. 31, an American, and a painter by occupation, was admitted to the Philadelphia Dispensary for 1 Reprinted from the ' New York Medical Journal ' for November 15th, 232 DR. DUHEING'S PAPERS ON Skin Diseases, Philadelphia, July 6th, 1874. He was in impaired health, and had been suffering from the skin disease for which he sought relief since 1871, a period of three years. He was of small frame and spare, and was apparently in a state of nervous exhaustion, being weak, tremulous, dyspeptic, and despondent about his condition. He was married, and was temperate in his habits. The following clear history was obtained : — In 1871 the first disease of the skin ever experienced manifested itself in the form of lesions which he describes as " hives." They came unexpectedly and suddenly, and occupied every portion of the surface except the face, being particularly numerous and thickly set about the elbows and knees. They were erythematous in character, and were split-pea and finger- nail sized, raised and flat. Some were discrete, but the greater number were confluent. The whole surface was pretty well covered with the efflorescence, and was the seat of violent itching. The attack is described as having possessed all the features of urticaria. It gradually sub- sided in the course of three or four days, when a crop of small, rounded, flat 'pustules began to appear here and there, especially about the knees and elbows, accompanied by itching. They increased slowly in size, and crusted with a brownish, adherent crust. A number of them came out, varying in size from a split pea to a small finger-nail. They all ran a similar course, lasting from five or six days to a fortnight. By the end of four weeks they had completely disappeared, but, almost before the crusts of the earlier lesions had fallen off, a crop of vesicles and blebs, of all sizes and shapes, suddenly appeared, distributed quite generally over the extremities and upon the face. There were great numbers of them upon the face, and they varied in size here from a pin-head to a hazel-nut. Upon the general surface they were mostly small — pin-head and split-pea sized. Some were raised and semi-globular in form ; others were flat. The lesions, as stated, were vesicles and blebs having per- fectly clear contents, and were without areolae. They were very itchy. There were no signs of pustules. This attack lasted about two months, new vesicles and blebs appearing from day to day, and gradually subsided. DERMATITIS HERPETIFORMIS. 233 The patient speaks of the experience as having been very trying, not only on account of the presence of the lesions and the discharge and crusting, but also because of the itching. For several months he remained comparatively well, when a copious mixed eruption — composed of small vesicles, pus- tules, vesico -pustules, and vesico-papules, accompanied with itching — made its appearance upon the regions previously affected. This was the first occasion of the lesions being distinctly multiform. This attack lasted only a fortnight, vanishing quite suddenly, and leaving the skin in a better state than for months. This last form of eruption, how- ever, soon recurred, lasting, as previously, but a few weeks, and, as before, leaving him apparently quite well. He has had many attacks of this character, at intervals of a few months, up to the present time. The disease has thus con- tinued it's course, uninfluenced by the varied treatment to which he has been subjected. He does not think that the seasons have at all influenced the natural course of the disease. It was at this period (July, 1874) that the patient first presented himself to me. He showed the pustular phase of the disease, which had but recently made its appearance. There were about a score of disseminated, split-pea and finger-nail sized, flat, mostly crusted with a yellowish-brown, adherent, flat, ecthyma-form crust, here and there distinctly clustered pustules. They occupied the lumbar and sacral regions, the buttocks, and the elbows and knees. They had appeared a fortnight previously, and had been and were still accompanied by itching. The more recent lesions I observed were surrounded with bright red, highly inflam- matory areolae, and were peculiar in that they inclined to crust in their centre and to spread on the periphery, forming more or less distinct, narrow rings of pustulation immediately beyond the line of the crust. This feature was not con- stant, but existed in connection with a number of the lesions, and constituted a symptom which at once arrested my attention. The case was regarded as an unusual one, the form of disease being entirely new to me, and this observation was 234 dr. duheing's papers on so recorded in connection with the notes. The lesions bore a close resemblance to cachectic ecthyma, but the localities attacked were those seldom invaded in this latter disease.. The pustular variety of eczema, aggravated by some irritating application, also suggested itself, as did, moreover, impetigo contagiosa. The contents of several of the pustules, as well as the crusts, were at the same time submitted to micro- scopical examination with a view of determining if any parasite was present. The patient was placed upon a saline laxative mixture, together with full doses of the tincture of chloride of iron. No local treatment was ordered. The case remained under observation three months, and, accord- ing to the notes recorded, the patient was in about the same condition at the expiration of this period as upon admission ; the Bkin, however, underwent several decided changes during the three months, having been on one occasion almost well, but the lesions soon reappeared. The disease did not seem to be in the least degree influenced by treatment, whether internal or local, new pustules, small and large, appearing from week to week. In November, 1874, he ceased attend- ing the dispensary, much discouraged. The diagnosis was as obscure at this time as on admission. In January, 1879, four years after the foregoing note, he presented himself for treatment at the hospital of the Univer- sity of Pennsylvania. I at once recognised my former patient of the Dispensary for Skin Diseases. He stated that he was still afflicted, but that until recently it had existed in a milder form, and that he had experienced intervals of from one to six months of comparative freedom, but he had never been entirely free of eruption. The general health had failed considerably, the nervous system had become more disturbed, and he was habitually constipated. During the four years he had employed various internal and local remedies, but without benefit. The general course of the disease had been about the same as when under observation four years before. He had noted four kinds of lesions, which would manifest themselves together or in different attacks of eruption : these were true pustules, containing from the beginning a whitish puriform fluid, and of variable size, from a pin-head to a silver quarter-dollar ; vesicles, containing a clear yellow- DERMATITIS HERPETIFORMIS. 235 ish fluid, likewise of variable size ; blebs, varying in size from a split pea to a half-cherry ; and, lastly, papulo-vesicles, acuminate in form, and exuding a small amount of a serous, gluey, gummy product. The " watery blisters," as he termed the vesicles and blebs, had, on every occasion of their ap- pearance, been very itchy ; the pustules itched but little. The vesicles and blebs grew rapidly, reaching their full size in a few days, and were accompanied by but slight inflam- mation about their bases ; the pustules, on the other hand, were always markedly inflammatory. On each occasion of the pustular form of eruption he "felt badly," and was in poor general health. He had had but three or four " pustular attacks," the rest having all been vesicular and bullous. The disease, whatever the form of lesion, always manifested itself in attacks, which would announce themselves atintervals of weeks or months, one scarcely subsiding before another would appear. He does not remember that any of the attacks were preceded by chills or fever. The seasons seemed to exert no influence on the course of the disease. He noticed that frequently the lesions inclined to come out in the form of groups or clusters, four or five appearing within a radius of an inch or two, and often coalescing. The regions invaded have been the same as in the beginning — the face, neck, elbows, knees, sacral region, and buttocks being the favourite localities. The genitalia, hands, and feet have generally been free ; the palms and soles have always escaped. His condition when I saw him in January, 1879, was very similar to that recorded as existing when I first observed the case in 1874, and therefore need not be described in detail ; so much did his condition resemble the former state, as regards the general character and distribution of the eruption, that it seemed as though the very same lesions were present. The pustules were the only lesions. They were of all sizes, most of them being as large as dimes and quarter-dollars ; rounded or irregular in shape ; crusted with yellowish-brown crusts ; flat ; here and there clustered, or about coalescing; in all stagesof development, and surrounded by highly inflamed, extended, bright red areolas. They, moreover, possessed the characteristic before noted of ex- 236 de. duhring's papees on tending around the periphery and just beyond the line of the central crusting. The patient was ordered wine of iron, with three-minim doses of Liquor Potassii Arsenitis thrice daily. With the view of observing the course of the lesions,, local treatment was withheld. March nth, 1879. — The case has been under constant observation since the previous note, six weeks ago, during which time the disease has behaved much as it did on the first occasion I had of studying it. The lesions have pur- sued a rather slow course, considering their highly inflam- matory nature, an average pustule lasting, from the beginning until the crust dropped off, from two to three weeks. Many new lesions, all strictly pustular in character, have from time to time appeared,' as a rule, in crops, while the older ones have, at the end of a variable period, disappeared, leaving persistent dark red, brownish, pigmented marks. No scars remain. One peculiarity of mature pustules has not been referred to, namely, the tendency for the inflamed skin around the crust to pucker, giving the skin a wrinkled, drawn-up, glistening appearance. The disposition of the lesions to group has always been present, though at times only to a slight extent. It has not, however, been observed with all of the lesions, many appearing singly. As they increased in size there would generally be noted a number of discrete or confluent small pin-head sized, flat pustules immediately around the circumference of the original lesion in the form of a ring. This feature varied, being much more pronounced in some cases than in others, and at times was wanting. The pustules, however, seemed to grow in this manner, a new ring of minute pustular points spring- ing up every few days around the crust until the lesion reached its determinate size. The crusts were adherent ; upon lifting them up, a superficial, reddish excoriation, covered with a slight puriform fluid — as in the case of ecthyma — presented itself. Little or no bleeding occurred. Itching has not been severe, but the lesions have " felt sore." 1 Three nights ago he was attacked with violent itching of the general surface, accompanied with an efflorescence which he describes as having been identical with certain attacks before experienced on several occasions, and which was DERMATITIS HERPETIFORMIS. 237 plainly urticarial in nature. It began, while in bed, upon the arms, but soon extended itself over the whole surface except the hands and feet, the backs, as well as the palms and soles, remaining free. The eruption was erythematous and very red, and exceedingly itchy ; so much so that he was kept awake all night. The next day the eruption dis- appeared, but he felt poorly, and complained of loss of appetite and malaise. Last night, just after going to bed, it suddenly reappeared in the same manner as two days before. The attack was preceded by chilliness and malaise ; later he perspired profusely. To-day he feels better, and the rash is leaving the surface. The skin, however, is still red ; rough in patches ; slightly papular and vesicular, and has the appearance on the arms of an erythema multiforme in the stage of declination ; scratch-marks abound. It seems as though the attack had been abortive, the development of the papular and vesicular lesions having been checked early in their course. 1 6th. — During the past five days the eruption has been disappearing, with slight desquamation and considerable pigmentation, some of the patches on the trunk somewhat resembling irritated tinea versicolor. Within the week a half-dozen, large and small, pustules have come on the arms and buttocks, identical with those which have been described. 25th. — A number of variously sized pustules have been appearing here and there over the surface, in particular on the neck, around the navel, on the lumbar and sacral regions, and over the buttocks and thighs. They all incline to dry and crust in the centre, sometimes as a depressed, cup-sbaped crust, and to spread on the circumference, thus extending their size. Their edges are more or less "puckered" and slightly raised ; their areola? large, dark red in colour, and contracted, presenting a somewhat, stellate, radiate appear- ance. There is now but little itching. He is still taking four minims of the Liquor Pobassii Arsenitis, which he has been using for a month, but with no benefit. June 29th. — Has been annoyed greatly with disease since the last note, which has manifested itself, as heretofore, in the form of distinct outbreaks appearing at irregular intervals. But at no time within the past three months has 238 de. duhring's papers on lie been entirely free. The lesions at present are vesicular and bullous, from the size of large pin-heads to coffee-grains, and are scattered especially over face, arms, and forearms, and over the region of the spinal column. They are accompanied with intolerable itching. During the last six weeks he has been using half-ounce doses of linseed meal, with the view of improving the nutrition, but without benefit. June ist, 1884. — Five years have elapsed since the last note, during which period I have not seen the patient until a few days ago. He is still suffering with the disease, having never obtained any relief from the manifold treatment to which he has been subjected. For the past three or four years the attacks have been lighter than formerly, and the lesions for the most part vesicular in character. At the present time the face, neck, and trunk are the seat of small, ill-defined vesicles and papulo-vesicles, accompanied, as before, with itching. The general health is improved, and he is able, when not suffering from an attack, to attend to his daily duties. I shall make no comments upon the case except to say that it illustrates a typical expression of this peculiar dis- ease, characterised as it is by rare multiformity. It shows almost all of the lesions to which I have called attention in describing the disease, and upon which its several varieties have been based. In conclusion, I may add that the affec- tion is usually well defined, having distinctive features which enable it to be readily recognised, although it may be confounded with eczema, herpes, and pemphigus, according to the lesions at hand. DERMATITIS HERPETIFORMIS. 239 PRELIMINARY NOTE RELATION OF DERMATITIS HERPETIFORMIS HERPES GESTATIONIS AND OTHER SIMILAR FORMS OP DISEASE. 1 In my original communication on Dermatitis Herpeti- formis/ the symptoms, characteristics, and the several varieties of the disease were described. It was also stated that the pustular variety was the same manifestation as that described by Hebra as impetigo herpetiformis. The view was likewise pat forth that the herpes gestationis of authors was probably merely another variety of this affection. In a more recent paper just read before this Association, 8 the relation of the impetigo herpetiformis of Hebra to dermatitis herpetiformis has been shown, and the conclusion reached that the former is but a variety of the latter disease. In the present note I desire to bring forwards supplementary views which have of late been forced upon me by study of the literature of the subject, to the effect that not only the herpes gestationis of writers, but also other similar forms of eruption reported with various titles are all merely instances of one process, namely, dermatitis herpetiformis as I have denned this disease. To be more definite, some of these cases may be men- tioned. 1 Reprinted from the ' Medical News,' November 22nd, 1884 ; read)before the American Dermafological Association, 1884. 2 Read before the Amer. Med. Assoc, May 6th, 1884, and published in the ' Joum. of the Amer. Med. Assoc.,' August 30th, 1884. 3 ' Journ. of the Amer. Med. Assoc.,' August 30th, 1884. 240 dr. duhring's papers on The " herpes ciroinatus bullosus " of Erasmus Wilson ? the " pemphigus prurigineux " of Hardy f the " herpes gestationis" of Milton/ Bulkley, 4 Thompson, 5 Liveing, 6 Cottle, 7 Gale, 8 and W. G. Smith, 9 all represent manifestly the same disease, and are expressions of the vesicular and bullous varieties of dermatitis herpetiformis. In like manner the " pemphigus " of Klein ; 10 the " pemphigus circinatus " of Bayer j 11 the " herpes phlyctsenodes " of Gilbert ; 12 the " pemphigus aigu pruriginosus " of Chausit, 15 and the " pemphigus compose " of Devergie. 14, Certain cases of so- called " hydroa " should, I think, also be viewed as forms of dermatitis herpetiformis, as, for example, the cases reported by Handheld Jones 16 and Bulkley, 16 and that of " Florence S.," described in the ' British Medical Journal,' 1870. Likewise such cases as that of Oswald, 17 reported with the heading " a peculiar skin eruption occurring during preg- nancy ;" and of Leigh, 18 a " bullous eruption of a peculiar character." The very unusual case of Jarisch, 19 designated " herpes iris," and the case of Meyer, 20 " a fatal pemphigus-like der- 1 ' Diseases of the Skin,' sixth ed., London, 1867. 2 'Le9ons sur les Mai. de la Peau,' 2nd part, p. 136, second ed., Paris, 1863. 3 'Path, and Treat, of Diseases of the Skin,' London, 1872, p. 205. 4 ' Amer. Journ. of Obstetrics,' February, 1874. 5 ' Archives of Derm.,' October, 1875. 6 'Lancet,' June 1st, 1S78, p. 783. 7 'St. George's Hosp. Rep.,' 1879. 8 'Lancet,' 1880, vol. i, p. 601. 9 'Dublin Journ. Med. Sci.,' 1881, 3 s., lxxi, p. 70. 10 ' Allg. Wien. med. Zeitung,' August, 1867 ; quoted in 'Journ. Cutan. Med.,' July, 1868, p. 203. 11 ' Treatise on Diseases of the Skin,' English translation, London, 1835, p. 219. 12 < ^ Practical Treatise on the Special Diseases of the Skin,' English translation, London, 1845, p. 118. 13 ' Annates des Maladies de la Peau et de Syph.,' March, 1852. 14 ' Mai. de la Peau,' p. 309, Paris, 18.57. 15 'Med. Times and Gaz.,' September 6th, 1873. 16 ' Archives of Derm.,' April, 1877. 17 'Lancet,' June 10th, 1882, p. 951. 18 'Lancet,' January 6th, 1883, p. 11. 19 'Viertelj. fiir Derm. u. Syph.,' Hefte 2 u. 3, p. 195, 1880. 50 ' Archiv fiir path. Anat. u. Phys.,' November, 1883, p. 185. DERMATITIS HERPETIFORMIS. 241 matitis," have also points in common with the disease under consideration. Finally, without doubt some cases of so-called pemphigus, especially of "pemphigus pruriginosus," might more pro- perly be regarded as examples of dermatitis herpetiformis CASE OF DEBMATITIS HERPETIFOBMIS PECULIAR GELATINOUS LESIONS. 1 John S — , set. 64, a native of Wilmington, Delaware, and a pedlar by occupation. He has always enjoyed good general health; weight, 175 pounds. No family history. The present skin disease is of five years' duration, but he has had the same only in winter. It has been in the habit of coming on with cold weather and disappearing about the middle of May, and it has pursued this course every year. He never had any skin disease or illness of any kind before seven years ago, when an "eczema" of the right leg ap- peared, which has been cured repeatedly by ointments, but has relapsed. He is of the opinion that the disease of the general surface which he now has is the same disease that he has had for the last five years, but that it is worse this winter than ever before. When it first came out (in October, 1 8714) he was in his usual good health. It manifested itself by intense itching on the back, localised chiefly about the lumbar region, which asserted itself in paroxysms, lasting from a half -hour to two hours. They were invariably re- lieved in the course of ten or twenty minutes by scratching. Unless scratched or rubbed, itching would persist for hours. The itching was unaccompanied by redness. The scratching did not injure the skin, notwithstanding that he was in the 1 Eeprinted from ' The Medical News,' March 7th, 1885. 242 DR. duhring's papbes on habit of employing harsh measures for relief. This pruritus continued all winter, confined to the back, and at no time was accompanied by any eruption. With May it disappeared quite abruptly, as soon, he states, as he began sweating in the course of his pedestrianism. He was entirely well all summer until October, when the disease again began as in the previous year with intense itching without eruption, and confined to the back, occupying, however, more surface than before. It continued all that winter, as during the previous season, and again disappeared in May. The following October it reappeared, and now for the first time in the form of small, pin-head sized, elevated, in- flammatory, acne-like, very itchy pustules, which, after having been emptied, disappeared. They were scattered over the back, and were not grouped. They came at irregular intervals and not in crops. They were present throughout the autumn and winter in varying numbers, and entirely left him in May. The itching was quite as intense as during the two previous years. He states that after these lesions were opened and scratched decided relief was experienced. In October (third year) itching upon the back again manifested itself, which gradually increased in severity, and continued all winter. The small inflammatory, acne-like, pustular lesions which were present during the second winter did not reappear ; but toward the middle of April what he describes as small " blind-boil-like " lesions appeared on the back. They neither discharged nor crusted. Two or three came at a time and were very itchy at first, but in the course of two or three days became sore. In the course of the following month there occurred some twenty of these lesions, when, toward the middle of May, they en- tirely disappeared. He remained well through the summer, as usual, until October, when the itching confined to the back began as before, unaccompanied by eruption, but a week later the itching began to subside, and now a new kind of lesion ap- peared, which he describes as follows. When first noticed, two were present over the right scapular region. They were the size of a large thumb-nail, distinctly raised, but flat, with little or no inflammatory areola, of a golden yellow DERMATITIS HERPETIFORMIS. 243 colour, and contained a thick, consistent, orange or deep golden yellow-coloured mass. These lesions were in many ways peculiar. They came suddenly, often in the course of ten or fifteen minutes. His attention would be directed to the affected part by a sharp sensation, " like the sting of a bee ;" examining the skin he would find one or more lesions pre- sent, and, as a rule, already fully formed. They were neither preceded by, nor accompanied with itching : the sensation was that of a sting. They were superficially seated, appearing to have their seat just beneath the epidermis. They would continue ," to sting " until opened with a knife or needle, a knife being the instrument usually selected for the purpose. (He was at this period an inmate of the Wilmington Almshouse Hospital, and was under the care of Dr. Thomas Ogle.) The lesions were too tough to permit of being ruptured with the finger-nail. He describes them as being circum- scribed, firm but not hard, " puffed up," raised but flat on their summits, and moveable under the skin. Some were raised as much as a quarter of an inch or more ; others less. As soon as he became aware of their existence, by the stinging sensation, they were opened ; the sting was sharp and persistent until they were evacuated. All of these lesions were much alike as to size, shape, colour, and other general characters. When opened with a knife, the mass or contents referred to would come out, or " pop out " entire without any pressure being exerted, and in the form of the pulp and of the consistence of an ox-heart cherry ; the mass was, however, flattened rather than round. These curious, pulpy, gelatinous masses, he states, could be picked up between the fingers, handled, and, if squeezed, would disintegrate. No blood accompanied them, nor did . the cavity which remained after the exit of the mass contain any blood, but it subsequently oozed a few drops of a yellowish fluid, of a creamy consistence. A cavity, of course, remained after the exit of these bodies, into which the tip of the index finger could be inserted ; but, under a stimulating lotion of iodide of potassium, this healed over, with slight scaling, in a few days, no stain remaining. Sometimes these cavities would refill, and often with surprising rapidity, 244 DR. duheing's papees on in less than ten minutes with a material similar to the first product, but not so yellow, and invariably thinner — more of the consistence of thick cream — which could be squeezed out by pressure with the blade of a knife. But not all of the lesions would refill ; some would refill as often as three times, and this in from one to twelve hours. He continued to have these very singular lesions throughout the autumn and winter, one, two, three, or more making their appearance, on the average, every day. They did not come in crops, but at irregular intervals, and, as stated, seldom oftener than at the rate of one or two daily. They were at first confined to the back, but subsequently attacked all portions of the surface except the face and scalp. They disappeared gradually in the following April, and he was free from these and all other lesions throughout the summer. Present condition (January 13th, 1879). — The patient was admitted to the Ward for Skin Diseases of the Philadelphia Hospital on November 1st, 1878, but did not come under .my observation until some weeks later. When admitted he presented a slight vesicular and papulo- vesicular eruption, in patches and much scratched, occupying the back, abdomen, and extremities. It appeared to be trivial eczema, although he complained greatly of the itching, declaring that it was intolerable. The case, as stated, was regarded as one of eczema, and was placed upon the usual treatment for this disease. The disease disappeared, in a great measure, in the course of a fortnight, but soon recurred, exhibiting the same characters as before. December 15th. — An outbreak of vesicular eruption has recently appeared, showing the lesions in a more positive form. They are vesicles, varying in size from a small pin-head to a pea, and possess irregular, angular, jagged borders such as are encountered in herpes zoster. Although manifestly inflamma- tory, they are unaccompanied by marked signs of inflamma- tion, being for the most part altogether without areolae, though the skin between them is somewhat reddened and excoriated from scratching. They are, as a rule, quite flat, but some are raised, looking as though they might develop into blebs. -Their contents are either clear and watery or pale yellowish. DERMATITIS HERPETIFORMIS. 245 Those which are flat, and contain a clear fluid, are incon- spicuous, and even in some places difficult to detect, and resemble sudamina. The lesions show a distinct disposition to form patches, and, moreover, to cluster, and here and there even to run together ; but the grouping is not pro- nounced, and might readily be overlooked by a casual observer. The back of the neck, shoulders, back, arms, and thighs are the regions especially involved, though other parts are also invaded, but with disseminated, abortive, papulo-vesicular, more or less excoriated lesions. Antipruritic lotions have been freely used, but with in- different results, an alkaline tarry preparation affording the most relief. The itching has been intense, preventing sleep and causing the patient to scratch incessantly day and night. The vesicular lesions above described gradually subsided in the course of two weeks, leaving the skin quite free of lesions, except a general dirty yellowish pigmentation, the result of scratching. The patient remained well, except that he was still much annoyed with general itching for a week, when the present lesions, pustular in character, began to appear. They have been very gradually increasing in size, and multiplying from day to day, until the existing condition has been reached. The lesions are distinctly pustular, varying in size from a pin-head to a finger-nail. They are of a yellowish white colour ; tensely distended in their early stage ; flat ; sur- rounded with marked areolae ; and of irregular, more or less rounded or angular outline, and have a contracted or puc- kered appearance. The older ones are crusted with a yellow- ish, slightly greenish, flat, uneven, honeycomb crust. The recent small crusts, in many instances, show a decided umbilicated or cupped formation, reminding one of tinea favosa. The lesions are numerous, and exist upon the scalp, neck, shoulders, arms, forearms, sacral region, buttocks, thighs, popliteal spaces, legs, breasts, and abdomen. The hands and feet and genitals are almost free. Viewing the erup- tion as a whole, the lesions may be said to be disseminated, though they are more abundant in some localities than 246 dr. duhring's papers on others, and in some places — as on the buttocks — even in- clined to cluster. The clusters or groups are made up of two, three, or four lesions, of different sizes, situated closely together, in some instances so closely as to run together. Two decided clusters, of a half-dozen lesions each, occupy either buttock, the lesions being small and large, inflamma- tory, more or less crusted, and evidently increasing in size, accompanied with severe itching. 27th. — The course of the lesions has been carefully noted from day to day. While the greater number of pustules appeared simultaneously during the first few days of the outbreak, new ones have not ceased coming out up to the present period. As a rule, the pustules have started as pin- head or split-pea sized lesions, and have slowly and gradu- ally increased to their determinate size, this varying from a split pea to a silver half-dollar. The time occupied for the growth to the largest size named has been from two to three weeks, a remarkably slow growth considering the character of lesions. Many of the smaller ones have assumed their determinate size and have begun to disappear in the course of a week or ten days. In almost all instances the increase in size has taken place plainly in the form of a complete or broken narrow ring of flat pustules, which has been kept up just beyond the line of the central crust ; as rapidly as this would form, the ring or circle (often imperfectly deve- loped) would appear, which in turn would become merged into the central crust. Many of the older crusts have been dropping off, leaving dark red, more or less pigmented areas of infiltrated skin. Since the attack began to subside the itching has decreased, and he now experiences great relief and comparative ease. During the outbreak, " liquor picis alkalinus," a drachm to two or three ounces of water, has been used as a lotion to one side of the body ; while on the other half, fluid extract of grindelia robusta, one drachm to the ounce of water, has been employed. The patient states that both remedies gave ■ relief, but that he prefers the tarry preparation. He has also been taking a pill of one thirtieth of a grain of arseni- ous acid and a saline laxative as required. February 4th. — No new lesions have appeared, and the DERMATITIS HERPETIFORMIS. 247 recent attack has completely subsided, the skin being in better condition than it has been for many months. Con- siderable pigmentation, however, remains, and the dark red spots, scattered and in groups, the seat of former pustnles, are likewise conspicuous. The itching has abated, though he states that he is still obliged to scratch at night. 22nd. — Improvement has been slowly going on during the past fortnight, the pigmentation and staining being, however, very tardy in disappearing. The patient remarks that he fears another outbreak, for within the last four days the itching has been violent. 28th. — The itching has been steadily augmenting from day to day, although until to-day nothing appeared on the skin. A slight papulo-vesicular eruption, indistinctly defined, with irregularly shaped, small, flat, pale red, disseminated, but aggregated lesions, has here and there, over the back, arms, and thighs, made its appearance. The lesions are so scratched that their features can scarcely be determined ; the itching, he states, is indescribably intense, and out of all proportion to the amount of eruption. Strong alkaline baths have been used, but without relief. March 6th. — There has been but little new eruption since the last note, the few lesions that have appeared being, as the others in the present attack, abortive papulo- vesicles. The itching has continued, and the patient is suffering con- siderably ; he is in expectation of more eruption, when, in the light of former experience, he looks forward to compara- tive relief. 22nd. — The condition has scarcely changed within the fortnight. The itching and the " pricking, picking sensa- tions " have been intolerable, especially over the trunk, arms, and thighs. To-day new vesicular lesions, as well as papulo-vesicles, have manifested themselves about the neck and over the abdomen, back, shoulders, and arms. They are numerous and scattered, or are in patches of a dozen or more. Some are raised, tensely distended, shining, irregu- larly rounded or angular in outline, varying in size from a pin-head to a split pea ; while others are flat, and often are difficult to detect. None have any areolse, but rise abruptly from the surrounding healthy skin. 248 DE. DUHEING'S PAPERS ON 27th. — The eruption, which threatened to become exten- sive last week, has again aborted. The lesions were, with- out exception, all scratched and lacerated almost as soon as they began to form. The itching still continues, but in a modified degree. The officinal sulphur ointment was to-day ordered, to be well rubbed into the skin twice daily. April 3rd. — The sulphur ointment gave decided and prompt relief, the patient stating that no remedy that he had ever before used had acted so effectually upon the itching. May 1st. — A few scattered papulo-vesicular and vesicular lesions, accompanied with itching, have shown themselves from time to time during the month, but there have been no signs of a serious outbreak. The patient is improving, he thinks, from week to week, and eagerly looks forward to the approaching warm weather as a source of relief. It will be remembered that every year he has recovered with summer. The internal remedies, consisting mainly of ar- senic, have some time since been discontinued. The patient, at his own request, has been discharged from the hospital, and has not since been heard from. The notes, extending over a period of several years, have been given at length, because the case is very interesting, especially with reference to the "gelatinous lesions" de- scribed. At present I shall not dwell on this subject beyond stating that these lesions have likewise occurred in several other instances of dermatitis herpetiformis which have come under my notice. I believe them to be peculiar to this disease, and to constitute a hitherto undescribed form of cutaneous manifestation. DERMATITIS HERPETIFORMIS. 249 CASE OF DERMATITIS HERPETIFORMIS OF THE PUSTULAR VARIETY. 1 In reporting the notes of a case of a rare disease no apology therefor need be made, for the reason that any in- formation on the subject must prove valuable. The disease under consideration being of infrequent occurrence, and, moreover, constituting a new field of observation, concerning which there seems to be some diversity of opinion among dermatologists, is for these and other reasons worthy of close investigation. With our present knowledge every case en- countered «is entitled to a place on record, with the hope that as the published data accumulate we shall better comprehend the process. The following case was under my observation at intervals during a period of five years. At the time the disease seemed to me incomprehensible, on account of the peculiar lesions, their behaviour and course, which were altogether different from those of any affection with which I was familiar. Classification of the disease was beset with diffi- culties, as the original notes testify, and the case was re- garded as an anomalous one — as representing, perhaps, an undescribed disease. The several provisional diagnoses (of eczema ? of ecthyma ? of tinea circinata ?) made from time to time show the resemblance of the lesions to those of well-known affections, and give an idea of the multiformity displayed. The case, moreover, is interesting as exhibiting a phase of this peculiar disease that has not been brought out in any of the cases that I have previously reported. These features will be referred to later. 1 Reprinted from the ' Medical News,' March 5th, 1887. 250 dr. duhring's papers on The patient came under notice in 1874, and the following history is an abstract of the notes taken at that date. Daniel Welsh, fifty years of age, Irish, and an ostler by occupation. He had previously been subject to "prickly heat " during the summer about the trunk, and was so affected year before last, this attack having been followed by a much more serious disease of the skin similar to that, he states, with which he now suffers. He describes the erup- tion he had at that date as being pustular and vesicular, with intense itching and burning. The itching was intolerable, and the disease continued for three months. Crusting followed the formation of the pustules, which remained for some time, the process eventually passing off with scaling. He recovered in the autumn, and remained well six months, when the present eruption appeared. It continued through- out the summer, becoming better toward autumn, but it never left him entirely. About a month ago it began to grow worse. It is now con- fined to the trunk, shoulders, and buttocks, and is particularly well defined upon the abdomen and sides of the thorax. The lesions are disseminated, but possess certain herpetic features, and consist of numerous minute, small and large pustules with yellowish contents, in all stages of development. They vary much in size, some being no larger that pin- points and pin-heads, while others have attained the size of peas and beans. The latter are not acuminated, but are flat and spread out, although considerably raised above the sur- rounding healthy skin. In outline the larger ones, as a rule, are oblong or irregular and angular, and have an herpetic, " puckered " appearance. The small recent pustules are not attended with any redness of skin, having no inflamed base or areola ; but the larger and older ones are surrounded with a deep red areola of considerable size. There are no vesicles. [A week's observation proved that this eruption began as a well-defined pustule, and continued as such until a crust formed, which became detached in four or five days, leaving a pigmented base.] In addition to the pustules there is considerable pigmentation, of a reddish, dirty yellowish, brownish hue, which is present here and there over the surface in a marked degree, and is a conspicuous symptom, DERMATITIS HERPETIFORMIS. 251 being much greater and more persistent than with other similar inflammatory processes. The disease at present is almost without itching, burning, or other annoying symptoms.' The eruption, he states, comes out in crops, one scarcely disappearing before another makes its appearance, and in this manner the process is kept up from week to week and month to month. Such was the condition when admitted to the Dispensary for Skin Diseases, April 28th, 1874. He was placed upon external and internal treatment, the disease being then regarded as pustular eczema. During the following month, under the use of iron and arsenic and varied external remedies, the cutaneous lesions increased. A few weeks later minute pustules began to appear in a grouped, circinate, herpetic form, as in typical tinea circinata, the appearances resembling an exaggerated phase of this latter disease, so much so that it was thought it might possibly be due to a vegetable parasite, but the microscopic examination revealed nothing of this nature. Itching and heat now began greatly to annoy the patient, and within a week some of the circinate patches increased in size until they became two inches in diameter. The pustules were minute and small, and hence the picture did not suggest herpes iris. Two weeks later the attack sub- sided and the lesions rapidly disappeared, but only to re- appear immediately as a new crop as before, in the form of numerous pin-point and pin-head sized pustules. The following week another crop, numbering thousands of lesions, invaded the trunk, accompanied with burning but no itching. This attack increased in extent and severity, but the lesions remained small, a few only being as large as a pea. Scales and thin crusts formed in large patches, and scaling and ex- foliation set in. The skin became intensely itchy and hot, and he was unable to sleep, and was depressed and discouraged. The patient now passed from under observation, having experienced no relief from the varied treatment which he had undergone. Five years afterwards he again presented himself to me, still a sufferer with the same disease. An ointment containing sublimed sulphur one ounce, lard two ounces, and oil of walnuts two drachms, was now used, and 252 DE. DUHEING'S PAPERS ON with positive relief to the itching and burning, and with the remarkable result of causing the lesions rapidly to disappear. The inunctions were made with friction, as in the treatment of scabies. I subsequently saw him in several attacks, in one of which the pustules were herpetic and grouped, as previously, in a crescentic or more or less annular form, new lesions, moreover, showing themselves on the periphery of the patches, accompanied with much itching. The ointment referred to was again (and on later occasions) employed with the same admirable result, the patient stating that during the many years of his suffering this was the first and only remedy that had in any degree benefited him. He spoke of the relief to the subjective symptoms as being instantaneous, and looked forward to a speedy permanent cure. Whether or not this occurred I am unable to say, as shortly afterwards he ceased attending the clinic. The interesting points of this case are, first, that during the period I had the patient under observation the lesions remained pustular, being at times minute (not larger than pin-points and pin-heads), and on other occasions larger — the size of peas and beans. At nil times, even when the eruption might be regarded as being disseminated, they possessed herpetic features, being either (when of large size) seated upon an angry-looking, drawn-up, puckered base, or (when small) grouped in close proximity, sometimes in an annular form, as in tinea circinata and herpes iris. As characteristic of the disease may be mentioned the disposi- tion of the eruption to appear in crops ; the pigmentation of the affected skin ; the obstinacy of the process to treatment; the tendency to relapse ; and the long duration of the disease as a whole. Finally, the subjective symptoms were peculiar, being ab one time marked and at another time almost absent. The variations on this point were remarkable if the statements of the patient are to be relied on. The fact, however, of the lesions being pustular would account for the comparative freedom from itching, this symptom, as is well known, rarely accompanying pustular lesions of any kind. DERMATITIS HERPETIFORMIS. 253 CASE OF DERMATITIS HERPETIFORMIS RESEMBLING ERYTHEMA MULTIFORME. 1 In January, 1884, I was requested by Dr. Mitchell of Elkton, M.D., to see a case of chronic cutaneous disease, exhibiting peculiarities which made the diagnosis difficult. The patient was a man seventy years of age, a lawyer by profession, neurotic and in poor general health. The disease had existed a year or longer, and was characterised by a profuse, multiform, general eruption, with violent itching and burning. None of ■ the various plans of treatment previously employed had afforded any relief. From his physician I further learned that the lesions of the skin had varied in character from time to time, having been sometimes vesicular, and on other occasions erythema- tous ; while more frequently there had existed a combination of these elementary forms. Itching had always been a marked feature. When I first saw the case the whole general surface was the seat of an abundant, diffuse eruption, characterised by ill-defined, marginate, annular, and circinate erythematous patches, upon which, in many places, were more or less well- formed, variously sized and shaped papulo-vesicular and vesicular lesions. The skin showed, moreover, signs of sub- acute and chronic inflammation, in the form of thickening, pig- mentations, excoriations, and blood-crusts, as well as lesions in all stages of development. The erythematous patches pre- dominated, and had coalesced to such an extent that their outline was only in places defined, but everywhere could be seen a disposition to form marginate shapes, as in erythema 1 Reprinted from the ' Medical Record,' April 2nd, 1887. 254 DR. DUHRING'S PAPERS ON multiforme. The patches were on a level with the sur- rounding skin or were slightly elevated, and were acutely- congested and infiltrated with inflammatory products, partly plastic and partly serous in nature. In colour they were bright red or violaceous red, according to their age, and were mottled, owing largely to the fact of their having run together. The whole general surface, but especially the trunk, was affected in this manner ; in addition to which seated upon these patches were, for the most part, flat, small and large papulo-vesicular and vesicular lesions, here and there well defined, elsewhere imperfectly developed or abor- tive. The picture, as might be imagined, suggested an extensive diffuse or generalised " chronic " erythema multi- forme, with papulo-erythemata, papulo -vesicles, and vesi- cles. The herpetic element was striking, as shown by the grouping and by the marginate peripheral extension of the process. Here and there the lesions were grouped in an ill-defined circinate form, as in tinea circinata, some of the patches being small, others large. In most localities they were so multiform and had emerged one with another so extensively that the elementary characters were to be noted only on close inspection. Scratch-marks, excoriations, and small and large blood-crusts were everywhere present, testify- ing to the intense itching which had been experienced. The patient stated that this had always been a distressing sym- ptom, was subject to exacerbations, and that it was always at its height during the time a new crop of lesions were develop- ing, occupying usually about a week. The pigmentation was of a dirty yellowish, muddy, or dusky hue, and was both localised and general. It called to mind that seen in the later stages of extensive pityriasis rosea of the trunk. Prom a diagnostic standpoint the eruption resembled diffuse, aggravated erythema multiforme of long standing. Herpes iris was not suggested, the erythematous element prevailing. It possessed a history, however, as well as features which precluded it from being classed here. The chronicity of the process, the tendency to repeated relapses, the obstinacy of the disease, together with the violent itching and burning, would not permit it to be considered as a case of this disease, at least as this affection is now DERMATITIS HERPETIFORMIS. 255 defined. At the same time I would state that the case possessed certain features in common with this disease, and certainly bore more resemblance to it than to any other well-known cutaneous disease. And this brings me to a question that has presented itself on several occasions in studying dermatitis herpetiformis, namely, where (in cer- tain cases) shall the line be drawn separating this disease from other well-defined diseases ? Shall, for example, the case I have just cited be regarded as erythema multiforme, or shall it be grouped under the title dermatitis herpeti- formis, where I have placed it ? Shall a new definition be framed for erythema multiforme, to include also a chronic process, in order that this and similar cases may be grouped under this title ; or shall we regard such instances as too far removed from erythema multiforme to be classed here, and relegate them to another group ? The line separating one disease of the skin from another in some instances is ill-defined, and there are cases occasionally encountered which may as properly be classified under one head as another. Instances of the kind are met with from time to time with eczema and psoriasis, pityriasis rubra, and psoriasis, and, to pass to more chronic forms of inflammation, with lupus erythematosus and lupus vulgaris. They exhibit symptoms common to both diseases, and defy precise sche- matic classification. The case under discussion, however, I think, may more properly be regarded as an example of the erythematous variety of dermatitis herpetiformis than of erythema multi- forme, especially if we take into consideration the history of the disease. In some respects it resembles that reported by Jarisch as "herpes iris," and referred to by me in the article entitled " Preliminary Note on the Eelation of Derma- titis Herpetiformis to Herpes Gestationis and other Similar Forms of Disease " •(' Medical News,' November 22nd, 1884). I saw the patient on several occasions during the subse- quent six months, his condition having somewhat improved, although he still suffered much. It is not necessary to enu- merate the various internal and external remedies that were employed ; suffice it to say that they were such as 256 DE. DUHEING'S PAPERS ON might have been prescribed for chronic universal erythema- tous eczema. Notwithstanding the treatment the disease persisted, and relapses, though milder in form, occurred as before. I report the case because it is interesting as portraying an unusual manifestation of the disease, namely, one bearing a resemblance to erythema multiforme. In a former paper I alluded to the possible relationship between these two diseases, and this case would go to show that the causes at work in these diseases are capable of giving rise to similar cutaneous lesions. Additional clinical information, however, is needed concerning unusual forms of both diseases before definite views can be expressed, and it is to be hoped that the experience on this point of other dermatologists will be forthcoming. UBER DIE DIAGNOSE DER DERMATITIS HERPETIFORMIS. 1 Bei der Durchsicht der Berichte iiber bestimmte, von Zeit zu Zeit in den letzten Jahren veroffentlichte Falle von Hautkrankheiten sowie auf Grand der verschiedenen mir bekannt gewordenen Kritiken und Referate iiber meine Abhandlungen iiber Dermatitis herpetiformis diirfte es scheinen, als ob die Krankheit von einigen nicht deutlich aufgefasst worden ist. Nach den Verhandlungen der New Yorker Dermatologischen Gesellschaft, in welcher dieses Thema diskutiert wurde (' Journ. Cutan. and Ven. Dis./ April, 1886, p. 20) deuten die Erorternngen wohl darauf hin, dass nicht alle Mitglieder mit den verschiedenen Phasen der Affektion vertraut waren. Die hierbei zu tage 1 Vortrag, gehalten vor der American Dermatological Association auf der II Jahresversammlung am 1 September, 1887. Sonder-Abdruck aus ' Monatshefte fur praktische Dermatologie,' Band vii, 1 888, No. 4. DERMATITIS HERPETIFORMIS. 257 getretenen Ansichten beweisen die iiber diesen Gegenstand herrschende, grosse Meinungsverschiedenheit. Aus diesen und andern Griinden wiinsche ich Ihre Aufmerksamkeit nochmals auf dieses Thema zu lenken, indem ich speziell die ch.arakteristisct.en Merkmale und Symptome der Affektion, durch welche sie sich von andern ahnlichen Dermatosen unterscheidet, in Erwagung ziehe. Mein erster, 1884 publizierter Artikel iiber diese Krank- heit griindete sich auf die Erfahrung, welche ich bei einer Anzahl von mir ab und zu beobachteten Hautaffektionen mit gewissen, alien gemeinsamen Merkmalen gewonnen habe. Diese Manifestationen schienen mir auf demselben Prozess zu beruhen und sollten daher zusammengefasst und unter einem Namen erortert werden. Die damals aufgestellten Ansichten sind, wie ich glaube, auch jetzt noch der Haupt- sache nach korrekt, sicherlich soweit sie die klinischen Studien betreffen. Da einige dieser Falle viele Jahre unter meiner Beobachtung waren, hatte ich wahrend dieser Zeit reichlich Gelegenheit die verschiedenen Eruptionsphasen und den Prozess als ein Ganzes zu studieren. Seitdem haben andre Beobachter iiber Falle derselben Krankheit berichtet, und ist daher zu erwarten, dass wir bald iiber hinreichendes Material verfugen, urn praziser definieren zu konnen, welche Falle unter obigem Namen zu rubrizieren, und welche andern wohlbekannten oder schon anderweitig untergebrachten Krankheiten zuzuweisen sind. Tiber die Existenz einer Krankheit " Dermatitis herpeti- formis," wie sie spezieller durch Varietaten von Blaschen, Blasen und Pusteln charakterisiert wird, hege ich keinen Zweifel. Der Zweck meines heutigen Vortrages geht dahin, die typische oder gewohnliche Bezeichnung der Affektion zu erortern. Denn es ist ausserordentlich wichtig, sich iiber diesen Punkt vollig zu verstandigen. Tiber die allge- meine oder gewohnliche Form der Erkrankung muss vor allem tJbereinstimmung bestehen, erst dann konnen die verschiedenen Abweichungen von diesem Typus beriick- sichtigt und an ihre richtige Stelle gebracht werden, je nachdem die Erkenntnis derselben fortschreitet. Meine Erorterungen werden sich demnach nur auf die gewohnliche Erscheinungsform der Krankheit beschranken. 17 258 dr. duheing's papers on Nach diesen einleitenden Bemerkungen mogen bestimmte allgemeinere Punkte hervorgehoben werden. Vor allem ist es fiir die Auffassung des Gegenstandes wesentlich, bei einer ihrem Charakter nach so polymorphen Affektion die einzelnen Varietaten und pathologischen Formen derselben in Erwagung zu ziehen. Im Bkzem z. B. haben wir eine Krankheit vor uns, welche mit verschiedenen Arten von elementaren Effloreszenzen und in verschiedenen Varietaten beginnen kann und dann einen von jeder andren Dermatose differierenden Yerlauf nimmt. Ohne binreicbende kliniscbe Erfabrung beziiglich dieser Affektion wird niemand imstande sein, die zahlreicben und besonderen Pbasen, welche sie wahrend ihrer Entwickelung annehmen kann, zu wiirdigen. Die meisten von mir beobacbteten Falle batten einen nocb wechselvolleren Charakter als das Ekzem. Vielleicht ist gerade die Polymorphic des Exanthems, wie sie sich im Verlauf des natiirlichen Prozesses manifestiert, ein Haupt- charakteristikum, — bald in Form von Blaschen, bald Blasen oder Pusteln, ja in einer oder mehr Eruptionsperioden bestehen alle diese Formen gleichzeitig und bilden eine reine Mischeruption. Und gerade wegen dieser charakter- istischen Eigentiimlichkeit, welche in bestimmten Umfang in fast alien Fallen verhanden ist, ist es zum Verstandnis des Prozesses als eines einheitlichen wesentlich, den Patienten unter fortgesetzter Beobachtung zu haben. In bestimmten Fallen ist es leicbt erklarlich, wie zu einer Periode ein vesikuloses Ekzem, ein oder zwei Monate spater irrtiimlicher- weise ein Pemphigus diagnostiziert werden kann. Doch kann es als feststehend erachtet werden, dass gegebenen Falles wahrend einer geniigend langen Beobachtungsdauer die Polymorphic des Exanthems in einer oder der andren Eruptionsperiode friiher oder spater sich offenbart, sowie dass diese Eigentiimlichkeit in verschiedenen Intervallen und dazu wei bei keiner andren Krankheit sich wiederholen wird. Die typische Form zeigt sich in der Produktion von Blascben, Blasen und Pusteln, die entweder gleichzeitig auftreten, also eine Mischeruption bilden, oder zu ver- schiedenen Zieten als mehr oder weniger deutlich charakte- ristisch vesikulose, bullose oder pustulose Eruptionen. Die gewohnlichste und haufigste Form ist die Mischeruption mit DERMATITIS HERPETIFORMIS. 259 vorherrschend vesikulosem Typus. Als gute Beispiele dieser Art mogen die beiden in dem ' New York Med. Journ./ April 9th, 1887, erorterten Falle erwaknt werden ; ferner die Falle von Mrs. N. P. ( f The Medical News/ June 2nd, 1883), sowie ron H. H. Mck. ('New York Med. Journ.,' November 15th, 1887) ; in diesen Fallen bestanden Blaschen, Blasen and Pusteln gewohnlich gleichzeitig, dock pravalierte stets die vesikulose Form. Diese Beispiele reprasentieren, den sogenannten Herpes gestationis von Milton, Bulkley und andern, wakrend uber ahnliche Falle unter andern Titeln von Zeit zu Zeit berichtet worden ist. Als ich meine Ansickten iiber diese Krankkeit urspriing- lick darlegte, sckien es mir ratsam, zur moglichst klaren Darstellung eines so komplizierten Tkemas die gewohnlichen Pkasen der Affektion unter dem Titel von Varietaten zu beschreiben, welcke sick auf die vorherrsckenden Elemen- tarformen in aknlicher Weise wie bei den Varietaten des Bkzems zuriickfiikren lassen. Denn man muss bedenken dass zwar der Prozess zum gleickzeitigen Ausbruck von zwei und mehr Exanthemformen inkliniert, aber dock auck Falle nickt fekleu, in denen bei der einen oder andren Eruptionsperiode nur eine Art von Ausscklag vorkanden ist. So bestanden in verscbiedenen meiner Falle f iir langere oder kiirzere Zeit nur Blaschen, spater kamen wakrend eines Eecidivs Blasen oder Pusteln zum Vorschein. Wie es sckien, lag fur die Annakme von Varietaten kein Grand vor, sie bestanden in erythematosen, vesikulosen, bullosen, pustulosen, papulosen und klinisck in polymorpken Formen. Die erytkematose Form ist ckarakterisiert worden durck den Fall des Advokaten aus Maryland Mr. Mel. ( f Med. Eecord,' April 2nd, 1887). Die Falle von N. B. E. (' New York Med. Journ./ July 10th, 1884) sowie von Capt. K. {' Amer. Journ. Med. Sci./ January, 1885) zeigen beide in ausgesprochenem Grade die bullose Form, wakrend . die pustulose Varietat sich in den Fallen von Annie Mel. ( f Journ. Cutan. and Ven. Dis./ vol. xi, No. 8) und von Daniel Welsh (' Med. News/ March 5th, 1887) mani- festierte. Ein Beispiel der polymorphen Art bot sich in dem Falle von Mrs. M. ('Med. News/ July 19th, 1884) dar, bei welchem fiir eine geraume Zeit alle Phasen und 260 dr. dcthring's papers on Stadien von primaren und sekundaren Eruptionsformen in solcher Ausdehnung bestanden, dass eine Schilderung kaum eine geniigende Vorstellung von dem vorhandenen Bilde erwecken wiirde. Lassen Sie mich liier auf eine kurze Schilderung der charakteristischen Symptome der Krankheit eingehen. Bs kann die Frage gestellt werden, ob sich bestimmte Charak- tere nnden, durch welche die Affektion von andern Erkrank- ungen unterschieden werden kann, ferner ob die Symptome eide eigenartige Affektion kennzeichnen, oder ob dieselben nur ungewohnliche Formen gewisser, woMbekannter Affek- tionen darstellen, wie z. B. des Erythema multiforme oder des Pemphigus. Besitzen wir Werner geniigende Thatsachen und Beobachtungen, auf Grund welcher wir eine Schil- derung einer eignen Erkrankung entwerfen konnen ? Die letztere Frage kann nach meiner Meinung positiv beant- wortet werden. Zur naheren Erorterung des Gegenstandes darf hervorgehoben werden, dass es nicht nur wohlcharak- terisierte primare Eruptionsformen verschiedener Art gibt, sondern dass auch sichere, offenbar abortive Formen eine augenfallige Eolle spielen. Zur Erlauterung meiner Ansicht fiber die letztere Art mochte ich die mangelhaft entwickelten Papeln und papelahnlichen Blaschen anffihren, wie man nie nicht selten beim Herpes Zoster trifft. Zu den primaren Manifestationen gesellen sich sekundare Eruptionsformen, welche bei chronischen Fallen ein ganz bestimmtes Bild darbieten. In Fallen mit vorwiegend erythematosen Effioreszenzen sind die Eruptionen weniger gut ausgespro- chen, es finden sich mehr oder weniger in Kreisform angeordnete, kleine oder grossere Flecke, auch Entziind- ungsherde, und auf denselben entstehen undeutlich abgegrenzte, erythematos-vesikulose Formen oder flache auch zerstreute Blaschen resp. blaschenartige Eruptions- formen ; dieser TJmstand hat einigen Autoren Veranlassung gegeben, ein " Erythema vesicans " zu beschreiben. Ein ahnlicher, wenn nicht damit identischer Zustand findet sich zuweilen in den vorgeruckteren Stadien des Erythema multiforme. Hinsichtlich der Gestalt und Grosse der andern Erup- tionen herrscht die grosste Verschiedenheit. Zuweilen DERMATITIS HERPETIFORMIS. 261 sind die Blaschen sehr klein, von Nadelkopfgrosse, in diesem Fall sind sie in der Regel sehr zahlreich ; zuweilen wieder sind sie viel grosser und im allgemeinen variieren sie hinsichtlich des Umfanges bedeutend. Ihre Umrisse sind irregular, gezakt oder sternformig und haben rundliche oder ovale Form, dazu haben sie die Neigung sich abzuflachen und sich eher auszubreiten als zu erheben. Dieser Umstand tragt dazu bei, dass die kleineren Blaschen nicht selten schwer zu entdecken sind und gewohnlich erst bei schrager Beleuchtung sichtbar werden. In der Regel sind sie prall gespannt und haben deshalb einen perlenartigen Glanz ; kurz, sie sind herpetisch. Sie erscheinen auf unbestimmt begrenzten, unregelmassig gestalteten und ausgedehnten Flecken, oder sie stehen dicht beisammen oder sind mehr oder weniger deutlich gruppiert. Dieselben allgemeinen Charaktere finden sich bei den Blasen. Die Pusteln sind entweder wie bei den Blaschen klein und zahlreich, wie eine miliare Eruption auftretend, oder sie sind von Erbsengrosse und grosser, in welch letzterem Falle sie wieder sparlich vorhanden sind. Die miliaren Bruptionen verhalten sich eigentiimlich, sie sind flach, gelblich oder weiss, erheben sich auf unregelmassig gestalteten oder kreisformigen Flecken und verleihen zuweilen der Obernache ein Aussehen, als ware sie mit Punkten oder Knotchen besat. Sie sind im allgemeinen isoliert. Die grosseren Pusteln von Erbsengrosse zeigen in der Regel einen Entziindungshof, sind flach oder wenig erhaben, haben eine entziindlich erscheinende Basis, ein etwas gerunzeltes und gefaltetes Aussehen, wie es bei den isolierten Effloreszenzen des Herpes Zoster gefunden wird. Die Papeln, welche zuweilen auftreten, sind gewohnlich breit, so gross wie kleine Spliterbsen und erscheinen als unvollkommene Eruptionen, zeigen aber einen deutlich herpe- tischen Charakter und gleichen den Papeln des Abortiv- zosters. Hinsichtlich der sekundaren Effloreszenzen ist zu bemerken, dass eine unrein gelbliche oder braunliche Pig- mentierung in chronischen Fallen im allgemeinen ein vorherr- schender Typus ist, viel mehr noch als das bei einem Ekzem von ahnlicher Vielgestaltigkeit und Ausdehnung der Fall ist. Krustenbildung kann als ein Charakteristikum nicht 262 dr. ddheing's papees on angesehen werden, doch treten gewohnlich infolge Kratzens Bxkoriationen zusammen mit betrachtlicher VerdickuBg der Haut auf. Nach dieser kurzen Betrachtung der auffallendsten Eigen- tiimliclikeiteii der Bffloreszenzen will ich das Gesamtbild, welclie sie darstellen, erlautern. Die verschiedenen bereits erwahnten Kombinationen bilden eine hervorstechende Eigentiimlichkeit der Affektion. Bei keiner andren Haut- krankheit trifEt man so sonderbare Kombinationen, z. B. Erythem, Blaschen und Blasen ; Blaschen und Blasen ; Blaschen, Blasen und Pusteln; oder Blaschen und Pustelh, welche haufig ganz nahe beieinander stehen, und von star- kerer oder geringerer Pigmentierung, ferner von Bxkoria- tionen und andern sekundaren Veranderungen gefolgt sind. Auch der subjektiven Symptome gescbebe bier Erwahnung. Jucken und Brennun, besonders in Anfang, sind gewohnlich in bohem Grade vorbanden. Diese Brscheinungen sind im allgemeinen sebr qualend und zeigen sicb bei jeder Exacer- bation oder neuen Bruptionsattacke. Dem Drange zum Kratzen konnen die Patienten nicht widersteben und bekom- men erst Linderung, wenn die Effloreszenzen vollig zerkratzt sind. Das intensivste Jucken veranlafst die vesikulose Varietat ; bei der pustulosen Form sind die subjektiven Symptome im allgemeinen milder, konnen sogar fur kurzere oder langere Zeit ganzlich feblen. Wiederbolt ist die Aufmerksamkeit auf die Eruption an sich, betracbtet als ein Ganzes, als herpetisch, gelenkt worden. Es ist von Wicbtigkeit in eine genaue Prazisie- rung des Begriffes dieser Bezeicbnung einzugehen. Was bedeutet der Terminus " herpetisch." Es kann wobl fest- gestellt werden, dass derselbe sicb auf gewisse Eigentiim- licbkeiten der Effloreszenzen bezieht; einen atiologischen Gesicbtspunkt involviert derselbe aber in keiner Weise. Unter dem Ausdruck " herpetiform " ist die Ahnlichkeit zu verstehen, welche die verschiedenen als Herpes bekannten Effloreszenzen untereinander haben, dazu gehoren der ein- fache und febrile Herpes, Herpes Zoster und Herpes iris. 1 Bei all diesen Affektionen treten sogenannte herpetische 1 'Ami. d. Ubers.' Englander und Amerikaner bezeichnen Herpes tonsurans nicht als Herpes, sondern als Tinea trichophyt., Ringworm. DERMATITIS HERPETIFORMIS. 263 Charaktere auf, und doch sind sie nicht alle untereinander gleich. So sind die charakterischen Momente beim Herpes Zoster sehr verschieden von denen des Herpes iris, trotzdem aber gibt es wieder andre Eigenschaften, welche beiden gemeiusam sind und zu der ganzen Gruppe gehoren. Spricht man von einer herpetiformen Krankheit, so liegt gewiss der Gedanke fern, dass dieselbe einer Varietat von Herpes mehr ahnelt als der andren, oder mit andren Worten, dass sie eine besondere Vai'ietat von Herpes bildet, dass sie vielmehr gewisse der Gruppe gemeinsame Merkmale besitzt. Hier ist zunachst das dichte Beieinanderstehen, die Anb.au- fung ung Gruppierung zu erwahnen, welche beim Herpes Zoster am ausgesprochendsten sind. Bine Tendenz zur Grup- penbildung wird auch bei Herpes iris beobachtet, doch in geringerum Grade, es besteht bier aber noch eine andre eigentiimlicke Neigung, namlich die Disposition, an der Peripherie in mehr oder weinger ausgesprochener Kreisform allmahlich sich weiter zu verbreiten. Dieselbe Tendenz findet sich auch bei einer ihrer Natur nach ganz davon ver- schiedenen Krankheit, namlich der Tinea circinata parasi- tica, die friiher der Herpesgruppe zugerechnet wurde — dem Herpes circinatus alterer Dermatologen. Blasenbildung, sogar oft typische, zeigen alle Pormen von Herpes, und bei Herpes Zoster ist auch Pustelbildung die gew6h,nliche Form. Bs besteht noch ein andres herpetisches Kennzeichen, das man bei alien Varietaten wiederfindet, es ist dies die ausser- ordentliche Hartnackigkeit der Bffloreszenzen, die fehlende Disposition zur spontanen Euptur derselben. Bin variabler Grad von Entziindung ist alien Herpesaffek- tionen eigen, am wenigsten ausgepragt ist er beim einfachen Herpes, am meisten beim Herpes Zoster und iris. Bei Herpes des Gesichts sind die Bffloreszenzen in der Regel kalt, d. h. sie zeigen nur einen geringen Bntziindung- shof, die Blaschen schiessen plotzlich von der Oberflache auf und sind von keiuer grosseren Stoning der umgebenden Haut begleitet. Beim Herpes der Schleimhaute und Ubergangsstellen ist die Entziindung gewohnlich viel mehr ausgesprochen. Beim Zoster ist dieses Symptom, wie bekannt, im allgemeinen ausserordentlich stark und iiberdies eigentiimlicher Art, umschrieben, intensiv um die Blaschen 264 de. duhring's papers on herum, und verleiht der ganzen Eruption oder Eruptions- gruppe ein etwas erhabenes (reliefartiges) Aussehen, welches um ainzelne Effloreszenzen und Heine isolierte Gruppen besonders deutlich ist. Derselbe Zustand findet sicn in viel geringerer Ausdehnung bei Herpes iris ; aber hier zeigt sich ein andres herpetisches Merkmal, namlich die peripbere Ausbreitung, in Form von einer oder mebreren Reihen von mehr oder weniger wohlbegrenzten Ringer von Effloreszenzen, insofern die zuerst im Zentrum des Fleckes gebildeten einer Involution unterliegen. Derselbe Entwickelungsprozefs findet in geringerer Ausdebnung bei Tinea circinata statt, und erscheint es mir daher wahrscheinlich, dass die Art der Hautnervenirritation, wenn aucb verscbiedenen Ursprungs, doch in beiden Erkrankungen ahnlich ist ; das kliniscbe Bild und die Entwickelung der Krankbeit wiirde sicherlich einer solcben Schluss rechtfertigen. Es wird demnach klar werden, dass der Ausdruck berpeti- form mebr als einen Begriff in sicb scbliesst ; er deutet auf verscbiedene Modifikationen von Effloreszenzen, die in ihrer Form ganz verschieden sind. Beini Zoster folgt die Erup- tion offenbar dem Verlauf eines Nervenstammes-astes odor- fadens. Bei den andern Varietaten lasst sicb eine so aus- gesprochene Beziebung zu den Nerven nicbt nacbweisen, obwobl hier nach meiner Meinung Grund zu der Annahme vorliegt, dass die Hautnerven affiziert sind, sowie dass eine eigentiimlicbe Art von Nerven storung die direkte Ursacbe der Eruption ist. Eine weitere Klarung erreichfc man durch Beriicksicbtigung des natiirlicben Verlaufes. Viele Beobacbtungen sind zu machen, wenn man den natiirlicben Verlauf der Krankbeit verfolgt ; er ist eigen- tiimlicb und voh dem jedes andren Prozesses verscbieden. In der Regel zeigt die Affektion einen deutlicb chroniscben Verlauf, der sicb iiber viele Jabre erstreckt. Icb habe liber zwei Falle referiert, wo dieselbe elf resp. dreizehn Jahre bestand und ohne Aussicbt auf Heilung nocb florid war ; in andern Fallen litten die Patienten ein bis fiinf Jahre daran. Es sind mir auch Beispiele erinnerlicb, in denen die Affektion nur wenige Monate dauerte, dies betrifft gewotmlich Frauen wahrend der Scbwangerscbaft, die Eruption ti'at von der Entbindung auf und endigte kurz DERMATITIS HERPETIFORMIS. 265 nachher, wie es z. B. bei Mrs. N. P. (' The Med. News/ June 2, 1883) der Fall war. Es besteht nach allem eine sehr lebhafte Tendenz zur Chronizitat und zwar trotz lokaler und interner Therapie, die in vielen Fallen nutzlos ist. Ein andres Charakteristikum kann erwaht werden ; es besteht darin, dass die Eruption in Form von mehr oder weniger deutlich abgegrenzten Anfallen auftritt ; jeder dauert zwei bis sechs Wochen, dann folgt wieder ein fast volliger Stillstand fiir Wochen und Monate. Recidive von gewohnlich kurzer Dauer zu verschiedenen Perioden bilden die Regel. Eine andre eigentiimliche Erscheinung wahrend der Entwickelungsperiode der Krankheit besteht darin, dass eine bestimmte Regel in der Manifestation der verschiedenen Arten derselben nicht befolgt wird. So kann gegebenen Falles die erste Effloreszenz vesikulos und bullos sein, die folgende pustulos, wahrend zu einein spateren Zeitpunkt Blaschen, Blasen und Pusteln gleichzeitig bestehen konnen, und solche Variationen konnen bis in infinitum erfolgen. Ich habe mir die Miihe genommen meine referierten Falle auf diesen Punkt zu priifen und finde, dass bei Capt. K. (' The American Journal of the Medical Sciences/ January, 1884) zuerst Blaschen auftraten, denen am sechsten Tage Blasen folgten ; der zweite Ausbruch kurze Zeifc nachher war pustuloser Natur, der dritte vesikuloser, bulloser, vesiko- bulloser und pustuloser, der vierte vesiko-pustuloser Art und so fort. In einem andren, lang dauernden Falle (13 Jahre und mehr), detn des H. H. Mck. (' New York Med. Journ., November 15th, 1884) ist die Krankengeschichte folgende; zuerst Erythem oder Urticaria, dann Pusteln ; das dritte Recidiv war vesikulos und bullos ; das nachste vesiculos und pustulos ; die folgenden Attacken waren vesiko-pustulos, vesiko-papulos, pustulos, erythematos, pustulos, vesikulos und bullos, und vesikulos, und so weiter, so dass man endlich mu.de wird die vielen und kapriziosen Veranderungen aufzu- zeichnen. Meinen Studien nach will es mir scheinen, als ob der Prozess eine regelmassige Reihenfolge in der Manifestation der Effloreszenzen nicht innehalt ; es besteht hier eine ausserordentliche Variation, und das ist ein so gowohnliches Merkmal bei der Entwickelung des Prozesses, dass es als 266 dr. dcthring's papers on ein charakteristisch.es angesehen werden kann. Bs kann anderseits von einigen Beobachtem der Binwand gemacht werden, dass ein ahnlicher Verlanf auch bei langdauernden Ekzemen sich findet, indessen sind hier die Variationen von einer zur andren Eruptionsform selten so rapid und scharf abgegrenzt wie bei der hier erorterten Affektion. Hinsichtlich der Entwickelung und Involution der einzelnen Bffloreszenzen ist zu erwahnen, dass dieselben sich von denen andrer, ahnlicher Affektionen unterscheiden. Sie entwickeln sich in der Eegel mit ziemlicher Schnelligkeit, wenige Tage oder eine Woche geniigen im allgemeinen zur Ausbildung der vollen Eruption ; neue erscheinenfortwahrend in einer odor zwei Wochen, tritt dann ein Nachlass der Bruptionen ein, so sind die ersten inzwischen schon in weiter Ausdehnung verschwunden . Beginnt einmal ein Nachlass,. so geht die ganze Affektion gewohnlich schnell zuriick. Nach dem Gesagten ist die Krankheit als eine ernste auf- zufassen, und so ist es. Denn abgesehen von dem chroni- schen Verlauf und der Hartnackigkeit des Prozesses sind die Attacken im allgemeinen sehr qualend nicht nur hinsichtlich der Anwesenheit einer so unangenehmen Eruptionsform an sich, sondern auch wegen des unertraglichen Juckens und Brennens. Solche Patienten konnen iiberdies fiir Wochen und Monate an das Bett gefesselt sein, noch kann man vorhersagen, wie ihr Zustand sich von Monat zu Monat gestaltet. Die Gegenwart oder Abwesenheit von Allgemein- storungen, Schiittelfrosten und Pieber, wei bei Malaria, wird hauptsachlich von der Schwere des Palles sowie von der Natur des wirksainen Agens abhangen. So konnen z. B. bei Schwangeren seiche Allgemeinsymptome in erhohtem Grade vorhanden sein. Anderseits konnen sie in einfacheren Fallen von verschiedenen Ursachen, wie z. B. von nervoser Depression oder vom Shok ahhangeu und dann nur leicht sein, auch konnen sie vollig fehlen. Sind sie vorhanden, so machen sie sich bei jeder Exacerbation besonders be- merkbar. Diagnose, Anamnese, Verlauf, Verteilung, Entwickelung der Eruptionen, ihre verschiedenen Kombinationen uud Eigentiimlichkeiten in Verbindung mit den subjektiven Symptomen miissen samtlich in Erwagung gezogen werden. DERMATITIS HERPETIFORMIS. 267 Meist ist die Diagnose bei gewohnlicher TTntersuchung leicht zu stellen, in inanchen Fallen ist eine langere Beobachtung erforderlich. Die Bntwickelung des Prozesses muss stets ein wichtiges Moment bilden und in alien Fallen beriick- sichtigt -werden. Welche Beziehungen bestehen nun zwischen Dermatitis herpetiformis und andern wohlbekannten Hautkrankheiten ? Ist sie eine ungewohnliche Art irgend einer der andern bekannten Affektionen, oder hat dieselbe besondere, eigne Merkmale, und kann ihr demgemass in dem System der Hautkrankheiten eine besondere Stelle eingeraumt werden ? Sind die sie charekterisierenden Kennzeichen geniigend klar ausgepragt, um eine solche Unterscheidung deutlich zu machen ? Die letztere Frage mochte ich mit ja beantworten und will ich nun Hire Aufmerksamkeit auf die ihr am meisten ahnlichen Krankheiten lenken. Im Anfang meiner Studien iiber dieselbe wurde in einigen Fallen ihre Ahnlichkeit in gewissen Entwickelungsstadien mit verwandten Affektionen aufgezeichnet ; so finden wir z. B. in den Krankengeschichten von verschiedenen von mir referierten Fallen die provisorischen Diagnosen " Tinea circinata," " Ekzema/' " Ekthyma," " Herpes/' und " Pemphigus/' und wurden diese Diagnosen nicht nur von mir selbst sondern auch von andern aufgestellt ; einige der letzteren waren geneigt die vesikulosen und bullosen Varie- taten als Herpesarten anzusehen und sie geradezu als Herpes gestationis, pyamicus, pruriginosus und Herpes circinatus bullosus zu bezeichnen. In anbetracht dieses Umstandes ist daher die Wichtigkeit einer Trennung der verschiedenen Varietaten der Krankheit, welche fiir sich bestehend so differente klinische Bilder zeigt, evident geworden. Wer somit nur gelegentlich die Krankheit sieht, mochte wohl nicht leicht geneigt sein, die erythematose und pustu- lose Varietat auf einen und denselben Prozess zuriickzu- fiihren. Die erstere hat eine grossere Ahnlichkeit mit dem Erythema multiforme als mit irgend einer andren Hautaffek- tion und hat, wie ich in einem meiner Falle festgestellt habe ('Medical Record, April 2nd, 1887) einige dieser Krankheit eigne Merkmale. Gewisse, gleiche herpetiforme Oharaktere besitzen beide. Die Manifestation scheint in einigen Fallen 268 dr. duhristg's papers on eine potenzierte Phase des Erythema multiforme mit chroui- schem Verlauf zu sein. In zwei Fallen, die mir erinnerlich sind, schienen ungewohnliche Fornien des Erythema multi- forme zu gewissen Zeiten zu bestehen, aber als audre diesen unahnliche Eruptionsformen plotzlich auftraten, war diese Ansicht natiirlich hinfallig. Der Umstand an sich, dass dieselben chronisch verliefen, widerstritt einer derartigen Auffassung. Es ist ganz bekannt, die Autoren verwerfen die Existenz eines Erythema chronicum multiforme, alle Schriftsteller nehmen nur einen akuten Prozess an und betrachten dasselbe als eine mit spontaner Heilung endende Affektion. So ist wenigstens z. Z. unsre Ansicht. Ich kann noch bemerken, dass die Effloreszenzen sich von denen des Erythema multiforme commune noch darin unter- scheiden, dass sie weniger scharf begrenzt sind ; sie sind weder hinsichtlich der Peripherie noch der Gestalt so deutlich markiert und bestehen mehr aus unbestimmt be- grenzten Inflammationsherden als aus umscbriebenen, scharf kontourierten Flecken. Indem ich mich zura Herpes iris wende, welcher, wie all- gemein anerkannt wird, dem Erythema multiforme am nachsten steht und iiberdies zuweilen nur ein vorgeriicktes Stadium dieser Krankheit darstellt, halte ich es fur unver- kennbar, dass diese Affektion gleichfalls Merkmale mit Dermatitis herpetiformis gemein hat. Es mass indes bemerkt werden, dass in beiden von mir beobachteten Fallen schwerlich die Diagnose von Herpes iris von je- mandem gestellt worden ware. Der chronische Verlauf des Prozesses, wie er bei Erythema multiforme besteht, wiirde die Diagnose auf Herpes iris ausgeschlossen haben. Die Effloreszenzen sind dazu gar nicht von derselben Beschaffen- heit wie die von Herpes iris ; sie erscheinen von schlim- merem Charakter und werden von Hautstorungen iutensi- veren Grades begleitet, wie dies schon aus dem Charakter der Entziindung und der gewohnlich vorhandenen Intensitat der subjektiven Symptome hervorgeht, wahrend die letzteren bei Herpes iris meist fehlen. Bei diesem ist die Eruption gewohnlich auch lokalisiert, z. B. auf die Hande und Fiisse. Universeller, iiber die gesamte Haut verbreiteter Herpes iris ist selten. Was das Erythema multiforme betriflt, so wird DERMATITIS HERPETIFORMIS. 269 es von den Autoren als eine benigne Affektion angesehen, die zwar stets einen akuten Verlauf zeigt, aber mit spon- taner Heilung endigt, nur muss man des bekannten Um- standes eingedenk sein, dass sie Eecidiven in verschiedenen Intervallen unterliegt. Die bullose Varietat kann Pemphigus vulgaris gleichen, wenn sie fur sicb allein besteht, und kann irrtiimlicb dafiir gehalten werden. Wenn aber vesikulose, vesiko-pustulose und pustulose Formen gleichzeitig vorhanden sind, ist ein Irrtum in der Diagnose kaum moglicb. Diese eigentiimliche Mischung von verschiedenen Erup- tionsformen findet bei Pemphigus nicht statt ; wenn dann ferner bei dem weiteren Bntwickelungsgang des Prozesses auf einen Schub Pemphigusblasen ein Ausbruch von herpe- tischen Pusteln und spater Blaschen folgt, wird es dem Beobachter klar, dass er es hier mit echtem Pemphigus nicht zu thun hat. Eine derartige Entwickelungsgeschichte ist unvereinbar mit Pemphigus, der stets eine Blasenerup- tion darstellt, mag er akut oder chronisch verlaufen, einen ersten Ausbruch oder ein Recidiv bilden. Der Fall von N. B. E. ('New York Med. Journ.,' July 19th, 1884) mit der bullosen Form der Krankheit wurde zu verschiedenen Perioden seines Bestandes von den behandelnden Arzten fur Pemphigus gehalten, aber diese Ansicht auf Grand der nachtraglichen Veranderungen und Entwickelung der Affek- tion bald wieder aufgegeben. Verschiedene andre Krankheiten mit ahnlichen Kenn- zeichen wie bei unsrer hier erorterten Affektion konnen hier kurz erwahnt werden ; so entwickeln sich gelegentlich bei Urticaria solche Symptome, und scheint diese Erkrankung ein Mittelding zwischen jener und Erythema multiforme zu sein, nichts destoweniger aber kennzeichnet der plotzliche Eintritt sowie der intensiv juckende Charakter der Efflo- reszenz die Urticaria. Eine bullose Form von Urticaria diirfte wohl in keinem Stadium derselben vorkommen. In dem Fall von James W. (* Phila. Med. Times/ July 12th, 1884) fanden sich zur Zeit Pusteln, welche flach, ausge- breitet und serpiginos waren ; hier war von einem Artze die Diagnose auf pustuloses Syphilid (Ekthymaform) zuerst ge- stellt und der Patient demnach einer antisyphilitischen Be- 270 DR. DUHRING'S PAPERS ON handlung unterworfen worden. Solch ein grober Schnitzer diirft indes selten jemandem begegnen, welcher nur einige dermatologische Kenntnisse besitzt. Denn keine einzige Varietat deutet auch nur irgend wie auf Syphilis hin. Der eben erwahnte Fall hatte in einer spateren Periode auch. einige Ahnlichkeit mifc einem starker entwickelten Stadium der Tinea circinata. Die kleinen steoknadelkopfgrossen, gelblichen, flachen Pusteln unmittelbar um die kreisformigen und sich ausbreitenden Flecke kerum liessen auf einen vege- tabilischen Parasiten als Agens sckliessen. Bs eriibrigt nur nock gewisser Krankkeitsnamen zu geden- ken, wie im besondern der Hydroa einiger Autoren und der Hebrascken Impetigo herpetiformis. Diese Krankkeits- formen konnen indessen nickt geniigend erortert werden ohne ein detailliertes Bingehen in dieselben, und erscheint es daker am besten hier sie gar nickt zu beriihren. Zum Sckluss muss ick noch kinsicktlick des Namens Der- matitis herpetiformis und der Griinde fur die Wahl dieser Bezeicknung ein Wort kinzufiigen. Ein neuer Name war erforderlick und zwar ein solcher, der, ohne auf ein schon okkupiertes Terrain iiberzugreifen, am genauesten das Wesen der Sache ausdriickt. In anbetracht der ausgesprochen entziindlichen Natur des Prozesses war der Allgemeinbegriff Dermatitis einwursfsfrei. Auf Grund der Thatsache, dass Polymorphie wahrend des ganzen Krankkeitsverlaufes ein hervorstechendes Zeichen war, hielt ick im Beginn meiner diesbeziiglichen Studien die Bezeicknung polymorpk oder multiform fur passend ; dieser Begriff sckien mir ausserdem weit genug, um gegebenen Palles eine lange Reihe von mekr oder weniger ahnlichen Bxanthemen in sich zu schleissen. Aber in Hinsicht darauf, dass unsre Nomenklatur bereits eine gut definierte und allgemein anerkannte Dermatitis von versckiedener Art mit einem sekr aknlicken Titel, namlich Erythema multiforme, enthielt, schien mir geniigend Grund vorhanden, mich nach einem andren umzuseheh. Verwir- rung, ja selbst der Schein einen solchen, musste vor allem vermiden werden. Dermatitis multiformis hatte man leicht und natiirlicherweise fiir ein vorgeriicktes Stadium von Ery- tkema multiforme ansehen konnen. Es war deskalb eine andre und prazisere Bezeichnung wiinschenswert ; diese DERMATITIS HERPETIFORMIS. 271 schien mir in dem Wort herpetiformis zu liegen, zumal dieser Terminus bereits mit einer verwandten Krankheit, der von Hebra beschriebenen Impetigo herpetiformis verbunden war. Herpetiform bezeichnete iiberdies das am meisten charakteristische Merkmal des pathologischen Prozesses. Es wurde als ein wesentliches angesehen, ohne welches die Krankheit iiberhaupt nicht existierte, und deshalb war herpe- tiform passender als multiform, welch letztere Bezeichnung nur auf das klinische Geprage der Krankheit sich beziehen konnte. Dieser ihr originaliter verliehene Name scheint mir ganz passend und kann auch vorlaufig beibehalten werden, bis unsre Kenntnis der Krankheit vollstandiger als jetzt ist. CASE OF DERMATITIS HERPETIFORMIS CAUSED BY NERVOUS SHOOK. 1 In November, 1878, I was asked by my friend the late Dr. F. F. Maury to see a " curious case of bullous skin disease " under his care. It proved to be a marked example of what I have described as dermatitis herpetiformis. 3 The following notes, which I think worthy of record, were made at the time. The disease was then fully expressed, and showed the lesions not only in abundance but in all stages of development. The patient (Capt. K — ) is a man thirty-four years of age, of large frame, stout and strong, and in the enjoyment 1 Reprinted from the ' American Journal of the Medical Sciences ' for January, l88g. 2 Communication read before the Section on Medicine of the American Medical Association, May 6th, 1884, 'Journal of the Am. Med. Assoc, Aug. 30th, 1884 ; see also ' Amer. Journ. of Med. Sci.,' Oct., 1884. 272 de. dtjheing's papers on of good general health. He never experienced any disease of the skin until six weeks ago, when the present eruption made its appearance. There is no family history worthy of record. While gunning in the meadows he unexpectedly found himself in a bog of soft, blackish, strong- smelling earth, into which he sank deeper with every step. He at once recognised the nature of the spot and the danger, and endeavoured to extricate himself, but this proved no easy matter, for with every step he sank deeper into the mire, until in a short time he was buried up to his armpits. He realised his extreme danger, and looked forward to a speedy and miser- able death. After struggling for a full half -hour in the above predicament he succeeded in seizing a tuft of grass just within reach. By gradually working himself loose and pulling on the grass he finally, in an exhausted state, managed to reach firm ground. He was carried home in a weak condition, bathed and cared for. Three days after this adventure, which had greatly shocked his whole system, the eruption appeared in the form of small, variously shaped, round, oval, and angular vesicles, or small "blisters con- taining clear fluid." They came out in number, and were scattered over the flexor surfaces of arms and forearms. When first noticed they were pin-head in size, and were not accompanied by areolae, but seemed to rise directly from the sound skin ; two days later, however, inflammation surrounded their bases. At first they were free of itching, but towards the fourth or fifth day, by which time they had slowly grown to the size of peas, this symptom set in violently. On the second day of the attack scattered lesions of the same character appeared here and there over the trunk, legs, and thighs, and were especially numerous on the posterior surfaces of the thighs, over the shins, and about the ankles, and were quite sym- metrically distributed. On the trunk they were on the back, chiefly between the scapulas, and on the abdomen about the umbilicus and pubes. On the chest they were few in number and disseminated. By the fifth or sixth day they had attained the size of large peas — in short, became llebs ; were tensely distended DERMATITIS HERPETIFORMIS. 273 with clear, serous contents ; showed no disposition to rup- ture; and were accompanied with slight areola?. The itching now became annoying and was constant, the desire to scratch being uncontrollable. The general health remained good ; no chilliness or fever. About this date he was rubbed with olive oil, which aggravated his condition, the skin by the next day becoming hot and more irritable. New lesions continued to appear, especially on the back, and the older ones increased in size without showing any sign of rupturing, and where two or more were in close proximity they often coalesced. Prom the sixth to the thirteenth day he had no rest, the itching being of the most harassing character. About the eleventh day the lesions became darker, the contents showing a distinct orange-yellow colour, and instead of being serous in character were thicker and of a "jelly-like " consistence, so that when the blebs opened with a knife the mass could be removed as a semi-solid gelatinous substance. On the fourteenth day the skin generally and the lesions assumed a dark reddish, bluish-red colour, while the latter contracted and in a few days became crusted and hard, so that with his finger he could "knock them off," a dark reddish stain remaining. The eruption at this date was at its height. The blehs were very numerous, the whole surface being literally covered. The scalp, face, ears, penis, and scrotum, and even the verge of the anus, were attacked, the palms and soles being the only regions that escaped. The mouth was likewise unaffected. The lesions varied in size from a pea to a walnut, the average size being that of a silver dime ; the larger ones were generally formed by the coalition of two or more lesions. They were semi-globular in shape, tensely distended, and in no instance flattened or umbilicated. None burst spontaneously, but many were ruptured by vio- lence ; they invariably burst with a " crack " or " explosion." As already stated, crusting took place in the course of a few days, the crust being of a yellowish-brown or dark brown colour, and not bulky. After these became detached, he observed about the bases of the original lesions a few small pin-head sized " whitish points " or pustules, which multiplied and grew rapidly, itched, and burned; were 18 274 DR. DUHEING'S PAPERS ON raised ; ran together in many instances ; and in four or five days developed into large yellowish pustules, some of them being as large as cherries. Nearly all of these lesions, hundreds in number, were punctured, the walls collapsing and the contents flowing freely, but being somewhat turbid. This outbreak constitutes what he terms the second attack. The lesions were as abundant as in the first attack, and while showing a disposition to appear on the sites of the old lesions yet came out also on sound skin. Poultices were applied, and later crusts formed as before, which in the course of a few days became detached, leaving dark reddish spots and stains. He now rapidly recovered and remained nearly well for a week, when the third attack set in. This was ushered in by malaise, chills, heat, nervousness, and a general itching of the surface, the eruption developing much more rapidly than before. The lesions were for the most part distinctly pustular in character, the others being vesico-pustular, vesi- cular, and bullous ; were flat, surrounded with inflammatory areolae, and itchy. They appeared only on the extremities and over the abdomen. They differed in their distribution from the former lesions in being grouped, two, three, or more manifesting themselves in close proximity, often co- alescing. Present Condition. — November 22nd, 1878. He is now suffering with the remains of the third attack, just described, to which within the week has been added a fourth outbreak. New lesions have been coming out from day to day. He is confined to bed, and is suffering with a profuse multiform eruption occupying the greater portion of the general sur- face. It consists of vesicles, blebs, vesico-pustules, and pustules of various sizes and shapes, and in all stages of evolution ; erythematous (light and dark red) patches and stains, for the most part the remains of former lesions ; excoriations and scratch-marks, and crusts, though these latter lesions are by no means abundant. The multiformity of the lesions is striking. Vesicles, blebs, and pustules are in about equal proportion, and are so intermingled as to exist side by side. The vesicles and blebs may be first considered, and I speak of together, them for it is impossibleto drawaline DERMATITIS HERPETIFORMIS. 275 of distinction between them ; the difference is merely of size. They exist in large numbers, in hundreds. They vary in size from a pin-head to a walnut and larger, the majority averaging between a split pea and a hazel-nut. They are semi -globular or flat in form, and are either tensely distended or flaccid, the former condition existing in all of the smaller lesions. They rise abruptly from the surrounding skin to the height of from one to several lines, have moderately thick walls, similar to the lesions of pemphigus, and show no disposition to rupture spontaneously. There is no sign of umbilication. They are of all shapes, the majority being circular or ovalish ; but some are irregular in outline and show angular, "puckered" borders, as is often seen in herpes zoster, in which event they are usually surrounded with bright red, highly inflammatory areola?. Many of the vesicles and blebs rise up without areolae, looking like magnified sudatnina. They have a pearly or pale yellowish colour, and, as in the case of other similar lesions, refract light, which gives them a glistening appearance. The con- tents are for the most part clear, but some are cloudy, and in many instances are more or less tinged with blood, pro- ducing a mottled or streaked bluish-red haemorrhagic look. The pustules are likewise in all stages of evolution both as to size and extent of pustulation. Some are distinct pustules no larger than pin-heads, flat or semi-globular in form, and circular or irregular in outline ; while others of the same size and larger have evidently been vesicles and blebs, and are passing into pustules. Still others are the size of peas and cherries, and are distinctly pustular, like the lesions of true simple impetigo, and contain whitish, pale yellowish puriform contents. Some are in a perfect state of preservation, semi-globular or acuminate in form; others are more or less collapsed. As stated, inflammatory areolae surround almost all of the larger pustules. As regards distribution, no region is free except the palms of the hands. It is a very general eruption, the lower ex- tremities exhibiting the most lesions. The flexor surfaces are especially invaded. Upon the thighs and legs there is not a square inch that is not the seat of disease. The skin which is not occupied by distinct lesions is dark red and 276 dr. duhring's papers on violaceous in colour. The ankles are literally encircled with blebs and pustules, many of which have run together, form- ing large, elongated, flaccid, partly bloody, dependent blebs. There is everywhere a tendency for the lesions to group, and while owing to their great multitude this is not striking in all regions, it is nevertheless very manifest in certain localities, as on the buttocks and thighs. The groups are for the most part small, consisting of from three to five lesions situated within a radius of an inch. In other places a dozen or more lesions occupy an area the size of the palm of the hand. A peculiarity of the lesions is their disposition to coalesce. Inclining to manifest themselves in ill-defined clusters of two, three, or more, as they increase in size they run together, forming larger lesions. Around the immediate circumference of these lesions, whether vesicular or pustular, smaller flat pustules or vesicles, the size of pin-heads, are in many instances present. When ruptured the lesions crust over with flat, light yellowish crusts. Removing these, super- ficially excoriated, moist, reddish surfaces, having sharply defined irregular vesicular or pustular borders, are exposed to view. Everywhere about the older lesions there is noted a disposition on the part of the process to extend itself in a creeping manner while healing in the centre. Itching is present, and is very distressing. December 19th. — A month has elapsed since the last note. Duringthisperiodfour distinct attacks orcropsof eruptionhave manifested themselves. The lesions in the first three attacks were of the same character as those in the outbreak of November 22nd, just described at length, namely, vesicles, blebs, and pustules, with but little inclination to intermediate forms, while in the present eruption vesico- pustules predomi- nate. The last two attacks have been milder, with smaller lesions, but accompanied with more itching. The general course of the disease, the disposition of the lesions to clus- ter, and the regions invaded, have been the same as on pre- vious occasions. At present the eruption is characterised by many small, and some large, variously shaped vesicles, vesico-pustules, and pustules, occurring in patches or scattered over the surface, in all stages of evolution, together with DERMATITIS HERPETIFORMIS. 277 numerous excoriations, ruptured or torn, lesions, crusts and, scales seated upon a dark red, violaceous, mottled, pigmented skin, the remains of former attacks. The patient is able to be about the house ; his general health is good. He has used lately alkaline tarry lotions. Arsenious acid, in doses of one-fortieth of a grain, has also been taken for the last three weeks ; also quinia, and a general tonic treatment. In December, 1882 (four years after the last note), I received a note from the patient, stating " I am still troubled with the disease, and it has not failed to put in an appear- ance at certain periods since you saw me in 1878, although the blisters and pustules have gradually become less, both in number and in size. At certain times since, within the year, I was so free of eruption that at one time I thought surely I was rid of my pest. I can always tell two or three days before the eruption will appear by the coming on of an itching sensation. During the past six months I have had two attacks." The history of this case, including the cause of the disease — a violent shock to the nervous system — is both interesting and instructive. The bullous variety predomi- nated, and when I first saw him, it was highly developed ; subsequently, however, (as in almost every case that I have encountered), other lesions, especially pustules, manifested themselves. The constitutional symptoms accompanying one exacerbation were marked. 278 de. duheing's papers on ON THE RELATION OP IMPETIGO HERPETIFORMIS (HEBRA AND KAPOSI) TO DERMATITIS HERPETIFORMIS (DUHRING). 1 As there have been considerable discussion and some diversity of opinion as to the propriety of grouping impetigo herpetiformis under dermatitis herpetiformis, I desire briefly to present my reasons for having originally adopted this view. It may be well to premise my remarks with the statement that heretofore, in my several communications on this disease, I have confined my observations largely, if not exclusively, to the cutaneous manifestation — to the skin disease proper — with the idea mainly of calling attention to the multiform phases of the disease. The symptoms alone, it may be said, have up to the present time received attention ; the equally if not more important subjects of etiology and pathology being for the time intentionally slighted. In all rare or obscure affections the eruption it- self, including its history, symptoms, evolution, and involu- tion, is first to be considered. After these points have been determined upon, as far as the material at hand will permit of, the questions of the cause and nature of the disease natur- ally follow for investigation and discussion. In addition to the clinical memoranda and observations presented from time to time, I have sought to bring together into one group such previously reported cases, scattered throughout literature, and certain other allied forms of disease, as seemed to me might properly be included under one head. Circumstances have, for some time past, prevented me from continuing my 1 Reprinted from the 'American Journal of the Medical Sciences' for March, 1890. DERMATITIS HERPETIFORMIS. 279 study on the subject, which will account for what may seem indifference or neglect of the question. It is now over five years since I first called attention to a disease of the skin which, up to that time, had not re- ceived special notice. A number of cases of a peculiar cu- taneous disease had, from time to time, previously come under my observation, all possessing certain striking features in common when viewed in their totality — that is, through- out their complete history, including relapses. There ex- isted manifestly several quite different varieties of the affec- tion, as shown by the presence in some instances of a decided predominance of certain lesions, while in other cases differ- ent forms even prevailed. But beneath this cloak of multi- formity, and notwithstanding the occurrence of diverse lesions simultaneously or of those which made their appearance from time to time as the affection ran its course, certain striking pathognomonic symptoms could not fail to impress themselves upon the observer, showing the existence of a peculiar and undescribed disease. Had a few cases only been encoun- tered at long intervals, these features might not have been recognised so readily. As the disease represented by these examples was practi- cally unknown and had no place in literature, it seemed necessary to bestow upon it a title. The relatively large number of cases that I had encountered seemed to warrant such recognition. By reason of the uncertain and variable character of the eruption, of its conspicuously diverse primary lesions and their distribution and arrangement, occurring in the several forms or varieties in which it usually appeared, and, moreover, because of its distinctly herpetiform feature, the name dermatitis herpetiformis was selected. The term dermatitis, owing to the idea of wide-spread or general and varied inflammation thereby conveyed or implied, and be- cause of its being non-committal as to etiology and pathology, appeared to meet the requirements better than any other that suggested itself ; while one of the most distinctive cha- racteristics was made plain by the word herpetiform. To this latter point I wish to direct special attention, and I would here say that the herpetiform element has been pre- sent in all of the cases (now, perhaps, twenty in number) 280 be. duhbing's papers on that I have seen, in some instances marked, in others exist- ing to a moderate or only* a slight extent. As the matter stands to-day, the disease is sufficiently well defined to he readily recognisable by all observers where typical cases are concerned. I cannot well see how pro- nounced forms, especially if held under observation long enough to note the ever-changing lesions and the varied aspect of the eruption, can be confounded with other better known affections. In ill-defined, atypical forms it is, of course, liable to be mistaken for certain other diseases to which it may bear more or less resemblance, more especially erythema multiforme, herpes iris, pemphigus, and eczema, according to the views held by the observer, precisely as in other doubtful forms of skin disease. Thus, for example, as is well known, discrepancy in diagnosis is not infrequently encountered in eruptions characterised by the formation of blebs, one observer regarding all such manifestations as varieties of " pemphigus," another merely as instances of "bullous disease," — a vague, non-committal expression, plainly indicating an unwillingness on the part of the ob- server to subscribe to the view that every bullous eruption must necessarily be pemphigus. The relations of dermatitis herpetiformis to erythema multiforme, herpes iris, and pemphigus are, I need not say, most interesting and important topics, to which I naturally have had my attention directed. But these sub- jects cannot be entered upon without a great deal of discus- sion. Here, at once, arises the matter of definition. For example, how shall these diseases — erythema multiforme, herpes iris, and pemphigus — be defined ? What forms of eruption shall be included and what excluded under these names ? Shall the. old, time-honoured, classic definitions continue to be observed, or should new ones be framed to take in enlarged views concerning these processes ? This question cannot be entered into at present, nor do I wish now to speak of the relation of dermatitis herpetiformis to the diseases just cited, nor to any other vesicular, bullous, or pustular affections, except one, namely, the impetigo herpetiformis of Hebra. At this point I must be permitted to go back a few DERMATITIS HERPETIFORMIS. 281 years, in order' to make my position; views, and reasons therefor clear. As is known to all, Hebra described, in 1872, a grave pustular disease of the skin, of which several instances had, from time to time, been observed at the Vienna General Hospital. The description given was brief, and in the dermatological world at large the subject attracted comparatively little attention. Dermatologists in other parts of Europe and in this country seemed at a loss to identify or recognise the disease. In the United States it did not seem to be known. My American fellow-derma- tologists in the large cities, with whom I conversed, were not familiar with it, nor was I myself able to reconcile Hebra's description . with any of the pustular affections encountered in my field of study. Nor was the disease recognised either in France or England. Moreover con- siderable confusion existed even in Vienna, competent observers there being by no means of the same opinion regarding the disease and its proper classification. Thus Hebra himself first looked upon it as belonging to the herpes group, and called it " herpes impetiginiformis," with the idea that it was a form of herpes ; subsequently he regarded it as an herpetiform impetigo. Nor was the subject materially elucidated by the publication of several of Hebra's original cases by Auspitz and by Geber, the first of whom looked upon it as herpes, calling it " herpes vegetans/' while the latter also endeavored to prove it to be herpes. Then Neumann, who was without doubt familiar with Hebra's cases, emphatically designated it herpes, terming it " herpes pysemicus " or " herpes puer- peralis." Even at this later date, notwithstanding all that had been written by the Viennese dermatologists, the subject was far from clear to the minds of foreign dermatologists. The consensus of opinion on the part of the Vienna ob- servers, however, seemed to be that the disease was an undescribed form of herpes, as is evidenced by the names decided upon by the several reporters. Nor, finally, was the matter made plainer by Hebra himself, who stated that the case previously reported by himself and Baerensprung as "herpes circinatus," and figured in their atlas of skin diseases, was also an example of this same disease, namely, 282 de. duhring's papees on impetigo herpetiformis. It need scarcely be said now, in passing, that if the views (to be referred to) recently put forth by Kaposi be accepted, this peculiar case must be excluded from the list. No further examples were at this period reported, and the matter for the time being remained quiescent. In the meantime, in Philadelphia, during this epoch (from 1870 to 1880), a series of cases of an unknown, in- flammatory, polymorphous affection of the skin had come under my observation — some in hospital, others in private practice. Among these was one which, when it first was brought to notice, appeared to me (and to other physicians who saw it) to be an example of the impetigo herpetiformis of Hebra. It apparently represented a mild expression of that disease, and showed the chief clinical features depicted in one of the portraits (case of 1871) in Hebra's atlas. The resemblance was striking. The cutaneous manifestation was altogether novel, and I was unable to classify it else- where. ■ The patient was a woman. The eruption was general and extensive, and was exclusively pustular (with no signs of erythematous, urticarial, vesicular, or bullous lesions) and crusted, the pustules being whitish and yellowish, and of varied shapes and sizes, some being distinctly -elevated and somewhat conical or rounded, others fiat ; some were miliary, others small, pea-sized, and some larger ; all being seated on more or less inflamed bases or arising from inflamed patches. The eruption, as a whole, was, moreover, herpetiform, showing a distribution and arrangement here and there similar to that seen in imperfectly developed or abortive herpes zoster. The lesions themselves were irre- gularly grouped, as is sometimes noted in small discrete patches of zoster. The central pustules, often aggregated in little bunches of two, three, or four, were small but of variable size ; the older ones were more or less crusted, and were closely encircled' in an incomplete, broken manner, with new, for the most part sparse, flat, minute pin-head sized pustules. There was, moreover, marked pigmentation in patches here and there ; also malaise, with a disposition to be cold and hot alternately, hardly amounting to a regular DERMATITIS HERPETIFORMIS. 283 chill. Finally, there were heat and burning and some itch- ing, but recent scratch-marks were not conspicuously present. In brief, the case possessed, so far as the skin was concerned, the chief characteristics of Hebra's impetigo herpetiformis, and this diagnosis was accordingly made. The disease persisted, the eruption repeating itself in a succession of crops with the same kind of lesions, and within six months disappeared, to be replaced, however, by an altogether different dermatological picture, — one with which I was quite familiar, namely, a polymorphous, mixed vesicular and bullous, inflammatory, herpetiform eruption, accompanied with, severe burning and itching, or, briefly, the typical form of derma- titis herpetiformis. Subsequently the previous impetigi- nous or strictly pustular form recurred, manifesting itself precisely as before ; and during the next year the , eruption again became vesicular and bullous. There was now, after several years of observation, but one conclusion to draw — namely, that these diverse cutaneous manifestations all belonged to one pathological state, were simply varieties, or forms, of one process. Other similar cases later came under notice which strengthened this view, and I accordingly expressed myself that Hebra's impetigo her- petiformis (as I understood that disease from Hebra's descrip- tion and portraits) might be regarded as a pustular mani- festation of an extensive multiform (erythematous, vesicular, bullous, and pustular) herpetiform disease of the skin. This view, moreover, seemed to be supported by a case of " im- petigo herpetiformis and pemphigus " reported by Heitzmann, of New York, which, while it presented the characteristic cutaneous features of Hebra's disease for a period of several months, abruptly changed from a pustular to a bullous affec- tion, the blebs being in all respects like those of pemphigus. From this case Heitzmann drew the conclusion that both diseases arose from identical causes, and should be considered as being kindred to each other. It may be added that in this case the disease did not occur in connection with preg- nancy, and that no cause could be assigned for its presence, the patient having been an apparently healthy woman, fifty- two years of age. The disease, nevertheless, ran a fatal course in about eight months from the beginning, oedema 284 de. duhring's papers on of the meninges setting in toward the end. There can scarcely be any question here concerning the diagnosis of impetigo herpetiformis, for Dr. Heitzmann had not only seen three of Hebra's cases in Vienna, but had, moreover, painted the portraits which portray this disease in Hebra's atlas. The subject remained in statu quo until my several com- munications appeared, and, later, Kaposi's valuable contri- bution on impetigo herpetiformis in 1887, in which the relations of that disease to some other affections (including dermatitis herpetiformis) are discussed. From this latter article a much more satisfactory idea of this disease is obr tained than from any previous publication. The subject is presented in a different if not a new light, and is fortified by reference to additional and more recent observations, and we are enabled to note what the author would have us regard as impetigo herpetiformis. If this definition, then, is to be accepted, and to be restricted so as to include only such cases as the author refers to, I admit that it becomes questionable whether the disease should be regarded as a variety of dermatitis herpetiformis. If the definition is to be rigidly confined to such cases (including their nature) as Kaposi quotes, the disposition of the matter would be simple ; but other observers of this disease (or what they assume to be the same affection) do not entirely agree with the Vienna dermatologist. According to Kaposi, the disease is invari- ably characterised by superficial miliary pustules, which begin as such and remain unchanged throughout their entire course, always arranged in groups and clusters, new lesions appearing on the border of older and crusted confluent pustules, in one or more series, on inflamed bases, while recovery takes place in the centre ; furthermore the disease occurs only in preg- nant or puerperal women, and is accompanied with chills and marked fever, and is almost invariably fatal. This defini- tion is clear and simple enough, but does it include all forms of the disease ? Is it sufficiently comprehensive ? The question might pertinently be raised, is it wise to make the definition so circumscribed ; is the disease not liable to vary from this type ; does it invariably show these very precise features ; are, for example, the pustules always DERMATITIS HERPETIFORMIS. 285 miliary, and from beginning to end ; may they not vary in size, and, more especially, be considerably larger ? Surely one portrait of this disease in Hebra's atlas (case of 1871, referred to before) fails to portray a miliary eruption ; on the contrary, not only are many of the pustules large, but there is, moreover, considerable variation in size ; nor is their arrangement and mode of extension or spreading ap- parently like that depicted in the other cases, namely, peri- pherally, as in herpes circinatus. I may remark further on this point that I find it difficult to reconcile this portrait with Kaposi's description of the eruption, and, finally, that it was mainly upon this illustration that I ventured to base the opinion of the identity of one of my cases (that of Annie McC — , ' Journ. of Cut. and Ven. Dis.,' vol. ii, No. 8) with the disease depicted. If Kaposi's views be adopted, Heitzmann's case, already referred to, cannot be regarded as impetigo herpetiformis, although, as previously remarked, from the fact that Heitzmann had the opportunity of seeing several of Hebra's original cases, it would seem that he must be entirely familiar with the subject. Nor can Zeisler's case ( f Monatshefte fur prakt. Dermat.,' 1887, No. 21) of so-called " impetigo herpetiformis," which he, Dr. Hyde, and others believed to be an example of the Hebra and Kaposi disease, be regarded as such. It may be questioned further, Does impetigo herpetiformis in all instances exhibit the same grave general symptoms and course, terminating in almost every case fatally ? Such symptoms and termination assuredly might be anticipated if it were generally admitted that the cause was uniformly septicaemia, — that the disease was always of ' septicemic origin. But may not various causes give rise to the same cutaneous manifestations, not only here, but elsewhere, as in the case of certain other affections of the skin — as, for example, eczema ? There was a time, not long ago, when Kaposi held that the disease occurred exclusively in women, but lately he has himself given the notes of a case observed in a man. From this criticism I wish merely to intimate or suggest that our definitions should not be drawn too closely. Most observers will agree that as our experience enlarges in dermatology we find in all directions the need of 286 dr. duhring's papers on more breadth or latitude. Expansion in almost all instances,, we note, comes sooner or later. I have thus endeavoured to present a concise historical sketch of impetigo herpetiformis, and also, more particularly, to state my reasons for having, in my earlier papers, re- garded it as one of the manifestations of a peculiar, poly- morphous, extensive process designated dermatitis herpeti- formis. Whether I was right or in error in advancing this view is a question depending largely, in my opinion, upon the definition that shall be accorded to impetigo herpeti- formis ; and here I may remark that it is far from my thoughts to undervalue the observations of the distinguished Vienna dermatologist, whose extended and unique experi- ence with impetigo herpetiformis entitles his communication to due consideration. My desire has been from the begin- ning simply to arrive at the true position which that disease occupies, and more especially to define its relationship to other allied affections. I may say, in passing, that had Kaposi's article been published at the' date of my several communications, I should probably have, in some degree, qualified the conclusions concerning the identity of the affections. In bringing these remarks to an end, I would say that I have always held to the opinion that all discussions tending to create perplexity should be avoided. On this point I feel strongly in the present case concerning the relationship of the two forms of eruption which are the subject of this paper. The matter can only be settled by fully recorded observations at the hands of competent reporters, and it is highly important for future studies and deductions that the cases be ranged under such titles as will convey the clearest idea of the clinical picture. Considering, therefore, the existing difference of views, and in order that no possible barrier may impede progress, it will perhaps be to the advancement of the subject to separate, for the present at least, the diseases ; and that, in the future, observations be reported under one caption or the other, as may seem most in harmony with the clinical facts of the case. DERMATITIS HERPETIFORMIS. 287 CASE OF TYPICAL DERMATITIS HERPETIFORMIS. 1 During the past month, a typical example of this affection has been under almost daily observation, and the symptoms have been so pronounced and so characteristic of the usual form of the disease that I desire to add the case to the list of those already published. I describe the case, moreover, because there seemed to be some doubt as to the diagnosis in the minds of the several well-known practitioners who had charge of the gentleman before he came under my observa- tion. Mr. S — , of Cincinnati, consulted me about the middle of January of the present year, with a letter describing his previous condition and treatment from Dr. Ransohoff, under whose care he had been for some time. The doctor's letter states that the patient (a man about fifty years of age and of dark complexion), who had before always enjoyed good health, manifested " squamous eczema " of both hands about a year ago. Pour months later the present illness began with the development of blisters of the size of a pea or bean on the hands, wrists, feet, and ankles. In July last a fully developed " pemphigus simplex " existed, the blebs being as large as a silver dollar, tense, and containing a clear fluid. These appeared in successive crops all over the body. During the four months of the acute attack hardly a square inch of the surface was left uninvaded. When the blebs disappeared excoriations of similar dimensions remained, but which were soon covered again with epidermis. Loss in weighs most distressing itching ("pemphigus 1 Keprinted from the ' American Journal of the Medical Sciences ' for Jane, 1890. 288 de. dtjhring's papers on pruriginosus "), and from time to time septic manifestations ; low, muttering delirium, slight elevation of temperature, rapid and irregular heart action, heavily coated, dry tongue, diarrhoea, and profuse night-sweats were all present. Under sustaining treatment and local remedies, such as the con- tinuous hath for two weeks, swathing in oil, oxide of zinc and bismuth bandages, the patient finally began to improve, and was able to leave home for a change of climate. When last seen the itching still persisted, and the skin, especially of the extremities, presented a livid hue and was sodden. It, moreover, was elevated in the form of large indurated papules where formerly vesicles (which did not rupture) had existed. Dr. Ransohoff concludes his letter by stating that at first the diagnosis of dermatitis herpetiformis was made, but that later, when at its height, the disease seemed to possess the features of pemphigus pruriginosus ; while still later, as improvement set in, it again approached dermatitis herpetiformis. When I first saw the case the skin was much inflamed, excessively pigmented, of a dirty-looking, mottled, yellowish- brownish colour, thickened, and the seat of an extensive eruption, consisting of small and large, more or less con- fluent, inflammatory patches, together with distinct indi- vidual lesions, occupying almost the entire general surface. The trunk and the upper and lower extremities were com- pletely covered with a multiform eruption of a mixed chronic, subacute, and acute character, arising from a chronically inflamed, infiltrated, and toughened skin. The greatest possible variety of inflammation existed in the form of a continuous mass or sheet of eruption, there being no healthy skin on the affected regions. The lesions were macules, maculo-papules, papules, ir- regularly shaped and defined, flat or spread out (as in ery- thema multiforme), and of variable dimensions ; vesico- papules and vesicles varying in size from a small pin-head to a pea, some being flat, glistening, and blister-like, others raised and surrounded with a somewhat drawn together or puckered, highly inflamed base, as in herpes zoster. Many of the vesicles were minute and scarcely visible, except in oblique light. Here and there blebs existed, some small, DERMATITIS HERPETIFORMIS. 289 otters large ; also small pustules, which evidently had begun as pustules, some of them being flat and punctate, pin-head and millet-seed sized. On the shoulders and upper part of the back the exist- ence of small, mostly miliary lesions (papules, papulo-vesicles, and pustules), commingled and in all stages of evolution, and grouped into patches, some of them marginate, together with the marked pigmentation, suggested a likeness to a subacute, copious, miliary, herpetiform syphiloderm. Excoriations and abrasions due to scratchings, blood- crusts, and slight yellowish and brownish crusts about the summits of vesicles and pustules, together with torn ad- herent epidermis, were also present, the whole picture being one of great multiformity, such as is noted in no other disease. As is well known, marked multiformity is often observed in scabies of several months' duration, but the affection here was even more polymorphous than occurs in that disease. The lesions were aggregated, grouped, and disseminated, but the eruption, as a whole, was herpetiform — the distribu- tion, general arrangement of the individual lesions and of the patches, the progress and the manner of extension, all suggesting certain symptoms common to erythema multi- forme, herpes iris, or herpes simplex. Here and there the close grouping or bunching of three or four usually minute or small vesicles or vesico-pustules upon an inflamed base resembled an abortive patch of herpes zoster. The disease, however, bore more likeness to erythema multiforme of an advanced stage and of a severe type than to any other affec- tion. Furthermore, itching and burning were present to an excessive degree, tormenting him by day and by night. He was, moreover, nervous, irritable, and anxious. I will now enumerate the local remedies that were em- ployed, and comment briefly on their action, which, it may be here remarked, was far from satisfactory. The patient stated that a number of remedies had been previously used without affording much relief, among them the various soothing and more stimulating washes and oint- ments useful in eczema. Those prescribed by me consisted of sulphur in the form of ointment, both weak and strong, 19 290 DR. DTTHEING's PAPERS ON and also in the form of a dusting powder, liquor carbonis detergens, ichthyol, as a wash and as an ointment, weak and strong ; mild salicylic acid ointment, fluid extract of grindelia robusta as a lotion, weak and strong, and carbolic acid as a lotion, all having been made use of from time to time. The most useful were sulphur ointment, two to three drachms to the ounce, and liquor carbonis detergens, from one half to two drachms to the ounce. These remedies, as well as others, were employed on various parts of the body, and with each experiment it was the rule to make the application of one remedy to one lateral half, and another to the other half of the body, with the view of determining the relative merits of each. The fluid extract of grindelia robusta on several occasions was found to be of some value, but the sulphur ointment was the most useful. This was used with considerable friction in order to break down the vesicles, as in the case of scabies, and on several occasions improved the skin and relieved the itching. Internally, antipyrin, antifebrin, phenacetin, chloral, and belladonna were all prescribed to meet symptoms, but with only moderate success. During the four or five weeks which followed, the disease on two occasions improved considerably, but again became worse, the process manifesting itself in the form of exacer- bations, each lasting about a week. Now and then large blebs formed here and there, especially on the thighs. On the trunk the lesions were at one time more erythematous, at another time more vesicular. The herpetiform element, more or less well-defined, remained constant, and constituted a feature of the disease. In conclusion, the case may be summed up as showing the disease in its typical form, characterised by a multiform eruption of slightly raised, erythematous, herpetic patches, more or less confluent, together with papulo-vesicles and vesicles and blebs of variable size, shape, and outline, like- wise, as a rule, herpetic. The thickening of the integument and the marked pigmentation from the oft-repeated attacks of eruption and scratching, and the itching and burning were also conspicuous symptoms. The general health was at times considerably disturbed, as shown by the nervous, DERMATITIS HERPETIFORMIS. 291 anxious, irritable state, the loss of appetite and of sleep, and the excessive sweating and great thirst. The urine was cloudy and dark, and variable in quantity, as is the case in other forms of general nerve depression. In the matter of diagnosis, the disease, during the period it was under my observation, could hardly be mistaken for any other affection ; surely not pemphigus, because blebs were the exception ; nor would eczema suggest itself, because of the prevailing herpetiform characters of the individual lesions and of the patches. Everywhere and on all occasions the eruption showed itself to be under the control of the peripheral nerves, as in the other more marked and better known forms of herpetic diseases. THE TREATMENT OF DERMATITIS HERPETIFORMIS. 1 In the several communications on this disease that have been published by me during the past five years, no special remarks have been made concerning its treatment. The subject-matter of these papers has been largely confined to a statement of the cases observed with the view of setting forth the symptoms and the more important clinical facts, in the hope that the disease might become better known. A number of cases (perhaps ten or twelve) have been reported by me, and others have been observed in my private and public practice, so that now it seems appropriate that some- thing should be said about the treatment of this exceedingly rebellious disease. At the same time, I would state here that in many cases the remedies employed, both ex- ternal and internal, seemed to exert but little or no bene- 1 Eead before the American Dermatological Association, September 3rd > 1890. Eeprinted from the 'American Journal of the Medical Sciences ' for February, 1891. i292 • dr. duhbing's papees on ficial effect. In severe cases, and especially during an exacerbation, no • form of local treatment used appeared capable of making a favourable impression on the skin. In such instances the disease is the most difficult to influence of all the inflammatory affections, surpassing even inveterate eczema. The internal treatment may first receive attention. The generally-recognised observation that the disease may arise from and be dependent upon several distinct or even diverse causes — precisely, for example, as occurs in the case of eczema — precludes positive statements as to remedies. Each group of cases, based on the etiological factors at work, requires special handling,' and hence I believe no class of remedies can be recommended which would be suitable to all cases. The origin of the disease, where this is ascertain- able, should ever be kept in mind, and the treatment be pursued in this direction on general principles. With a •disease which in most instances is exceedingly persistent and chronic in its course, a speedy cure is not to be looked for, cither from internal or local remedies. I shall make my remarks as practical as possible and be brief. The local treatment may first be considered. It must be remembered that the disease, as a rule, is multi- form in character, and that, as in the case of eczema, we have to deal with varied lesions, at one time erythema, at another vesiculation or pustulation. The several varieties of the disease, therefore, naturally call for different formulas, certainly as to strength, and sometimes even for different remedies. Thus, my experience has shown that milder preparations are required for the erythematous than for ■either the vesicular or bullous, and I would here remark that this (erythematous) variety is the most difficult of all to control by local means, while the vesicular is the most •easily influenced. It is not my purpose at present to take up the treatment of the several varieties of the disease specially, but rather to ask attention to the principles of treatment applicable to the disease as a whole. From a therapeutic standpoint the affection may be considered under the headings of acute, subacute, and chronic, the two latter stages being those we are generally called upon to treat. It DERMATITIS HERPETIFORMIS. 293; must be kept in mind that the disease involves in most cases the greater part of the general surface ; that therefore there is a good deal of cutaneous surface requiring attention, and that the remedies must be selected and prepared to meet that end. Another difficulty that we have to contend with is that the eruption tends to repeat itself in the form of more or less frequently recurring outbreaks or crops, a new one often coming out before the old one has disappeared, the skin thus being in a peculiar state, interfering with and ; complicating the treatment. It is this condition and the variety of elementary and secondary lesions generally present at the same time that render the treatment so difficult. Almost all the cases that have been under my observation have been chronic, and previously had undergone all manner of treatment ; in some instances at the hands of competent dermatologists. Long experience has taught me that the, disease is most difficult to control, and that some of the remedies from which good results might be looked for — such, for example, as are useful in eczema — exert but little or no influence in arresting the process. The milder so- called, soothing preparations, as boric acid, calamine and Oxide of zinc lotions, ointments, and pastes, sometimes so useful in acute or subacute erythematous and vesicular eczema, are of no value in this disease. I have long since arrived at the conclusion that the only class of remedies from which benefit is to be expected is stimulants, especi- ally those which act revulsively. I will first enumerate a few of the more important substances that have been em- ployed. These are : tar, in the form of oil, ointment, and alcoholic and alkaline tarry lotions j carbolic acid, sulphur, Vlemmgkx's solution of sulphurated lime, thymol, ichthyol, hydronaphthol, resorcin, and fluid extract of grindelia robusta. On account of the peculiarity of the eruption, in- cluding its multiformity, mixed acute, subacute, and chronic stages, and distressing subjective symptoms, it is difficult both for the patient and physician to estimate the value of any remedy. Such sufferers, moreover, are seldom content to remain long under the care of any one physician, hoping continually to derive benefit from frequent change of treat- ment. Of the remedies just referred to, the most valuable 294 dr. duheing's papers on is sulphur, and in the form of ointment, about two drachms to the ounce. I was first led to employ it through the state- ment of a patient many years ago, who had derived more benefit from it than from any other substance. He had suffered long with the vesicular variety, and had sought the advice of many physicians without obtaining even temporary relief. On one occasion, in desperation, he rubbed himself vigorously with a strong sulphur ointment, made soft by the addition of walnut oil. This afforded immediate and grati- fying relief, such as no other application had ever given, and, moreover, soon caused the eruption to disappear. On subsequent occasions he had again employed it, and he re- garded it as the most valued remedy known to him. The remedy and mode of application seemed to me harsh and unlikely to succeed, but a trial proved satisfactory and bore out the statement made. My experience with it leads me to regard it as especially useful in the vesicular and pustu- lar varieties, and also in the bullous, but that in the ery- thematous variety it usually proves irritating. Let me here say, however, that in some cases it has failed to act favor- ably, and I by no means wish to lay too much stress on its value, nor to put it forth as a specific. I merely desire to state that in the vesicular variety it is the best remedy that we are acquainted with. It should be applied with friction and with sufficient force to break down the vesicles, pustules, and blebs as speedily as possible. As already intimated, the ointment should be strong, about two drachms to the ounce, and should be used in the manner indicated, with the view of making a positive impression on the skin, by causing, as it were, local shock to the nerve-endings. The rubbing should be long continued and thorough. It is useless merely to smear it on, as the object by this means is not accom- plished. In suitable cases acceptable relief to the itching and burning is usually obtained after one or two applica- tions. Remedies of this class, I believe, are the kind from which most benefit is to be looked for. They should not be too harsh nor too stimulating in their action. The strength and the amount of friction must be regulated by the effect. They should be applied as early in the attack as possible, as soon as the lesions begin to form. DERMATITIS HERPETIFORMIS. 295 In some cases tar, especially in the form of the alkaline solution known as liquor picis alkalinis, is useful, especially in allaying the itching. It is, of course, to be diluted, one drachm to about eight ounces of water, according to the caustic effect produced. Another equally valuable tarry solution, and one that is safer to use, is that known as liquor carbonis detergens, an alcoholic solution of coal-tar. This also is to be similiarly diluted, though sometimes it may be advantageously used strong, one drachm to from one to four ounces of water. Both of these preparations are useful in relieving itching, but I do not think that they exert much influence in arresting or modifying the progress of the eruption, and hence they can hardly be looked upon as curative. In the erythematous variety they prove of most value, because here the friction ointments are usually not tolerated. Ichthyol I have used in varied strength in the form of ointments and lotions, and, as in the case of tar, the latter have proved more serviceable, but the remedy is not so efficient as tar. Nor can I speak favorably of re- sorcin, thymol, and carbolic acid. The last-named remedy, especially, has proved less useful than one would expect, considering its well-known powers in other allied inflamma- tory states of the skin. Of the various remedies and com- binations which have been employed on various occasions none can be specially recommended, and hence they need not be enumerated. Baths, for the most part simple and hot, have been used with some benefit in relieving the burn- ing and itching. A patient exhibiting the erythemato- vesicular variety, recently under my care, regarded a hot bath of an hour's duration at night as grateful, but he did not seem to sleep better than when it was omitted. The same patient had, during a previous severe attack, endured a fortnight's experience with the continuous bath, which had afforded a certain amount of ease and comfort, but had not proved in any degree curative. Concerning the internal treatment not much that is favorable can at present be said. With a disease tending to pursue an emphatically chronic course, speedy cure is hardly to be expected. This observation is borne out by experience. Several cases under my notice some years ago 296 de. duhring's papers on recovered in a short time under, for the most part, internal treatment, but I am not prepared to state that the cure was due to the remedies used. In the relapsing and obstinate form relief is to be obtained, I believe, only from such remedies as favourably impress the nervous system. The cutaneous symptoms are such as point distinctly to the neurotic nature of the disease. The eruption, as a whole, possesses features in common with the well-known and established neurotic inflammatory diseases, such as herpes simplex, herpes zoster, herpes iris, and pemphigus. The nervous system, it may be centrally or peripherally, is un- doubtedly in some manner and in a variable degree de- ranged, and it is to aid this important function that we must look in the choice of remedies. Among such drugs I would first speak of arsenic, which in suitable cases offers, I believe, more hope of benefit than any other remedy. By suitable cases I mean more particularly the simple, uncomplicated chronic cases, whose history and cause are obscure, and not those manifestly due to a deranged uterus and the like. At the same time, from my experience and from that of some other practitioners with whom I have been in commu- nication on the subject, it must, on the whole, be regarded as disappointing. No reliance can be placed upon it, and sometimes it seems rather to aggravate the disease. Upon inquiry I have found that most of the patients who have been under my observation had at one time or another pre- viously taken a course of arsenic, and without experiencing much, if any, benefit therefrom. I may add that it has often been a matter of surprise to me how little influence for good or for bad it possessed over the disease. While, therefore, some cases seem to have been benefited, the majority have not been so, possibly, in some instances, because the drug had not been administered in sufficiently large doses. In one case, however, very large doses of Fowler's solution (as much as forty or fifty minims a day) were tolerated, and seemed for the time being partially to control the bleb-formation, but the results, upon the whole, were not beneficial. I believe it to be well worth a trial in the vesicular and bullous varieties, and the dose should be gradually increased. From the well-known power of arsenic DERMATITIS HERPETIFORMIS. 297 to relieve and to cure some cases of true pemphigus, one would naturally look for good results in suitable cases of the disease under consideration, which is, without doubt, allied to the pemphigus process. As far as our knowledge of the treatment of dermatitis herpetiformis extends to-day, no other remedy offers so much hope of benefit in suitable cases, and the results, whether beneficial or harmful, should be duly chronicled with the reports of future cases. Of the value of quinine and strychnine, there is not much to be said beyond that they do not appear to possess any special power over the disease. The same remark may be made concern- ing certain other general remedies that have been employed — as, for example, iron, cod-liver oil, and ergot. In several cases that are called to mind, it was thought that the hygienic influences of change of air and scene might prove beneficial by giving tone to the nervous system, but in this the results were not commensurate with the trouble incurred. But I would by no means undervalue both moral and hy- gienic treatment, both of which should receive full con- sideration ; for experience with this disease shows that in most cases general physical and mental depression are con- spicuous features. THE SENSATION OE ITCHING. 1 By EDWAED BENNET BEONSON, M.D., PBOEESSOR OF DEBMATOLOGY IN THE NEW YOBK POLYCLINIC. It is a somewhat remarkable fact that a manifestation of cutaneous irritability so common as itching, and one with which as a symptom we are so familiar, has been almost entirely neglected as an independent subject of study. Of other anomalies of sensation, such as hyperesthesia, an- aesthesia, and pain, we have tolerably clear and definite notions. But who has explained for us the cause and nature of pruritus ? What is this disturbance of sensation ? To say that it is a form of cutaneous irritation that produces an inclination to scratch (for such is the usual definition) , is as much as to tell us that itching is the desire to scratch. We itch to scratch, and scratch because we itch. It is clearly a nervous disturbance of some sort ; but what produces it, and why scratching relieves it, are questions which, so far as I know, have never been satisfactorily answered. Itching, or something closely akin to it, is in all probability common to most if not all animals, though most marked in those that are hairy or feathered. Though often provoked 1 Read before the American Dermatological Association, September 2nd, 1890. Reprinted from the ' Medical Record,' October 18th, 1890. 300 BRONSON ON THE by irritants extraneous to the body, it also is very frequently spontaneous, occurring under apparently healthy conditions, as well as in disease. When in repose an animal will often by various actions or movements, that answer more or less to the act of scratching, betray the fact that it itches, even when the skin is neither diseased nor molested by insects. And in the human subject spontaneous itching is common enough, and it is often only the sense of propriety that represses the inclination to the desired gratification. The child stripped for bed and begging to have his back scratched is more in the state of nature. Let anyone sit quietly for a moment, fixing attention upon the skin, and the chances are that sooner or later he will become conscious of a slight intrusive irritation at some point, a prickling or picking sensation, and the longer it lasts the more it demands atten- tion. You pass the finger or nail over the irritated point and it is gone. What was it ? Was it pain ? If all uneasiness is pain, yes. If desire is pain, yes. If the in- clination to stretch the limbs, to wink the eyes, to eat is pain, so is this trifling disturbance of sensation, this desire to scratch. In severe itching, and especially in disease, the feeling becomes more complex. This is evident from the multiplicity of expressions used to describe it — such as " tickling," "prickling," "picking," "creeping," "crawling." But always there goes with it the impression of intrusive con- tact, together with the longing to scratch. Closely con- nected with it are other sensations that are secondary and probably entirely independent of the feeling of itching. Such are the smarting, burning, or stinging sensations which only accidentally are coincident with this feeling, and are clearly painful sensations. They are not only independent of the pruritus, but are distinctly antipathic to it. As soon as the scratching becomes violent enough to produce a painful sensation the itching is, temporarily at least, extinguished. Furthermore, any painful sensation of the skin would most likely be aggravated by scratching. Though pruritus has sometimes been described as a variety or phase of pain their characters are totally dissimilar. The feeling of pruritus always carries with it the suggestion of something extra? SENSATION OF ITCHING. 301 neous to the body. There is in the sensation an element of objectivity, while in a painful sensation the feeling is purely subjective. In the one there is the consciousness, whether deceived or not, of something outside of self. In the other, one is only conscious of the suffering. One is resent- ment, with the instinct to repel an attack, an intrusion ; the other is a suffering self-consciousness without cognizance of the producing agent. One is a longing desire to resist ; the other the passive endurance of penalty. Though a certain consciousness of the agent may accom- pany pain, it is very different from that in pruritus. One resents a stinging blow, as the lash of a whip. The soldier struck by a spent ball curses the enemy. But there is no consciousness of the presence of a whip in the smarting flesh, nor of an enemy in the aching limb. Cause and effect may be a mile apart ; it is only the effect that remains, and of that only is the subject directly conscious. At the first instant of injury, the organ of touch is sufficiently involved to give intimation of the locality injured, and perhaps some- thing of the quality of the injurious agent, but the sensa- tion of pain per se gives no such intimation. It is simply a passive condition. In pruritus, on the other hand, cause and effect are presented to consciousness as one. The consci- ousness of the object, the irritant, is not an instantaneous intimation, but persists while the itching lasts. But if pruritus is not pain in the ordinary acceptation of the word, is it any more nearly related to the special sense of touch ? What are its relations to the so-called special senses on the one hand, and to common sensation on the other ? The distinction recognised between common and special sensation is that, while the former communicates only im- pressions of subjective states of the body, the latter imparts knowledge of external things. Through the former we are made aware only of somatic conditions, changes or pheno- mena that transpire in the ego ; while through the latter we take cognisance of changes or phenomena in the outside world, the non ego. By means of the special senses the presentations to consciousness are such that we are enabled to appreciate the qualities of external objects, and through a 302 BRONSON ON THE series of such presentations to know, to perceive, what the thing producing the sensations is. Such definite and com- petent sensations, perceptive sensations, exist only in con- nection with the senses of seeing, hearing, smelling, tasting, and touching. All other sensations, though widely diverse in character among themselves, are little more than varying phases of ease and discomfort, of well-being and ill-being, of desire and gratification. Except through association of ideas, through imagination, they have no connection in con- sciousness with the outside world. But notwithstanding the fact that the special senses in their present state are so far removed, in respect to the knowledge they yield to consciousness, from common sen- sation, there doubtless was a period when the distinction did not exist. Their differentiation has been the result of gradual and long-continued processes of evolution. There can be little question that the sensory organs, to which the several senses owe their special attributes, have all originally developed from simple nerve-endings that could give but the vaguest intimations of external objects. At the very beginning there was simply a common sensitive exterior that reacted to the various irritations it encountered in general, and more or less indefinite movements of the protoplasmic mass. Beginning with the protozoa, the protrusion of pseudopodia, as in the rhizopoda, was among the first simple attempts at adaptation. In further progress, and by a similar process, tentacles and sensitive hairs appeared. Nerve- terminals, at first homogeneous, gradually resolved themselves for division of labour in special organs. From the common sensitive exterior there were separated in the course of time the optic and auditory vesicles, with nerve-filaments distri- buted over their interiors. Over little clefts or depressions in the integument other nerve-filaments became differentiated, as the organs of smell and taste ; while the common integu- ment, retaining its primitive common sensations, evolved a special sense of touch. The facts of evolution are exactly reflected in the parallel development of the embryo. Out of the ectoderm or outermost germ-layer the organs of special sense are gradually developed, and traverse the same general phases of progress, as may be traced in the SENSATION OF ITCHING. 303 evolution of the higher creations of the animal kingdom. Both ontogenetically and phylogenetically the simple origin of the organs of sense appears too obvious for dispute. Diverse in their individual characters, as well as in their divergent routes of descent, as these organs are, they all converge toward a common source in a general sensitive exterior composed of homogeneous nerves. The earliest attempts at specialisation in this common sensitive exterior could have effected little more than certain modifications of common sensation. To fix the exact period when these primitive modifications began to develop into the special senses, through which the animal is placed in intelligent communication with its environment, is needless, if it were possible. It must in general correspond to that period when the animal's movements first showed indications of purpose. When the amoeba comes in contact with a foreign substance the reflex movements that are excited are vague, haphazard, and apparently purposeless. According as the contact occurs, or as the object is presented to it, the animal shrinks away from it, or contracting about it envelops it in its interior, where, should the substance happen to be nutritious, it may be absorbed. The first beginnings of adaptation would naturally be associated with the simple consciousness of contact, a sort of primitive sense of touch. With the first intimation to the animal of a difference between one kind of contact and another, we reach the threshold of an objective consciousness and the commence- ment of perspective sensation. Partly empirically and partly through natural selection the differentiation of sen- sation gradually proceeds. The animal now directs its move- ments with intelligence and purpose. It acquires the ability not only to feel but to perceive. It can select and seek its food, evade or attack its foes, and so gradually is equipped for the struggle for life. Thus, as all the sensory organs can be traced to one elementary and homogeneous organ, so all sensations, whether common, special, or perceptive, may be traced to one undifferentiated and elementary sen- sation, which is common sensation. In this evolution the impelling force, the directing im- pulse, has been derived from the two grand principles of 304 BBONSON ON THE life known as the instincb of self-preservation and the in- stinct of reproduction. To one or the other of these instincts every sensation that arises in the body must be directly or indirectly referred. All sensations, as we have seen, were originally tegumentary. To the common integument must be ascribed the source and potentiality of all sensations. As the result of specialisation, most of these sensations have been withdrawn from the exterior. What traces of the special senses thus abstracted still persist in the skin may be infinitesimal. That such traces do exist there can be little doubt. At least, that the skin is sensible to waves of light, has been demontrated by curious experiments. There still remains to the skin and adjacent mucous orifices a variety of sensations, some of them undifferentiated from the elementary common sensation, others more specialised, including a special sense with perceptive faculties, and, finally, the most important representative of the reproductive instinct, the aphrodisiac sense. The objective or perceptive sensations of the skin consti- tute what is known as the sense of touch or tactile sense. It is the sense by which we apprehend the form, size, loca- tion, temperature, and various other qualities of external objects, such as softness, hardness, smoothness, roughness, and the like. Many of its attributes it owes to the so-called muscular sense, which in many tactile operations cannot be disassociated from the sense, of touch. Moreover, the sense of temperature is really an independent sense, depend- ing actually upon nerve-terminations, especially adapted to this purpose. This independence has long been recognised in certain pathological conditions, where one sense has been annulled irrespective of the other, while the recent experi- ments of Goldscheider have established the fact still more positively. Goldscheider, having first established experi- mentally that there were certain areas of the skin sensitive to touch and others to temperature, on excising these areas found microscopically that the innervation was also distinct. Of the existence of a specialised sense of touch there is no question, nor that it is limited to the skin and adjacent mucous orifices. It is not wholly expressed by pressure SENSATION OP ITCHING. 805 sense, for it is incomplete without the accessory muscular and temperature senses. Again, there is a sense of contact, the sense of being touched without perceptible pressure, which has come down from the earliest periods of animal development, and which, originally at least, must have been unassociated with tactile sense as we now understand it. Before any consciousness of pressure exists we are sensible of contact. But something more than this is necessary before there can be anything like sense of form or quality. It is this sense of contact, doubtless, that is the beginning — the threshold of pressure sense. What is meant, then, by the phrase " sense of touch " ? As we have seen, it has a composite character, but, though made up of heterogeneous elements, the perceptions that flow from it are as definite and as distinctly individualised as those afforded by its sister senses. Nevertheless, the term is a vague one, and inadequately expresses the sense implied. As we have seen, simply touching an object, simple contact, evokes a sensation or sensations that are only preliminary to the specialised sense. We become conscious of local contact before any quality of the object touched can be distinguished. It is only when the feeling of resistance begins and we are aware of pressure that there can be any appreciation of quality. It may be said that such appreciation is purely an intellectual act ; but as the brain would be incapable of appreciating the different tones in sound except for the organ of Corti, or the different colours of the spectrum except for the intervention of the retina, so is it probable that the tactile perceptions would not exist but for the presence of special sense organs in the skin. Such organs have been aptly termed " organs of reinforcement." The expression, therefore, for the special perceptive sense that belongs to the skin should imply more than mere touch. It is not simply sense of contact, it is not simply feeling, but it is contact phis something else ; it is feeling of the object as well as simple feeling it. The word palpation better expresses the act whereby the sense is evoked, but etymologically that term would be too restricted. Palpa- tion (from palpus, the palm) relates more particularly to manipulation ; it is feeling with the hand only. A still 20 306 PR. BRONSON ON THE better term would be pselaphesia. The Greek ipri\ar)aiQ conveys the idea of feeling for or of a thing, or groping as a blind man or as one in the dark. The Latin tactus (from tango) , on the other hand, signifies only the act of touching, as expressed in the words tangent and contact. The only sense with which the skin is endowed that can properly be called perceptive, and that is worthy of comparison with seeing, hearing, smelling, and tasting, is the sense of psela- phesia. It includes the sense of contact, which, as we have seen, is its most primitive form ; its more important element is pressure sense, while the temperature and muscular senses are more or less essential auxiliaries. Common sensation is represented in the integument in its highest positive aspect by the voluptuous sensations ; in its lowest negative aspect by pain. From analogy with its sister senses, the sense of psela- phesia should depend upon a special arrangement and adap- tation of the nerve-endings. There should be an organ or " organs of reinforcement." It is scarcely probable that in the skin there is any such highly specialised arrangement as in the eye and ear, and yet we find nervous structures in the skin whose distribution and peculiar development mark them as organs of special importance to cutaneous sensation. What the exact functions of these different structures are is yet uncertain. It is little more than conjecture what special parts are played by the corpuscles of Meissner or those of Pacini, by the terminal bulbs of Krause, the nerve plexuses beneath the epidermis and about the hair-follicles, the tactile cells of Merkel, the free nerve-endings, and, finally, the nerve-distributions to the epidermis, including the remarkable intracellular nerves described by Pfitzner and Unna. Suffice it for the present to say, that from analogy we should expect the most highly developed of these to correspond to the most highly developed sense, to pselaphesia. To turn from this long, though not purposeless digression, what relation to all these sensory organs of the skin and to their various sensations does the sensation of itching bear ? First of all, the sensations of pruritus must have to do with nerves that are very superficial. There is no reason to SENSATION OP ITCHING. 307 believe that of pressure sense, properly so called, there is the slightest intimation. If, with the end of my pencil, I gently approach a sensitive surface, such, for example, as the cheek or one of the alas nasi, I become aware of a sense of contact the instant the surface is touched. A little pres- sure and I receive the impression of a smooth, rounded body, and a moment later a slight sensation of coolness. I have a perceptive sensation. If, instead of making any pressure, the pencil be retained just at the point of contact, presently a feeling of annoying irritation is excited. Still more marked is this irritation if, instead of using the pencil, the part be lightly touched with a pointed wisp of soft paper or feather. There is elicited directly the sensation of a minute local shock, associated with an instinctive desire to escape from the irritating cause. If the same be repeated the ex- citement of the part becomes so great that the desire to rub or scratch it becomes almost irresistible. This sensation is pruritus, and it is evidently a nervous disturbance provoked by touching the sensitive surface. What and where is this disturbance, and why should it be apparently so much greater than would be produced by a much more forcible contact ? First, how is it related to pselaphesia ? The certain amount of pressure necessary to evoke this special sense implies that the organs on which it depends lie deep in the skin, and are doubtless those highly developed nerve-struc- tures that are situated below the epidermis. It is evident that whatever connection the mere sense of contact may have with these organs it does not bring them actively into play. It is a well-known fact that in certain pathological states apselaphesia may coexist with hyperesthesia of the surface, i. e. an exaggerated sensitiveness to impressions of contact. Moreover, those areas of the body most highly endowed with special tactile sense, with the sense of pselaphesia, are by no means necessarily the ones most sensitive to contact ; nor are they to pruritus. While itching has no apparent con- nection with the sense of pselaphesia, it cannot be dis- associated from the primary sense of touch, the sense of con- tact. Now, obviously, this sense of contact should pertain to those nerve-endings but slightly differentiated and those 308 DR. BEONSON ON THE most superficial. Such nerves exist in abundance in the epidermis. While I can present no absolute proof of the proposition, I believe there is sufficient evidence to locate the essential seat of pruritus in the epidermis. Itching is evoked by such irritants as act upon this tissue much more uniformly than by those that act on the derma. "We have seen how it may be excited by external irritants that barely touch the surface without the least intimation of a pressure sense. The itching that is commonly observed in connection with the healing of superficial wounds is not attributable to the granulating process. There is no itching in the granula- tions of an ulcer. It is only when the part begins to heal and to " skin over" that the itching begins. It is a sym- ptom of keratoplasia, not of dermatoplasia. In those cuta- neous diseases also that more especially affect the derma, itching is present only exceptionally. In the erythematous, erysipelatous, and phlegmonous inflammations the sensations are of a smarting, burning, or aching character, i. e. pain- ful sensation, and if ever pruritus it is because of secondary implication of the epidermis. Likewise, of papular affec- tions, as, for example, in syphilodermata, that are charac- terised by infiltrations confined to the corium or papillary body. If itching occur it is due to a similar and accidental implication. On the other hand, the essentially pruriginous affections, such as eczema, pemphigus, scabies, or lichen planus, are those invariably associated with decided trophic changes in the epidermis. In urticaria the implication of the epidermis is not so obvious, but, as shown by Unna, urticaria is not primarily or essentially an inflammatory disease. It is often a neurosis, and the itching is the pri- mary factor, an irritation reflected to the terminal nerves from the nervous centres. The cedematous effusion that accompanies it, together with the local ischasima, is doubt- less the direct effect of muscular spasm. However provoked, the sensation of itching is always associated with a presentiment to consciousness, as though a foreign body were in contact with the surface. It is that sensation that experience through many stages of animal life has taught is often followed by a prick or a sting, and the SENSATION OF ITCHING. 309 inclination to escape-the threatened hurt has grown into an animal instinct. The sense of contact at a minute portion of the sensitive surface is immediately interpreted to mean a miniature attack that must be repelled. If no attack has really been made, but only the threat, the intimation, then the excitement should disappear without returning the moment the cause producing the sense of contact is with- drawn. But it is the peculiarity of itching that it persists in spite of such withdrawal, and is only relieved by the act of scratching. It seems as though the contact, or whatever the change may be that gives rise to the irritation, produces a molecular commotion in the nerves that goes on like the jangling of an electric bell, with a continuance of the sensa- tion until such time as the surcharge of nervous energy is released. In pselaphesia the nerve-force, or the molecular vibrations excited by the impact, is directly transmuted into some intelligent form of activity, and the accumulation of nerve excitation — the nervous engorgement — does not occur. The circuit is complete, with no point of resistance interven- ing to create obstruction, and so commotion. With regard to the sensations of pain, the view was maintained by Funke 1 that they passed into the gray tracts of the spinal cord, where their further progress was arrested ; while tactile sensations (the sensations of psela- phesia) traverse the less resisting white tracts, and thence passed directly to the brain. Whether this explanation would apply also to the sensation of itching, whether the obstruc- tion that produces it is the same as for painful sensations, is a question that can neither be affirmed nor denied. It may be that the same process which produces what is called pain, when proceeding from nerves deeply seated, becomes itching if it starts from the nerves of the epidermis. Or, on the other hand, it might be alleged that the only difference lies in the amount or severity of the irritation, the nerves involved being the same. There are reasons, however, for believing that the epidermic nerves are not susceptible to pain. If with a knife we gradually pare away the epider- mis, or if we thrust a fine needle through it, no pain is pro- 1 See in 'Hermann's Physiology' (1879, iii, 2), "Physiologie der Haut- empfindungen und der Gremeingefuhle." 310 ])E. BEONSON ON THE duced until it reaches the papillary body — until it " goes to the quick/' as the common phrase is. But it may be ob- jected that neither does this cause itching. The explana- tion is easy : An essential condition to the production of pruritus is the uncertainty, the vague and indefinite cha- racter of the sensation. The impression that the knife or needle produces as it forces its way through or between the cells of the epidermis is one which offers a clear and inter- pretable presentment to the sensorium ; the sensation under- goes immediate transmutation into other forms of nerve- activity, thus obviating the accumulation or stasis of nerve- force. It is a definite and perceptive sensation, which doubtless calls into play the special organs of pselaphesia that may serve to turn the course of the molecular vibrations into the direct channels of the spinal cord. A priori reasons for differentiating pain from pruritus have been given already. We have seen that they are not only inconsistent with, but antipathic to each other. The means to which the animal instinctively resorts for their relief are distinctly opposed to each other. While pain demands rest, pruritus incites to action. It is also probable that they engage distinct elements of the nervous system. The reflex muscular movements excited by itching doubt- less had for their object originally the expulsion of a foreign body, often an insect. Such movements are frequently spontaneous and more or less unconscious. Analogous responsive muscular movements are seen in sternutation and the act of coughing. The tickling sensations of the nasal or laryngeal mucous membranes which are their provocation correspond very closely to cutaneous itching. But the relief afforded by sneezing is not wholly explained by the expul- sion of the irritating substance, but, partly, by the fact that the effort affords an avenue of escape for the retained nerve- force, a means for the transmutation of this force into mus- cular energy. In those animals in which the platysma myoides is more highly developed than in man, as in the horse and bovine genera, a certain relief may be afforded to pruritic sensation through its energetic contractions, which is not wholly due to expulsion of the insect or what- ever else may have caused the sensation. The same ten- SENSATION OF ITCHING. 811 dency to dissipate pruritic irritation through liberation of muscular force is evinced in the cutis anserina as well as in the hypertrophy of the arrectores pili muscles observed in many pruriginious diseases. May it not be that the changes in urticaria are the consequence of misdirected and ineffectual efforts of the cutaneous muscles to expel an irri- tant that produces on the sensorium the counterfeit present- ment of some tangible body, as it were an offensive insect ? With regard to the effect of scratching in relieving itch- ing, it is analogous to that produced by muscular exertion. Both cause a deflection of the pruritic irritation into other and freer channels. In the action of scratching there is substituted a decided and definite sensation for one that is simply vague and incomplete. It is the substitution of an effective energy for an ineffectual vexation. Thus we arrive at something like a rational explanation of what itching is, why the sensation is attended with, greater perturbation than are sensations produced by more tangible and appreciable contacts, and, finally, why it is relieved by scratching. Inasmuch as the presentations it yields to consciousness are vague and indefinite, it is closely related to common sensation ; but inasmuch as it contains the glimmerings of an objective sense, it is just one stage removed from it. It concerns those primitive nerves of contact out of which originally were developed the organs of special sense. It disturbs sensibility that was the pre- cursor of, and doubtless is preliminary to, the sense of pselaphesia. Inasmuch as it concerns a sense of touch, it might be characterised as a paraesthesia of tactile sense ; but regarding it more particularly as a disturbance due to inter- ference with, to obstruction of, sensation, a condition in which there is vexation and annoyance of consciousness through the very indefiniteness and uncertainty of the sensa- tions, the word parsesthesia does not express enough. Un- fortunately, a term that most fitly expresses this condition has been already appropriated. Charcot has given the name " dysesthesia " to a form of hyperaesthesia or paresthesia occurring in myelitis, in which slight irritations of the sur- face, such as pinching, or the application of cold, are directly followed by painful vibratory sensations coursing up and 312 DK. BEONSON ON THE down the region irritated, and often appearing symmetri- cally on the other side of the body, and that continue for a considerable time after the irritant has been withdrawn. In some respects the dysesthesia of Charcot corresponds to the phenomena of itching. At all events, the term employed is, etymologically at least, as appropriate to pruritus as to the painful sensations just described. To explain in detail, or even enumerate all the different phases of itching would be impossible. While some of them are associated with pathological changes in the epidermis incident to certain cutaneous inflammations, others have their source more deeply situated and are referable to the nerve- centres. To the latter belong the form of neurosis, of which pruritus is at the same time the symptom and sole appella- tion. Still, other sources are doubtless to be found associated with apparently normal physiological conditions. It would seem as if a certain amount of scratching were, under some circumstances, salutary and requisite for an animal's integu- ment, and that the sensation of itching were the necessary incitement. It would facilitate the fall of deciduous hairs, it would promote the normal exfoliation of the cuticle, which, under certain conditions, may not separate rapidly enough to permit the upward growth and expansion of the prickle- cells of the rete. It would tend to dislodge accumulations in the crypts of the skin, the sweat, and sebaceous follicles. While these represent the most obvious sources of itching, or provocations for scratching, there is another factor of which hitherto but little account has been taken. Both the English words itch and itching and the Latin prurio and pruritus, in their secondary significations, convey the idea of a longing, teasing desire. It is apparent in such expressions as " the itch for gain," " the itch for praise," " the itch for scribbling ; " while pruritus was commonly used by the Latins as a synonym for lasciviousness. There is an element of desire in the sensations of itching, and it is not improbable that the common, more or less definite recog- nition of this element is accountable for the derived or secondary meanings just alluded to. By desire in this con- nection, something more is meant than merely the inclina- tion to brush or scratch away a foreign body, of which the SENSATION OP ITCHING. 313 sensation is apparently an intimation. It is, rather, a kind of desire closely akin to a lustful feeling, and one that some- times makes scratching veritably a sensual indulgence. When pruritus reaches a certain degree of intensity, the subject is not content with that moderate amount of scratch- ing that would ordinarily create a sufficient diversion to give relief, but there is a disposition to attack the itching surface with a vehemence that amounts to passion. Observe the motions of a dog when scratching. Sometimes its violent movements and muscular exertions betray an agitation that is not unlike the excitement of the sexual orgasm. The very act of scratching appears to evoke a condition of erethism and excitement that is far in excess of the mere pruritic irritation. And in the human subject voluptuous feelings are not infrequently accessories to the sensation of itching. The delight of having one's back scratched is doubtless chiefly due to a longing for a voluptuous gratifica- tion that would not exis,t but for the pruritic titillation. When the scabious Scotchman at the " scratching-post " fer- vently ejaculutes his " God bless the Duke of Argyle ! " it is not only the negative satisfaction of relief that he feels, nor that combined with clannish loyalty, but his sensations include an element of positive enjoyment, he is having the pleasures of a gratified sense. Eecognising this peculiar element of desire in pruritus, the sexual excitement and depraving tendencies that are so commonly associated with pruritus genitalium are most easily explained. But it is not so surprising that voluptuous sen- sations should attend itching here where they have their natural seat. Such sensations, however, are not confined to the genitals. They also affect the anus, where, more espe- cially under certain conditions of moral perversion, as well as in association with pruritus ani, the erectile tissue in this situation may become the seat of erethism, and in a measure there is excited an aphrodisiac sense. The female nipple also is susceptible to voluptuous sensations. These facts are well known, but the more general distribution of such sen- sations has received little consideration. They may be con- comitants of itching in almost any situation. Persons sub- ject to pruritus of the external auditory meatus are often in 314 DR. BRONSON ON THE the habit of introducing the tip of the finger into the ear and making rapid vibratory movements that do not merely quell the itching, but produce sensations that are distinctly voluptuous. The same is true, if in a less degree, of exces- sive rubbing or scratching of any surface that itches. There must be, however, the provocation of the pruritic irritation. By means of a violent excitation, superinduced by severe scratching, a liberation or discharge of nervous energy takes place, accompanied by pleasurable sensations, together with the relief of the pruritic irritation. A temporary inertia and rest follows and continues till a renewal of the pruritus provokes another resort to the same method of relief. How is this voluptuous feeling explained ? We have already seen that the only special senses that remained to the common integument after the differentiation of the special senses had taken place were the tactile senses, including the senses of contact, of pressure, and of tempe- rature and the aphrodisiac sense. We saw also that the special sense of pselaphesia, while most highly developed in certain parts, existed to a greater or less degree over the whole surface. The same thing would seem to be true in a measure of aphrodisiac sense. Like the former, the latter is but a higher development of the primitive sense of con- tact. It has a special organ or instrument — the penis in the male, the clitoris in the female — much as pselaphesia has as its especial organ or instrument thehand; moreover, like the latter sense, though perhaps in a less degree, it is distributed over the entire cutaneous surface. Now, sexual excitement has for its incentive the desire to gratify a special appetite, the agent or vehicle of which exists in the cutaneous nerves of contact. A plethora of nervous irritation is generated in thecommunicatingnerve-centres, which can only be released by a violent general agitation, an explosion, as it were, of nerve force, which is followed by equilibrium or by a minus state of depression. This is the sexual orgasm. The whole process is in close analogy with what we observe in connection with the relief of the intenser forms of itching by violent scratching. In each case the stored up energy has to do with the nerves of contact or the centres with which they directly communicate. These are the non-con- SENSATION OP ITCHING. 315 ductors that accumulate and retain the charge ; the motory apparatus furnishes the channels through which the charge is conducted away in muscular energy. As to why this process is attended with pleasurable sen- sations, it suffices to say it satisfies a law of being. Gratifi- cation of appetite is a condition of life, either of the pre- servation of life or of the reproduction of life. The sexual, the aphrodisiac appetite can only be secondary to the instinct and appetites of self-preservation. It is the outcome of superabundant vitality. With the surplusage there is engendered the instinct, the impulse to increase, to give life, to make more life. The acme of this impulse is passion. When the increments of vital energy reach high-water mark there is tumultuous overflow, as in the syphon of an invisible spring. It is not only in the aphrodisiac sense that this impulse is displayed. It actuates many of the highest intellectual and emotional faculties of man. Through it the mind con- ceives and reproduces ; the purest sentiments of love are its offspring. In the control of all the forces, both of the body and of the mind, the reproductive instinct shares with the instinct of self-preservation, the one being the opposite and the complement of the other, as in the conduct of life the spirit of altruism is the opposite and complement of the spirit of egoism. The one prompts to give more than it gets ; the other to get more than it gives. The one dis- sipates energy ; the other conserves force. One or the other of these two great instincts provides the mainspring of every human action and is the source of every animal appetite. Their combined product is life. Aphrodisiac sense, the lustful sense of contact, is but a phase, a single factor in the great domain of the instinct of reproduction. The appetite it engenders, the lust of the flesh, at the same time the most ignoble and the most dominating appetite of exuberant animal life, is but a means to the grand end, and when prodigal nature established its chief seat and " sacred " organ, she neglected to withdraw from the outlying regions of the general surface those traces of a congenetic sense that remain in a more or less primitive form, but never- theless engage corresponding elements of the nervous system. 316 DR. BRONSON ON THE SENSATION OP ITCHING. From the foregoing considerations I believe we are war- ranted in drawing the following conclusions : I. That there is a sense of contact independent of the sense of pselaphesia. II. That this sense of contact is the sense disturbed in pruritus. III. That it concerns primarily, simple cutaneous nerves or nerve-endings, situated superficially and probably in the epidermis. IV. That the disturbances in pruritus is of the nature of a dyssesthesia due to accumulated or obstructed nerve exci- tation with imperfect conduction of the generated force into correlated forms of nervous energy. V. That scratching relieves itching by directing the excitation into freer channels of sensation, sometimes, espe- cially when severe, substituting for the pruritus either painful or voluptuous sensations. VI. That the voluptuous sensations that may attend pruritus are a manifestation of a generalised aphrodisiac sense, representing a phase of common sensation that has its source in the sense of contact. KEPORT OP A CASE MYCOSIS FONGOIDE OF ALIBEET. 1 Bt HENRY WM. BLANC, M.D., DEBMATOLOGIST TO THE CHAEITT HOSPITAL, NEW OELEANS. The rare affections of the skin first described by Alibert under the name of Mycosis Fongo'ide, and of which he gave an illustration in his atlas more than half a century ago, 3 has of late years been described by a number of observers under a variety of titles. Among the Germans we find the name granuloma fungoides to prevail ; the French prefer to call it lymphademe cutanee ; while the Americans recognise this disease as the inflammatory fungoid neoplasm of Duhring. But these names are simply tentative, and even the in- ventors of them confess that all designations will remain imperfect and unsatisfactory until the true nature of the affection is understood. Independently of the one here reported, it has been my good fortune to have observed two other cases of this dis- ease within the past four years. One of these was in the service of Prof. Geo. H. Pox, at the Skin and Cancer Hos- pital, New York ; and my position there as house physician 1 Eeprinted from the 'Journal of Cutaneous and Genito-Urinary Dis- eases,' vol. vi, July-August, 1888. 2 ' Clinique de l'H6pital Saint-Louis, ou Traite complet des Maladies de la peau,' Paris, 1883. 318 DR. BLANC ON THE permitted daily observation for several months, during which time the most careful notes were taken. The other case observed by me was under the care of Prof. Stephen Mackenzie at the London Hospital, in the summer of 1886 j 1 and I had the satisfaction of having my opinion as to its nature confirmed later on by a number of prominent specialists. In the clinics and hospitals on the Continent I saw no examples of this disease ; but the exquisite wax models of M. Baretta at the Hopital Saint-Louis, Paris, were sufficient to convince me that the two cases just referred to, and the one here reported, are very closely related to those figured by the French dermatologists. The patient whose disease is now to be described, was admitted into my service at the Charity Hospital on August 10th, 1887, with the following history : — White man, set. 34 ; native of Germany. Occupation was that of a tailor in New York City previous to 1883. Is of blonde complexion, and was formerly quite fair. While in Mound City, Kansas, in May, 1883, a scaly and itchy eruption, unaccompanied by any discharge, appeared on legs. In about four months this "dry tetter," as he calls it, broke out on the hands also, when rhagades appeared on the palms, and the erup- tion began to discharge. It then spread to the breast and arm-pits ; the hands in the meantime becoming so much improved that he could work again at his trade. This he continued to do until the spring of 1884, when there appeared on the body a number of " red blotches covered with yellow pimples which con- tained a little black spot in the centre." He then entered a hospital in Omaha, where he remained about twenty-one months, suffering with a disease which was called " general eczema," and pronounced non-contagious by the physicians. Patient states that while he was in the Omaha Hospital the hair of his scalp, eyebrows, lashes, and beard all fell out, but had begun to return before he left the institution in March, 1886. The eruption disappeared while he was in this hospital, 1 Neither of these cases has yet been reported, as far as the author is aware. MYCOSIS FONGOIDE OF ALIBERT. 319 but the skin remained red and tender, and continued to itch over its entire surface. Departing for Quincy, 111., in June, 1886, he was there able to pursue his vocation until the middle of January, 1887. At this time he had a swell- ing of the feet which resembled frost-bite, and the toes were cut and cauterised by physicians of the place. Eemaining under medical care until April 13th, 1887, he then came south by advice, stopping for a short time at Hot Springs, Ark., where he took frequent baths which were always followed by chills. He then came to New Orleans, and under my observation. Condition on admission. When admitted to the hospital the patient was very weak, nervous, and emaciated, and was compelled to take to his bed. Two facts about him were particularly noticeable ; one was the great number of multiform tumours covering his trunk and extremities, and the other was an extremely disagreeable and pungent odour emanating from his hands and feet. Head. — The skin of the face was slightly thickened, espe- cially about the eyebrows, which were scanty and nibbled off in places as in ringworm of the scalp. The skin was flushed, the nose red, and expression of face nervous and uneasy. Beard straight and growing only from the chin, though, according to his statement, it had been much thicker before he pulled it out when loose from inflammation in the skin. Scalp pale and covered with fine dry scales. The only tumour on head was one the size of a buckshot, just within the meatus of left ear. Tongue and throat normal, but projecting from the hard palate was a purplish tumour the size and shape of a filbert, which had been as large as an English walnut several months before, and seriously interfered with deglutition. On the neck just below chin was one small sessile tumour. Trunk. — The skin of the trunk, considerably pigmented in the abdominal region, was covered indiscriminately with forty distinct tubercles and tumours. While some of these growths were merely hard, purple deposits, slightly raised 320 DE. BLANC ON THE above the skin, others formed sessile or pedunculated tumours that could be caught up between the fingers. The average size of these was that of a split cherry. Upper extremities. — The skin of the upper extremities was rough, scaly, and slightly pigmented from the irritation of constant rubbing. On the right arm and forearm were twelve tumours distributed over the surface. The majority were about the size of a pea, and projected prominently above the skin ; while two or three, a little larger than the rest, projected from eight to twelve lines above the surface as raw, elongated growths, with narrow pedicles, and which secreted an ichorous fluid. The right hand was much swollen, and covered with red, thick skin. In the palm of this hand were three pedunculated tumours the size of a cherry. The fingers were stiff, and could be moved only with pain and difficulty. They were about three times as large as normal, and covered with a fungous mass of a pur- plish-blue colour, soft to the feel, and irregular in shape, being larger at the distal extremities. This outgrowth on the fingers was most marked on the terminal phalanges, where it was heavier and more nodular, obliterating the out- line of the digits, which could only be recognised as such by the presence of smooth, clubbed nails, that projected through the mass undisturbed by the disease. The general appear- ance of the left upper extremity was like that of the right, except that the tumours on the arm and forearm were about sixteen in number, the largest being about the size of a filbert. The left hand closely resembled the right in appearance, except that it was less swollen, and had the first phalanges of the third and fourth fingers free from disease. Lower extremities. — The skin of the thighs and legs, par- ticularly the former, was covered with whitish scales and much roughened by rubbing. Innumerable papules, and many prominent tumours the size of a cherry and larger, studded the surface of the thighs and legs. One tumour on the left thigh, just below the trochanter of the femur, greatly resembled a door-knob in size and shape. The most remarkable appearance presented by the dis- ease was seen upon the feet, from the dorsal and plantar surfaces of which projected fungous masses resembling in- A CASE-NAEEATIVE. 321 ternal haemorrhoids more than anything else/ except that they were more of a purple hue. These tumours, when not flattened • to the skin by bandages, projected, in several in- stances at least an inch and a half from their attachments, and were very narrow and flat. The toes, : though present, could not be distinguished in the mass of fungous growth that projected from the end of the tarsus ; though the interlacing nodes could be separated from one another by careful manipulation. The toe nails, unlike those of the fingers, were displaced and deformed, being turned upward towards the dorsal surface of the foot. None of the nails were missing. The very foetid odour already referred to was due to a sero-purulent discharge from the hands and feet, particu- larly the latter ; and originated in the thin membrane-like surface of the fungous masses, which constantly poured it forth without well-defined ulceration. On examination the lymphatic glands were found to be notably enlarged, more especially the axillary, epitrochlear, femoral, and inguinal, all of which could be detected with the eye as well as by sense of touch. In addition to these the following could be distinctly felt, and in several cases seen : — the zygomatic, post-cervical, dorsal (just outside of the axillary border of the scapulae), and the thoracic glands at the lower border of the pectoralis major muscle. Several smooth red patches on the skin were declared by the patient to be the remains of tumours which had just disappeared, similar processes of resolution having frequently occurred in his history since the frost-bite in January, 1887. Examination of the internal organs disclosed no special form of disease, and the spleen could not be felt beneath the abdominal walls. The patient was in a very nervous condition, jumping if any of the tumours were touched, and complained of intense itching, particularly at night, in con- sequence of which he kept up a continual rubbing of the skin at all times. The appetite was poor and bowels moderately regular. Urine examined chemically and micro- scopically,andnothingabnormalfound. Specific gravity 1010. Such was the case as it first came under my observation. Recognising in it a rare disease, and believing it to be 21 322 MYCOSIS FONGOIDE OP ALIBEET. similar to the two cases already referred to, I determined to administer iron and arsenic with the idea of increasing the blood-cells and improving the nutrition of the skin. Being about to leave the city on a six weeks' vacation, I ordered the following mixture, to be continued, if practicable, until my return : ft Perri et Quiniae Citrat., 313 ; Liq. Potass. Arsenit., 3J ; Syr. Aurant. Cort., 3] > aquas, q. s. ad gij. Dose a dessert-spoonful three times a day after meals. This was administered in my absence, and no other directions given, except for a powder of ten grains of hydronaphthol with half an ounce of bismuth to be applied to the discharging surfaces on feet and hands. This powder did good service, and greatly diminished the foetid odour. During my absence small specimens were cut from the tumour of the foot and sent to the pathologist, Dr. Schmidt, with the request that they be examined for the bacillus leprae. The report showed, as might have been anticipated, that not only were there no bacilli, but that the neoplasm did not in the least resemble deposits of leprosy. On my return frequent notes were made of the case, and I shall endeavour to give those that best show the progress of the disease, Clinical History. November 15th. — Patient has been taking arsenic andiron for three months, and shows decided improvement in skin lesions. The tumour in mouth has diminished to the size of a pea, that on thigh is now the size of a hazel-nut, and several small ones on the arms and legs have disappeared altogether, leaving no cicatrices, and very slight pigmen- tation. Hands are less swollen, and have lost their raw appearance ; feet discharge less, and are not as tender. Ordered ichthyol (sulpho-ichthyolate of ammonium) and vaseline, equal parts, to be applied constantly to fingers and hands. 25th. — Thickening of fingers has notably diminished under use of ichthyol. On removing a tumour for micro- scopical examination great nervousness was produced, fol- A CASE -NARRATIVE. 323 lowed by a chill and slight elevation of temperature, after which patient perspired freely. These nervous chills have occurred several times of late, particularly after a handling of the tumours or stripping of the patient for examination. The temperature seldom rises higher than ioo° during vyhat he calls his " fever attacks," though he perspires pro- fusely after them, the face remaining redder for two or three days at a time. Says he has sensations similar to these, but milder, after the feet are dressed in the evening. The fever is easily controlled by cinchonida. Intense itching is a con- stant symptom. December 1 2th. — Had one of his nervous attacks, followed by sweating and great prostration, after being removed to another part of the hospital to be photographed. Hands are looking well, but feet have been painful of late. Sub- stitute the following for the hydronaphthol mixture on feet : Iodoform, Bismuth. Subnitrat., aa 5J. M. January 16th. — Tumours on the trunk have decreased to, ten in number ; and those on extremities had ceased to grow until two weeks ago, when diarrhoea set in, and arsenic mixture was temporarily stopped in favour of opium and bismuth internally. Several tumours have rapidly increased in size and taken on a fungoid appearance since discontinu- ance of the arsenic. But bowels have improved, and arsenic is now resumed with twenty grains of subnitrate of bismuth at a dose. As the feet are better, it is determined to try the effects of ichthyol in place of the powder of December 1 2, though this has given great relief : Ichthyol, ^ss ; Iodo- form., 3iss ; Vaselin., q. s. ad 3ij- M- 27th. — Feet are swollen, and ichthyol discontinued in favour of hydronaphthol powder, which has been most suc- cessful in drying and deodorising the surfaces. Face remains flushed now, but tip of nose is less red. Tumour in mouth has entirely disappeared, and nothing remains but a dark spot the size of a pea, which is flat, and level with surface. Tumour on thigh near the trochanter is gone, and nothing remains to mark its former site. For the first time it is noted that the thyroid gland is slightly enlarged. February 8th. — Had herpes facialis last week, most marked about the corners of the mouth, but it is now fading 324 MYCOSIS FONGOIDE OP ALIBBRT. rapidly. Says lie lias had herpetic eruptions on face several times during the past two years. Arsenic, iron, and bismuth administered regularly. gth. — No nervous paroxysms lately, and has been walking about the ward. Hair of scalp is thinning from constant Scratching, and the skin of scalp is redder than formerly. The back, between the shoulders, and the chest at root of neck, are scaly from scratching. Abdomen less dark than formerly. All the tumours have disappeared from the trunk except one just above the left nipple, one three inches to the left of right nipple, and one in right axilla, making a reduc- tion from forty to four in six months. The largest tumour now on the trunk is not larger than a split cherry. No cicatrices have been left, and only three tumours are followed by pigmentation. For the intense itching patient has used strong ointments of carbolic acid before coming under my care, and without good results ; so a salve containing a drachm of dilute hydrocyanic acid and an ounce of vaseline is ordered, with the hope of diminishing friction. Bismuth discontinued. 28th. — Walking causes feet to swell, so horizontal position is ordered. Bowels have been loose again, and patient has been taking only bismuth for past week ; and to-day three drops of Fowler's solution are added to the dose. Many tumours on the extremities have increased in size. It seems that whenever the arsenic is stopped the tumours begin to grow, and discharge more profusely. It is also a queer fact, first noticed by the patient himself, that whenever single tumours enlarge and discharge, the smaller ones in their vicinity diminish or disappear. March 1st. — Has had two bloody stools, accompanied by an odour similar to that of the feet, and very offensive. Rectum feels very sore. The small toe of left foot is ulcerating and quite painful, so a mixture of iodoform, bismuth, and starch is applied. General health remains about the same. Bowels have been moving twice a week. 10th. — The aspect of the extremities has changed a great deal ; four new tumours have come, and old ones disappeared. In the evolution of these growths, there is never any loss of tissue. The smaller ones disappear by absorption, leaving A CASB-NAEEAT1VE. 325 a bluish- red mark level with the skin. This in turn dis- appears, leaying a temporary pigmentation. The larger growths usually become moist and raw in appearance, dis- charge an ichorous pus for a while, then become dry, con- tract, and disappear. In accomplishing this last process it is not uncommon to see a long tumour with narrow neck contract to a spheroidal shape, and rest in a sort of crater of raised skin. Attached to the centre of this crater by a narrow pedicle, it rests there like a ball in a socket, and can easily, though not without producing pain, be detached from its cup. The right arm and forearm now present five tumours for inspection, the largest of which is the size of a pecan-nut ; while on the left arm and forearm are seen fourteen of these growths, the largest of which is the size of a split cherry. There are no tumours on the back of the hands, and only two or three indurated spots indicate the site of former tumours of the palms. None of the first phalanges are diseased, and the first two -fingers of the left hand are unaffected. Flexion of the fingers is performed now with ease, and the deep red colour of former disease now exists only at the edges of the nails. Both hands are swollen, but the left is better than the right. Seven tumours can be counted on the left lower limb near or about the knee, and ten on the right in the same locality. These are irregularly distributed above and below the joint, being for the most part on its lateral borders. They are larger than those of the upper extremity, several being the size of pecan-nuts, only somewhat flatter. They are not unlike haemorrhoids in appearance. Pigmentation and roughness of thighs and upper half of legs remain as before. Toes are smaller and have lost the appearance of a continuous mass of tissue, and their divi- sions can be distinctly seen. Feet are swollen and cedema- tous, and have no tumours on dorsal surfaces. Not so with the lateral and plantar surfaces, for the right fopt presents six moist, tender, pedunculated tumours, about the size of a large cherry, growing from its outer side. Under both feet are numerous prominent and slightly pedunculated tumours, which are largest, at the heels, and prevent the patient from taking his wonted exercise- about the ward. 326 MYCOSIS PONGOIDB OF ALIBERT. Hydrocyanic acid salve is still used to lubricate the skin, though its effect on the pruritus is very slight. 1 8th. — Bismuth to be omitted, as bowels have not worked for six days. Has not taken iron for one month. Eesumes to-day the iron and arsenic mixture, taking five drops of the Fowler's solution at a dose. Fingers are swollen, and ichthyol replaced by iodoform salve. April 5th. — A swelling the size of a hen's egg divided in half longitudinally has been present several days on the left arm, just in front of and above the enlarged epitrochlear gland. It is very tender to the touch, and gives pain ; but the skin above it is not inflamed. Corresponding to this on the right arm is a tender nodule which has been present only a few hours. Patient states that he had a number of similar painful spots, with swelling along the course of the saphenous vein in the thigh, about a year ago, and confi- dently asserts that these will soon pass away as did the others. nth. — No new tumours have appeared, and all old ones are smaller except a fungoid growth the size of a walnut on the left arm. The trunk and thighs are covered with a smooth, reddish, indistinct, macular eruption, resembling secondary syphilitic manifestations. These macules are about the size of a silver dime, or smaller. Bowels have been loose again, but have been checked with bismuth. Rectum and anus are tender, but no new growths are found. Swelling and tenderness of arms above the elbows have greatly diminished. Complains of a burning sensation in meatus urinarius when he passes water. The glans penis, though not swollen, is red and tender, and the meatus a little puffed, as in acute gonorrhoea. Urine remains normal, the specific gravity being 1019. 28th. — A careful examination to-day discloses the follow- ing : — Condition of face just as formerly, only the skin is thicker and more permanently red. The macules on the trunk are not so numerous, but the skin remains pigmented. There are many excoriations produced by scratching. Not a single tumour can be found upon the trunk. On the right arm are counted three tumours, all about the size of a pea. On the left arm are likewise three tumours, two of which A CASE-NARRATIVE. 327 are the size of a pea ; while the third is the size and shape of a silver dollar, only twice as thick, and attached to the skin by a short pedicle which passes to its centre, and has the thickness of a lead pencil. The tender new growths just above the elbows give no more pain, and are now the size of the enlarged epitrochlear glands already noted. These are now regarded as lymphatic glands which were formerly too small to be felt, but which have enlarged with irritation. Both forearms remain pigmented and rough : on the left are two small tumours ; the right is free from them. Both hands are somewhat cedematous and swollen, and the left more so than the right. There is a decided improvement in the hands, though the thickened skin remains ; and small, fungous swellings are still found on the thumbs and little finger, more particularly on the left hand, which was the better of the two some six months ago. Projecting from the gluteo-femoral sulcus on the right side is a tumour the size of a large chestnut. This is dry and in a process of resolution, as are also two pea- sized tumours on the right thigh. The prominent tumours noted upon the knees a month ago have diminished in size and number, for the right knee has but three small nodes, while the left has two pedunculated tumours, size of a filbert, projecting from the prominences made by the head of the fibula and internal tuberosity of the tibia. Both legs are cedematous, shiny, and red, but not painful ; and on them can be found but one tumour. This is the size of a pea, and situated in the lower half of left leg. It is now recalled that, several months ago, a large discharging tumour which was just above the right ankle, and which gave con- siderable discomfort, has disappeared, leaving nothing but a slight redness of the skin. The feet, though never as well as now, still show the worst phase of the disease. The tumours occur about the prominences only, though the skin of the instep above and below is red and tender. The toes of both feet are equally affected, and can now be moved separately by the patient. The right heel is in good order, but attached to the left are five fungoid masses, each about the size of a filbert, discharging a watery fluid. The adeno- pathies remain about the same. 328 MTOOSIS FONGOIDE OF ALIBEET. Bemarks. Such is the clinical history of this interesting case during a period of eight months. It would be interesting to com- pare it with other cases which do not exactly conform to the characters of the fungoid mycosis of Alibert, reported by Tilbury Fox, 1 Van Harlingen, 3 Hardaway, 3 and Hyde/ and with which cases the one here recorded has many sym- ptoms in common. But space forbids. When the man came under observation he was weak and emaciated, and though he cannot be fairly said to have gained in weight, he has not lost ; and if not stronger, he is no weaker now than then. That arsenic has been useful in the treatment I do not doubt, for the tumours have become worse when- ever this was discontinued, even for brief periods. On the other hand, we find that the patient has taken this medicine with few intermissions for eight months, and during this period the tumours have all diminished in size, while many have disappeared entirely. As the notes show, iron was fre- quently combined with the arsenic, and has doubtless proved itself useful. We know also that ichthyol was useful as a local application, for it was continued on the hands, and there only, often when the arsenic was stopped ; and while new tumours appeared elsewhere the hands steadily im- proved. The persistent pruritus remains unabated, and it is possible that the arsenic may have aggravated it, or at least impeded its improvement. It will be noticed that the nervous paroxysms and fevers referred to in early notes gradually ceased, and that the patient has not been harassed with them for some time. Freshly drawn blood has been recently examined in the ward by my friend Dr. A. McShane, who used the hasmocy- tometer of Gowers. The doctor found in a cubic millime- tre of blood 4,680,000 red corpuscles and 36,000 white cor- 1 Fibroma Fungoides, ' Skin Diseases,' 2ndAmer. ed., New York, 1873. 1 Ulcerative scrofuloderm, 'Arch, of Derm., 5 April, 1879. 3 Multiple tumours of the skin, accompanied by intense pruritus, ' Arch, of Derm.,' April, 1880. 4 Myeloma cu.tis, 'Diseases of the Skin,' 1883. The author has just received the second ed. of Dr. Hyde's work, in which he refers to the same case as one of mycosis f ungoides. HISTOLOGICAL DETAILS. 329 puscles, and remarks, " The ratio of white corpuscles to the red is thus i to 130, which ratio is much greater than that observable in health." Now when we consider that the usual proportion is 1 white to 350 — 500 red, we see that there are at least three times as many leucocytes in the blood as there should be in health. There seems to be no very marked diminution of red cells. Examination of Tissues. For microscopical study tumours were removed from the patient at three different times, and sent to the pathological department of the hospital. The first specimen, already referred to, was stained for leprosy bacilli, and none found after the examination of many sections. A second, the size of a cherry, was removed November 22nd, and a third about six weeks later. The last specimen was the smallest focus of disease that could be found, and was the size of a small pea, having healthy tissue attached, and included the whole thickness of the skin. These were all sent fresh to Dr. H. D. Schmidt, the dis- tinguished pathologist of Charity Hospital, New Orleans, who has studied them carefully, and, after much labour, has submitted to me the following report, with drawings from his own skilful and accurate pen : " The tumour first sent to me for examination had been taken from the side of the patient just over the liver, and from my microscopical examination of thin stained sections of it I was rather inclined to regard it sarcomatous in its nature. Being unable to discover in the sections any trace of a reticulated adenoid tissue, mentioned by some authors, and to which you particularly directed my attention, I suggested to you to remove from the body of the patient one of the smaller tumours of recent growth, on which we might possibly observe the histological development of the neo- plasm. What I had suspected proved true, for the sections made of this second and smaller tumour which you removed from the arm of the patient, though not showing the very first stage of the disease, exhibited, nevertheless, the true 330 MYCOSIS FONGOIDE OP ALIBBET. structure and development of the growth to full satisfaction. As will be seen directly, there was some difference observed in the structure of the two tumours, though they were de- rived from the same patient — a phenomenon which, however, admits of a satisfactory explanation. Although the larger tumour, taken from the side of the patient, was the first examined and studied, I shall commence my description of the nature and development of this neoplastic growth with the smaller and last specimen taken from the arm of the patient. " To illustrate the subject, and to render its description more perspicuous to the reader, I have carefully made from the microscope a number of drawings representing the different phases of development of the tumours of mycosis fungoides ; they will accompany this report. " In turning now our attention to Fig. i, which represents a section of the smaller and younger growth, magnified about 40 diameters, we notice at a the so-called horny layer (stratum corneum), at b the layer of the prickle-cells, or mucous layer (rete or stratum mucosum) of the epidermis, and at c the papillary layer (pars papillaris) of the corium. In the latter we notice a number of well-defined round spaces, or areolae, d. These spaces are also met with in the pars reticularis of the corium, where they represent the areolae, or lymph-spaces, situated between the bundles of connective tissue of this part of the skin from which the radicles of the lymphatic vessels take their origin. These spaces, which differ considerably in diameter, increase in size during the development of the tumour. In some in- stances, even, a number of the lymph-spaces fuse with or coalesce into one another (Fig. 1, e), forming, surrounded by a sort of a capsule of hyperplastic connective-tissue bundles (/), a compact mass, which, as may be observed in this figure, constitutes the greater part of the whole tumour. " Let us now trace the mode of development of this neo- plasm by referring to Fig. 2, which represents a small portion of the tumour seen in Fig. 1, including the epider- mis and a small part of the corium, magnified about 250 diameters. Leaving the strata of the epidermis to a later consideration, we shall first direct our attention to a number HISTOLOGICAL DETAILS. 331 •of small round cells (so-called leucocytes or lymph- cells) observed between the bundles of connective tissue of the papillary and the adjacent reticular layers of the corium. In the drawing (Fig. 2) before us these cells do not appear very numerous, for the reason that this specimen of the neoplasm did not represent its very first stage of develop- ment. But judging from my own observation, and from the statements of other pathologists, I may safely presume that these small cells are the first pathological elements appear- ing in the history of the neoplasm under consideration, giv- ing rise to the subsequent pathological changes in the •corium of the invaded part of the skin. Though not repre- sented in my drawing (Fig. 2), I have observed two nuclei in a number of these cells, and also, in many instances, two of the cells lying very close to one another, thus showing that their multiplication takes place by the mode of division. As regards their origin, it will, of course, be difficult to determine whether they are derived from the blood or lymph, or from the normal connective-tissue cells. " Throughout both the papillary and reticular layers of the corium will be observed a number of smaller or larger elliptoidal spaces closely packed with small cells (Fig. 2, e) , which cells have become polygonal in shape by mutual pres- sure. These cell-nests, as they may properly be called, have very probably been formed by the multiplication of one or even more of those individual cells met with between the connective-tissue bundles. In the loose tissue of the pars reticularis (Fig. 1, /, and Fig. 2, h) these cells, when in- creasing in number, simply fill up some of the small oblong interspaces of the loosely arranged connective-tissue bundles, whilst in the denser tissue of the pars papillaris (Fig. 1, c, and Fig. 2, d) the small elliptoidal spaces are formed by the cells, which, during their increase in number, press asunder the parallel and closely arranged connective-tissue bundles. At any rate, in both instances the cells gradu- ally assume a more multipolar form, from which filiform processes are growing out, which, by growing toward and fusing with those of neighbouring cells, eventually form a sort of reticulated so-called adenoid tissue (Fig. 2, /) men- tioned by some of the authors in their description of the 332 MYCOSIS FONGOIDE OF ALIBERT. pathological anatomy of these tumours. The final conver- sion of the small round lymph- cells into adenoid tissue, however, does not only take place in the cell-nests, but also in those single individual cells distributed throughout the connective tissue of the papillary and reticular layers of the corium (Fig. 2, d and h), where they may be observed to assume also, as in the case of the cell-nests, a multipolar form ; while the filiform processes, proceeding from neigh- bouring cells, likewise unite to form an imperfect reticulum -throughout the connective tissue. " The adenoid networks above described, formed both from the cell-nests and from those single cells distributed through- out the connective tissue, consist of fine fibrillae connecting the individual multipolar or stellated cells with one another. There are, however, other so-called lymphoid networks ob- . served in this tumour, which consist of more or less coarse connective-tissue fibres, and contain, besides a very small number of multipolar cells, also a number of single nuclei. These networks (Fig. 1, e) appear to be derived from the endothelial cells lining the round and larger lymph-spaces of the connective tissue of the pars reticularis. From the protoplasm of these cells also, as in the case of the cell-nests above described, processes grow out, which by meeting and uniting with the processes of neighbouring cells form the reticulum, which here, however, consists of more or less thick and heavy bundles of connective-tissue fibres and comparatively small meshes (Fig. 3, a). In the coarse bundles of this reticulum a number of small single nuclei are observed, which represent the remains of the nuclei of the original multipolar cells, the whole protoplasm of the latter having been used up in the formation of the fibres of the reticulum. Only here and there some of the original multipolar cells are still observed in the meshes of the reti- culum, as seen magnified about 250 diameters in Fig. 3, c. "In referring again to Fig. 1, which represents a section of the whole small and more recent tumour, there will be observed a considerable number of these coarse reticula (e) just described. They are enclosed in a sort of a capsule, formed by coarse bundles of hyperplastic connective tissue of the pars reticularis (/), from which processes are seen to HISTOLOGICAL DETAILS. 333 arise and proceed into the interior of the whole mass, form- ing septa (Fig. 3, b) between the original reticula. The latter, circumscribed by the capsule, form almost the greater part of the whole tumour. " Some of the spaces, filled with multipolar cells united by the fibriilas of their processes, are also observed at the borders of the papillary layer, as represented in Fig. 2, g, and Fig. 1, d. These spaces are likewise, as it appears, original lymph-spaces, and the cells which they contain may possibly be derived from the endothelial cells lining these spaces ; though, on the whole, it may be said that it is very difficult to determine the true origin of these cells. " In reviewing the process of the formation of the adenoid network from the cell-nests, such as I have described it above, a certain obscure point relating to this process will be noticed to still remain unexplained ; this point involves the question, in what manner can the interspaces or meshes observed between the fine fibrillar processes of the multi- polar cells, and forming the adenoid network (Fig. 2, / and g), be formed from a closely packed mass of cells as seen at e ? The only plausible explanation which I find to meet this question is, that the multipolar cells, while they give rise to their filiform processes, secrete a fluid which, by gradually distending the space or wall of the cell-nest, makes room for the growing processes and their filaments, which room or space becomes eventually identical with the meshes of the network. " As regards the connective tissue of the corium, it is found to be in a hyperplastic condition, indicated particularly by the coarse bundles of connective-tissue fibres of the pars reticularis (Fig. 1, /, and Fig. 3, b), as well as by the de- formity or even complete disappearance of the papillae by the hyperplasia of the connective tissue of the pars papil- laris (Fig. 1, c, and Fig. 2, d). " In passing now from the consideration of the corium to that of the epidermis of the tumour in question (Fig. 2, a, b, and c), it may be Stated that here the mucous and granu- lar layers, as well as the septum lucidum, showed no ab- normal changes ; whilst the horny layer, besides having diminished in thickness, presented a peculiar appearance, 334 MYCOSIS PONGOIDB OP ALIBERT. namely, the walls of its component cells, instead of being: marked by a fine double contour, appeared in this case to be composed of several superposed layers, indicated by several lines, as may be observed in Fig. 2, a. In examin- ing the drawing more closely, however, it will be observed that these lines do not correspond to the outlines of the in- ; dividual cells, as they should in representing the outlines of individual layers, or deposits, upon the interior of the cell walls ; but that, on the contrary, the greater number of . these lines pass from one cell to a neighbouring one, either in a parallel or oblique direction. For the latter reason it appears to me more probable that the supernumerous lines of this cell wall indicate the walls of collapsed cells — a phenomenon which at the same time would satisfactorily account for the decrease in thickness of the horny layer. " Having thus far treated of the structure and development of the smaller and more recent tumour, which you took from , the arm of your case of mycosis fungoides, let us pass to the . consideration of the structure of the tumour which I first examined, and which you took from the side of the patient just over the region of the liver. In doing so we shall refer , to Fig. 4, which represents a small portion of the irregular surface of this tumour, magnified about forty diameters. " At the first glance upon this drawing we must notice the considerable deformity of the layers of the epidermis caused by the abnormal growth of the corium. As in the younger tumour above described, we likewise find here the horny . layer (a) of the epidermis reduced in thickness. The mucous layer (stratum mucosum, b and 6), also, is found deformed by the abnormal growth of the papillae (c), as well as by the rest of the corium (d). Although this tumour was larger, and represented an older growth than the one described above, its microscopical examination and study showed the absence of any formation of , lymphoid so-called adenoid tissue, the principal pathological changes simply consisting in the production of very numerous cells, and, besides some spindle-celled sarcomatous stroma, a hyperplasia of the con- nective tissue of the corium, indicating a lower grade of organisation than met with in the smaller tumour above described. HISTOLOGICAL DETAILS. 335 In referring again to Fig. 4, d, which represents the corium of the tumour, the cells will be observed arranged in larger or smaller groups, which, on their part, are arranged in rows ; they are embedded in the hyperplastic connective tissue. Most of the empty spaces observed in this part of the tumour represent the sections of blood- vessels, while others may represent sections of lymph- spaces. If we now examine Fig. 5, representing a small portion of corium, as exhibited in Fig. d, magnified about 250 diameters,, one part of these cells will be found lining sections, of lymph- spaces (a), while the other part is embedded in the hyper- plastic connective tissue (d). At the same time a slight difference may be observed in the comparative shape and size of these cells ; for whilst those in the lymph-spaces exhibit a somewhat irregular form, resembling the endo- thelial cells of vessels, the other, placed between the fibrous bundles of the connective tissue, are somewhat smaller in size and more spindle-shaped. Judging from the small groups (6), in which the cells are placed closely to one another, their multiplication must take place by the mode of division. In this drawing, also, a number of empty spaces (c) are met with, which here very probably represent sections of lymph-spaces. From what I have already said above, it may, then, be pre-, sumed that the cells met with in this tumour are derived from the endothelial cells lining the areolae or lymph-spaces of the connective tissue, as well as from the small cells placed between the fibrous bundles of this tissue itself. But in referring again to Fig. 4, and in carefully examining the greatly deformed remains of the papillae, as shown in this drawing at c, a number of rows, formed by groups of cells, will also be observed in this part of the tumour. And it will furthermore be noted that these rows correspond in their arrangement to that of the blood-vessels of the normal papillse of the corium, for which reason I am much inclined to regard these latter cells as having been derived from the cells contained in the walls of the blood-vessels. A part of the cells met with in the pars reticularis may have originated in the same manner ; this postulate appears to me justified, 336 MYCOSIS FONGOIDE OF'ALIBERT. as I Lave failed to discover any minute blood-vessels in the sections of this tumour. Although throughout the greater part of this tumour the groups or nests of cells appeared to be embedded in a hyper- plastic connective tissue, as represented in Fig. 5, there were, nevertheless, a number of places met with, particularly in the deformed papillae, in which a stroma, consisting of minute spindle-shaped cells, could be distinguished, and in which, besides, the whole mutual arrangement and character of all the histological elements of the growth pointed to the character of sarcoma, which observation, during my first examination of this tumour, had inclined me to regard the whole growth as sarcomatous in its nature. As regards the epidermis of this tumour, it may be stated that whilst its horny layer was greatly reduced in thickness, and exhibited the same changes in the walls of its cells, already described in connection with the smaller and younger tumour, the stratum mucosum appeared, though deformed in its general shape, to have undergone but very slight changes in its histological character. In reviewing the descriptions of the structure and deve- lopment of the two tumours taken from one and the same patient, though from different parts of his body, a difference in the character and arrangement of the histological elements of the tumours, as well as in the general construction of the latter, will be found to exist. At first sight this difference appears so striking that, without the knowledge of both tumours having been developed upon the same patient, the pathologist, in studying the character of these tumours, might very easily be led astray, and regard them as dis- tinctly different in their structure, and as being derived from two different patients. In knowing, however, that these tumours have in reality been developed upon the same patient, and in studying and comparing their structures with one another a little more closely, it will be found that the two growths simply represent different stages of deve- lopment. For whilst in the one the pathological process advances only to the formation of a great number of cells, appearing mostly in the form of groups or nests of cells — as well as, though only in some parts of the tumour, to the HISTOLOGICAL DETAILS. 337 production of a number of small spindle-shaped cells, repre- senting, as already mentioned above, a sarcomatous stroma — we find in the other tumour the same production of cells, probably of the same origin, but endowed with a superior force of organisation, and in consequence developing into a higher kind of tissue, resembling in structure that met with in the lymphatic glands known as adenoid tissue. And it is this difference in the degree of development observed, as in the case under consideration, to exist in the tumours derived from different patients suffering from the same disease, and causing a different appearance of the structure of these growths, that has given rise to the discrepancy of opinion as regards the exact nature of the tumours and the disease in question, which has existed, and to a certain extent perhaps still exists among some pathologists. Abstaining from making any special remarks as to the etiology of this peculiar affection, I will simply repeat that the first pathological change observed in the skin consists, very probably without regard as to their origin, in the appearance of very great numbers of small round cells. In the small tumour examined and studied by myself, this very first stage of the development of the neoplasm had, as I have already mentioned before, almost passed, though many of these small cells were still observed throughout the papillary layer of the corium, as seen in Pig. 2, d. But in examining Fig. 1 of the illustrations accompanying the statements of Dr. Longstreet, concerning his examinations of the tumours of Dr. Duhring's case of this disease ('Archives of Dermatology,' January, 1879), this stage, characterised by the appearance of great numbers of small lymph-cells in the corium, will be found represented. As regards the adenoid networks which I have described above, I may state that it is only the one consisting of fine fibrillas which I have thus far seen described and repre- sented by a few authors in their writings on the subject ; whilst the reticulum, consisting of those coarse bundles of fibres as represented in Fig. 3, I have as yet never seen mentioned or represented by drawing. As to the etiology and exact nature of mycosis fungoides, I shall for the present likewise forbear from expressing any 22 338 MYCOSIS FONGOIDE OP AL1BERT. positive opinion, and, in consequence, classification of this neoplastic growth, though I may simply say that thus far I am rather inclined to regard it as being in some way or other related to the lymphatic system. The designation " mycosis f ungoides," at any rate, appears to me wrong. Ranvier's " lymphademe cutanee," though it may not be perfectly correct, nevertheless appears to express somewhat closer the true nature of the neoplasm than the above original designation. In reviewing the history of this remarkable case, we find that without apparent cause the disease began as an erup- tion similar to, if not identical with eczema, accompanied by an intense pruritus which has continued to this day (May 12th, 1888). The tumours, which later on formed a conspicuous feature of the disease, did not appear until after the frost-bite in January, 1887, or three and a half years after the beginning of cutaneous inflammation. The tumours have spared no portion of the body except the face and scalp, and occur on the thinnest as well as the thickest surfaces. Though tender to the touch they are not painful, and though con- gested they have never bled from ulceration. Their occurrence on the hard palate, the external auditory meatus, the glans penis, aDd occasional tenderness within the rectum during defecation, with bleeding therefrom, go to show that the mucous membranes are by no means exempt from the disease. How far the mesenteric glands and internal organs are affected it is at present impossible to say. The spontaneous appearance and disappearance of the tumours is an interesting and curious feature of the disease, for several that grew to the size of a pecan-nut were ob- served to pass through their stage of growth and resolution within six weeks, while certain others, half the size, would remain three times as long. In a general way it may be stated that the soft, discharging tumours grew largest and disappeared soonest. Thus far the disease seems to be dermal rather than hypo- dermal, beginning in the skin and remaining there. It were hard to say how true this statement may be with re- HISTOLOGICAL DETAILS. 339 ference to the toes ; but as the inflammation has not yet destroyed the deeper structure after months of disease, it can be understood how superficial the morbid process must be. The only subcutaneous inflammation noted has been that of the numerous enlarged lymphatics ; and it is possible that the swelling mentioned as having occurred in the region of the saphenous vein in the thighs was also due to inflam- mation of the lymphatic glands distributed along the course of that vessel. Conclusion. We see, then, in this disease an unusual involvement of the lymphatic glands, many of which, so small and insig- nificant in the normal state as not to be noticed in the majority of dissections, become irritated and swell to the size of a butter-bean, in one case attaining the size of a pigeon's egg. In addition to the clinical fact of slight but constant to water, 1 pint, painting the surface with a solution of cocain (2 per cent.), or of menthol (grs. ij — x to the ounce) ; lotions of lead and opium, the black wash, grin- delia robusta (31 — ij tojiv of water), &c, are recommended. 400 DR. MORROW ON DRUG ERUPTIONS. Bland ointments, as TJng. Zinci Benzoati, Ung. Diachyli, ot an ointment of oleate of bismuth prepared after the follow- ing formula — Bismuthi Ox., 33 ; Acidum Oleici, 3vij ; Cera Alb., giij ; Vaselinum, ^ix ; 01. Rosae, gtt. ij, M. ; or, when the skin is not broken, an ointment of chloral and camphor (aa 3ss — 3J to 3j of vaseline) may be employed. In the treatment of the severer forms of pustular and ulcerative lesions the use of powdered iodoform or dressings of carbolised vaseline will be found to hasten the reparative' process. In the treatment of furuncular lesions the continuous application of camphorated oil is serviceable in relieving pain and promoting resolution. ACIDUM BBNZOICUM SODII BENZOAS. Friar's balsam, which is but another form of the comp. tincture of benzoin, 1 is credited with the production of erup- tive phenomena. Fox reports a case of a very extensive eruption of purpura urticans in a patient who had been directed to inhale the vapour of Friar's balsam two or three times a day. The eruption was confluent upon the trunk, more discrete and urticaria-like upon the extremities. Fox says that the rash may result from reflex disturbance or from the presence of the drug in the cutaneous capillaries ; the latter he thinks probable from the strong odour of the drug exhaled. Benzoic acid, upon the presence of which the virtues of the balsam chiefly depend, is irritant to both cutaneous and mucous surfaces. Vanini observed in a patient, for whom he had ordered small doses of benzoic acid, a maculo-papular eruption deve- lop on the fourth day. The skin of the trunk became covered with an eruption composed in part of somewhat pale, rose-coloured macules of irregular form and extent, and in part of bright red papules, from the size of a poppy seed to that of a grain of millet. In some places the papules, were distinctly discrete, while in others they were notably ~ l TTriar's balsam contains the balsamic resin benzoin, storax, balsam of Tohi, and Socotrine aloes. — T. C. F. : > BORAX. 401 confluent, giving to the skin a uniform raised aspect. Around the papules and the erythematous spots the skin presented a normal colour. The following day, under continued use of the drug, the eruption extended to the face, neck, upper and lower ex- tremities ; only the surface of the thighs remained free. The use of the medicine was now suspended, and on the fourth day the macules had faded, the papular element disappearing in about ten days without treatment. Rohe reports two cases in which the internal use of ben- zoate of soda in medicinal doses caused eruptive disturbance. The rash was erythematous, with well-defined borders, and was attended with considerable itching. The eruption dis- appeared, with slight desquamation, upon discontinuance of the drug. It was redeveloped several times by a repetition of the use of the drug. 1 ACIDUM BOEACICUM SODII BOEAS. According to Stille, the long-continued use of borax some- times produces an impetiginous eruption of the skin. Modadewko 2 reports two cases in which a 5 per cent, solu- tion of boracic acid, used for washing out the pleural cavity, occasioned an erythematous rash over the face, trunk, and extremities. Bruzelius saw a wide-spread erythema make its appear- ance after a few days' use of a 4 per cent, solution of boracic acid taken as an injection 3 in chronic diarrhoea. The eruption was confluent about the neck, and well developed over the body. 1 Hampeln gave, in twenty hours, three grammes of henzoate of sodium to a boy, aged eight years, for pultaceous amygdalitis. A diffuse scarlatini- form exanthem appeared on the neck, trunk, and arms, and reappeared in a patchy form on the readministration of the drug. Ehrenhaus is quoted as having seen erythema and purpura. — T. C. F. 2 ? Molodenkow, quoted in ' Lancet,' May 6th, 1882. A pleural and a lumbar abscess-cavity were each washed out for an hour, and " the next even- ing erythema appeared on the face, and spread on the third day to the neck, chest and abdomen, then on to the thighs, small vesicles appeared on the face and throat, the sight became dim, and both patients died, conscious to the last, one on the fourth, the other on the third day." — T. C. F. 3 Two pints per rectum. — T. C. F. 26 402 DE. MOREOW ON DRUG ERUPTIONS. Gowers reports three cases in which borax administered for a long period to epileptics determined an eruption per- fectly characteristic of psoriasis. Scaly patches of variable dimensions, some of them three quarters of a centimetre in diameter, occupied the trunk and limbs, especially the upper extremities, and were spread over both extensor and flexor surfaces ; the face was not invaded. The aspect of the erup- tion was quite characteristic of psoriasis, although there was less thickness of the scales than in spontaneous psoriasis. In two of the cases the addition of a small quantity of arsenic to the borax caused the rapid disappearance of the eruption. 1 Johnson reports a case in which the injection of 3"6 grams of boric acid was followed by headache, fever, injection of the conjunctivas, and the appearance of an eruption consisting of a bright erythematous redness, papules, and bullae, The eruption was localised on the extensor surfaces of the limbs and around the articulations, and disappeared within four days. The acid was readily detected in the urine. In a number of experiments with the application of boric acid in the form of an ointment to the skin, the urine became promptly charged with the borate. Tests for Boric Acid and Borax. When notable quantities of boric acid or borax are present in the urine, they may be detected by evaporating the urine, previously rendered alkaline by soda, to a small bulk, then acidulating (slightly) with hydrochloric acid, and dipping into it one half of a strip of turmeric paper ; the latter, when dried upon a watch-glass at 21 2° P., will exhibit a peculiar red colour upon the immersed portion. If this is then 1 Liveing confirms the observation of Growers. Alexander (quoted by Crocker) described a diffuse, erythematous, morbilli- form eruption following the administration of " tartarus boraxatus " in large doses for two weeks. Welch records cases of poisoning from packing the upper third of the vagina with boric acid. Burning of the skin, especially of the face, hands, and feet, followed in one case ; the skin swelled and looked charred, and subsequently exfoliated. In another case there was severe collapse, and after a week desquamation of the skin. Fere and Lamy record two cases of an eczematous eruption provoked by the ingestion of borax. — T. C. P. CARBOLIC ACID. 40$ moistened with a solution of a caustic alkali or alkali car- bonate, the colour changes to bluish black or greenish black. But a little dilute hydrochloric acid immediately restores the previous tint. If the urine is rendered alkaline by soda, then evaporated to a syrup, the latter mixed with a proper quantity of pure white sand and then evaporated to dryness, the residue powdered, covered with alcohol, and concentrated sulphurio acid added, on igniting the alcohol this will burn with a green or green-bordered flame. ACIDUM CAEBOLICTJM. The irritating effect of carbolic acid directly applied to the skin varies from a slight erythema to complete destruc- tion of the tissues, depending upon the strength of the pre- paration used and the duration of its contact. The applica- tion of strong carbolic acid to the skin causes a painful burning sensation, less pronounced, however, than in the case of other caustics ; the affected tissues become white, their vitality is destroyed, and a slough is formed. Abundant opportunity has been afforded for the study of the effects of weak solutions of this agent upon the skin by the general employment of carbolised dressings in the anti- septic treatment of wounds. The most common eruptive form is an erythema which is especially manifest upon regions where the skin is fine and delicate. The inflammatory reac- tion may result in the formation of vesicles resembling eczema. Strong solutions of carbolic acid may cause gan- grene of the skin, which is usually limited to the region of application. The use of this agent in the form of a spray no doubt facilitates its rapid absorption through the skin by the minute subdivision of the particles. Irritation of the skin may appear on parts not subjected to the action of the spray from absorption. Similar effects may follow the introduction of carbolised preparations in abscesses and in cavities lined with mucous membrane, as the vagina and rectum. The cutaneous effects of carbolic acid poisoning are usually 404 DR. MORROW ON DRUG ERUPTIONS. accompanied with nausea, headache, vomiting, and diminu- tion in the quantity of urine voided. The urine becomes of a dark olive colour. Koster-Syke reports a remarkable idiosyncrasy against carbolic acid in his own person ; and his susceptibility was so marked that merely handling a vessel containing carbolic acid sufficed to develop the outbreak of an eczematous eruption. Zeissl reports a case of erythema urticatum following the application of Lister's bandage. The eruption appeared upon the back, sides, and extremities in the form of an erythema- tous redness, studded with artificial wheals. The eruption subsided when the carbolic acid dressing was withdrawn. Browne reports two cases of carbolic rash under his care resulting from antiseptic dressings. The eruption was of a bright scarlet, which commenced about the edges of the wound, spread over the contiguous surfaces, and became generalised. The eruption was followed by desquamation and some albumen in the urine, resembling in many par- ticulars scarlatina, for which it was at first mistaken. Dreyfuss observed, as the result of phenic acid dressings to the wonnds caused by circumcision in two Jewish infants, a generalised erythematous eruption accompanied with abun- dant perspiration and hyperemia. There was also a ten- dency to the formation of furuncles lasting several weeks thereafter. In a case of poisoning from drinking impure carbolic acid treated by Penasse, he observed in conjunction with other toxic symptoms an eruption, preceded by violent itching, papular in character, situated upon the arms and anterior superior region of the trunk. Rose reports the occurrence of gangrene of the finger from the application of a strong carbolised cotton dressing. This result may possibly have been due to interference with the circulation from compression, as similar results have been observed from simple collodion dressings to the fingers. 1 1 It has been stated that warts, which may degenerate into epithelioma, are commonly produced amongst those employed in the manufacture of carbolic acid, but this has been denied. — T. C. P. CHRYSAEOBIN. 405 Tests for Carbolic Acid. Normal urine contains small quantities of phenol-sulphuric acid, which does not readily respond to reagents until it has been split up into free phenol and sulphuric acid by boiling the urine with hydrochloric acid. Urine containing notable quantities of carbolic acid has often a dark colour, particularly when the drug has been absorbed from external application. It may be detected in the following manner. i. Place into a test-tube about two grains of chlorate of potassium, pour upon it about one half a fluid drachm of hydrochloric acid, and allow the reaction to proceed for about one minute. Then dilute with about three fluid drachms of the urine. Now carefully pour down, along the inner side of the test-tube, a little water of ammonia, so that this will form a layer on the liquid contained in the test- tube. If any carbolic acid is present there will be a coloured ring — varying from faint rose-red to dark brown — at the line of contact of the two liquids. 2. Or mix the urine with one fourth its volume of water of ammonia, then add a little solution of chloride of lime (i in 20), and warm gently. A fine blue colour, more or less deep, will make its appearance. The treatment consists in suppression of the exciting cause. When the cutaneous effects of the drug are accompanied with symptoms of general phenic intoxication, diuretics should be given to hasten the elimination of the drug. Sulphate of soda internally, as recommended by Baumann and Sonnersburg, injections of atropine, and vigorous frictions are probably the best measures for overcoming the toxic effects. ACIDUM CHBYSOPHANI CUM CHRYSAROBIN. Araroba or 60a powder, from which chrysarobin is prin- cipally derived, is extremely irritating to the skin and mucous surfaces. Workmen employed in cutting up and pounding the wood from which the powder is obtained are 406 DB. MOEEOW ON DBUG EEUPTIONS. compelled to protect their hands, eyes, and throat against the irritating dust. The application of chrysophanic acid to the skin causes an irritation which varies with the strength of the applica- tion and the susceptibility of the patient. The effect of the irritation is by no means limited to the seat of application, as in the case of most external irritants, but may extend over a considerable contiguous surface, or may leap to a cutaneous area some distance removed. Chrysophanic con- junctivitis not infrequently follows the application of this agent in the treatment of parasitic diseases of the scalp. The following forms of inflammatory disturbance may be described : i. A Sypersemia with a Peculiar Purplish or Prune-juice Discoloration of the Shin, which is quite persistent. 2. An Erythematous Eruption. — This may appear as a slight erythematous halo around the points of application, or the congestive redness may become intensified with tume- faction of the tissues, and take on the characters of a general dermatitis. It usually disappears with a slight desquamation. 3. A Papular Eruption. — The inflammation may manifest itself as pin-head sized, reddish-brown, firm papules, some of which may become vesicular and pustular ; according to Kaposi, who first described this eruptive form, they corre- spond to the openings of the follicles. This drug has also the property of irritating the sebaceous glands, producing a chrysarobin acne, with a tendency to the formation of nodules rather than of papules or pustules. As in tar acne, each lesion has a black point in the centre. Farquharson reports a case in which the application of an ointment of chrysophanic acid to a patch of tinea tonsurans caused a dusky red condition of the entire scalp. From the scalp the inflammation extended to the face, which was covered with very minute papules, thickly studded over perfectly normal skin, and attended with a good deal of itching. The eruption disappeared on leaving off the oint- ment. 4. A Pustulcvr and Furuncular Eruption. — This form of eruption is by no means uncommon. The pustules and furuncles are hard and painful, and suppurate slowly. I CHRYSAROBIN. . 407 have reported a case of tinea barbae coming under my care in which the application of an ointment (twenty grains to the ounce) produced a number of large inflammatory nodules, with much infiltration and congestion, resulting in a hard, brawny condition of the sides of the face and neck, and which persisted for two or three weeks. Brocq observed a man dying at the St. Louis Hospital, with the most intense general erythema accompanied by symptoms of severe poisoning from chrysophanic acid. He also saw, in the service of M. Vidal, a case of general exfoliative dermatitis of two months' duration, which had been occasioned in the same way. An erysipelatous condition 1 has been observed in connec- tion with the use of this drug. It most usually affects the head and face with considerable swelling and puffiness of the tissues, sometimes leading to closure of the eyes. The genitals, as well as the face, are specially liable to the irri- tant action of the drug. It would seem that these irritating effects depend less upon the strength of the preparation than upon the susceptibility of the skin of the individual to irritant action. In a number of cases which have come under my observation an intense dermatitis has been deve- loped by the use of a comparatively mild ointment (5 grs. to 3j)- I n * w0 °f these cases there was exfoliation of the epidermis in large flakes, as in exfoliative dermatitis. These irritant effects from mild applications are specially liable to occur in women and children, particularly blondes, with fine delicate skins, and render the employment of the agent in any strength impossible. Tests for Chrysarobin and Chrysophanic Acid. Chrysarobin appears in the urine either as such or as chrysophanic acid. It may be detected by adding to the urine — concentrated if necessary — a little caustic potassa. If this produces a reddish or red tint, chrysophanic acid is present. If the tint is rendered deeper by blowing air through the liquid, or if it only makes its appearance after the passage of a 1 An erysipelas-like condition. — T. C. F. 408 DR. MORROW ON DRUG ERUPTIONS. current of air, chrysarobin was present. It is only when this has been converted into chrysophanic acid by contact with air, in solution, that the colour is developed. ACIDUM NITEICTJM. According to Stille, a fine pustular eruption sometimes appears upon the skin after the internal use of nitric acid in medicinal doses. Bazin found, after two or three frictions with a dilution of nitric acid, that the skin presented a diffuse redness, over which were scattered small solid elevations ; after the fourth friction these little elevations became pustules, which soon gave place to small ulcerations, extremely superficial, pre- senting a blackish point at the centre, and a whitish zone of pseudo-membranous aspect at the periphery, which was surrounded by an inflammatory areola. As the eruption disappeared, small epidermic scales were seen disseminated over the patches. ACIDUM PTEOGALLICUM — PYROGALLOL. The topical application of pyrogallic acid may occasion irritation of the skin of varying degrees of severity, from a slight dermatitis to a destruction of the skin, followed by ulceration and sloughing. According to Jarisch, who first introduced the drug to the notice of the profession, it ex- cites localised inflammation, which may lead to epidermic desquamation and the formation of vesicles. This is specially liable to occur on the extremities. Its most common and characteristic incidental effect upon the skin is, according to Besnier, the production of an erythemato-vesicular eruption. Allen reports two cases in which a ten per cent, ointment of pyrogallic acid produced a blackened and charred con- ACIDT/M PICEICUM. C. H. Hughes found that in a case of chronic malaria one and a half drachm doses of picrate of ammonium set up an urticaria, and probably was the cause of jaundice. The administration of quinine was also followed by urticaria. Such a case obviously requires confirmation. — T. C. P. SALICYLIC AOID. 409 dition of the skin for an inch or more beyond the area of the application, with a dermatitis of the adjacent surface. In one case the charred tissues sloughed off, leaving an ulcerated surface which slowly healed, succeeded by a dis- figuring cicatrix. Tests for Pyrogallic Acid. "When this acid has been absorbed, the urine generally appears dark-coloured, varying from brownish to near black. When the urine is not loaded with colouring matters, pyrogallic acid may be recognised by its behaviour with iron salts, giving a deep blue colour with ferrous sulphate, and a brownish red with ferric chloride. These tints are, however, comparatively faint when only traces are present, and the blue tint, particularly, will be modified to a sort of muddy green. Additional proof may be obtained by shaking an- other portion of the urine, rendered alkaline with caustic potassa, for some time in a test-tube. If it becomes darker in tint, pyrogallic acid may be assumed to be present. Or a little hot nitric acid may be allowed to react with a piece of starch in a test-tube, and a few drops of the nitrous acid thereby produced added to the urine, which will be rendered brown if pyrogallic acid was present. The irritant effects of pyrogallic acid upon the cutaneous surface are often accompanied with symptoms of general poisoning. In the treatment of the toxic effects of pyrogallic acid, Besnier recommends the inhalation of oxygen and the sub- cutaneous injections of ether. Unna has suggested the administration of dilute hydrochloric acid as a prophylactic measure. ACID DM SAL1CTLICDM SODII 8ALICYLAS. Irritation of the cutaneous surface has been frequently observed after both the external and internal use of sali- cylic acid. Its substitution for carbolic acid as an anti- septic in the treatment of wounds has shown that it is even more irritating than the former agent. Callender has stated that a two per cent, solution tends not only to irritate the 410 DR. MORROW ON DRUG ERUPTIONS. wounds, but to bring out irritable vesicles in their neigh- bourhood. He observed that an ointment of salicylic acid, one part to twenty, brought out a vesicular eruption, the vesicles containing a clear fluid, the intervening skin much inflamed. The area affected was limited to the surface covered by the dressing. Sir Wm. Jenner records a case where the application of salicylic acid to a burn developed a rash very like that of scarlet fever. Various forms of eruptive disturbance, erythematous, urticarial, vesicular, petechial, &c, have been observed from the internal use both of salicylic acid and salicylate of sodium. Farquharson reports a case where the use of the drug produced a peculiar bright, punctate rash with erythema- tous patches, eventually surmounted by vesicles, accompanied with sore throat and constitutional disturbance suggestive of scarlatina. Erb observed after several days' use of seven-and-a-half- grain doses of salicylate of sodium, an eruption which was at first regarded as an anomalous form of scarlatina. Upon the face, neck, and body it showed itself as a bright red, confluent exanthem. Upon the arms and legs the redness was more blotchy, without papular elevations. The con- junctiva and mucous surfaces of the throat were intensely reddened. The eruption disappeared within two days after cessation of the drug. Three weeks later a similar eruption was developed by three seven-and-a-half -grain doses of sali- cylic acid. Dreschfield observed in the case of a lady an erythema- tous eruption which was repeatedly developed by the internal use of salicylate of soda. The whole body became covered with an erythematous rash. The face, arms, and legs were very cedematous, and the lips very much swollen. Upon examination of the urine with perchloride of iron, a distinct salicylic acid reaction was obtained. Within a few days the rash and oedema disappeared, aud the skin peeled off from the face, legs, and arms in thin flakes. Another patient, suffering from acute articular rheumatism, for which he was ordered fifteen-grain doses of salicylate of sodium three times a day, was soon troubled with a well-marked urticaria. SALICYLIC ACID. 411 A second attack of urticaria was promptly developed upon resuming the use of the drug. He also reports a case of skin eruption very closely resembling erythema nodosum, following the use of a vaginal wash containing salicylic acid. On a previous occasion salicylate of sodium, taken internally by the same patient, had produced an eruption of similar character. Parsons saw in the case of a lady who was taking small doses of salicylate of soda a rash resembling measles upon the face, hands, arms, and body. The rash disappeared upon discontinuance of the drug, and reappeared when its use was resumed. Heinlein observed from the use of four 3J doses of salicylate of sodium a diffused redness of the left half of the face, the lower extremities, and the right side of the chest, with slight oedema of both eyelids, the upper lip, and the legs as far as the middle of the thighs. 1 These sym- ptoms promptly disappeared with the cessation of the medi- cine. After a remission of several days a drachm dose was administered ; half an hour afterward there appeared a diffuse erythematous redness over the greater portion of the body, while a profuse eruption of wheals was observed over the abdomen and lower extremities, with considerable cedema of the face. The urticarial phenomena disappeared in the course of an hour or two, the erythema by the next day. Leube also saw an eruption of urticarial wheals follow the use of a drachm dose of salicylate of sodium. 3 Wheeler reports a case where the drug produced an erup- tion of vesicles and pustules upon both upper and lower ex- tremities, accompanied with profuse perspiration. It disap- peared on stopping the medicine. Rathery says, " Every time I have occasion to use salicy- late of sodium in my own person, my hands and body are covered with a pemphigoid eruption." Cavafy reports a peculiar eruption from the use of sali- 1 Albuminuria was induced, and this symptom is recorded in conjunction with the eruption by Leube and Freudenberg. — T. C. F. 2 Leloir observed a giant urticaria accompanied by plantar and palmar nodosities simulating pseudo-rheumatic nodosities.; — T. C. P. 412 DR. MORROW ON DRUG ERUPTIONS. cylate of sodium. It consisted of erythematous patches; which became covered with, vesicles, some very minute, others larger and confluent, while others were grouped, resembling herpes. Preudenberg saw, after five-grain doses of salicylic acid taken daily for five days, a petechial eruption in which some of the petechias were as large as a half-dollar ; other extra- vasations occurred in the shape of vibices. They first appeared on the back, but spread the following day over breast, arms, shoulders, hips, and thighs. The spots became pale in the course of a week, and the epidermis was exfoliated in great scales from the affected parts. Second experiments in the same patient produced a similar result. Eosenberg observed an eruption of purplish spots all over the body of a patient from the use of salicylic acid. The medicine was discontinued, but upon another trial a month later, in addition to the purpuric eruption, there appeared a number of blebs filled with serum, situated on the back and extremities, and also upon the conjunctiva and mucous membrane of the tongue and lower lips. A third trial of the medicine resulted in a precisely similar eruption. Watelet reports two cases of rheumatism treated with salicylic acid, in which the drug occasioned coldness of the extremities, and in one case gangrene of the lower extremi- ties. The erythematous eruption produced by salicylic acid and its salts bears a striking resemblance to that of antipyrin, belladonna, chloral, &c. The rise of temperature, sweating, oedema, with which the erythema is usually accompanied, are undoubtedly vaso-motor phenomena. Experiments upon animals have shown that the salicylates act primarily and principally upon the vaso-motor centres. Tests for Salicylic Acid and Salicylates. On adding to the urine a little solution of ferric chloride, there will at first appear a nocculent precipitate of phos- phate of iron j but on further addition of the reagent the liquid will assume a more or less intense violet colour. If there is doubt, concentrate the urine to a small bulk, TANNIC ACID — ACONITE. 413 acidulate it with hydrochloric acid, then shake it with a mixture of equal parts of chloroform and ether. Evaporate the latter after separation, and apply the above test to the residue. ACIDTJM TANNICUM. It is well known that tannic acid exerts an influence upon the functions of the skin, notably diminishing the insensible perspiration. The sole reference which I have found in medical literar ture relating to the irritant effects of tannic acid upon the skin is that of Dr. Williamson. He records the case of a lady in whom an erythematous eruption, affecting the face and neck, was developed three separate times by the use of tannic acid. Tannin injected into the rectum, tannin acci- dentally inhaled, the ingestion of an infusion , of uva ursi leaves, which contain 35 per cent, of tannin, were all fol- lowed by identical symptoms. An interesting fact in this connection was that gallic acid, taken internally, produced no untoward symptoms. Gallic acid passes off through the kidneys unchanged within one hour after its ingestion. Tannic acid is con- verted into gallic or pyrogallic acid before excretion. 1 ACONITUM. This drug, as is well known, exerts a marked influence upon the cutaneous system. The external application of aconite to the skin causes first a sensation of tingling and then numbness, from the paralysing action of the drug upon the sensory nerves. Congestion, redness, and an eruption of itchy vesicles have also been observed, and according to Dierbach, quoted by Piffard, it may produce an erysipelatous inflammation. Many writers on materia medica speak of an irritable vesicular eruption, which frequently follows the internal 1 Lange saw tannic acid applied to the pharynx produce serious cedema of the larynx, a general urticaria, and marked prostration. Schramm also observed oedematous swelling of the nose and general urticaria follow, the use of a 1 to 300 tannic acid nasal douche. — T. C. P. 41 4 DE. MOEEOW ON DEUG EEUPTIONS. use of aconite. It is attended with a sense of formication and excessive itching. Pustules and blebs have also been observed. AMYGDALA AMABA. Phillips says that an eruption resembling urticaria often comes out on the skin after the ingestion of this drug. Gregory noticed such an eruption upon himself after eating a bitter almond. The same effects may follow the use of' bitter almond and cherry-laurel water, depending no doubt upon the hydrocyanic acid present in both prepara- tions. Rayer observed from the use of frictions with Vhuile de laurier-cerise an extensive patch of erythema over the loins, nine by six inches in extent. The exanthem consisted of a large non-elevated, red patch, the redness not uniform, the skin appearing as if spotted and discoloured at certain points. The red spots gradually became paler, followed by desquamation on the seventh day. ANACAEDIUM. 2 The oil of the cashew nut is extremely irritant when applied to the skin, producing dermatitis and erysipelas. The effect is not limited to the parts with which it comes in direct contact, extensive inflammatory disturbance being observed upon parts distant from the point of application. (Edema and eczematous inflammation of the face have been observed. ALCOHOL. Nevins Hyde reports a case of urticaria from alcohol. Gr. Eaempfer saw, in a man suffering from articular rheumatism who had been a heavy-drinker, a transient erythema appear half an hour after taking brandy, whisky, beer, &c, but not after absolute alcohol. There was hypersemia of the retinal vessels, and a scarlatina-like pharynx. — T. C. F. i I find references to A. orientate, or the Malacca bean tree, A. or Cassu- liium occidentals, or the cashew of the English and the acajou of the Indians, and Semecarpus anacardivm. Burnett, in his ' Outlines of Botany,' London, 1835, refers to the irritating black varnishes made from Semecarpus, &c, and widely used in India, China, Burmah, &c. The action of these varnishes seems to be identical with " lacquer " poisoning. — T. C. F. OIL OF CASHEW NUT. 415 Stickney noted, from its local application, pain, itching, red papules changing to pustules, crusts, and desquama- tion. According to Bazin, the oil, when applied to the skin, sometimes produces vesicles which rapidly become purulent. Schwerin reports a case of a woman who had put one half of a bean in her ear to relieve toothache and pain in the face. A violent erysipelas resulted. The face was bloated, both eyelids infiltrated, and the ear, cheek, and front of the neck reddened and swollen. The external auditory canal, the external ear, and the adjacent surfaces were covered with vesicles. In another case, also quoted by Lewin, an anacardium bean, divided longitudinally, was placed upon a string hung around the neck in such a manner that it lay over the manubrium sterni. Two days later an erysipelas had developed, extending over the whole front of the chest, the mammae, the region of the shoulder as far up as the lower jaw, and presenting a number of vesicles upon its surface. Hughes states that, taken internally, anacardium has a remarkable influence upon the skin. In its slightest de- gree of action it causes the appearance of wheals like those of urticaria tuberosa, with itching, burning, and swelling, terminating in desquamation. When operating more in- tensely it develops eczematous vesicles, and even bullae. It is claimed that the irritating effects which are so often observed from the use of preparations of vanilla are due to the oil of cashew, with which the vanilla pods are coated before being sent to market. 1 1 J. C. White gives illustrations of the irritative qualities of Semecourpus anacardium (cashew nut). Its active principle is a yellowish oil called cardol.— T. C. F. ANILINE — ACETANILIDE (aNTIFEBBIN). The effects arising from the local application of the numerous aniline dyes are considered under arsenic. Acetanilide (antifebrin) is aniline in which an atom of hydrogen is replaced by the radical acetyl. Many cases are reported in which toxic effects have been caused, often associated with cyanosis ; and Morehouse records an eruption which I have been unable to refer to.— T. C. F. 416 DR. MORROW ON DRUG ERUPTIONS. ANTIMON1UM ANTIMONII ET POTASSII TAETEAS. The external application of tartarised antimony to the .skin excites a very characteristic eruption, which in its course, and the anatomical form of its lesions, resembles the eruption of variola. Its contact produces a hyper- emia, then papules which are converted into vesicles, which later develop into pustules. The pustules mature about the fifth day, desiccate, and form scabs, which often leave, on falling, indelible cicatrices. Sometimes it pro- duces large ecthymatous ulcers, with deep sloughs and ex- tensive loss of tissue, resulting in permanent disfiguration. Jacobi, of Wurzburg, reports a case in which there was destruction of the bony tissue, the application of antimonial ointment to the scalp causing a perforation of both tables of the parietal bone. Applied on distant parts of the body, it may cause eruptions on the genitals or around the anus, without direct contact. Pustular eruptions not infrequently develop secondarily on the genital parts several days after inunction with tartarised antimony, without there having been, so far as could be ascertained, a transference of the drug to these parts from the original point of application. This would seem to be due to the absorption of the drug and its presence in the circulation. Opinion is divided as to whether the effects are due to the irritant action of the drug upon the peripheral nerves leading to inflammatory changes, or to a direct action upon the coats of the vessels themselves from the presence of the drug in the vascular channels. Trousseau says that the internal administration of tarta- rised antimony will produce a vesiculo-pustular eruption, like that produced by the salt applied to the skin. Imbert Gourbeyre cites five cases in which eruptions closely resembling those produced by tartar emetic oint- ment have appeared during the internal administration of the drug. He also quotes a case where a red eruption occurred over the whole body from a single large dose of antimony. This observation has been duplicated in the experience of others. In other cases urticarial and pustu- ANTIPYRIN. 417 lar eruptions have been observed from the internal use of antimony. Langston states that, after the administration of tartar emetic for three or four days to his wife, an eruption, con- sisting of a dense crop of tartar emetic pustules, broke out all over the surface of the upper part of the body, including the arms. The outbreak of the eruption was preceded by an alarming sensation of numbness and tingling. Tests for Antimony and Arsenic. Among the various methods available for their detection, the following will probably be the most expeditious in the hands of the physician : Acidulate the urine strongly with hydrochloric acid in a narrow-mouthed flask ; immerse in it a piece of bright copper wire or foil, and boil for some time. If, after the urine has boiled down to one half, there is no visible metallic deposit upon the copper, the above two metals may be regarded as absent. If a metallic coating has been pro- duced, this is to be examined as stated below. Should the urine contain constituents which are coagu- lated or precipitated by boiling or acidification, they must first be removed. The coated copper wire or foil is taken out of the flask, washed thoroughly in water, dried, and then heated in a glass tube closed at one end, the further procedure being that laid down in all text-books. ANTIPYEIN (ANALGESIN). Although the introduction of antipyrin as a remedial agent is of comparatively recent date, yet a large number of cases have been reported in which eruptive disturbances have followed its employment. The eruption of antipyrin is usually erythematous in character. It consists of small, irregularly circular, slightly elevated reddish patches, which may be discrete, or con- fluent forming large patches resembling the exanthem of rubeola. The redness disappears on pressure, leaving a 27 418 DR. MORROW ON DRUG ERUPTIONS. brownish pigmentation. The duration of the eruption is rarely more than five days ; it is occasionally followed by desquamation. ■ It is frequently attended with profuse sweating, and causes more or less itching. Its seat of predilection is the chest, abdomen, and back, but it may also occur upon the extremities ; it affects the extensor rather than the flexor surfaces. The face and upper part of the neck are usually spared. The eruption may excep- tionally follow a small single dose of the drug, but ordi- narily it is only provoked by a continuous course of anti- pyrin treatment for several days, although, in a large number of cases experimented upon, the . eruption did not occur in the exact period during which the largest quantity of the drug was taken. It begins to subside promptly on the disuse of the drug, and generally, but not always, recurs when the drug is again administered. Ernst was the first to note the incidental effects of anti- pyrin upon the skin. He reports five cases in which an eruption resembling measles was developed upon the trunk and extremities, and also upon the palmar and plantar surfaces. Leube records a case of a " measly eruption " following the employment; of antipyrin, which promptly disappeared with the cessation of the use of the drug. Its resumption brought out a uniform scarlet-red eruption over the entire surface of the body, attended with swollen eyelids, injected conjunctivae, and free lachrymation. Biermer, reported by Alexander, observed in three cases measly eruptions, and one case in which the use of the drug was always followed by an urticaria. Frankenberg observed in seven patients, out of a large number submitted to antipyrin treatment, an eruption of reddish, irregularly round spots, the size of a lentil, giving the skin the appearance of a "rose marbling." In two cases of antipyrin rash reported by Bloomfield the eruption consisted of slightly raised erythematous patches, one eighth to one half inch in diameter, of an Indian red colour, covering the entire body. Here and there were a number of vesicles the size of a No. 6 shot. Bielschowsky observed, after the use of antipyrin in a ANT1PYEIN. 419, case of typhoid fever, an eruption of hemorrhagic wheals on the extremities. 1 They followed the subsidence of the typhoid rash, and were succeeded by a scarlatinoid erup- tion. Graham reports the occurrence of a patch of purpuric macula3 on the back of a patient who was ordered five, powders of antipyrin, twelve grains each. Strauss reports a case in which moderate doses produced^ in conjunction with severe constitutional effects, a purpura- like eruption on the back and limbs. Draper treated, twenty cases of typhoid fever with anti- pyrin. In six of these cases the drug produced an erup- tion resembling measles, and in one case, in which large doses were continued for a prolonged period (twenty days), the drug caused a copious erythematous rash, which was followed by an eruption of furuncles. In one case there was a macular eruption of a purpuric character. The mode of production of the cutaneous effects of anti- pyrin is to be explained by the action of the drug upon the vaso-motor system of nerves. It causes paralysis of the vaso- motors, which is followed by dilatation of the cutaneous vessels. The largely increased amount of blood present would naturally favour the production of the characteristic erythematous and urticarial eruptions. The hsemorrhagic exudations occasionally observed are probably produced in the same way. 2 1 Drasche and Grrandclement also record a hemorrhagic eruption. — T. C. F. 2 Our enlarged experience shows that eruptions follow the ingestion of antipyrin with considerable frequency, judging from the literature of the subject, and the number of cases I have seen and heard of in London hospitals. Germain-See estimated the frequency of its occurrence as I in every 12 or ig women, and I in every 50 to 60 men to whom the drug was administered in repeated doses. The morbilliform rash is the usual one, and may be associated with oculo-nasal catarrh. It usually begins on the limbs and spreads to the trunk, but a wide extent of surface may be almost simultaneously affected. There is never much rash on the face. The eruption is brighter than that of measles, less crescentic, and generally disappears quickly when the drug is discontinued or diminished, and more slowly when continued. The eruption tends to run into more or less extensive patches, especially on the extensor aspects of the limbs and trunk, leaving areas of healthy skin. There may be considerable swelling and in- filtration. The rash may be limited to the limbs, but is always bilateral. The 420 DR. MORROW ON DRUG ERUPTIONS. Tests for Antipyrin. Antipyrin may be volatilised when distilled with, water. Urine, however, after small doses of antipyrin, does not yield the latter by distillation until after it has been boiled with hydrochloric acid, which fact permits the conclu- sion that antipyrin is, at least partly, eliminated as a copu- morbilliform eruption may appear exceptionally after small doses and very quickly. A scarlatiniform eruption has been recorded by Wilson, Hardy, Spitz, Durand, Tuczek, and others. Urticaria is of fairly common occurrence, and it is to be noted that, unlike the morbilliform rash, it usually follows very quickly (ten to twenty minutes) the ingestion of the drug, and often arises from single small doses {four to ten grains). It may be provoked again and again, but in Martini's case, where this resulted, there was no eruption on giving a hypodermic injection. The urticaria may be intense and generalised, or scanty and more localised. Dutt records a case in which itching and tingling occurred without eruption. Several authors mention, more or less marked congestive redness of the face, often associated with a similar condition of the conjunctivae and buccal and respiratory mucous membranes and hypersecretion. There may be very considerable oedema of the eyelids or face. Watkins records a case in which the swelling was limited to the upper lip. Short mentions the case of a man who took five grains of antipyrin on three occasions, and each time suffered from marked flushing of the face, an unpleasant choking sensation in the throat, then redness and swelling of the nose and lips, followed by herpes-like vesicles on the nose, lips, and inside of the cheeks, swelling, redness, and itching of the hands and feet, penis and scrotum, and anal margin. Archer saw a case in which an intense itching was experienced, and bullae formed in a ring round the anus. In a case reported by Veiel there occurred, immediately after taking the drug, violent pruritus of the lips, palms, soles, glans, followed by oedema of and formation of bullae on the lips, and bullae between the toes and on the palatine vault. On the palms and soles itching, urticated patches formed. Three similar recurrences at intervals were observed. Petrini observed itching and the formation of bullae on the face, mouth, neck, shoulders, arms and forearms, trunk, back, breast, abdomen, buttocks, and to a less extent on thighs and legs. This result was probably due to a dose of 3 or 4 grammes, whilst later on a dose of 2 grammes produced only a few bullae, and one gramme only erythema. As in the case of other drugs, toxic effects are frequently produced with- out the occurrence of a rash, but the latter frequently arises without other toxic symptoms. Sometimes intoxication and a rash are co-existent. A spirituous breath may be noticed. NITRATE OF SILVER. 421 lated compound, probably as antipyrin-sulphuric acid. When much antipyrin has been taken, however, it is found free (probably only in part free) in the urine. Urine containing free antipyrin, or in which it has been set free by boiling 1 with a little hydrochloric acid (in which latter case the excess of acid should be subsequently neu- tralised), is rendered red by ferric chloride, and bluish green by nitrite of sodium or by dilute nitrous acid. The latter is best prepared by allowing hot nitric acid to act upon starch, and dilating with a little water. AEGENTI NITEAS. The peculiar discoloration of the skin following the pro- longed ingestion of nitrate of silver, which has been variously described as " bluish-grey," " steel-grey colour," " greyish- black," and which is most marked on the face and flexor surfaces, is comprehended under the general term " argyria." It is caused by a deposition of granules of the metal in the tissues, most abundant, according to Neumann, in the papil- lary layer. Granules are also found in the other layers of the skin, also on the external wall of the hair-follicles, seba- ceous glands, and sweat-tubes. I have seen in the case of a young woman under my care for syphilis, who had pre- viously used for several months a solution of nitrate of silver for the relief of an obstinate granular conjunctivitis, a copious deposit of the metal upon the conjunctival mucous membrane which had caused a blackish discoloration, quite noticeable even at a distance. 1 Charcot observed, after the long-continued ingestion of nitrate of silver, an erythematous and papular eruption attended with pruritus. Argyria derives a certain clinical importance from the fact that it may be mistaken for Addison's disease. According to Gamberini, the internal administration of iodide of sodium or potassium, and the long-continued use of warm baths, has proved successful in removing the dis- coloration of the skin caused by nitrate of silver. 2 1 This disfigurement is well known to ophthalmologists.:— T. C. P. s I have not attempted to collect the bibliography of argyria, but it will 422 DR. MOBEOW ON DRUG ERUPTIONS. AENICA. 1 Arnica, which is popularly regarded as a sovereign remedy for contusions, sprains, &c, is often prescribed by the physician under the mistaken impression that, even if it does no good, it can do no harm. Oftentimes, however, the external appli- cation of the tincture of arnica, even when largely diluted, 3 is- far from proving innocuous and inoffensive. The strong tincture always exerts a local irritant action when applied to the skin, and in susceptible persons it causes eruptive disturbances of various forms and degrees of severity. 3 The most common form of arnica dermatitis is an ery- themato-vesicular eruption which presents certain analogies with the poison oak eruption. The irritant action of arnica is first manifested by a hypersemia of the affected surfaces, attended with a sensation of burning and intense itching. Ordinarily within a few hours there is developed upon the erythematous base an eruption of pin-head sized, reddish papules, intensely itchy, and which soon become converted into miliary or pea-sized vesicles, which may remain discrete, or form, by their fusion, bullae of considerable size and irre- gular outline. The walls of the vesicles are usually ruptured by rubbing and scratching, and the exudation dries, forming yellowish or brownish crusts. be useful to point out that many cases have been recorded in which the characteristic leaden-blue or violet-grey discoloration has followed the application of lunar caustic to* the mouth and throat. In such cases the inquirer may be put off the scent by the patient denying the ingestion of any drug. The mucous membranes and other structures may be involved in argyria. Lewin and Blaschko have written on the localised argyria found in workers in silver. It occurs on exposed parts of the skin in bluish " taches," which are permanent. These taches are due to grains of silver lying in the corium in ramified streaks. Its distribution appears to differ from that found in the so-called " medical argyria." — T. C. P. 1 The limited literature on the subject of arnica dermatitis is probably no guide to the frequency with which the eruption may occur. The knowledge that arnica occasioned such results was wide-spread, and cases were nof recorded. The drug is now comparatively little used. — T. C. F. a And to the unbroken skin. — T. C. P. 3 Febrile disturbance may be associated with the dermatitis. — T. C. P. ARNICA. 423 According to White, most cases of arnica dermatitis pre- sent a distinctly eczematous type in the development of hyperemia, papules, vesicles, excoriations, and crusts in regular order, yet many cases have been observed in which the primary immediate effect was th& production of large blebs or blisters. Exceptionally the dermatitis may spread over surfaces remote from the region of original application by transference of the irritative agent by scratching or otherwise. 1 Pox has observed that the tincture of arnica may produce an erythema and tumefaction of the parts to which it is applied, and even a veritable eczema. Wilson reports a well-marked eczematous eruption from application of tincture of arnica to a contused shoulder. The whole of the front of the shoulder was of a deep red colour, and presented the character of an eczema vesiculosum •et ichorosum, and extending over the whole of the right side of the chest was a crop of pimples of eczema papulosum seu lichenoides, the pimples being large and of a dull red colour ; same eruption on thighs, scrotum, head, face, and hands. He refers to numerous cases reported by Professors Galassi and Mazzoni, of Rome, in which the symptoms of the erup- tion were slightly elevated red puncta, which are quickly converted into middle-sized vesicles similar to those produced by croton oil, swelling and burning heat, and spreading to surrounding parts. Violent erysipelatous inflammation, even ending in death, has resulted from the application of arnica. Purpuric erup- tions have also been recorded. Parquharson reports a case occurring in Hebra's clinic, in which an acute inflammation of both hands, with huge blisters almost running into gangrene and causing partial destruction to the tissues, was caused by the application of the tincture of arnica. He also records a case coming under his observa- tion in which a weak solution of tinct. arnica caused an ery- sipelatous inflammation which slowly spread over the entire body. 1 This spreading dermatitis has been described as erysipelas, and Davidson mentions the formation of abscesses at a considerable distance from the original seat of application of the arnica. — T. C. P. 424 DE. MORROW ON DRUG ERUPTIONS. Laissus reports two cases in which tincture of arnica applied for contusions produced well-marked symptoms of vesicular erysipelas; both patients were females, with fine, sensitive skins. Paul de Molenes reports four cases, coming under his personal observation, in which compresses of tincture of arnica applied to contusions caused vesicular and phlyc- tenular eruptions. Cartier reports, as a result of the application of tinctuce of arnica to the face for contusion, an erysipelatous swelling ; the face became enormously swollen, closing the eyes ; skin bright red and covered with phlyctcenulse, which discharged abundantly a clear lemon-coloured fluid : the redness ex- tended to the neck, which was occupied by small vesicles ; the submaxillary glands were swollen, producing dysphagia ; temperature increased, urine scanty, mahogany colour, like that of an icterus patient ; although redness and inflamma- tion disappeared under liniment of lime-water and oil, desqua- mation was not completed for two weeks afterward. Hendrix reports two cases of erysipelatous eruption from application of tincture of arnica. In one case the skin was everywhere oedematous, and the eruption covered the whole body and extremities. The entire abdomen was covered with a continuous blister, serum exuded freely from the whole abdominal surface, saturating cloth after cloth. Paul Cagny states that the tincture of arnica has the same intensely irritating action upon the integument of the horse as in man. He reports a case in which arnica was applied to a bruise caused by the kick of another horse. The parts became hot, swollen, and excessively painful, and presented a blistered appearance. Such results, he observes, are of common occurrence from the use of this application in veterinary surgery. The internal use of arnica is often followed by diaphore- sis, erythema, and a sense of pricking and formication of the skin. Phillips asserts that the irritating effects observed from arnica never follow the use of an aqueous solution, which contains none of the arnicine or volatile oil. Piffard has suggested that the irritant properties of pre- ARSENIC. 425 parations of arnica flowers may be due to the presence of an insect, the Atherix maculatus, and recommends that pre- parations made from the root should always be used. 1 ARSENICUM. The cutaneous eruptions which follow the external and internal use of arsenic are similar in character. 2 While the external contact of arsenic produces certain changes in the skin which can in no way be distinguished from a dermatitis caused by other local irritants, the severer eruptive forms are probably due to absorption of the drug, and its specific action upon the skin, The irritant effect of the external application of arsenic was known to the writers of antiquity, and has since been studied by numerous observers. If arsenious acid in a watery solution, or in the form of an ointment or paste, be applied to the healthy skin, there results inflammatory redness; and if the contact be con- tinued sufficiently long, vesicles, pustules, &c, will form, attended with sensations of heat, burning, and pain, pre- cisely as in the application of other vesicants. The hairs on the affected surfaces generally fall out, and there is exfolia- tion of the epidermis in large flakes. A higher degree of inflammatory disturbance is manifest in the production of erysipelatous swellings, sanguinolent eruptions, and ulcers, attended with toxic effects similar to those consequent upon the internal administration of the drug. Numerous cases are on record where arsenical lotions, plasters, and pastes have proved fatal. The application of an arsenical ointment (i to 32) to a cancerous breast covering the space of one and a half inches, for one night only, caused death from poisoning on the second day. A strong application of arsenic is much safer than a weak one, since the intensity 1 PifEard quotes Mercier (' Ann. de Cliniques,' 18 11) as a recorder of sym. ptoms of general irritation caused by ingestion of preparations of arnica flowers. Mercier referred these results to the contamination of the eggs and larvse of insects in the flowers. Piffard never observed accidents with a tincture made from the root. — T. C. P. a This statement is, we think, open to criticism, as will appear later on. — T. C. F. 426 DE. MOEEOW ON DRUG EEOPTIONS. of the inflammation it excites interferes with the action of the absorbents, and the effect remains local. Abundant opportunities for the study of the changes in the skin caused by external contact have been afforded by the extensive use of arsenic in the form of lotions for the complexion, dusting powders, &c. A remarkable skin affec- tion which prevailed among infants and children in Brighton in 1878, at first thought to be erysipelas, was traced to the use of a dusting powder containing 50 per cent, of white arsenic. Of twenty-nine attacked, thirteen died. The cases were carefully studied by W. H. Power, and the character of the eruption may be briefly described as follows : — In very mild cases there was erythema and the formation of minute vesicles ; in severer cases blisters and bladders formed in the creases of the skin where the powder was applied ; some of the bullae when collapsed left black excavated sores, with indurated and discoloured edges. In fatal cases there was a generally blackened condition of the skin of the groins and pudenda, which quickly became somewhat swollen and hard. A like condition upon the abdomen was occasionally observed about and below the umbilicus, as also the skin of the axilla and folds of the neck. Invasion of these several parts where it occurred was simultaneous. In some instances vesication, variously described as " little white blisters," " yellowish bladders," or " bags of water," preceded or appeared about the same time as the blackness. The vesicles breaking discharged clear fluid, and left raw, black surfaces, which did not, it would seem from the description, take on suppurative or sloughing action. The average duration of the fatal illness was four or five days. The eruption was localised on parts of the body to which the powder was applied. The various industrial uses of arsenic in the manufacture of artificial flowers, green-coloured cards, paper boxes, wall paper, and carpets, fixing dyes, &c, are the prolific source of numerous forms of eruptive disorders. "Wood records a large number of cases of poisoning from arsenic contained in wall papers. 1 1 Carr points out that colour, even French white, whether in papers or other fabrics, or distempers, is no guarantee of freedom from arsenic. " The ARSENIC. 427 It is well known that persons who wear cheap under- clothing coloured with fuchsine, containing a large percent- age of arsenic, or socks dyed with the same material, are subject to eczematous eruptions on the parts exposed to contact with the colouring matter. 1 Seifert reports the case of a lady who had been wearing stockings coloured with an aniline red containing arsenic. She was suddenly seized with all the symptoms of a gastro-enteritis and an danger is simply in proportion to the quantity of arsenic contained in the colour, and to the facility with which it may be removed from the fabric either as dust or as gas," i. e. arseniuretted hydrogen. Workers engaged in mines, in the manufacture of arsenical compounds, or in the many industries in which the brilliant arsenical greens were formerly so much employed, are readily affected.— T. C. P. 1 Erasmus Wilson, who drew special attention to the dermatitis anilina, wrote thus : — " Of a nature allied with arsenic, and according to some chemists as a consequence of the presence of arsenic itself, the aniline dyes have the property of exciting inflammation of the skin. Their effects have been observed both in the hands and in the feet, from the use of gloves and stockings coloured with those pigments. The feet, however, have been most frequently the victims, and the dyes in some instances have been transferred to the skin, while in others the pattern of the stocking has been found represented on the skin by tracings and figures of inflammatory hyperasmia. The dermatitis occasioned by the coal-tar pigments is frequently set up in the course of a few hours ; it presents the characters of an aggravated eczema, and is attended with considerable effusion beneath the epidermis, which it raises up into large blebs, sometimes occupying the whole surface of the sole of the foot Not unfrequently the inflammatory rash is transferred to the hands, even when those members have not been in contact with the poison, and a general irritation of the entire skin is some- times set up by the process, which once was called sympathy, but is recog- nised now as propagated irritation. The progress of the dermatitis is always slow, and the inflammatory irritation liable to recurrences at intervals of a few weeks for a considerable period of time, sometimes for several months, and in a few instances for years." Dresses, silk handkerchiefs, underclothing, chest protectors, hat linings, &c, have also been incriminated. The aniline dyes, brilliant or otherwise, of all colours, were largely used at one time for tincturing goods of all qualities. Arsenic, mercury, chromium, antimony, vanadium, &c, were often associated in the manufacture, and hence in any given case of derma- titis there is a difficulty in determining without analysis to what extent the irritation is due to the aniline dye or some other agent. A great number of cases of aniline dermatitis might be collected in addition to those here referred to. Wilson mentions a severe dermatitis excited in workmen by contact with an acid volatile " aniline orange dye." — T. C. F. 428 DE. MORROW ON DRUG ERUPTIONS. acute hemorrhagic nephritis, besides an eczematous eruption on the dorsal surfaces of both feet. The urine for some time afterward contained a small amount of albumen. Impetiginous eczema has been seen on the arms of a lady who wore a bracelet composed of a paste containing a large proportion of arsenite of copper. According to Rollet, who- has made a careful study of the cutaneous lesions from the industrial uses of arsenic, erythema is the first degree of arsenical dermatitis. Generally upon the erythema are developed other elementary lesions ; papules which enlarge and extend, and are covered with small scales of greenish tint, fine, transparent vesicles, and, finally, pustules. These pustules form with conical projections, red at the base, purulent at the summit, and are covered with a small, opaque, yellowish- green crust. If the irritation continues, the pustules become the points of departure of ulcerations, which progressively increase in breadth and depth. Arseni- cal eruptions are situated upon parts exposed to contact with the irritating cause, as the face, forearms, hands, inter- digital spaces, also the feet and inguino-scrotal region. The genital parts are peculiarly susceptible to the irritant action of arsenic. Frequently there are large ulcerations with oedema of the scrotum. 1 1 Guy described the eruptions as appearing under many forms ; as a diffuse erythema, as small and crowded vesicles, as papules which grow flatter and wider by contact with an opposed portion of skin, and lastly, as pustules running into ulceration and gangrene. He commends the portraits given by Vernois. The ulcers on the scrotum, he adds, are peculiar and highly characteristic, i. e. small shallow ulcers, with even surface and thin soft edge, barely moistened with a light yellow discharge, perfectly circular, as if cut out by a sharp round punch, penetrating through the skin, and no further. It is such ulcers as these which, forming on the face and other parts of the body, leave the circular scars so similar to those of smallpox. The arsenical powder diffused through the air, and conveyed by the fingers, inflames the mucous passages by which it enters, and the skin, especially of the face, neck, the large flexures, the pudenda, &c. The ulcers on the green-stained hands in those who handle the products are very characteristic. These changes are evidently solely due to direct contact with the arsenical compound, hut as poisoning progresses the local effects probably become intensified, and other eruptions may arise. Butlin discusses the alleged liability of tin and copper smelters to cancer of the scrotum from the effects of arsenious acid, and concludes that these workers have no such special liability. — T. C. F. AESENIO. 429 I observed several years ago at the New York Dispensary an eczematous eruption, with deep-seated pustules, on the hands of two young women who were employed in a paper box manufactory, in which variously coloured glazed papers were used. White reports several cases of arsenical dermatitis, one of intertrigo in an infant, the brown spots resembling pity- riasis maculata et circinata of the mother, which were probably due to absorption of arsenical pigments contained in the wall paper, as every other possible factor was elimi- nated — a theory sustained by the fact that there was im- mediate improvement upon removal of the patients from the room. Clarke records eczematous eruptions and nasal ulcerations as due to the emanations from arsenical wall papers. Allen reports having observed several cases of arsenical dermatitis, especially marked on the hands, legs, and feet, in longshoremen engaged in unloading a cargo of dry hides which had been cured with arsenic. The arsenical dust had sifted through their clothing and low shoes, producing large vesicles and bullae, followed by ulceration with swelling of. the feet, legs, and hands. Papular and erythematous patches, attended with burning and itching, were scattered over the legs and thighs. 1 Perhaps no drug in the materia medica exerts a more marked influence upon the nutrition of the skin than arse- nic. Almost all observers have noted its tendency to aggra- vate eczematous and other acute inflammatory disorders of the skin. Devergie was the first to signalise the fact that cutaneous lesions may be caused by the internal use of arsenic. A most complete and careful study of the arsenical eruptions has been made by Imbert Gourbeyre, and embodied in his admirable monograph upon this subject. According to this authority, the pathogenetic influence of arsenic may be manifested in the form of papular, petechial, urticarial, 1 Steel has called attention to the occurrence of a pustular rash from sheep-washing. Cooper Forster described a painful inflammation of the finger ends and nails, which was exceedingly common years ago among the students, when the use of arsenic was first introduced to preserve subjects for the dissecting room. — T. C. F. 430 DR. MORROW ON DRUG ERUPTIONS. vesicular, erysipelatous, and pustular eruptions. 1 To these may be added an erythematous or scarlatiniform eruption, the occurrence of which has been attested by numerous observers. 1 The various preparations of arsenic differ in no sensible degree in their effects upon the skin, so that observations relating to arsenious acid will apply to Fowler's solution, the arsenite of soda, Asiatic pills, &c. The erythematous form. — Although an erythema is the commencing stage of several of the forms of arsenical erup- tion, it rarely represents the acme or completion of the in- flammatory process. Martens Pereira observed in a gouty patient, after taking one sixth grain of arsenious acid a day, on the third day an intensely red eruption on the face, neck, upper part of the body, and flexor surfaces of the joints, with oedema of the eyelids. 2 The eruption disap- 1 Erasmus Wilson states that besides occasioning erythematous dermatitis, inflammation of certain mucous membranes, such as the conjunctiva, nose (leading to ulceration and perforation of the septum), and pulmonary passages, the internal administration of arsenic may produce discoloration from exces- sive pigmentation and desquamation, and on the palm of the hands and sole of the feet not only desquamation, hut also thickening of the epidermis to a considerable degree from hypernutrition, and may occasion the formation of minute granular corns, each little corn corresponding with the aperture of a sudoriferous duct. Jonathan Hutchinson maintains also that the prolonged use of arsenic may seriously depress the nutrition of the skin, and set up local neuritis, leading to the formation of scaly patches like psoriasis, most obvious on the elbows and backs of the knuckles, and to warty or corn-like indurations (keratoses, arsenic corns), which may acquire a tendency to pass into epithelioma. The skin generally may assume a dry, harsh, muddy, or hyperpigmented appearance. The corns tend to form mostly on the dry palms and soles. Hutchinson suspects that certain opacities in the vitreous humour own a similar causation. Keboul cites cases in which the palms and soles were the seat of a desquamating erythema. Hunt says that " in the exceptional cases tenderness of the soles of the feet, and more rarely of the hands, present the first indications of a full dose. The tenderness is some- times succeeded by a thickening of the epidermis, which subsides ultimately." James Stewart noted a recurrence of wart-like excrescences on the dorsal surface of the fingers and hands, which quickly disappeared when the arsenic was stopped. McCall Anderson says " an erythematous rash, too, is not uncommon, especially on the face, neck, palms, and soles, and in the last situation this may be followed by great thickening and induration, which has'a papulated character." See Pringle, Crocker, and Brooke on arsenical keratosis and hyperidrosis of the palms and soles. — T. C. F. 2 Hunt laid great stress on the conjunctivitis which " in about forty-nine AESENIO. 431 peared between the third and fifth days, but desquamation in large flakes continued for nearly two months. Macnab has observed a rubeola-like exanthem in patients who had taken small doses of arsenic, three-drop doses of Fowler's solution, daily for three weeks. Hyde saw in a young woman, who had taken only three medicinal doses of Fowler's solution, a light red scarlatini- form blush, with a few isolated vesicles, covering both shoulders, the eruption being present, but less distinct, on the hands and face. Piffard gives numerous references of erythematous and rubeoloid eruptions consecutive to the internal administration of arsenic. The papular form. — According to Imbert Gourbeyre, the papular form occurs as discrete, pin-head sized papules, first in scattered groups, which unite later to form lenticular papules, occasionally large disseminated patches, which sometimes resemble a papulo-syphiloderm, although of a less coppery hue. The parts affected by preference are the face, neck, hands, and genital organs. The eruption usually dis- appears in five or six days, followed by furfuraceous de- squamation. In one case the papules increased in numbers until they gave the skin the appearance of " goose-flesh." The eruption was attended by decided itching, and lasted some days after the discontinuance of the medicine. Stewart reports the case of a powerfully built man, who was ordered five-minim doses of Fowler's solution after each meal. After the sixth dose he felt feverish, and he noticed that his hands and arms were red, swollen, and very hot; the redness of the skin spread rapidly, until it involved the entire surface except the face. The skin was covered with countless papules, about the size of millet seeds. 1 cases out of fifty takes precedence of the more grave afiections which indi- cate an over-dose." Observers have recorded considerable oedema of the eyelids and face, which has been described as "erysipelatous dermatitis." Crocker and McCall Anderson mention pufliness or plumpness of the hands and f ace.— T. C. F. 1 Devergie says an eruption may appear consisting of red, isolated, papular boutons, of the size of a lentil, which slowly multiply and increase if the treatment is continued. Hunt stated that " now and then a delicate papular eruption (lichen arsenicalis) will show itself suddenly under a course 432 DE. MOEBOW ON DRUG ERUPTIONS. Keys, cited by Piffard, reports after the use of arsenic, doses not stated, a papulo-erythematous eruption, dry and livid, on wrists and neck ; general papular eruption on trunk and extremities, attended with, pruritus. Baglie observed dryness of the skin, heat, and itchiness of the eyelids, with the production of a minute papular rash, followed by de- squamation. Faithful observed a papulous eruption about the face, attended with a decided amount of pruritus. The papules varied in size from a pin-point to that of a No. 4 shot ; they were discrete, and more or less scaly upon their summits. The eruption disappeared after a few days upon the discontinuance of the drug, followed by furfuraceous desquamation of the parts affected. The urticarial form. — Fowler, whose name is so well known in connection with this drug, in his medical reports on the effects of arsenic, was the first to instance urticaria as one of the results of its employment. According to Imbert Gourbeyre, it is one of the most frequent forms of arsenical eruption. The wheals are white or rosy-red, and extremely pruriginous, differing in no essential particular from urticaria as commonly observed. Berenguier reports the case of a young lady treated with arseniate of iron, which brought out a copious eruption of white, somewhat reddish elevations of the uniform size of a lentil, and accompanied by intense itching. Broadnax states that arsenic produced a rubeolous eruption in two per cent, of one hundred and ninety-seven cases in which it was administered. The vesicular form. — The occurrence of a vesicular erup- tion from the ingestion of arsenic has been recorded by numerous observers. This eruption may sometimes assume an eczematous character which, according to Balfour, may prove extremely obstinate. Ringer says eczema or urticaria may arise, or perhaps vesication or mere desquamation with tenderness of the hands and feet; again he says, in arsenical poisoning, a petechial papulo-vesicular or wheal- like rash often appears from the second to fifth day. Finlayson saw an eruption of clusters of vesicles on an inflamed base, extending from lower part of the arm down of arsenic, and as suddenly disappear under a few doses of the Liq. Amnion. Acet."— T. C. F. ARSENIC. 433 the back of the forearm and hand, including backs of the fingers. Herpes labialis and preputialis, and an eruption of herpes upon the scrotum, have also been observed from the use of arsenic. Faithful states that in one case herpes pre- putialis always made its appearance after giving arsenic for a few days. It has been asserted that herpes zoster may occur as the result of the ingestion of arsenic in medicinal doses. Hutch- inson, while not claiming that a causal connection has been absolutely demonstrated, yet suggests its extreme probability in view of the well-known fact that herpes zoster has been more, often observed in patients who have been taking arsenic than in those not subjected to this medication. He reports a number of cases, fifteen or sixteen, in which the coincidence was so marked as to furnish strong presumptive evidence of an etiological relationship. His observations have been supplemented by the experience of many other dermatologists who have noted this coincidence. 1 The pustular and ulcerative forms. — According to Imbert Gourbeyre, the internal use of arsenic may produce a pustular eruption resembling variola, the lesions terminating in crusts or ulcerations leaving cicatrices. Orfila lias noted, as one of the toxic effects of the drug on the cutaneous system, an eruption of pustules on the face, shoulders, arms, and chest. Bazin reports a case in which there appeared after minute doses of arseniate of sodium, continued for fourteen days — one half of a grain altogether — an eruption of discrete pus- tules in various stages of development, limited to the hypo- gastrium and right flank. One of the pustular lesions had 1 This observation has now become the common property of the majority of dermatologists, though many still hold that the occurrence is a mere coincidence. Our increased knowledge of the production of peripheral neuritis by arsenic furnishes a ready explanation, though it may be noted that in many cases of arsenical peripheral neuritis zoster is not developed. The occurrence of zoster in carbon dioxide poisoning is an analogous fact. Neilsen examined the statistics of psoriasis cases in the Copenhagen Hospital, and found that zoster occurred in 7 - 8 per cent, of those to whom arsenic was given, whilst no eruption of zoster was found in those who received no arsenic. The latter class was, however, more than a third less numerous than the former.— T. C. P. 28 434 DR. MORROW ON DRUG ERUPTIONS. become transformed into an ulcer, a centimetre in diameter, surrounded by indurated and inflamed tissue. Near by were two large ecthymatous pustules just breaking down in the centres into ulcers ; other lesions were passing from a papular into a pustular form. The evolution of the lesion through its various stages, from appearance of papule to cicatrisation of ulcer, occupied only a few days. The patient rapidly re- covered as soon as the arsenic was stopped. In this case as in others, pustular lesions are the points of departure of the ulcerations encountered in various parts of the body, more especially on the head, limbs, and scrotum. Gangrene some- times occurs around the genitalia. Erysipelas with bullse, erysipelatous inflammations about the face and eyelids, and eruptions of a petechial character, affecting by preference the trunk and genital parts, have been recorded by Bazin, Imbert Gourbeyre, and others. According to Morris, boils 1 and carbuncles occasionally result during a course of arsenical treatment. This state- ment is confirmed by Foster, Vaudry, and others cited by Piffard. Srownish pigmentations. — Among the incidental effects of arsenic upon the skin may be mentioned certain greyish or brownish discolorations, which are especially liable to occur upon the face and various parts of the body after its pro- longed use. Wilson reports the case of a patient with gutta rosacea, who had taken arsenic for two months, when there was noticed a change in the colour of the skin, first over the abdomen, then on the neck, breast, face, and hands. The face was of a yellowish-brown colour, the eye ball dark, the skin of the entire body more or less pigmented; chronic erythema affected the palms ; there were hard dry points at the orifices of the sweat-glands ; the eyelids and the extre- mities were cedematous. In a case of arsenical dermatitis recently presented by me before the New York Dermato- logical Society, there was an erythemato-papular eruption 1 Eeboul cites two cases, and H. C. Wood records the case of a man who ate a preparation called " Hough on Rats," and suffered from gastro- enteritis, and in some days swelling of the face, then of the body, and from a red rash with small watery blisters, a general outbreak of boils, and multiple neuritis. — T. C. P. AKSENIO. 435 with a greyish-brown, almost black discoloration of the surface, especially marked over the abdomen and inner surface of the thighs. Guaita reports that, in fourteen children placed upon Fowler's solution for four or five months, there was observed a bronzed appearance similar to that of Addison's disease, beginning on the neck, extending to the chest, then to the abdomen and hands ; at times it is seen on the back and legs. It disappears by desquamation in about four weeks. Bazin has characterised this pigmentation as a tint comparable to the staining of nitrate of silver. This condition depends, according to Gubler, not upon a chemical combination, as is the case in argyria, but on abnormal pigmentation. 1 Wyss saw alopecia areata deve- loped by the prolonged internal use of arsenic. This result 1 Devergie called attention to the fact that when a scaly disease is under- going cure under the influence of continued arsenical treatment, the healed patches assume a brown colour. He called these patches "taches arseni- cales," and considered them an indication of the perfect cure of the patches of disease. According to his observation they only disappear after eight or ten months. Thomas Hunt, on the other hand, claimed priority for the observation that a secondary effect of continued arsenical treatment was to- cause a wide-spread pigmentation. " The trunk of the patient first, and subsequently all those parts of the body which are by the dress protected from the access of light and air, become covered with a dirt-brown, dingy, unwashed appearance, which under a lens reveals a delicate desquamation of the epidermis, and is, in fact, a faint form of pityriasis." He stated that this effect was so common among persons of fair complexion or delicate skin, that he was not sure it was not the rule rather than the exception. It quickly disappeared in a very few weeks afHer the arsenic was discontinued. The occurrence of this diffuse pigmentation, the melasma arsenicale of Wilson, the arsenmelanose of Wyss, with desquamation has now long been a well-established fact, and the appearance is familiar to those who have occasion to carry out a continued arsenical treatment. Several observers mention the occurrence of a less intense pigmentation on exposed sites, such as the face and hands. Wyss made sections of the skin in two cases of diffuse pigmentation. He found that the pigment in recent and slight cases is deposited as little grains in the lymphatic spaces of the papillae, and to a less extent in the derma. In inveterate and intense cases the pigment is in far greater quantity in the lymphatic area of the dermis. It is to be found also in the rete. Conges- tion of pre-existing areas of eruption is frequently seen during arsenical treatment, and I agree with Hyde that erythism of the healthy skin is not uncommon, though often unnoticed, and I believe that the pigmentation and desquamation is a sequence of such constantly recurring hypersemia. — T. C. P. 436 DR. MORROW ON DRUG ERUPTIONS. lie thought due to the effect of the drug upon the trophic nerves of the hair-follicles, causing disturbance of nutrition. As regards the pathogenesis of arsenical eruptions opinions differ. It is known that arsenic is eliminated, not only by the kidneys, but by the glands of the skin, the mucous membranes, the salivary and lachrymal glands, &c. Chatin found arsenic in the contents of a bulla, and Bergeron and Lemattre in the sweat of patients undergoing arsenical treatment ;* while Barella claims to have demon- strated the direct elimination of arsenic by the sweat-glands. Therapeutically arsenic has been classed as a neuro-tonic, and is supposed to modify cell untrition through its influence upon the peripheral nervous plexuses. In view of these facts we can understand how it may cause disorders of the capillary circulation and disturbances of the nutrition of the skin, as manifested in the various forms of eruptive disorder above described. The tests for the detection of arsenic are so elaborately considered in text-books that it is unnecessary to describe them in detail. The reader is referred, for information upon this point, to page 419. The treatment of arsenical eruptions may be restricted to the simple expedient of suppressing the offending cause. In the more severe forms the same local measures are to be resorted to as are indicated in dermatitis from other causes. BALSAMUM PERUVIANUM. An erythematous and also an eczematous eruption are by no means infrequent from the irritant action of this agent. Mogling, quoted by Lewin, reports an urticarial eruption following a single application of the balsam of Peru for the cure of scabies in his own person. Redness of the skin in 1 Reboul failed to detect arsenic in the sweat and scales of a psoriasis patient, who on the fifteenth day of treatment was taking sixty drops of Fowler's solution daily. — T. C. F. AVA. Numerous references will be found in books of travel and works on the diseases of Polynesia to the influence of the Macropiper methysticum (the ava or kava of the South Sea Islands) in producing a severe scaly disease of the skin.— T. C. F. BELLADONNA. 437 patches appeared on the inner surfaces of the knees and on the shoulders, attended with intense itching. The wheals first appeared on the abdomen, arms, and shoulders. The urti- caria successively affected the face, neck, hack of forearms, legs, and dorsum of the feet. It disappeared when he removed the woollen shirt he had worn, and which was satu- rated with the balsam, and had taken a warm bath. BELLADONNA ATKOPIA. The exanthem produced by the external or internal use of belladonna, or its alkaloid, is usually erythematous in character. It consists of a bright diffuse redness, strikingly suggestive of the rash of scarlatina. 1 It is usually confined to the face and neck, but may extend to the upper portion of the chest, and, exceptionally, may become generalised over the surface. It is quite fugitive, disappearing in the course of a few hours, leaving no trace, and is not, as a rule, followed by desquamation. The belladonna rash is most commonly and character- istically seen in children with fine, delicate skins, in whom it appears after small doses of the drug. Its evanescent character is a marked feature. Lusanna reports a case in which, after a small dose of atropia, the skin became intensely red, and presented the appearance of having been exposed to the intense heat of the sun. The erythema lasted from one half to one hour, and came out each time after taking the drug. Stadler saw a similar eruption appear upon a child within a few minutes after the administration of one two-hundredth grain of sul- phate of atropia, which lasted five hours. Smaller doses 1 Diffuse or patchy flushing of the face and neck and trunk, sometimes with swelling, and a pungent heat of the surface generally, are common incidents of belladonna poisoning. The wide-spread, punctate, scarlatinif orm eruption, " la scarlatine belladonnee," is of rarer occurrence. The local eruption excited by the external application of belladonna (emplastrum, linimentum, glycerhram, &c.) frequently becomes vesicular or pustular, and then has been described as herpetic. It may extend consider- ably beyond the site of application of a plaster, or the more or less generalised scarlatiniform rash may ensue. The belladonna rash is referred to in many works on diseases of the skin, therapeutics, medicine, and toxicology. — T. C. F. 438 DR. MORROW ON DRUG ERUPTIONS. brought out the eruption each time, but it was of shorter duration. In a case reported by Gray, the face, the upper extremities, and trunk exhibited a diffuse scarlet efflorescence studded with innumerable papillae resembling very closely the rash of scarlatina. A patient of Dreyfous took two grains of extract of belladonna in three days, followed by a vapour-bath. On the night following the third day there suddenly appeared a scarlatiniform eruption mingled with lesions like those of papular erythema, and in places with vesicles. The eruption, which was attended with intense pruritus, occupied almost the entire surface of the body, disappearing on the fourth day without desquamation. Boecke reports a case in which one quarter grain of extract of belladonna, ordered three times a day to a consumptive patient, produced, after the second dose, erythema and partial gangrene of the skin of the scrotum. In a case which came under my observation, a child four years of age was given an aperient pill containing one quarter grain of extract of belladonna, which had been ordered for his father. In the course of an hour or two there was an excessive flushing of the face, which soon ex- tended over the body. When I saw him, two hours later, the whole surface of the body presented a " boiled lobster" appearance ; there was redness of the eyes and throat, and mydriasis. The next day the erythema had disappeared, leaving no trace. Kobner observed a characteristic hypersemia of the face from the use of suppositories containing extract of bella- donna introduced per vaginam. Wilson reports the cases of two lying-in women who applied belladonna to the breasts to produce galactostasia. On the fourth day a scarlatina-like exanthem came out, which disappeared in the course of three or four days without desquamation. 1 Mackintosh reports a case of herpes following the ex- ternal use of belladonna and atropine. The application of belladonna liniment to an inflamed knee-joint was followed 1 Dr. Herbert Spencer and others have informed me that such a rash will occur on rare occasions afterithe application of belladonna applications over the breasts or abdomen. — T. C. P. BELLADONNA. . 439 by an eruption of herpes with a good deal of swelling over the seat of application. Two months later he was ordered a solution of atropine for iritis ; some of the solution ran over the cheek, and was in a few hours followed by an her- petic eruption of exactly the same character as had followed the use of the belladonna liniment. 1 It is a clinical fact familiar to ophthalmologists, that the use of atropine drops, instilled into the eyes, occasionally causes an erysipelatous inflammation about the lids, and face, sometimes giving rise to considerable disfigurement. Chislom has recorded a case of severe facial erysipelas from the topical use of atropia. Liebreich has noted that conjunctivitis, erythema, eczema, and peculiar pearly granulations on the conjunctiva are ob- served after the long-continued use of a solution of atropia instilled into the eyes. 2 Fialkowski reports a case in which a solution of atropine instilled into the eyes produced on the second day an ery- thema and eczema of the eyelids. The atropine being continued for ten days, almost the entire face of the patient presented a general confluent eczema. The solution being discontinued, the eczema disappeared in the course of ten days. A new instillation of a single drop of a weak solu- tion caused the appearance of vesicles, with pruritus of the borders of the lids. The belladonna rash derives its chief clinical importance 1 Caesar records a case in which blistering followed the use of a bella- donna plaster, extending just beyond the site of application. Some time later a plaster was again applied, and caused a vesicular eruption on a red base occupying the whole left side of the trunk, and bounded by the iliac crest and the mid-lines before and behind. Later again it was shown on two occasions that fifteen drops of Tinct. Bellad. given thrice daily brought- out a scarlatinal rash on face, chest, and arms, with the usual dryness of the throat, &c— T. C. F. 2 Brudenell Carter has written that when atropine has been long in use, even the purest and most neutral solution is apt to cause local irritation in some persons, and this irritation is usually more manifest in the eyelids, and especially on the lower lid and on the adjacent skin of the cheek, than elsewhere. It may be readily recognised by a peculiar dryness and stiffness of the inflamed skin. The severe erysipelas-like acute inflammation seen in certain persons with a special idiosyncrasy is rare, although but few ophthal- mologists have failed to meet with such cases. — T. C. F. 4-10 DR. MORROW ON DRUG ERUPTIONS. from the fact that it sometimes simulates scarlatina with alarming accuracy, especially when associated with conges- tive symptoms of the throat and fauces. The bright scarlet hue of the eruption renders this similitude quite complete, although the punctate character of the scarlatina rash is usually not present. The absence of fever and other pro- dromal symptoms, the dilatation of the pupils, and the transi- tory existence of the belladonna exanthem soon clear up the diagnosis. 1 The mode of production of the belladonna eruption has been attributed either to a direct excitation of the sympa- thetic or to a paralysing influence of the drug upon the vaso-motor centres, causing dilatation of the cutaneous capillaries. The exceedingly evanescent character of the eruption renders special treatment unnecessary. BENZOLE. Lewin has observed that the application of benzole as a parasiticide on the inner surfaces of the thighs and scrotum, and on other sensitive surfaces, causes intense pain, lasting several minutes, which is followed by more or less extensive erythema. BEOMINE BKOMIDES OF POTASSIUM, AMMONIUM, SODIUM, LITHIUM, ETC. The cutaneous disturbances which may follow the inges- tion of the bromine compounds have been long recognised by the profession. All of the salts above enumerated pro- duce similar effects upon the skin. The eruptions recorded as due to the use of bromide of potassium may be regarded as typical of those produced by the other bromine prepara- tions. The so-called " bromic acne " occurs in so large a pro- portion of persons who take the bromides that it is difficult 1 It is well known that children tolerate belladonna to a remarkable degree. The rash is certainly rare, when it is remembered in what large doses belladonna is frequently administered. Dreyf ons says the rash, which is scarlatiniform at the outset, may later on approach the eczematous or erythema papulatum type. — T. C. ~F. BROMINE AND BROMIDES. 441 to separate these irritative effects upon the skin from the recognised physiological effects of the drug. This propor- tion is given by Clark and Amory as sixty- six per cent., and by Voisin as seventy-five per cent, of all patients treated with bromide of potassium. The latter observer records the fact that, of twenty-four epileptics successively treated, all were affected by bromic acne on the face, scalp, back, and other parts of the body. The term " bromic acne," it may be remarked, is quit© comprehensive in its signification, and has been used to designate a variety of anatomical forms, some of which are in no way connected with disorders of the sebaceous glands. 1 The bromic eruptions have been most carefully studied by Voisin and Veiel. The classification of the former, which embraced all changes in the skin which had at that time been recognised as due to the administration of the bromides, has been enlarged by the addition of other va- rieties of eruptive disorder which have since come under observation. The erythematous form. — Veiel describes a diffuse ery- thema, always limited to the lower extremities, accompanied by high fever, and quite painful. According to other observers, it may occur as a bright red or dusky red rash, in patches the size of a finger-nail or a pea, and not abso- lutely confined to the lower extremities. Bedford-Brown has noticed the occurrence of a roseola from bromide of potassium in children. Comparatively few observations of this nature have been recorded, probably because this drug is seldom administered to children, and not because they are insusceptible to its pathogenetic effects. Carlos reports a 1 The bromic eruptions have a remarkably close resemblance to those produced by iodine preparations, but the experienced eye can generally separate them by delicate characteristics which it is difficult to portray in words. The essential lesion in both is a dermatitis with a special localisa- tion about the sebaceous apparatus. The primary lesions in both may take the form of maculo-papules, papules, papulo- vesicles, papulo-pustules, tubercles, tuberculo-pustules, tubers, vesicles, and bullse. There is a tendency to the formation of conglomerate lesions by confluence. We can also observe secondary crusting, papillomatous overgrowth, and ulceration. Bromic erup- tions, however, tend to be more indolent and tardy, and acute bullous lesions are rarely observed. — T. C. F. 442 DR. MORROW ON DRUG ERUPTIONS. case in the service of M. Voisin in which bromide of am- monium produced an eruption of slightly elevated patches of a vivid red colour, with subcutaneous induration. The erup- tion first appeared on the thighs and abdomen, and became general. It disappeared with considerable desquamation. The urticarial form. — Voisin observed in two cases, out •of ninety-six upon which his studies were based, an erup- tion, preceded by pain and pruritis, of oblong or irregu- larly rounded elevations of the skin of varying size, from one fifth to two and a half inches in diameter, and of a rose-red or cherry colour. They presented the shape, colour, and hard base of erythema nodosum, but resembled urti- caria in reappearing when rubbed. 1 These lesions persisted so long as the bromide was given, but they rapidly disap- peared on the discontinuance of the drug, always leaving behind the subcutaneous nodosities which were slower in evolution. Yeiel also observed coin-shaped, wheal-like ele- vations, varying in size from one quarter to one half inch in diameter, develop on erythematous patches of skin, but only upon the legs. They were very sensitive to the touch, and if the drug was continued they took on a suppurative action. Richard, cited by Deschamps, reports the occur- rence of an eruption developed upon erythematous patches, and presenting the objective character of an urticaria, in a boy six yearsold, from large doses of bromide of potassium. The eruption was distributed over almost the entire surface of the body. The papular form. — The papular bromide rash is most often observed as the first stage of bromic acne, to be suc- ceeded by a papulo-tubercular and pustular stage. Duhring describes a case of maculo-papular eruption, in which small doses of the bromide produced an erythematous condition of the skin of the face and neck, accompanied by a copious eruption of maculo-papules and flat papules. The dark coppery colour of the eruption simulated very closely a maculo-papular syphiloderm . Bcheverria describes a papular 1 Inflammatory nodules involving the skin to a considerable depth, and closely simulating erythema nodosum in appearance, have been frequently observed. These nodes may become covered later on with little pustular points and finally a dark crust, and they may fungate or ulcerate. — T. C. F. BROMINE AND BROMIDES. 443 eruption distributed over the elbows and surfaces of' the hands, knees, and legs. The papulo-pustular form, " bromic acne." 1 — This is by far the most common and characteristic form of bromine eruption. Bromic acne exhibits in the manner of its develop- ment, its seat of election, and the anatomical form of its constituent elements many points of similarity, if not of identity, with acne vulgaris. As in acne vulgaris, we find associated papules, tubercles, and pustules affecting by pre- ference regions rich in sebaceous glands, such as the face, back of shoulders, front of chest, &c. ; but, unlike ordinary acne, they often surpass these habitual limits, and they always develop without the antecedent existence of comedones. Bromic acne manifests a special preference for parts where hairs abound ; it attacks the hairy scalp, eyebrows, hairy portions of thighs and legs, and many of the pustules are found pierced with a hair. It is not limited to the young, as acne vulgaris. Sex, age, disorders of the reproductive organs, &c, do not act as predisposing causes. The papular form usually precedes the pustular form. It is most commonly seen on the hairy scalp, about the fore- head and nose and back of shoulders, rarely on other parts, in persons who have thick, greasy skins, or a free secretion of sebaceous matter. They commence as pin-head or pea sized hyperaemic patches developed from an indurated base, and surrounded by areola ; the majority of the papulo-tubercles are pierced by a hair. They may remain in this condition for weeks, indolent aud without tendency to undergo pro- gressive change, or they may rapidly develop into the pus- tular form. The pustules are of a yellowish-white colour, similar to those of acne vulgaris, and may sometimes present an ecthymatous aspect. Sooner or later the contents of the pustules are discharged, and a firm indurated nodule or a pigmented spot remains. After healing, they not infre- quently leave small depressed, rounded cicatrices. The pustular condition may persist almost indefinitely if the use 1 The eruption here described is that usually seen in adults. The phase occurring in infants is that described further on under the term " con- fluent acne."— T. C. F. 444 DR. MOEEOW ON DRUG ERUPTIONS. of the drug be continued. Veiel found that the number and development of the pustules increased with the aug- mentation of the dose. Exceptionally, it has been observed that the eruptive accidents, after having persisted for some months, rapidly disappear and are not again reproduced, although, the medicine may be continued in the same or augmented doses. Ordinarily, the eruption disappears in the course of one to three weeks after suspension of the drug. Voisin describes an eruption of small tumours formed by groups of indolent acneiform pustules, inflamed at the base and depressed at the centre, very painful to the touch, except at the centre, which is anaesthetic. They discharge a matter like that of furuncles, and are sometimes trans- formed into foul atonic ulcers, which heal slowly and leave cicatrices. 1 They are usually seated upon the legs, and may coexist with acne over other parts of the body. Confluent acne. — Under the designation of " confluent a,cne," Cholmely has described an eruption occurring in a boy thirteen years old who had taken twenty-five grains of the bromide three times a day for a week. The eruption was at first varicelliform, but the vesicles, instead of drying up, became in many places confluent, the clusters so formed continuing to enlarge and showing numerous points of suppuration. The eruption, though occurring on other parts of the body, was most active on the legs. The lesions were of various sizes, from a pea to a fourpenny piece, larger than those on the face, irregularly oblong. The most recently formed consisted of a prominent circular vesicle, filled with milky-white semi-fluid matter, seated on a slightly elevated and hardened base, and surrounded by a vividly red areola, pierced by one or more broken hairs. The larger spots were flattened elevations, covered by a flaccid cuticle or thick light brown crusts, and surrounded by a dark red areola. On removal of the crust, the surface beneath presented numerous millet-seed-like, yellowish pro- tuberances. The eruption died away after seven weeks' duration. The bromide, in full doses, redeveloped the eruption on the sixth day. 2 1 Beneath the crusts papillary hypertrophy may occur. — T. C. F. 2 The eruption described by Cholmely is the type of that usually met BEOMINB AND BROMIDES. 445 Neumann states that he has observed an eruption very- much like molluscoid acne coming out in successive out- breaks, and in another case a carbuncular eruption, consist- ing of infiltrated tumours, with considerable loss of substance in the centre. The furuncular and anthracoid forms. — A furunculoid eruption has been observed by Voisin and many others. Smith and Neumann saw numerous boils on different parts of the body from the use of the bromides ; the latter observed them on the hairy portions of the face and on the forehead and neck. These boils were for the most part of small size, and without central core. It is doubtful whether they differed in their anatomical seat from ordi- nary boils. Quite recently I have observed an eruption from the pro- longed use of bromide of potassium which cannot be grouped with any of the preceding forms. In June, 1886, a patient who had been taking a mixture of bromide of potassium and tincture of iron almost con- tinuously for several months presented himself, with a large carbuncular swelling upon the right arm at the insertion of deltoid. He stated that three days before it appeared as a " large reddish pimple/' which within twenty-four hours developed into a blister. This broke the following day, showing four or five openings from which pus exuded. Within the next two weeks similar lesions developed upon other portions of the body. One appeared upon the with in infants. The earliest lesions consist of miliary follicular papules, which become capped with fluid, either opaque or puriform in character. Here and there vesicles are seen with comparatively little solid base, and varicelliform in appearance. More rarely vesicles and even bullae may be seen rising directly from the skin, apparently without a precedent solid stage. There is a marked tendency for the lesion to evolve in groups, and thus larger patches are formed, often seen to be studded with minute puri- form heads. These patches may extend by a vesico-pustular margin, become covered with dark crusts, and raised up by an increase of inflammatory exudation. There is a tendency to papillary hypertrophy, so that many lesions may closely simulate condylomata. I have a drawing of a case in which large formidable-looking tumours existed on the legs of an infant. This so-called "confluent acne" is sometimes seen in the adult. The peculiar brownish-red, encrusted, papillated patches on the legs are very characteristic. — T. C. F. 446 DE. MORROW ON DRUG ERUPTIONS. left wrist, two on inner side of left thigh, two on right leg, one on left cheek, and another on the back of the right shoulder near posterior axillary space. I had an oppor- tunity of watching the mode of their formation and evolu- tion, which was as follows : — First there appeared a circum- scribed inflammatory swelling, which in twenty-four hours was surmounted by a flat bulla, filled with a sero-purulent fluid. The swelling rapidly increased in depth and extent, resulting in the production of a hard phlegmon, surrounded by an intense inflammatory areola two or three inches in diameter. Upon rupturing the blister there was disclosed a number of openings, from which a rather thin pus could be pressed out. On probing, the openings were found to be shallow. The lesions differed from ordinary anthrax in their more indolent and superficial character, the com- parative absence of pain, and the rapidity of their involu- tion. After the bromide was discontinued, they disappeared within a few days under the influence of dressings of cam- phorated oil. The ulcerative form. — Seguin has narrated three cases in which a peculiar cutaneous lesion, termed by him ulcus elevatum, was produced by bromide of potassium. The lesions were described as large, irregular ulcerated patches, raised from two to four millimetres above the surface, sym- metrically situated on legs. The elevated floor of the ulcer was firm, greyish red in colour, with here and there an adherent crust. It secreted a sanious, foetid, puriform liquid, and bled upon being touched. It did not look like ordinary granulating tissue ; it was much firmer, and com- posed of large masses. At several points it presented a slightly villous, or rather papillomatous appearance. The cicatrix of a similar lesion, which had existed ten years ago, was seen. The patient at that time had been taking large doses of the bromide. In the third case the lesion had been twice developed by bromides, but it was more carbun- cular in character. Amidon describes what he terms an " epithelial ulcer," peculiar to the prolonged use of the bromides in large doses, of which he had observed two or three cases. It begins as a large-sized, single acne spot, with a large base, which BROMINE AND BROMIDES. 447 apparently takes on an inflammatory process, and afterwards breaks down into what appears to be a simple ulceration. Vesicles appear in circular form about the ulcer, the con- tents of which become cloudy and purulent, and are finally covered with dark-coloured crusts. The centre of the affected surface heals, while a superficial ulcerative process extends at the periphery sometimes to the distance of several centimetres. The true skin is not involved ; the process simply denudes the skin of its cuticle, with hyper- trophic changes affecting the papillae. Sangster reports a bromide eruption presenting the fol- lowing characteristics : — On the outside of the right leg there was a round, considerably raised patch, about the size of half a crown. The surface was partly crusted ; here and there it exhibited little subcutaneous dots of pus closely set together. There was a crop of smaller blotches over the same thigh and buttock, the size of a threepenny piece, elevated and partly covered with a brownish crust. Two symmetrical groups of similar lesions, four in number, on either side of the face, completed the eruption. The verrucose form. — Yeiel records an anomalous form of bromine eruption in which he observed large wart-like pro- minences upon the face, cheeks, nose, and eyebrows of a boy sixteen years of age, soon after he commenced taking the bromides. These lesions exactly resembled the verruca ordinarily seen upon the hands of young persons. This phenomenon has not been encountered, or at least recorded, by other observers, and it may have been a coincidence, rather than an effect directly due to the drug. The vesicular form. — In Voisin's classification of the various forms of bromine eruption, he reports a case coming under his observation of moist eczema of the legs, with pity- riasis of the scalp, in a patient who had never before suffered from any cutaneous affection. So far as I have been able to ascertain, there has been no similar observation recorded in the literature of this subject. The bullous form. — Wigglesworth reports a case of a lady in whom bromide of potassium produced an eruption of bullae which were somewhat acuminated, and varied in size from that of a pea to that of the end of the finger. Some 448 DR. MORROW ON DRUG ERUPTIONS. of the bullae appeared to contain blood, and on rupturing exposed an ulcerated surface. 1 In addition to the various forms of eruptive disorder from the use of bromide of potassium already noted, Veiel and others have described a squamous eruption, seborrhceic in character, preceding or coincident with the outbreak of acneiform lesions. Clinical experience would appear to indicate that there is no essential difference in the pathogenetic influence of the various salts of bromine. Numerous observations have shown that the bromides of sodium and ammonium exercise the same irritating effects upon the skin as the bromide of potassium. Pathological anatomy. — The pathological histology of the various lesions has not been carefully studied. Neumann made a microscopical examination of a pustular lesion in a child resulting from the ingestion of twelve scruples of bromide of potassium. He found the sebaceous glands, the hair- follicles, and the upper part of the corium to be the seat of the disease. The papillae were increased in size, and the whole of the corium highly developed. The most marked feature of the changes was epithelial hyperplasia. Seguin gives the histology of the lesion reported by him as follows : — Sections of the piece of tissue removed from ulcer showed great increase in the thickness of the rete Malpighii, with hypertrophy of the whole skin in places. The deeper layer of the skin and, to a certain extent, the subjacent connective tissue are infiltrated at certain points with young cells. The papillae, hair-follicles, and sweat- glands do not appear to be the seat, of any primary or im- portant inflammatory change. 2 Pathogeny. — Various theories have been advanced to ex- plain the mechanism of the production of the bromine erup- tions. Prom the fact that certain forms of bromine erup- 1 The formation of bullae, either with fluid or thicker contents, has been described by Neumann, Horrocks, Jacquet, and others. True bullae, without more or less solid base, and with fluid contents, are, however, tare. When they occur it is generally in association with other characteristic lesions. — T. C. F. 2 See also the papers by Waren Tay and Stephen Mackenzie, Colcott Pox and Heneage Gibbes, and Jacquet. — T. C. F. BROMINE AND BROMIDES. 449 tion, especially the papulo-pustular, appear in such a large proportion of all cases treated with the bromides, it is evident that idiosyncrasy, which plays so important a r61e in the production of other drug eruptions, does not figure pro- minently as a predisposing element. Without being constant, they are sufficiently common as to lead to the belief that they are, in a great measure, independent of individual predispo- sition, and may be developed in almost every case, provided the dose be sufficiently large and long continued. The changes which take place in the skin, like other symptoms. of bromine cachexia, may therefore with propriety be classed among the exaggerated physiological effects of the drug, and it is plainly within the sphere of the nervous system that we, must seek an explanation of these effects. It is well known that the alkaline bromides are eliminated principally by the kidneys as well as by the salivary, lach- rymal, and sudoriparous glands in a less degree. 1 It has been, claimed that the sebaceous glands may also participate in this excretory action, and that the cause of the cutaneous disturb- ance observed after the internal administration of the bromine salts is the irritation attending the elimination of the drug through this channel. Plausibility is given to this hypothesis by the experiments of Guttman, who found bromine in the contents of the pustules. 2 On the other hand, Veiel and numerous other observers have failed to find the drug in any of the cutaneous lesions caused by its use, although it is always readily detected in the urine. While they do not deny the possibility of its excretion through the sebaceous follicles, yet they contend that the quantity thus eliminated is too minute to set up inflammation of the follicle, and thus give rise to acne by direct irritation. Clark and Amory regard bromine acne as a tropho-neurosis resulting from the direct action of the bromide upon the peripheral nerves, producing a derangement of the nutrition of the skin, of which the eruption is the outgrowth. 1 Tilbury Fox, Shirley Murphy, Kaposi, and Coloott Fox have recorded cases of bromic eruption in infants nursed by mothers taking bromide of potassium. — T. C. F. 2 Jaequet also detected bromine in the liquid secreted by patches of bromic eruption. He considers the eruption due to " peri-adenites sebacee's «t sudoripares."— T. C. F. , , , i . > , j 29 450 DE. MOEEOW ON DEUG EEUPTIONS. Diagnosis. — The appearance of the bromine rash is seldom attended with fever and other symptoms of constitutional reaction. As compared with other drug eruptions, it is more gradual both in its development and decline. The acneiform eruption is most often observed after the use of the drug in small doses has been continued for a long while. It increases in severity with the augmentation of the dose, and declines with its diminution. These characteristics have a certain importance from a diagnostic point of view, although there are few affections of the skin with which it could be con- founded. In the maculo-papular form its brownish-red or copper tint might suggest syphilis. It is more liable, how- ever, to be confounded with acne vulgaris, from which it may be differentiated by the absence of comedones, its develop- ment at periods of life which would exclude ordinary acne, and on parts of the body where this latter affection does not occur. Its association with other symptoms of " bromism," especially fcetor of the breath, and the presence of bromine in the urine, would leave no doubt as to the diagnosis. Tests for Bromine and Bromides. Both bromine and iodine are liable to escape detection if an attempt is made to set them free in the urine. This is par- ticularly the case with bromine. The reason is that both are prone to combine with some of the organic constituents of the urine, forming substitution compounds. To avoid error, it is best to proceed as follows : Render the urine alkaline with potassa, evaporate it to a small bulk, transfer this to a crucible, and apply heat gently, until the contents are apparently dry and somewhat charred. Then cover the crucible and heat it to a low red heat until the mass is carbonised. Allow to cool ; add water and boil for a short time, then filter. The filtrate, with washings, will now contain, besides other inorganic salts, any iodine or bromine in form of iodide or bromide. Concentrate the filtrate, and add to a portion of it some disulphide of carbon, and afterwards dilute chlorine water, drop by drop, shaking after each addition. If bromine was present, the disulphide will assume a yellow or yellowish- BROMINE AND BROMIDES. " 451 brown colour. Should it have a violet tint or colour, iodine is present. In this case the test is to be applied very slowly, and chlorine water added as long as the colour of the disulphide deepens, when this is to be removed and the test continued with a fresh portion of disulphide as above directed. Treatment. — The main indication in the treatment of the cutaneous disorders caused by the internal use of the bro- mides is the suppression of the exciting cause. In certain conditions, however, the nervous symptoms of the patient may be of a nature to render the continuance of the medi- cine desirable, if not imperative. In order to realise the full therapeutic advantage of the drug, without its incon- veniences, a number of adjuvants or correctives have been recommended. Arsenic has been recommended by Bartho- low, Gowers, and others. Gowers found that five-drop doses of Fowler's solution caused the pustules of bromic acne to disappear in two weeks. This was evidently a post hoc conclusion, since experience teaches that the cutaneous erup- tion usually vanishes in this time without any treatment whatever. Sulphide of calcium is another drug which, on account of its well-known antipyogenetic influence, has been recommended to antagonise the tendency to the formation of pustules. Seguin found, however, that both arsenic and sulphide of calcium failed to influence the eruption in his cases. Another expedient which suggests itself would be to give the bromide in doses just short of those sufficient to cause irritative effects upon the skin. But Palvet claims that the favorable results from bromide of potassium only begin to appear when an eruption of pimples appears on the skin of the face. Brown-Sequard thinks that the cropping out of an " acne-like eruption on the face, neck, and shoulders," IODIDES. 491 wrist to the tips of the fingers. The colour was a steely blue, bearing a striking resemblance to the appearance of a coil of intestine. The general condition of the patient unchanged ; resp. 23, pulse 112. Catheter will not pass on account of stricture at four and a half inches, admitting No. 10 sound with difficulty. Urine duct kept in bed with patient. He was placed upon an extra diet, and ordered whisky, giv per diem, the face and hands to be dressed with carbolised vaseline. Some of the bullae were punctured, yielding a reddish serum, which was examined for iodine with negative results. 1 ith. — No change in appearance, except that some of the older bullae on hands have become dirty-blue in colour, and on puncture give exit to a dirty-red sero-pus instead of a clear serum as before. Examination of heart showed a systolic apex murmur transmitted towards left axilla. Diagnosis of mitral insufficiency. Temperature, ioo - i°; resp., 22 ; pulse, 114- 1 2th. — Infiltration of the skin has subsided somewhat ; examination of the urine shows it acid in reaction, sp. gr. 1 'oio, with a considerable amount of albumin, 10 to 15 per cent. Under the microscope a few pus and blood globules are seen ; no casts. 14th. — On the back of the neck the skin has returned to its normal level, but is still red, the face less swollen, eyes well open and bright in appearance, leonine appearance of coun- tenance gone. The bullas on hand present a blue-black coloration. A bloody pus, slightly offensive, comes from one or two ruptured bullae. All the bullae were ordered to be cut open, washed out with i\ per cent, carbolic solution, and dressed with carbolised vaseline. The floor of some of the bullae is bathed in pus, apparently due to superficial ulcera- tion. 2 1st. — Continued improvement in general condition of patient ; the backs of the hands cleared of and presenting a healthy appearance. 29th. — The skin of the neck and a good part of the face has returned to its normal condition, though still somewhat hyperaemic. Raw surfaces on dorsum of hands and fingers healing. 492 DR. MORROW ON DRUG ERUPTIONS. November 5th. — Almost all traces of tlie eruption gone, though no gain in the patient's general condition. Patient has cough. Examination of chest shows dullness at apices of both lungs, with increased fremitus, prolonged high respi- ratory murmur, and few moist rales. Passes urine and faeces in bed as on entrance. 1 5th. — Patient has continued to fail. Increasing frequency and feebleness of pulse (120) ; resp. 32. Examination of chest shows pulmonary oedema. 16th. — Patient died quietly at 2 p.m. Autopsy showed heart enlarged and dilated on left side. Insufficiency of mitral valve and atheromatous deposits. Aorta atheromatous. Lungs oedematous ; phthisical con- solidation at both apices ; no cavities. Kidneys somewhat diminished in size and heightened in colour ; consistence in- creased ; surface granular ; capsule adherent. Liver and spleen normal. The drawing representing the face in the picture (vide Frontispiece) was made on the second day after the admission of the patient, when the more acute eruptive features had begun to subside. The direct dependence of the eruption upon the iodide of potassium in this case would seem to be conclusively established ; first, by the appearance of the cutaneous phenomena within three or four days after com- mencing the use of the drug ; second, by the intensification of all the eruptive features under its continued use ; third, by the subsidence of the eruption soon after the drug was withdrawn, and, fourth negatively, by the absence of any other known exciting cause. In this case the eruption did not attain its maximum de- velopment until four or five days after the iodide was dis- continued. Whether the sulphide of calcium, given in the interim, exerted any material influence in intensifying and perpetuating the eruptive tendency, is open to question. The comparatively slow involution of the lesions was probably due to the profound systemic depression caused by the drug, and the existence of the grave organic troubles, which ultimately proved fatal. As early as 1842 Eicord refers to a rupia-like eruption, presenting the characters of a cachectic rupia, which he had IODINE AND IODIDES. 493 observed upon the forearms and legs of a patient who was taking iodide of potassium. The eruption disappeared upon discontinuing the drug, and reappeared when its use was resumed. While this eruption was probably closely allied, if not identical, with that under consideration, its clinical characters were not traced with sufficient precision to justify its inclusion under this category. The first authentic case of bullous eruption caused by iodide of potassium was reported by Dr. John O'Reilly in the ' New York Medical Gazette/ January, 1854. 1 The special features which characterise this eruption are the development of bullae of varying size, often commingled with vesicles and small pustules. The lesions usually make their appearance as vesicles or vesico-pustules, which rapidly increase in size, forming regular rounded or globular bullae, from the size of a pea to that of a pigeon's egg, or even larger ; they may remain discrete, or coalesce with neigh- bouring bullae ; in which case they may attain enormous dimensions. In other cases they begin as hard papules, the shot-like character of the papules suggesting the commencing stage of variola. This resemblance is heightened by the rapid transformation of the papules into vesicles, and their tendency to umbilication, which is quite manifest in some cases. There is generally more or less thickening or infil- tration of the skin, and the lesions may be surrounded by an inflammatory areola, variously described as " erythematous," "bright-red," or "a dark wine colour." In some cases the epidermis is uplifted without inflammatory swelling of the skin, presenting the appearance of a blister produced by a burn. In one case the eruption was described as " an eruption of blisters, compared to " potato apples," each blister surrounded by a series of bright-red concentric rings. 2 1 Sloughing occurred in the sites of bullae, and the penis was lost. Crocker refers to a case in which a case of " hydroa " was aggravated into a gangrenous condition by the use of iodide of potassium. — T. C. F. 2 Hallopeau in 1888 recorded a remarkable case in which a similar erup- tion and intoxication effects recurred seven times in a man suffering from phthisis and albuminuria. Bullae were produced on the face, forearms, and lingual and palpebral mucous membranes. The bullae had citrin or puru- lent thickish contents. If the drug was continued new bullae evolved, inflammatory effects increased in the old ones, and led to crusting, atrophy^of 494 DE. MORROW ON DRTTG ERUPTIONS. In a number of the cases there was a coexistence of renal and cardiac complications which may explain the compara- tively large fatality observed. We can readily understand' why defective elimination of the drug should act as a co-factor in the causation of cutaneous irritation. The greater part of the iodine is normally eliminated by the 1 kidneys within twenty-four hours after its ingestion ; when this channel of egress is blocked up, the drug is longer retained in the vascular channels, and exerts its irritant action upon the tissues. But why cardiac disorders should produce a morbid determination of the drug's action towards the cutaneous system is not so evident. Thin has suggested that this may be due to the feeble heart impulse and consequent sluggish circulation in the cutaneous capillaries, allowing the iodine, or its compounds present in the blood, time to attack and injure parts of the vascular wall. It is needless to say that the retarded elimination of the drug does not explain the occasional occurrence of the eruption within a few hours after the ingestion of a single insignific- ant dose. The papulo-pustular form. — This may be regarded as typical, as it is the most common, of the eruptions provoked by the action of the iodides. It presents certain analogies with the acneiform eruption produced by the bromides. It usually appears upon the face, backs of shoulders, upper part of chest and arms, where the sebaceous glands are the derma, condylomatous vegetations, and remarkable cicatricial bridles. The diagnosis was obscure for a time, and tertiary syphilis and pemphigus vegetans had to be eliminated. Taylor has met with three instances of the bullous eruption, in which after rupture of the lesions, surfaces varying in appearance between the slightly warty and the vegetating were left. He states that all cases of bullous iodic eruption shew a condition of inflammatory thickening of the skin in marked contrast to pemphigus. This statement is, however, 'too absolute. Hyde has insisted on the point that in addition to a polymorphic eruption two types of bullous or quasi-bullous eruption are met with, viz. the bullous type, pure and simple, and a type of quasi-bulla or molluscoid formation, with solid bases and thick or almost solid contents, not developing like true bullae and never attaining that form. Compare on this subject Morrow's, the Sydenham Society's, and Tilbury Fox's plates. The truth is, I believe, that these two types are connected by a complete chain of links. The lingual and buccal mucous membranes may be involved. — T. C. F. IODINE AND IODIDES. 495 abundant. Sometimes, however, it surpasses these limits, and is found distributed over a large surface of the body. The eruption commences as hard shotty papules, which usually enlarge and become surmounted by small pustules, when fully developed. The iodic pustules may be described as consisting of acuminated or rounded eminences, more or less voluminous, with a reddened, somewhat infiltrated base, suppurating sometimes only at the summit, at other times in the totality of the pustule. The contents of the pustule concrete into a yellowish crust, which may persist for some time, and on falling leave a distinct cicatrix. Sometimes the tubercles, instead of ulcerating, become transformed into nodules of firmer consistence, intensely red, deeply, seated in the tissues, which are remarkably slow in their involution. 1 The anthracoid form. — In this connection may be described an eruption of carbuncular lesions which resembles the " confluent acne " produced by the bromides. Besnier designates it as acne anthracoide iodo-potassique. In his two cases the face and thorax were covered with veritable tumours of variable volume, of a reddish coppery hue, flabby, almost fungous, and presenting punctate depressions or vacuoles analogous to those of anthracoid furuncle. It was impossible to express their contents ; incision gave exit only to blood. In Duhring's case there was a confluence of the nodules, forming a sharply-defined, rounded, inflam- matory patch, violaceous in colour, its centre depressed and crusted, while the periphery was studded with numerous deep-seated, yellowish, sebaceous-looking pustules, present- ing an acneiform appearance. When cut into, the yellowish 1 It is to be noted also that the papules may vesiculate and pass into the bullous form of eruption. The amount of inflammatory base present, the depth to which the skin is involved, the intensity of the process, the size of the lesions, and degrees of confluence vary widely in different cases and even in the same case. Prom these papulo- vesicular and papulo-pustular lesions, often resembling acne, varicella, and variola, may arise the ecthymatous, bullous, molluscoid, condylomata-like, and other forms of eruption. In infants the eruption may closely simulate the bromide eruption both in aspect and site. Koplik, it may be well to mention, has observed an iodic eruption in an infant nursed by a mother taking iodide of potassium. — T. C. F. 496 DR. MOEROW ON DRUG ERUPTIONS. pustular points bled, but did not exude their contents. When the crust was lifted from the central lesion, it showed a red, glistening, firmly-mammillated or warty surface. There were four of these lesions occupying the forehead, cheeks, and nose. The one on the forehead was two inches in diameter. In a case of Dr. Costa's, referred to by Atkinson, the lesions were situated upon the back and chest, as well as the face. The suppression of the medicine was followed in all of these cases by the involution of the lesions in about two weeks, some of them leaving a brown- ish macule, with cicatricial depression. 1 The petechial form. — Although Ricord, as early as 1842, mentioned among the eruptions produced by the iodide of potassium the occurrence of " petechise resembling the spots of the morbus maculosus Werlhofii — a veritable pur- pura hemorrhagica' 5 — Fournier was the first to carefully study the purpuric eruption. He describes the lesions as discrete, miliary, millet-seed to lentil-sized spots, usually rounded, more rarely oval or discoid in form. Its seat of predilection is the legs, more especially the middle three- fifths, avoiding the knees and feet, and developed more profusely on the anterior than the posterior surfaces. Or- dinarily there are as many as one hundred discrete spots on each leg. Petitjean describes a case in which the eruption appeared on the dorsal surface of the feet, and another observer saw it upon the forearms and wrists. According to Fournier, the explosion of the petechial accidents almost invariably occurs soon after the commence- ment of the treatment, usually in from one to three days. 1 E. W. Taylor, in recording a case of the so-called Acne anthraeoide iodo-potassique under the name Dermatitis tuherosa, holds the view that the essential lesion in all forms of iodide eruption, except the purpuric, is a dermatitis, and that they only differ in non-essentials of form, degree of development, modification, and transformation. In the particular phase under consideration there is added to the dermatitis a peculiar involvement of the sebaceous glands, evidenced by the exuding cribriform openings and pus crusts. The tumours may develop into sessile and mushroom forms, simulating mycosis fungoides, and present a papillary hypertrophy of various degrees of intensity. Papules, papulo-pustules, tubercles, tuberculo-pustules, diffuse inflammatory patches often fungating, and subcutaneous nodular inflammation may co-exist, and are all phases of dermatitis with secondary modifications. — T. C. P. IODINE AND IODIDES. 497 The eruption reaches its height in two or three days, and, if the medicine be discontinued, disappears in the course of two or three weeks. In certain persons the same eruption may occur several times after each new use of the iodide. 1 In the course of a continuous treatment, each notable eleva- tion of the dose was followed by a marked recrudescence of a new crop of purpura (" une poussee subintrante "), con- trasted by their vivid colouration with the faded earlier eruption. Fournier regards the eruption as rare, as he had observed it only in fifteen cases. I have seen several cases. In one old lady, I redeveloped the eruption four different times, in order to test its causal connection with the iodine. She had been taking the medicine some time in small doses when my attention was called to the eruption. Each time thereafter it was reproduced within forty-eight hours by the use of five-grain doses of the iodide. S. Mackenzie reports a remarkable case of iodic purpura in a child, caused by a single dose of two and one half grains. The case terminated fatally. 2 It has been suggested that iodic purpura is more apt to occur in anaemic, debilitated persons who have taken the drug for some time. This view has not been confirmed by my own experience, nor that of many others. Fournier emphasises the statement that an anasmic condition or syphilitic cachexia could not be regarded as a predisposing cause. Two thirds of his patients were absolutely exempt from every manifestation of syphilis at the time when the iodide, given as a preventive of further accidents, deter- mined the eruption. Nodular form. — Vallanur reports a case in which a woman, after taking two and one half grams of the iodide for four days, was attacked with acute pains in the but- 1 Besnier holds that pure iodine will not cause the haemorrhages, and he illustrated this fact in the person of a man who had purpura on the lower limbs every time he took iodide of potassium, hut though tincture of iodine caused symptoms of iodism there was no purpura produced. — T. C. P. 2 A portrait is given of the head of the child in the ' Illustrated Medical News,' November 17th, 1888. See also the fatal case of pemphigoid eruption and Purpura hsemorrhagica reported by Eisner ; also Wilson's case. — T. C. P. 32 498 DE. MORROW ON DRUG ERUPTIONS. tocks, thighs, calf of the leg, and dorsal region ; then there appeared upon the painful points small indurated nodules of the size of a nut, of a deep red colour. During three days they increased in size, one or two attaining the size of an egg. The iodide was discontinued, and the nodosi- ties rapidly disappeared. Some days later the iodide was again administered, and the same cutaneous accidents were reproduced. This experiment was repeated three times, always giving the same results. Talamon reports the case of a woman in whom two and one half grams of iodide of potassium produced an eruption resembling erythema nodosum. There were at least twenty red and indurated nodules situated upon the lower limbs, the loins, and buttocks. The lesions were made to reappear at three different times by the use of the iodide. Hallopeau observed the development of painful nodes in one of his patients, which was repeated every time he took the iodide of potassium. The tumours were oval in shape, reddish at the surface, and painful on pressure ; they were situated chiefly on the anterior surface of the thighs. In conjunction with the nodular eruption the patient also had iodic purpura. 1 Polymorphous eruptions. — While the particular form in which the iodic eruption is manifested in different persons is, as a rule, unique, and determined principally by the con- stitutional reaction of the individual, yet it sometimes hap- pens that a combination or association of different eruptive- elements is met with in the same individual ; we have seen above that papules, tubercles, and pustules may co-exist in the papulo-pustular form, the papule representing the first stage of the morbid process, of which the pustule is the acme or completion. Ecthymatous pustules and furuncles may begin as hard papules, nodules may suppurate and 1 Hallopeau points out how these subdermio nodosities may simulate gummata or rheumatismal nodules. See also the cases reported by Kicord, Pellizari, Morrow, and Hutchinson. Kaempfer noted similar cutaneous infiltrations on the legs, recurring with increased violence and profound intoxication each time the drug was resumed, so that some of the infiltrations attained the size of the palm of the hand. The eruption reappeared after the administration of the drug in very small doses per rectum. — T. C. F. IODINE AND IODIDES. 499 follow all the evolutions of a subcutaneous abscess, the suc- cessive stages representing different forms of lesions. I recently presented a case before the New York Der- matological Society in which ten-grain doses of iodide of : potassium developed a polymorphous eruption, preceded by intense lachrymation, coryza, and oedema of the face and eyes. The whole of the nose presented on the third day of the eruption a red, fungoid appearance, being greatly enlarged. The forehead, face, neck; and forearms were also the seat of the eruption. On the left cheek was seen a furuncle ; over the malar bone a large, dark bulla ; on the forehead were many papules and pustules. The eruption on the back of the neck very much resembled molluscum contagiosum. On the forearms there was a variety of eruptive elements — papules, tubercles, vesicles, pustules, and bullae. In a case reported by Celso Pellizari, three eruptive forms of an entirely different character were present at the same time, viz. on the left forearm, near the wrist, there were three slightly elevated papules, the size of a cent, with a rough surface and a dark strawberry colour. Upon the arms and legs were eight or ten eruptive elements, about one half inch in diameter, similar to the bulla? of rupia, surrounded by a circumscribed dark-red areola ; and on the top there was a bulla like that produced by a burn, altogether different in character from the cachectic or syphilitic form ; the third form was represented by three tumours, from the size of a nut to that of a small apple, deeply seated in the subcutaneous tissue. On stopping the iodide the papules quickly disappeared ; the bullae dried up, leaving scars which soon became white ; the nodules disappeared more or less quickly, according to their size. The eruption was redeve- loped in this case several times by the renewal of the iodide, each time accompanied by a high temperature, &c. The distinguishing characteristics of iodic eruptions are their multiformity, their frequent occurrence after small doses of the drug, their usual prompt disappearance after its use is suspended, their frequent association with its well- known physiological, as well as incidental abnormal effects upon other organs, their proneness to develop in connection 500 DE. MORROW ON DRUG ERUPTIONS. with cardiac and renal disorders. Though usually of tran- sient duration and insignificant import, they may be attended with the gravest symptoms, and exceptionally may lead to a fatal termination. The length of time which intervenes between the ad- ministration of the drug and the first appearance of the eruption varies according to the size of the dose and the predisposition of the individual; usually it is from the third to the sixth day. This period may be reduced to a few hours, or lengthened to several weeks; in general it may be said that, while it may require several days to develop the eruption the first time ; after its disappearance a single small dose may suffice to redevelop it in the course of three or four hours. A half-grain of iodide of potassium has been known to reproduce an urticarial eruption developed in the first instance by five-grain doses. In a case reported by Duffy, the patient had taken the iodide for over a month, thirty grains a day at first, afterwards sixty grains per day — two and one-half ounces in all — before the eruption appeared. It was redeveloped by forty-five grains in one day. Exceptionally the eruption may continue to come out after stoppage of the drug. In Besnier's case a bullous eruption was first developed by two grams, the second time by one gram, and the third time by ten centigrams. There seems to be no definite relation between the size of the dose and the form of the eruption ; this would appear to be a matter of individual constitution. The acneiform eruptions have been more often observed after protracted use of the drug, while the bullous and petechial forms have shown themselves more promptly. The exceptions which have been noted to this rule, however, prove that the determination of the different varieties is independent of the mere fact of chronicity of treatment. The cutaneous phenomena caused by the internal adminis- tration of iodide of potassium are undoubtedly due to the contained iodine, and a priori we should conclude that identical effects would follow the use of all the iodine com- pounds, especially the alkaline salts. It has been affirmed, however, that the different salts exert this irritative influ- ence in different degrees of intensity, the iodide of ammonium IODINE AND IODIDES. 501 representing the highest degree of pathogenetic power, the iodide of potassium the next, and the iodide of sodium the least. It must be admitted that the observations upon which this comparative estimate is based are too few in number to justify conclusions possessing scientific value. In Duffy's case, iodide of sodium was given in ten-grain doses three times a day for eight days, with failure to reproduce an eruption of " iodic purpura " which had previously been twice developed by iodide of potassium. Iodide of ammonium being then substituted, two doses, twenty grains, brought out the eruption within twelve hours. In a case reported by Einger, thirty grains of iodide of potassium for five days developed a pustular eruption, which disappeared within a few day after stoppage of the drug. The eruption was redeveloped by the same treatment, to again disappear when the medicine was discontinued. The iodide of am- monium was now ordered in ten-grain doses three times a day, and the eruption appeared after the second dose. The iodide of sodium was then substituted in the same doses, and continued for four days, but without bringing out the eruption, which, however, promptly reappeared after a single dose of iodide of ammonium. Pathogeny. — The first requisite for a clear understanding of the pathogeny of iodic eruptions is the determination of the anatomical seat of the lesions. It was formerly believed that the sebaceous glands constituted the points of depar- ture of all iodic eruptions, but it is hardly probable that eruptive elements so dissimilar as pustules, petechia?, and bullae, &c, should have a common starting-point. 1 Their very multiformity constitutes a fatal objection to such an assumption. It is well known that iodine, while princi- pally eliminated by the kidneys, has been found in the saliva, sweat, and other physiological secretions. Adam- kiewitz claims to have demonstrated its presence in the pustules of iodic acne, and therefore concluded that the sebaceous glands secrete iodide of potassium. He believes 1 The congestive conditions in the face, &c, are common to many drugs, and with the urticaria and petechias possibly own a causation different from the various forms of dermatitis which are special to iodine and bromine. — T. C. P. 502 DB. MORROW ON DRUG ERUPTIONS. that the iodide undergoes a chemical modification by con- tact with the contents of the sebaceous glands, forming irritating compounds. Fox asserts that the iodic lesions are situated in the follicles, and are due to excessive stimulation of the sebaceous structure consequent upon elimination of the drug through this channel. The bullous form and other unusual and severe phases of the eruption he regards as exaggerated acneiform lesions, with excessive and altered secretion of sebum. This view is opposed by other authorities, who go so far as to deny the existence even of iodic acne. Duckworth says that the glands are not the seat of pustular acne, and records a case in which the same eruptive form appeared in cicatricial tissue, where probably no glands remained. Other observers have noted its occurrence on the palms, where the presence of sebaceous glands has never been demonstrated. Thin, who rejects the theory that iodine eruptions are produced by stimulating effects on the secret- ing elements of the sebaceous glands, believes that all the varieties of the eruption may be explained by the tendency of iodine, when present in the blood current, to attack and disorganise the vessels at special points. "The injury in its mildest form is seen in common iodic acne, in more severe forms in the bullous and pustular eruptions, and in the worst form in iodic purpura. In the first we have limited oedema with congestion of the vessels ; in the second, an effusion of serum, with more or less of the formed elements of the blood ; in the third, destruction of the wall of the vessel and haemorrhage." In the explanation of the severer forms he suggests that a sluggish circulation and deficient excretion may find a place. In his microscopic examination of a bulla produced by iodine, he found that the lesion was formed by injury to the walls of the blood-vessels of a limited area and by conse- quent escape of blood, which displaced the connective tissue, pierced the rete mucosum, and accumulated under the horny layer of the epidermis. That this injury to the blood-vessels is independent of the glandular elements is shown by the implication of blood-vessels not in immediate proximity with these structures. IODINE AND IODIDES. 503 Duckworth made a microscopic investigation of an iodic pustule, and found that the superficial layer of the cutis vera was principally implicated. The papillary layer at the affected parts was flattened out, stretched, and even exca- vated, and contained a large number of small cells and a quantity of newly formed fibrous tissue. The blood-vessels were numerous and enveloped in sheaths of exudative cor- puscles ; no evidence of the rupture of any blood-vessel was to be obtained. The sweat glands seemed entirely un- affected, even in close proximity to the pustules. There was no implication of the hair follicles. He infers from .this that the lesions are not of the nature of acne, but are due to a superficial localised dermatitis resulting in cica- tricial tissue. Farquharson attributes a marked influence in the pro- duction of iodic eruption to defective elimination of the drug, thus allowing it to remain longer in contact with the tissues of the body. This view gains support from the fact that the severer forms of the eruptions have sometimes been found associated with grave cardiac and renal disorder and the presence of albumin in the urine. The irritative effects of the iodide of potassium on the skin are, it is alleged, often corrected by the simple expedient of giving larger doses, which stimulate the kidneys, causing enure- sis and a more rapid elimination of the drug from the sys- tem. Whether the potassium combined with the iodide con- tributes to promote the functional activity of the kidneys has not been definitely determined. Incidentally, it may be stated that patients treated at the Hot Springs of Arkan- sas often take large doses of iodide of potassium, as much as one ounce per diem, without liability to incidental bad effects. The copious use of the waters, both internally and in the form of baths, no doubt produces a hyperactivity of the sudoriparous glands, as well as the kidneys, and the consequent rapid elimination of the drug. It is worthy of note, however, that the retarded elimina- tion of the drug does not explain the occasional occurrence of eruptive accidents within a few hours (four or five) after the ingestion of a single insignificant dose. This fact also contravenes the fanciful theory that iodic eruptions are in 504 DR. MORROW ON DRUG ERUPTIONS. all cases the outward expression of evidence of a saturation of the system with iodide of potassium — an opinion formerly held by a majority of authors. Diagnosis. — Certain forms of the iodic eruption may be confounded with variola and syphilis. The shot-like pap- ules which precede the development of bullae were said by Hutchinson to resemble those of the early stage of variola, but as they run their course rapidly the diagnosis is soon easily made. The occasional appearance of umbilication, caused by the vesicles spreading at its margin and sinking in the centre, is an element of confusion. The exudation is sometimes so free that crusts form not unlike those of sy- philitic rupia. Other forms have been mistaken for syphilis, and iodide of potassium may be continued, possibly in in- creasing doses, for the very condition which it has caused. Pox says, " I have often been consulted for supposed syphilis, when the disease has been simply an iodide rash." 1 Tests for Iodine and Iodides. When the quantity in the urine is small, and other tests produce doubtful results, it is necessary to eliminate organic matter by the method detailed under bromine, in which the disulphide of carbon will acquire a fine violet colour if iodine was present. If notable quantities of iodine are contained in the urine, it is often possible to detect it by one of the following methods : i. To detect iodine in the urine, the compound is first to be decomposed by fuming nitric acid and dilute sulphuric acid, then a little starch paste, and a few drops of the sul- phide of carbon are to be added, whereupon a beautiful blue colour appears. On shaking it, a small portion of the iodine is dissolved by the bisulphide of carbon, and a dark-blue 1 A case in point is the very severe tuberose eruption figured by Hutchin- son in the ' Archives of Surgery,' July 1889. Pye-Smith observed in a patient suffering from an ordinary pustular syphilide that some of the lesions on the face and back of the hand became hypertrophic and warty under the influence of iodide of potassium. — T. C. F. IODINE AND IODIDES. 505 ring of iodide of starch is formed on the layer of bisulphide of carbon. 2. A less reliable method is as follows : — After starch paste and dilute nitric acid have been added to the urine, a few- drops of fuming nitric acid are added, when a blue colour appears, which on heating disappears, and returns again on cooling. 3. After sulphuric acid and fuming nitric acid are added, the fluid is shaken with chloroform. Then occurs, through solution of iodine in the chloroform, a violet colour. 4. Sometimes the iodine is in such combination that the above agents do not free it, and it may be necessary to add chlorine water for this purpose, or the urine may have to be incinerated and then tested. Treatment. — The treatment consists in the suspension of the drug until the eruptive accidents have disappeared. Various expedients have been suggested with a view of pre- venting the occurrence of the untoward effects of the drug while continuing its use. Arsenic in the form of Fowler's solution, two to ten minims with each dose of the iodide, has been recommended, and tried in some cases with good results. Paget recommends aromatic spirits of ammonia. Aubert has recently recommended belladonna as a means of preventing the disagreeable effects of iodide of potassium. Fournier recommends that the iodide be administered with claret. According to Keyes, tolerance of the drug may often be secured by giving it in a glass of milk or large quantities of Yichy. As mentioned above, intolerance of the drug may sometimes be overcome by simply increasing the dose. It will be found that a single dose of two or three scruples in a cup of tea at bedtime is less liable to produce irritative effects upon the skin than a less quantity taken in a little water in divided doses. If evidences of the. so-called " supersaturation " appear, the drug should not be again administered for four days, as that period is required for its complete elimination. Besnier claims that the drug introduced hypodermically does not give rise to the same accidents as when introduced by the stomach. A more extended clinical experience on the part of others has not verified this claim. Free use of acetate of potash and 506 DR. MORROW ON DRUG ERUPTIONS. remedies of this class is to be recommended with the view of charging the system with an abundance of alkali, which may combine with any free iodine that may be present.. Ehrlich has extolled the value of sulphaniline as a pro- phylactic, as well as a corrective measure after symptoms of iodism have been developed. As soon as the iodism appears a dose of four to six grains of sulphaniline is given, followed by smaller doses, often repeated if necessary. The success in many of these cases, he claims, is remarkable, well-marked, and even exaggerated symptoms, being removed in some cases by a single dose, and after-tolerance being established. In other cases the results were not so decided. No bad results were observed from this treatment. IODOFORM. The cutaneous irritation which sometimes follows the ex- ternal application of iodoform is doubtless due to the con- tained iodine. It may result from dressings of iodoform gauze, or the use of the drug in powder, in ointment, or in solutions of ether, or from its absorption from the mucous surfaces of the vagina and rectum when used in the form of suppositories or injections. The eruption is usually of an erythematous character, but the inflammation may proceed to the development of vesicles and bullae. In an examination of the literature of iodoform poisoning Cutler found numerous references to eruptive accidents developed in connection with other toxic symptoms. They consisted ordinarily of simple erythemata or papular eruptions sometimes covering the whole body. The eruption usually disappeared rapidly upon leaving off the iodoform. 1 1 E. W. Taylor, in 1887, reported 011 twenty-five cases of iodoform eruption, nine of them personal. He found that toxic effects were most frequently manifested hy systemic trouhles without cutaneous changes. In sixteen cases of eruption constitutional symptoms were present ; in nine a rash occurred without systemic symptoms. In order of frequency the eruption was erythematous (simple, papular, vesicular, hullous) or eczematous, or rarely purpuric. So strong may he the idiosyncrasy that an eruption may follow the simple smelling of the drug. The eruptions are charac- terised hy prompt invasion and rapid extension, either commencing at the point of application or at various centres. These general manifestations IODOFORM. 507 Zeissl records two cases of iodoform rash. In one case, in which an iodoform dressing was used, there appeared over the skin of the body, flexor surfaces of the arms, and the inner surface of the thighs an erythematous eruption of a diffuse bright-red colour, disappearing under pressure. In the second case the eruption was consecutive to the intro- duction of iodoform pencils into a sinus every second day. On the tenth day there was itching, of the extremities, fol- lowed by the appearance upon the skin of the body and extremities of an eruption of urticaria nodules of a reddish colour, from the size of a lentil to that of a three-cent piece. Hoepfl reports a case in which an exanthem of small red spots covering the entire body was caused by an iodoform dressing to an amputated breast. Neisser records eight cases of iodoform rash, characterised by the formation of small vesicles, and closely resembling acute eczema. In a few hours after the application a deep redness of the surface comes on, accompanied by violent burning and itching; then vesicles filled with clear fluid appear, and soon form crusts. In some cases the wounds dressed with iodoform took on an apparent erysipelatous action. In two of Neisser's patients a tormenting eczema of the anus and perinseum was caused by the use of iodoform suppositories. In two cases of females similar eruptions broke out over the inner surface of the thighs whenever iodo- form had been applied to the vaginal orifice. 1 Pabret observed an eczematous eruption in a syphilitic subject provoked by the application of an ioddform ointment. Taylor holds, in agreement with Neisser and at variance with J. C. White, are not to be confounded with the local dermatitis due to the direct local contact of iodoform (especially the crystalline drug) as frequently seen on the face and hands of dressers, &c. The problem is often somewhat compli- cated in the case of iodoform by the difiusibility of the powdered drug and its possible transmission by scratching, &c. This complication has, however, been most carefully eliminated in many cases. — T. C. F. 1 It is to be noted that although a remarkable idiosyncrasy existed with respect to iodoform, no accidents followed its internal administration. As far as I am aware, there is not any case on record of an eruption due to the ingestion or hypodermic injection of iodoform. Bolowski observed the occurrence of intoxication and an eruption after the introduction of a uterine suppository containing 1| grains of the drug. — T. C. P. 508 DR. MOEKOW ON DRUG ERUPTIONS. Treves reports a case of iodoform exanthem which was somewhat peculiar in its mode of development. After iodo- form had been used for three weeks to a wound of the fore- arm the entire member became red, swollen, and cedematous. On the following day a crop of vesicles, about thirty in number, appeared upon the forearm. The iodoform was dis- continued, and the vesicles suppurated and healed up. Three days later a remarkable exanthem appeared, covering the arm and shoulder and greater part of the face, the sides of the neck, and frontal aspect of the chest. The eruption con-i sisted of patches of closely packed minute papules seated upon an erythematous base. The patches varied in size from a sixpenny to that of half-a-crown piece. They were irregu- larly circular, with a clearly defined margin, and ran the one into the other. The eruption disappeared in two days. 1 The production of the iodoform rash would seem to depend upon a peculiar susceptibility of the skin to irritant influences, as in many cases the slightest trace of iodoform in any ap- plication will cause the eruption to appear. Koster-Syke reports his personal idiosyncrasy against iodoform, so marked that within a few hours after dressing a wound with an iodoform bandage he experienced a most intense itching over the entire body, attended with a slight elevation of temperature. The following night his face, hands, and arms to the elbow were enormously swollen, and the seat of a vesicular and pemphigoid eruption. On another occasion he used a little iodoform powder, this time taking the precaution to protect his hands with kid gloves. In ten minutes he experienced an itching sensation in the hands and face, and in a few hours the dorsal surfaces of the hands to the tips of the fingers, the face below the eyes, and the integument behind the ears were covered with itchy red points. A pronounced idiosyncrasy was also manifested in his case against carbolic acid. 3 1 This case demonstrated a fact, illustrated by others, that iodoform may be applied to a wound for some time without producing ill effects, but that directly the surface becomes favourable to absorption an eruption and often a systemic intoxication may occur. — T. C. F. 2 Taylor applied iodoform to two small chancroids on the inner layer of the prepuce, and within three hours the whole penis and scrotum were red, IODOFORM. 509 Tests for Iodoform. To separate iodoform from the urine ifc is best to subject the latter to brisk distillation, taking care to use a cold con- denser. The distillate is tested in the same manner as directed for chloroform (see chloral) by applying the isonitril reaction. In addition, it is necessary to recognise the iodine swollen, and the seat of intense pruritus and burning. The symptoms recurred on touching the sores, after an interval, with ethereal solution of iodoform. There was no systemic reaction. Campbell Pope dressed an inflamed bursa of the arm on three separate occasions, at intervals, with (i) iodoform gauze, (2) again with iodoform gauze, (3) with iodoform ointment. After each dressing an eczema-like dermatitis attacked the .whole limb, Taylor dusted a bubo cavity with iodoform and stuffed it with plain gauze, retained by a spica bandage. On the following day an erythematous rash had spread nearly to the umbilicus and half way down the thigh. There was no systemic reaction. Marcus Beck dressed with iodoform a wound made by the removal of an atrophic scirrhus of the breast. Forthwith, an eczematous dermatitis spread continuously over the whole side of the thorax. Taylor dusted iodoform freely on some rupial ulcers on the left leg of a man in wretched health and bandaged the limb. Local irritation arose at once, and next day a deep red erythematous eruption had spread from the leg to the thigh, coincident with systemic poisoning. A scarlatiniform erythema appeared about the neck and shoulders, increased rapidly, merged with the invading erythema of the thigh, and in forty-eight hours covered the whole body. "Wallich dressed a finger with iodoform for a month. Dermatitis then set in locally, subsequently attacked the other hand, and a rubeolar rash appeared on the forearm, arm, thorax, and abdomen. Janovsky dressed an ulcerated gumma of the left calf with iodoform, and in three days there was ephemeral febrile disturbance and dermatitis of the left thoracic region, the back and the left shoulder blade. The same observer dusted some iodoform over soft chancres. Febrile reaction occurred in two days, and an erythema appeared on the thighs, the right hypogastrium and lumbar region, extended to the left side, and then invaded the forearms. This experience was repeated. Gerlach dressed an ulcer of the leg with iodoform ointment (5j to gj) spread on lint and bandaged. A few hours later the whole leg was swollen and the seat of bullous dermatitis. In twenty-four hours there was enormous swelling of the face, temples, and ears. In forty-eight hours there was swelling and papular eczema on the forearms, arms, neck, and upper third of the chest, and back. The Petechial Form. — Janovsky applied iodoform to a scraped lupus patch of the right thigh of a girl. Three days later purpuric spots appeared over the surrounding skin, and continued to develop as high up as the breasts. Fourteen days later the drug was reapplied with a similar result — T. C. F. 510 DR. MOEROW ON DRUG ERUPTIONS. forming one of its constituents. This may be done by adding to the liquid a little nitrous acid (prepared by acting upon starch with nitric acid and heat, and diluting with about an equal volume of water). On subsequently adding some gelatinised starch a tint varying from faintest purplish to blue will be obtained. 1 IPECACUANHA. The prolonged application of ipecacuanha to the skin causes irritation characterised by redness, and the formation of papules, vesicles, and pustules, which, on healing, are not followed by pitting or scarring. According to Baudot, the papules are large, few in number, red from base to summit, without circumferential areola. The lesions have no tendency to run together. They are intensely itchy, and from the scratching which they provoke, they frequently become covered with blood-crusts analogous to those of prurigo. They disappear slowly. According to Delioux, the pustules may be umbilicated like those produced by antimony. A diagnostic feature is that the former do not ulcerate and leave scars. The internal use of ipecacuanha may also occasion eruptive disturbances. Turner describes a case in which there was burning heat diffused over the whole surface of the body, together with a kind of erysipe- latous eruption covering every portion, similar to what is seen after exposing the naked skin to a burning sun. Circular patches, with elevated, thick, and rounded edges, and of a fiery colour, characterised the eruption. NUX VOMICA. STRYCHNIA. Dierbach, quoted by Piffard, says that strychnia internally administered will produce formication and pruritus, and a sensation as if the skin were pricked with needles, or there may be diaphoresis and a miliary eruption. 1 Burlureaux confirms the tests of iodoform toxaemia given by Poneet that (i) a piece of silver placed in the mouth gives rise to a taste of garlic, (2) that when a pinch of calomel is mixed with the saliva a canary-yellow tint is produced due to the formation of iodide of mercury. — T. C: P. OIL OF CADE. 511 Skinner reports a case in which one twenty-fourth grain of strychnia produced a scarlatinoid exanthem. OLEUM CADINI. The oil of cade frequently excites inflammatory action when applied to the skin. The most common form is an erythematous and papular eruption, which may extend beyond the original point of application and involve a large extent of surface. This dermatitis may take on an erysipe- latous f orm, through the implication of the lymphatic vessels in the inflammatory process. A papular eruption presenting many features in common with tar acne is one of the forms of cade irritation. Baudot describes it as follows : the papulo-pustules are dissemi- nated or united in groups, slightly confluent, but distinct from each other, implanted in the skin upon a large papular base terminating in an acuminate summit, and each perfo- rated by a hair. The papulo-pustules are hard, solid, red, and surrounded by an areola of the same colour. The suppuration is localised at the summits. Since this eruption is most abundant and characteristally developed on the hairy parts, Bazin has designated it as sycosis cadique. Kleinhaus says that the hair-follicles are projected above the skin in the form of nodules of the size of a hemp-seed. The susceptibility to the irritant action of the oil of cade varies in different individuals. Women are specially liable. Quite recently a woman, aged forty, came under my obser- vation with an eczema affecting the forearms, wrists, backs of the hands, and interdigital surfaces. A single application of the oil of cade (one to seven of vaseline) produced an intense burning, itching, and swelling of the fingers and backs of the hands extending to the wrists. Two days later a number of large blebs were observed over the dorsal surface and sides of the middle and index fingers. The backs of the hands were enormously swollen, and the skin studded with a large number of pin- head sized vesicles. A week later the hand was still cedematous, and the epidermis had peeled off from the middle and index fingers. 512 DR. MORROW ON DRUG ERUPTIONS. OLEUM M0REHU.2E. The internal use of cod-liver oil may cause an eruption of a miliary or eczematous character. Duclos says that the eruptions of cod-liver oil are always vesicular, and spread over the entire body. 1 Other observers, among whom is Farquharson, says that it causes an eruption of acne, presum- ably from the passage through the cutaneous glands of some of its acrid constituents. oleum Eicnjri. The only reference to the irritant effect of castor oil upon the skin which I have found is in Piffard's ' ' Materia Medica and Therapeutics of the Skin." Langier is quoted to the effect that pruritus and erythema have been caused by the ingestion of the oil. 2 OLEOM TIGLII. The application of croton oil to the skin causes more or less irritation, according to the duration of contact and sen- sibility of the skin. Ordinarily, after a few hours redness appears, and a copious crop of papules which rapidly become converted into vesicles and then into pustules. The lesions may first develop as vesicles without passing through the preliminary papular stage. The vesicles may be discrete or confluent ; sometimes bullae of irregular outline and of con- siderable size may form from their fusion. The contents of the vesicles, at first transparent, soon become turbid and purulent. The pustules are usually rounded or globular, rarely flattened or umbilieated. At first they are tensely distended, but soon wrinkled from partial resorption of the contained fluid. The walls of the bullae are easily ruptured, disclosing a superficial excoriation which becomes covered 1 Lewin (quoted by Crocker) refers to these eczematous eruptions. — T. C. P. 3 OLEUM SANTAII. A general petechial eruption arising on the thirteenth day in a young woman has been described. The eruption ceased when the drug was discon- tinued. In respect to eruptions attributed to this medicament possible adulteration with copaiba must be considered. — T. C. F. opium; mokphia 513 with a yellowish, crust. The crusts usually fall off within a week or ten days, leaving a coppery pigmentation. When the inflammation involves the true skin they may be followed by permanent cicatrices. The volatile portion of the oil may occasion a dermatitis of neighbouring parts, or secondary vesicular eruptions may appear, particularly upon the face and genitals, from acci- dental transference of the oil by the fingers or otherwise. In some cases it would seem that secondary eruptions are consecutive to absorption. Trousseau observed an eruption upon the scrotum when distant parts of the body were rubbed with croton oil. opium ; MOKPHIA. The irritant effect of opium upon the skin has been recog- nised from the time of its introduction into the materia medica. While the older observers speak of an intense burning and itching as a frequent accompaniment of the use of this drug, it does not appear that they were familiar with its property of producing changes in the skin of an eruptive character. Dioscorides and Paulus .iEgineta describe the pruritus opii as a tormenting and unbearable affection. Tralles, quoted by Lewin, published in 1774 the first obser- vations relating to the eruptions produced by opium, which he regarded as due to increased sweating. Incidentally it may be said that Trousseau connects the opium exanthem with a modification in the sudoral secretion occasion by the drug, which alteration of secretion, he says, determines an irritable condition of the skin, resulting in erythematous red- ness and pseudo-measly patches, sometimes in vesicular erup- tions, and even in veritable papules when the action of the medicament has been prolonged. The production of the erup- tion, however, bears no relation to the stimulation of the sweat- glands, as it may occur without any increase in this secretion. The most common manifestation of the irritant effect of 1 Ringer also points out the powerful sudorific action of opium, and states that " the cutaneous emunctory is especially charged with its elimination." To meet the argument that the eruption may occur without any increase in the sweat secretion, Trousseau supposed that the eruption was due to a, peculiar quality imparted to the sweat. — T. C. P. 33 514 DR. MORROW ON DRUG ERUPTIONS. opium upon the skin is an erythematous eruption which may occur as diffuse uniform redness simulating scarlatina, or it may be macular like that of measles, consisting of small isolated spots of a bright or dusky red. They first appear upon the face and neck and flexor surfaces of the body, and are preceded by a hot itchy sensation in the .skin. Usually the eruption disappears promptly after dis- continuing the medicine, and is followed by a slight de- squamation. Behrend reports a case of opium eruption which appeared after taking a few powders containing one quarter grain. It was a pale scarlatinoid eruption, which on near inspection was found to consist of minute papules closely studded, distributed over the chest from clavicle to end of sternum, upon the inner side of the arms, flexor surfaces of forearms and wrist-joints, spreading down the thighs and inside of knees, and terminating at the ankle in a stripe of livid colour. The pruritus was of so violent a character as to prevent sleep. The eruption subsided on suspension of the opium, but was promptly redeveloped on resuming its use. Desquamation of a branny character, foliaceous over hands and feet, occurred several days later. Morod ordered pills of opium to a lady patient who declined to take them, declaring that every time she took opium it made her as red as a lobster. He prescribed instead syrup diacode. The next morning the patient was indeed red as a lobster, the eruption being accompanied with intense itching. An exanthem resembling scarlatina has been observed on the face, neck, hands, arms, and legs of a lady patient after she had taken a single drop of laudanum. It has been observed that women are much more subject than men to the incidental irritating effects of opium. 1 1 Russell cites a case in which a single enema of laudanum was followed by an intense attack of urticaria. Brand records a case of a man in whom an erythematous rash of a whole limb followed a rubbing of the part with an opiated ammoniacal liniment. This man had previously suffered from generalised erythematous rashes after a second dose of opium and after hydrochlorate of morphia. It is a striking feature of opium and morphia eruptions that where they occur there is a remarkable susceptibility to the drug in whatever way it is MOEPHIA. 515 MORPHIA. Intense pruritus, with or without eruptive disturbance, may follow indifferently the ingestion or the hypodermatic ■introduction of this salt into the system. An exudative, erythematous eruption is the most frequent form of morphia eruption. Apolant reports a case of a man who, after taking twelve to fifteen drops of a weak solution of morphia, equivalent to about four drops of Magendie's solution, had an eruption of red wheal-like prominences on the hands and other por- tions of the body. The eyelids were swollen and the whole face cedematous. It was accompanied with intense burning and itching. Desquamation in large lamellae occurred five days later. The patient, who had been ignorant of the kind of medicine ordered, recognised it from having before had a similar experience. Scheby-Buch reports a case in which the smallest doses of morphine produced an urticarial eruption upon the face, chest, and arms, and sometimes over the whole body. Steinboemer records a vesicular eruption after one sixteenth grain of morphine. In the same patient one eighth grain of opium produced a similar eruption. Comanos reports a case of eruption from the hypodermic injection of o"02 morphia muriate. It consisted of an intense, uniformly diffused, scarlatinoid redness over the throat, breast, back, and left leg (the right was slightly reddened). Recovery took place in four days, with de- squamation of the epidermis. The same quantity, given in pill form, produced a similar scarlatiniform eruption over the entire body, accompanied with intense itching. Desquamation continued for several days. Three weeks later, inunctions of morphia were used three times daily for relief of sciatica. On the fifth day, after thirteen inunctions, in which 0*05 morphia was used, the leg became reddened, and over places of inunction there appeared small pustules and blisters. Then there appeared three furuncles over the buttocks, the redness used, and the eruptions will reeur again and again under the influence of the medicament. — T. C. P. 516 DE. MOKROW ON DEUG EEUPTIONS. extended upwards on the back, and terminated in the for- mation of a large carbuncle, attended with high fever. Brivois observed, after the injection of o"oi of hydro- chlorate of morphia, a generalised eruption of discrete papules like those of prurigo, accompanied by intense itch- ing. It was eight days before the papules disappeared. I myself have frequently observed an urticarial eruption after the hypodermic injection of morphia, which appeared indif- ferently after the use of small or large quantities. 1 Surroville reports a case in which multiple ulcerations were caused by the ingestion of morphia. The use of the drug in increasing doses from five to twenty-five centigrammes caused dryness of the throat, loss of appetite, constipation, &c, soon followed by multiple ulcerations, both superficial and deep, with sharp-cut edges in the buccal cavity and pharynx. The ulcerations promptly healed after suppres- sion of the drug. Again morphia was prescribed, and the ulcerations reappeared with more severity, accompanied by the same symptoms as before. Hypodermic injections of morphia are frequently followed by inflammation and dermic abscesses, which may give rise to indolent ulcers persisting for a long time without showing any disposition to heal. Two such cases have recently come under my observation ; in one, a chl orotic young woman, the ulcerations persisted for some months, and were finally healed up by strapping, with topical application of ung. iodoformi and internal use of potassio-tartrate of iron. It has been observed that injections carried deep down into the subcutaneous tissues are not nearly so apt to be followed by phlegmonous abscesses as when the injection is discharged directly underneath the skin. It is also a matter of observation that hypodermic injections of mor- phia may be used for a long time without causing any local disturbance, when suddenly inflammatory reaction will 1 Kirn ordered at midday a suppository containing ten centigrammes of the hydrochlorate, and next morning there was intense pruritus, with bullous erythema of the perinieum and scrotum and a general erythema. This patient had previously suffered from a generalised, erythema, followed by desquamation after a hypodermic injection. Mobius also observed a generalised erythema and urticaria following the use of a suppository. — T. C. P. MORPHIA. 517 appear, not only in recent punctures, but in those which were made two or three weeks previous. Daniel reports an aggravated case of tubercular ulcerations from hypodermic injections of morphia frequently repeated during a long period. The arms were a mass of sores from the wrists to the shoulders ; the legs in like condition from ankles to knees. The eruption was tubercular in form, many of the tubercles in a stage of ulceration, discharging a peculiar greyish matter, mixed more or less with blood and very offensive when allowed to remain for a time without cleans- ing the parts. The discharge was acrid in its properties, excoriating or scalding the surrounding parts painfully, leaving a wide-spread angry-looking surface which was especially marked on the patient's back and upper parts of the legs. Tests for Opium and Morphine. If morphine alone is detected in the urine, or meconic acid and morphine, it may be concluded that the alkaloid has been administered in form of some salt (sulphate, meconate, &c, as the case may be). If meconin can be detected in addition, opium may be assumed to have been administered. It is best to first prepare an acid extract of the urine by evaporating it to one fourth, adding four times its volume of alcohol containing two per cent, sulphuric acid, filtering after twenty-four hours, and then evaporating off the alcohol. The residuary liquid is filtered when cold. If this is shaken with two successive portions of benzin (about equal volumes), boiling at about 176 F., the benzin solution evaporated, and the residue treated with a few drops of colourless concentrated sulphuric acid, this will gradually assume a greenish tint, deepening to red in twenty-four hours, if meconin was present. If meconin has been found, it is advisable to test at once for morphine. For this purpose the remaining acid liquid is rendered alkaline, and then shaken immediately with an equal volume of warm amylic alcohol, twice in succession. The alcoholic solution is evaporated, and the residue tested as follows : 518 DR. MORROW .ON DRUG ERUPTIONS. A portion transferred to a watch-glass is treated with a few drops of dilated, hydrochloric acid, evaporated to dry- ness below 120° F., the residue dissolved in a few drops of water, and then a drop of highly dilute solution of ferric chloride added (free from acid). There will be developed a fine blue colour. A drop of nitric acid upon another por- tion of the residue will produce an orange or red colour, destroyed by sulphide of ammonium. A few drops of Froehde's reagent (concentrated sul- phuric acid containing, in each cubic centimetre, coi grm. of- molybdate of sodium or ammonium) brought in contact with even traces of morphine assume at once a magnificent violet colour, which soon turns green, brownish green, and yellow, becoming bluish violet after twenty-four hours. Treatment. — On account of the exceedingly evanescent character of the opium eruption, treatment is unnecessary. Bromide of potassium is said to prevent the irritant effects of this drug upon the skin. PHOSPHOBUS ACIDUM PHOSPHOBICUM. The stimulating effect of phosphorus upon the cutaneous circulation, producing flushings and other evidences of peri- pheric capillary expansion, is well known. More decided evidences of irritative action upon the skin occasionally follow its use. A bullous eruption has been sometimes observed. According to Farquharson and Ringer, purpura some- times occurs as a symptom of its toxic action, and is usually developed in connection with gastro-intestinal derangement, PHENACBTIN. The occurrence of an exanthem following the ingestion of this coal-tar derivative has been reported hy Valentin. An anaemic woman, who had taken bromide and antipyrin for headache without much result, was given six decigrammes of phenacetin on two successive evenings. This caused great heat in the face. Eight days later a dose of one gramme /was given at night, and two hours afterwards there was flushing of the face, an erythe- matous general exanthem, most marked on the arms and legs, and next morning a temperature of 38'6° C. The skin lesions were not larger than lentils, in part acuminate, and darker in the centre. There was no itching, and the rash disappeared on the following day. — T. C. P. BURGUNDY PITCH — TAR. 519 icter»us, &c. This observation has been confirmed in my own experience with the drug. Hasse reports a case of pemphigoid eruption which occurred in a young girl who had been taking phosphoric acid. It disappeared on cessation of the use of the medi- cine, and reappeared on its resumption. FIX BUBGUNDICA. The local effect of Burgundy pitch applied to the skin is that of a mild irritant. It may cause, after prolonged use, an inflammation of the skin of a vesicular or pustular character, and which is apt to be persistent. Trousseau observed that a Burgundy pitch plaster, having caused the local development of a great number of vesicles, sometimes occasions a general eczema, at first acute, which may afterward become chronic. Cazenave also alludes to its property of causing eczema- tous eruptions. 1 PIX LIQUIDA. TAE. The external application of tar may cause an erythema- tous, papular, vesicular, or pustular eruption. The tar acne, which so often develops in connection with the external use of tar, consists of small, hard, red nodules, which persist for a long time after the application of the irritating agent has ceased, usually requiring from three to four weeks for their complete involution. According to Hebra, the hair-follicles become inflamed and swollen so as to form papules of the size of hemp-seeds, or even as large as lentils. The eruption is readily distinguished from ordinary acne, in that a black tarry point always occupies the centre of each papule. Farquharson reports, as the 1 Kuehn observed an erythema papulatum follow the application of a pitch plaster.— T. C. P. PIMPINBLLA. Kaufmann reports a case of urticaria resulting from twenty-drop doses of tincture of pimpinella. A repetition of the drug evoked the eruption a second time. — T. C. F. 520 DE. MOEBOW ON DBUG ERUPTIONS. result of an application of Ung. Picis Liquidse to a patch of psoriasis, an intense inflammation of the sound skin over an area several inches in breadth. There was a greyish discolora- tion, indicating the formation of a slough, which accident was only averted by careful sedative treatment. The internal use of tar, says Anderson, occasionally pro- duces a copious red rash upon the skin, accompanied by fever, nausea, and other evidences of digestive derangement. Waldeck reports a case of an erythematous eruption, rubeo- loid and urticarial in character, which followed the use of this drug in the form of Gruyot's tar capsules. PLUMBUM PLUMBI ACETAS — PLUMBI CAKBONAS. The external application of the salts of lead in the form of solutions or ointments sometimes produces discolorations of the skin of a brownish or blackish character. Foucaud de l'Espagne reports the case of a lady who was ordered the acetate of lead as an eye-wash ; under the advice of another physician she was at the same time using sulphur baths for rheumatism. A black discoloration of the eyelids ensued, which spread over the surface of the cheek-bones, and was only removed after six days by washing the parts with infusions of herbs. The internal administration of the salts of lead may cause an erythematous rash of the skin. Snow, quoted by Piffard, reports a case where the body became spotted with petechise from the internal use of the carbonate of lead. 1 Crocker says, " In some people a very moderate external use will produce swelling, redness, heat, and pain, and sometimes itching ; vesicles and bull® may form In a few cases papules of tar acne may break down and ulcerate. "When absorption occurs from its vigorous inunction over a large surface, shivering, fever, nausea, vomiting, and diarrhoea may ensue, with olive-green urine, hlack vomit, and faeces." Quite a considerable literature has arisen with regard to eruptions occa- sioned amongst workers in tar distilleries, and the various products separated as naphtha, creasote oil, naphthaline, carbolic acid, anthracene, pitch, &c.— T. C. P. PODOPHYLLUM — BICHROMATE OP POTASSIUM. 521 PODOPHYLLUM PELTATUM. Workmen employed in pulverising podophyllum find it extremely irritating to the mucous surfaces with which it comes in contact, as well as to the skin. Winterburn states that workers in podophyllum peltatum suffer from a cutaneous irritation, affecting more particularly the scrotum and genital parts. According to Bentley, the topical application of an alco- holic solution of podophyllum will produce rubefacient and vesicant effects. POTASSII BICHEOMAS. The extensive use of bichromate of potassium as a mor- dant in the manufacture of woollen goods is a prolific cause of dermatitis. The irritant action of the bichromate is shown in the .production of eruptions of a papular and pustular character ,upon the hands, forearms, and exposed parts of the body. Deep ulcers and sloughs not infrequently occur, with ulcerations of the mucous surfaces and perforations of the septum nasi, constituting the so-called "chromic disease" of the dyers. Richardson reports five cases of eczematous eruptions in workmen who were employed in a manufacturing business where the bichromate was used in a watery solution of five or six, per cent. The first symptoms of irritation are heat, itching, and tingling felt in the ends and middle joints of the fingers, which soon become covered with irregular red patches, upon which numerous minute elevations are seen ■ clustered together. In the course of a day or two these enlarge into bead-sized vesicles. In a short time these clustered vesicles run together, forming large blisters, which rupture, causing the most acute pain and itching. At this stage pustules begin to form over the body, .mainly down the spine, neck, sides, arms, and ankles, accompanied with marked constitutional disturbance, as headache, fever, loss of appetite, &c. The eruption in some 522 DB. MOEBOW ON DEUG EKUPTIONS. cases presents, in addition to these cutaneous symptoms, the appearance of pityriasis rubra. Harrington records a number of cases of bichromate of potash poisoning, resulting from the manufacture and wear- ing of caps, gloves, and other articles of clothing dyed with this substance. One case was that of a strong healthy woman who worked in cloths used in making boys' caps. Her sym- ptoms were intense itching of the hands, scalp, face, neck, and body. These were followed by ulcerations of the neck, breasts, hands, and thighs. The ears were much swollen, and became, as she expressed it, " running sores." The ulcerations about the nails resulted in the loss of three nails from one hand and two from the other. Another case was that of a clergyman, sixty years of age, who wore a pair of brown woollen gloves. The der- matitis was limited to the parts covered by the gloves ; it began with slight redness and irritation, " at first in the form of pimples, but afterwards many of them ran together forming blisters." These resulted in large and deep ulcers, many of them requiring over a month to heal. Symptoms of poisoning were also observed in two boys from wearing suits of brown woollen cloth. In all of these cases chromium was found to be abundantly present in the offending articles of clothing. In large doses bichromate of potassium acts as an irri- tant poison, causing nausea, high temperature, sometimes suppression of urine and bloody stools. Few examples of cutaneous eruption are recorded from its internal use. Quite recently, an eruption caused by wearing a greyish- brown flannel shirt dyed with bichromate of potassium came under my observation. The patient presented him- self with an erythematous eruption surrounding the lower portion of the neck and covering the entire surface of the trunk and the arms, and extending over the buttocks and upper portion of the thighs. About the neck and over the shoulders the eruption was fiery red, and upon the erythematous base were observed a large number of minute papules. The eruption, which had appeared two or three days previously, was intensely itchy BICHEOMATB OF POTASSIUM. 523 Its exact limitation to the portions of the body covered by the under shirt naturally suggested the nature of the irritating cause. Chemical examination revealed the presence of chro- mium in the colouring matter with which the shirt was dyed. The eruption disappeared within a few days under the influence of a simple protective powder of oxide of zinc, bismuth, and starch. According to Burness and Mavor, it may produce a papu- lar eruption, which later assumes a pustular character. Hughes states that the most characteristic effects of this poison upon the skin are seen in papules, pustules, and ulcers ; the ulcers have hard bases and overhanging edges, are deep, and generally dry. 1 Guntz, as is well known, claims the most remarkable beneficial results from the use of bichromate of potassium as a substitute for mercury in the treatment of syphilis. Tests for Chrome Compounds. The only salt of chromium which has been administered internally is the bichromate of potassium. Yet chrome alum and other compounds are not infrequently used externally. If chromium is to be looked for in the urine, the follow- ing method may be recommended for its detection. Treat the urine with an excess of ammonia, heat it to boiling, replace the excess of ammonia if necessary ; when cold, saturate the liquid with chloroform and set it aside for forty-eight hours. Pour off the liquid from any sediment ; treat this with solution of soda, which will dissolve any chromic oxide present, and boil with an excess of brown peroxide of lead, whereby the chromic oxide is converted into chromic acid. 1 Delpech and Hillaivet established that the neutral chromate, and still more the bichromate, determines special lesions in workmen engaged in certain stages of the manufacture. Like arsenic, the powders produce rhinitis, peculiar and often severe ulcerations of the feet, hands, and scrotum, and papular and vesicular eruptions on other parts. Various animals exposed also suffer. Besides those engaged in the manufacture of the chromates, and dyers, it may be noted that photographers, electricians, &c, are liable to be afiected. — T. C. F. 524 DR. MORROW ON DRUG ERUPTIONS. Pour into a test-tube eight cubic centimetres of diluted and acidulated peroxide of hydrogen (commercial peroxide 5 volumes, water 24 volumes, hydrochloric acid 1 volume), pour upon it one half cubic centimetre of ether, and then add a few drops of the liquid, which should contain the chromic acid. If the latter was present, the upper portion of the aqueous peroxide layer will turn blue. On reversing the tube a few times without shaking, the ether will dissolve out the peroxide of hydrogen, and also assume a blue or bluish colour. POTASSII CHLOBAS. Although the internal use of the chlorate of potassium may cause irritant effects upon internal organs, especially the kidneys, it is not generally accredited with the property of producing cutaneous disturbances. The only references which I have found in medical literature relating to such incidental effects are the following. Wegscheider reports, in connection with other toxic sym- ptoms of the drug, the development of an eruption of red; non-elevated spots which became momentarily somewhat paler on pressure. They first appeared upon the arms and forehead, and spread, in the course of the following three days, over the entire body, becoming larger and of a copper- red colour. In Stel wagon's case, the patient, a syphilitic, was ordered tablets, each containing five grains of potassium chlorate — several to be taken daily. Four days later he returned with a " fiery erythematous and papular eruption over the neck and trunk, especially well marked over the upper part of the back." The tablets were not renewed, and the eruption, which was regarded as erythema multiforme, disappeared in two days. 1 Six weeks later the patient was again ordered the tablets, and after using them for three days, an eruption, the same in 1 Wohlgemuth, after 150 grains had been administered over eight days, noted purpura on the legs and albuminuria. Brouardel and Shote (quoted by Crocker) " noted bluish spots on the skin, sometimes a general cyanosis and sometimes an icteric tint, where poisonous doses of chlorate of potassium had been given." — T. C. P. RHUS. 525 character as before, appeared ; the trunk and neck were involved, and also several slightly raised erythematous spots were seen upon the legs. The eruption disappeared within forty-eight hours after discontinuing the use of the tablets. Twice again, at the suggestion of S., who was desirous of testing the relation of the eruption to the drug, the patient took the tablets, and each time a similar eruption was' deve- loped. RHUS TOXICODENDRON RHUS VENENATA RHUS VERN1X. 1 The irritating effect of rhus upon the skin depends largely upon individual susceptibility. "While many persons are BESET. Jacob attributed an urticarial eruption to this agency. A woman, aged 36, took about as much, powdered resin as two walnuts for the relief of diarrbcea. Next day her face began to swell, and a papular eruption of urticarial nature appeared on the chest and arms. BHUBAEB. Kuehn recorded a case of a generalised and desquamative recurrent scarlatiniform exanthem following the ingestion of rhubarb, ipecacuanha, &c, in the same individual. Groldenberg saw an instance in the case of a man aged 64. The eruption occupied the two cheeks, and was formed of reddish-brown pustules, of unequal dimensions, reposing on an infiltrated base, and forming in certain points, by their union, tumours, riddled with orifices and covered with thick crusts, and a similar eruption occupying the back of the two hands, reproducing itself on three different occasions after the administration of rhubarb. It was at first attributed to salicylate of soda, of which the patient made use, but its reappearance on several occasions after the employment of rhubarb did not permit any doubt of its real origin. Litten, of Berlin, also recorded a case in a man of 45 some hours 'after taking rhubarb. There was rigor, fever, limb pain, and a visible papulo-pustular eruption generalised all over body and scalp and mucous -membranes (mouth, pharynx, eyelids). After the development of the erup- tion all general symptoms went. The eruption was composed of hBemor- rhagic taches of various forms, then pemphigoid pustules, confluent in certain places, and presenting then the aspect of foliaceous pemphigus. The lips were enormously swollen, were covered with pustules and bloody crusts. The tongue was affected. Many recrudescences and profuse uretrorrhagia , occurred. General state was nevertheless excellent. Twice before a similar eruption resulted after rhubarb. Litten, however, after cure, again gave infusion of rhubarb from another chemist, in case impurity was in the first. The same evening rigors were experienced, and a similar eruption occurred. — T. C. F. 1 J. C. White gives the three species of plants growing abundantly in the 526 DR. MORROW ON DRUG ERUPTIONS. entirely insusceptible to its toxic action, others are so ex- quisitively sensitive that mere exposure to the volatile principle of the plant, without actual contact, is sufficient to cause the most violent cutaneous irritation. Curious examples of the remarkable potency of the poisonous emanations are vouched for on good authority, such as poisoning from walking through the damp grass in the vicinity of the plants, passing in the direct current of the wind blowing from them, sleeping in a chamber in which fresh ivy has been hung, exposure to the smoke of burning wood around which the ivy had clung, &c. After exposure there is a period of incubation, varying from several hours to three or four days or longer, before the phenomena of cutaneous irritation begin to be manifest. The eruption is usually of an eczematous type. It is characterised by redness, sensations of burning and itching, and the appearance upon the erythematous surface of innumerable vesicles. The vesicles spread rapidlyfrom the starting-point, if it be the fingers, along the dorsum of the hands, the wrists, and upwards along the arm. If the face be first affected, the inflammation rapidly involves the neck, and extends down the trunk towards the genitals. The vesicles often run together, forming blebs of con- siderable size ; these may be ruptured by scratching or otherwise, and expose large denuded surfaces, which soon become covered with thin crusts and scales. The contents of the vesicles are less limpid and transparent than in ordinary vesicles ; sometimes, but rarely, they become purulent, absorption slowly taking place, leaving a slight pigmentation. The oedema and swelling of the integument assume an ery- sipelatous character, and occasion much disfigurement, espe- cially when affecting the face. The rapid extension of the disease may be due to direct transfer of the irritating agent by the nails in scratching, or a systemic effect consecutive to absorption. The swelling of the glands which is so fre- quently observed in connection with rhus poisoning gives United States as B. toxicodendron, or the poison ivy ; R. venenata (vemix of LinnEeus), or poison sumach ; and R. diversiloba, or poison oak. A full account of rhus poisoning will be found in Prof. White's work, ' Dermatitis venenata.' Maisch isolated a volatile acid. — T. C. F. RHUS. 527 colour to the probability of it being a phenomenon of absorp- tion. Lavini states that he applied two drops of the juice of rhus to the first phalanx of his index finger, leaving it on only two minutes, which produced, in about one hour, two black spots. Twenty-five days later he experienced a great burning in the mouth and throat, with rapid swelling of the left cheek, the upper lips, and eyelids. The night following the forearms swelled to twice their natural size, with a coria- ceous skin, insupportable itching, &c. Taylor brought before the New York Dermatological Society a patient who had had two attacks of an eruption pre- senting the characters of a dermatitis exfoliativa, from handling the twigs and leaves of the rhus venenata. The eruption commenced on his wrists and spread over the entire body ; there was an abundant desquamation, and the lunulas of the nails were affected, being wrinkled and thicker than natural. The second attack was experimentally produced six months later by rubbing the dried leaves over the left hand. Four days later he complained of itching and burning over the left deltoid muscle, the thighs, and genital organs. The conjunctivas soon became reddened, and the entire skin was covered with large red blotches, which soon became diffuse, resembling a scarlatinal exanthem. The exfoliation was much slighter than in the first attack. White observed in a pregnant female an eruption of papules and pustules upon the abdomen, arms, and dorsal surfaces of the hands from ivy poisoning. One of the pus- tules on the left arm attained the proportions of a well- developed boil. Confinement took place about the time the disease ' was disappearing. On the sixth or seventh day after birth there was observed on the child's belly an eruption identical with that from which the mother suffered. White regards this as an instance of the communication of a maternal affection to the child in utero. 1 1 Brown, of Pirbright, Surrey, called attention, in 1889, to the fact that the B. toxicodendron was becoming more widely distributed in English gardens. I have heard of several cases of rhus poisoning in the British Isles. Ehus poisoning is mentioned in several of the older books on botany and allied subjects. Prichard says there are eighty-five species of the genus Rhus, all more or less poisonous. — T. C. P. 528 DR. MORROW ON DRUG ERUPTIONS. Hubbard observed in a patient a vesicular eruption cover- ing the whole body, attended with severe burning and itching, from eating a root of rhus which he had mistaken for sarsaparilla. The eruption differed from that produced by external contact only in the size of the vesicles, which were smaller. The same character of cutaneous disturbance may follow the internal use of rhus in medicinal doses. Piffard reports a case of a female patient for whom he had ordered two-drop doses of the tincture of rhus to be taken morning and evening. On the third day he was called to treat the patient for erysipelas of, the face, which presented all the characteristics of a rhus eruption. Other observers speak of erysipelatous inflammations, pustules, boils, &c, resulting from the ingestion of rhus in small doses. The rhus vernix, which grows in Japan, seems to be en- dowed with more marked irritating properties than either of the other varieties. A number of cases of erythematous and vesicular eruptions have been observed from the handling of Chinese lacquer-work, in the varnishing of which this variety of rhus is used. In a personal communication from Dr. H. S. Allen, of Seoul, Korea, he states that natives as well as foreigners are often attacked with what is termed in that country " varnish poisoning." It comes on after contact with furniture or other articles recently varnished. Some persons cannot pass a furniture shop where articles are being varnished without being poisoned. His personal experience is thus related : — " My first eruption occurred in Nanking. The dermatitis first developed over my left eye, spreading to my forehead and nose ; it itched and burned, causing great discomfort and inconvenience. Being ignorant of the effect of the Chinese varnish, I diagnosed the trouble as herpes zoster frontalis. The next attack was in Shanghai, after receiving a new chair from a Chinese cabinet-maker. The skin of the forehead became hot and itched intolerably, and was soon covered by an eruption of minute vesicles on a raised base. The swelling increased until the eyes were nearly closed. It RHUS. 529 was first diagnosed as a facial erysipelas, but consultation being called, it was pronounced ' varnish, poisoning/ " 1 Treatment. — The inflammatory changes in the skin met with in rhus poisoning are essentially the same as those determined by other irritating agencies, and the general principles of treatment indicated in rhus dermatitis will be found applicable to other drug eruptions of an eczematous type. The various therapeutic measures which have been re- commended may therefore be considered somewhat in detail. It is well to remember that in all these cases the inflamma- tion is self -limited, with a tendency to spontaneous recovery ; the principles of rational treatment are to relieve the sub- jective sensations of burning and itching, and to modify the inflammatory action. With a view of circumscribing the spread of the eruption, the patient should be cautioned against bringing the hands in contact with other parts of the body ; especially should he be enjoined against handling the genital parts, as the integument of this region is peculiarly susceptible to the irritant action of the rhus. It is a matter of common observation that the genital parts of the male are much more frequently the seat of the eruption than the corre- sponding region in the female, and the explanation is found . in the direct transfer of the irritating agent by the fingers in handling the parts during the act of micturition, in dressing, &c. The treatment of the acute stage of the eruption should be essentially soothing and protective. For this purpose, dusting powders and sedative or mildly astringent lotions should be used. The following lotion may be employed : — R Sodii Hypo- sulphites, gj ; Glycerinae, gss ; Aq., ad 5™j- ^. Apply with compresses dipped in the solution and frequently renewed. A strong solution of the sulphite of sodium may 1 Junker says that almost all the workers in lacquer suffer repeatedly from dermatitis. It may be accompanied by severe headache, dizziness, fever, coated tongue, sickness, irregular action of the bowels, congestion of the conjunctivae and of the nasal mucous membrane. Those who sleep or live in a room in which freshly lacquered goods are drying may become affected. The lacquer is made from the inspissated sap of the stem and leaves of B. vernicifera. — T. C. F. 34 530 DR. MORROW ON DRUG ERUPTIONS. be used with benefit. In cases where the continuous appli- cation of a lotion is impracticable, freely dusting the surface with an absorbent powder is to be recommended. Pear's fuller's-earth, which is perfectly bland and unirri- tating, may be employed, or the following combination : — ft Pulv. Zinci Oxidi, 3ij ; Pulv. Bismuthi Subnitratis, 3] ; Pulv. Amyli, 3V. M. It is important that the affected surface should be kept copiously covered with the powder ; an occasional sprinkling does little good. If there is much burning heat present, a little powdered camphor (353 to the gj) may be added. When the more acute eruptive features have begun to subside, a mild soothing ointment should be employed. For this purpose nothing is better or more universally applicable than the ordinary benzoated zinc ointment. An- other very excellent dressing in this stage of the disease is the Lassar paste : ft Pulv. Zinci Ox., Pulv. Amyli, aa 3ij ; Vaselini, 3iv. M. The good effects of the same treatment will be found to vary in different patients. There is a great difference in the susceptibility of different individuals to irritant action, and the difference in susceptibility is perhaps equally marked in relation to the influence of medication. It is not possible to here enumerate the entire list of remedies which have been recommended in the treatment of rhus poisoning, for their name is legion. To give only a few which are claimed to possess a remarkable efficacy in subduing the symptoms : lime water, carron oil, alum curd, a saturated solution of bicarbonate of sodium, a strong solution of chlorate of potassium, a solution of sulphate of zinc (gss to the pint), a solution of carbolic acid (grs. ij — iv to the gj), a weak solution of sulphate of copper, dilute lead water, &c. Compresses to be wet with these lotions, and applied every hour or two through the day. Dr. White, of Boston, and others highly praise the efficacy of the ordinary black wash. Dr. Brown, U.S.N., claims that bromine (ten to twenty drops to the ounce of olive oil or cosmoline) is a specific. To turn now to the vegetable materia medica : a decoc- tion of white oak bark ; a decoction of the bark or leaves ■SANTONINS. 531 of the elder, an infusion of the sweet fern, the tincture or fluid extract of serpentaria, lobelia, sanguinaria, infusion of the bark of the red sassafras, with sassafras tea ad libitum internally, have all been highly spoken of. Probably the most efficient of the vegetable remedies is the grindelia robusta, which may be used in the form of the fluid extract, diluted in ten to thirty parts of water. Dr. Hyde speaks enthusiastically of an ointment made by incorporating a decoction of the inner bark of the American spice bash (Benzoin odoriferus) with cold cream. Bella- donna, the green vegetable bruised and mixed with cream, or in the form of the officinal ointment, has also been recommended. Dr. Bdson highly extols the virtues of gelsemium in the treatment of rhus poisoning. His formula is — ft Acidi Carbolici, 33s ; PI. Ext. Gelsemii, 3ij ; Glycerini, 3ssj Aq. ad fry. M. Cloths to be moistened with this lotion, and applied to the affected parts. This, he claims, with the internal administration of the fluid extract of gel- semium every three hours, effectually relieves the burning and itching, and the eruption speedily disappears. Dr. White, of New York, recommends the following formula : — ft Acidi Carbolici, nixx ; glycerite of cocaine (4 per cent.), 3ij ; vaseline, 5j- M. ; or ft Acidi Carbolici, 3ss ; glycerite of cocaine (4 per cent.), 3iv ; Aq. Laurocerasi, 3j ; Aq. Rosse, ^ij. M. Either ointment or lotion to be applied several times daily. The plan of treatment found most serviceable in China for rhus dermatitis is, according to Dr. Allen, the constant bathing of the affected surfaces with an infusion made from freshly cut shavings of camphor wood. The officinal preparations of camphor were not found so serviceable. SANTONINUM SODII SANTONAS. Sieveking reports the occurrence of an eruption in a child after taking three grains of santonine. A wheal first appeared on the nose, and later there appeared an urticarial eruption over the entire surface of the body. A second dose of three grains promptly reproduced a general urticaria, attended with so much oedema as to render the child 532 DB. MORROW ON DRUG ERUPTIONS. unrecognisable. After a warm bath the eruption disap- peared in the course of an hour or two. Hubert observed in a number of patients who had been taking from ten to twenty centigrams of santonate of soda an eruption characterised by a large number of pin-head sized vesicles situated upon the trunk and limbs, but sparing the face. The vesicles never became confluent ; they gradually shrivelled and disappeared, giving place to a slight epidermic exfoliation. S1NAPIS. The external application of mustard causes sensation of itching, burning, and violent smarting, and, if the applica- tion be long continued, vesication and even ulceration may result. According to Dierbach, pustules and violent erysipelatous inflammation may follow. Rayer observed, towards the close of the cholera epidemic in 1832, in a large number of patients, erythematous inflammations which lasted several weeks, produced by cataplasms of farine de moutarde. STBAMONIUM. The demonstrated identity of daturia With atropia, the active principle of belladonna, would lead us to infer a similarity of action upon the skin. In the property of producing cutaneous disturbances, stramonium seems to occupy a position intermediate between belladonna and hyoscyamus, the two drugs with which it has such close botanical affinities. The most common form of eruptive disturbance from the internal administration of stramonium is erythematous. The eruption is scarlatinoid in character, the redness bright and vivid, and attended with a sense of burning and itching. Roth reports a case of stramonium poisoning in which the face and body were swollen, as if dropsical, and covered with a scarlatiniform rash. Liegey records a case of generalised scarlatiniform erup- tion, with pronounced angina, from the use of this drug. SULPHUR. 533 Meigs observed from the use of stramonium hundreds of small brilliant petechise on the face, neck, and breast of a patient, many of which had a stellate form. An erysipela- toid inflammation has also been observed to follow the use of this drug. SULPHUE. Sulphur exerts a stimulating influence on the skin. Strong applications cause irritation, characterised by red- ness, papules, confluent and painful vesicles. An artificial ^eczema is a common result of the application of strong sulphur ointment. The simple contact of the vapour in fumigations may produce a similar effect. Bayer says that he has often seen persons attacked with vesicular or papular eruptions after the employment of sulphur vapour baths. According to Bazin, the sulphuret of potassium or sodium dissolved in water determines an intense irritation of the skin, which may be extreme if the strength of the sulphur be considerable, or the temperature of the bath elevated. StTLPHONAl. Engelmann reports the case of a woman, forty years old, a sufferer from metritis and dysmenorrhcea, who had been accustomed to taking, on account of insomnia, five tenths to one gramme (l§ to 15 grains) of chloral without evil effects. Sulphonal in two-gramme doses (30 grains) failed to produce sleep, but was followed by a diffuse scarlet eruption upon the outer side of both breasts. The eruption spread symmetrically and disappeared on the third day. It was attended by intense itching. The symmetrical arrange- ment suggested a central disturbance of the vaso-motor system. Merkel observed a symmetrical eruption of small scarlet macules begin- ning in the axillary and inguinal folds, and spreading upon the outer surface of the shoulder and arm and on the thigh, the macules running together and forming large red patches. The eruption faded slowly, and ended by desquamation. Schotten records a case characterised by nervine troubles and a morbilli- form eruption following the employment of sulphonal in large doses. Leloir mentions an eruption due to sulphonal constituted by a generalised macular erythema, localised chiefly on the thorax and flanks, and simulating a syphilitic roseola. Lastly, Bresslauer observed in lunatics after prolonged sulphonal treat- ment great constipation, dark brown urine, slow, or in some cases rapid but feeble pulse, purpuric patches on the limbs, and great prostration. — T. C. ¥• 534 DE. MORROW ON DRUG ERUPTIONS. He observed as a result of four or five frictions over the lumbar region of four grammes of sulphuret of potassium to thirty grammes of water, a violent inflammation, characterised by pustules, dermic abscesses, and veritable phlegmons. Baudot states that, under the influence of sulphur lotions and ointments, there results an irritation which is manifested by an active fluxion, quickly followed by a crop of very minute confluent vesicles, which are distended with a puru- lent or sero-purulent fluid, and surrounded by an inflamma- tory areola, two or three times the diameter of the vesicles ; this eruption is quite painful. According to Trousseau, the critical fluxion to the skin, ' known in technical language as la poussee, is a familiar phenomenon in patients who use thermal sulphur baths. It is manifested by small papules, and often a painful, conflu- ent vesicular eruption. The internal use of sulphur in medicinal doses often produces a dark coloration and much irritation of the skin, with eruptions of an eczematous character. Phillips has observed a red, papular eruption from the internal use of sulphur, and also, occasionally, boils and carbuncles. The waters of Harrogate, Bareges, Aix-la-Chapelle, &c, have been known to produce such effects. De Schweinitz reports a case of scarlatinal rash which covered almost the entire surface of the body, especially well marked upon the face, chest, and neck, supposed to be due to the free use of flowers of sulphur in a gargle. It was observed that the exanthem grew worse after each employment of the gargle. TANACEXUM TANSY. The only instance of eruptive disturbance from the in- ternal use of tansy found on record is an observation of Porter. He observed a varioliform eruption in a young woman produced by the ingestion of one and a half ounces of oil of tansy, taken for the purpose of abortion. THAPSIA — TURPENTINE. 535 THAPSIA. The application of this resin to the skin in the form of a plaster produces a rubefaction, accompanied by a very intense miliary eruption, analogous to that caused by croton oil. 1 Trousseau states that the eruption produced by thapsia differs from that produced by croton oil in the following points : — i, in its uniformity and regularity, all the pustules being alike ; 2, in the large number of pus- tules ; and 3, in the rapidity with which pus appears in the vesicles. According to Tournadre, the redness and swelling pro- duced by thapsia may be mistaken for erysipelas. 2 I have seen a pustular eruption on the face from the application of a thapsia plaster on the chest for the relief of bronchial irritation. TURPENTINE — OL. TEEEBINTHINE! TEEEBENE . The external application of turpentine causes irritation, manifested by sensations of burning and smarting, redness, vesicles, blisters, and other inflammatory changes. The vapours of turpentine may also produce a burning, itching, erythematous eruption. The dermatitis caused by oil of turpentine is often of an obstinate character, and may per- sist long after the cause which occasioned it has been withdrawn. It proves very intractable to treatment. 8 The internal use of turpentine in medicinal doses may also cause eruptive disturbances of different degrees of 1 The gatherers of this herb, and workmen employed in making the extract, are liable to dermatitis. J. C. White states that " if the action of 'the resin is prolonged the eruption becomes confluent, and leaves a suppu- rating ulcerating surface, with subsequent scars resembling those of small- pox."— T.C. P. 2 The title of this thesis may be mentioned : " Des eruptions de la face consecutive a. l'application des emplatres de Thapsia sur le devant de la ■-Poitrine."— T. C. F. 3 BurtzefE and Morel-Lavallee describe more or less generalised eruptions following local frictions with terebinthinate preparations. — T. C. F. 536 DE. MORROW ON DRUG ERUPTIONS. severity. The most common form is an intense erythema of vinous red hue, invading by preference the face and upper portion of the trunk. It may be accompanied by a profuse eruption of minute papules which often develop into vesicles, and then into pustules presenting a distinctly eczematous type. Brochin reports a number of cases in which an erythematous or urticarial eruption was observed after the ingestion of turpentine. Berenguier reports a case in which large doses of the drug produced a scarlatina-like eruption, spreading over the face and upper part of the body in irregular patches ; numerous minute acuminate papules covered the surfaces. The next day, the oil having been continued, the eruption spread to the lower limbs. 1 As in the case of dermatitis from the external application of turpentine, the eruptions from its internal use manifest the character of persistency. Even after the eruption has disappeared, and desquamation has taken place, the subjec- tive symptoms of itching and irritation may continue for an indefinite period. Terebene, one of the derivatives of turpentine, likewise possesses the property of producing cutaneous irritation. Garland reports the case of a patient, aged sixty years, who took five-minim doses four times a day for chronic bron- chitis. After taking six doses he had to desist on account of a profuse bright red papular rash, intensely itching, making its appearance first on the left hand, then on the ankles, extending up the legs to the knees. The patient had previously displayed an idiosyncrasy against turpentine. A turpentine liniment applied to a sprained wrist caused a 1 Ernst Feibes observed a case in which, on the ninth day after the administration of 10 - 8 grammes of essence of turpentine in eight days for a gonorrhoea, there was intense pruritus and the evolution of acuminate, bright red papules over all the surface except the head and face, but mostly on the lower part of the trunk and legs. The rash disappeared three days after discontinuance of the remedy, but reappeared on the resumption of the drug in a more patchy oedematous form. Gaucher records a case of generalised erythema with swelling of the face, extremities, and buccal mucous membrane. The rash appeared on the third day after taking ten to, twelve capsules a day. Suffocative feelings were experienced. The erythema lasted four to five days. — T. C. P. VERATRIA AND VERATRUM VIRIDE. 537 rash identical with that above described, and a swollen condition of the other arm. 1 The presence of oil of turpentine, or of terpenes or camphenes in general, is chiefly recognised by the peculiar odour of the urine. It is often possible to distinguish the source in this manner. VEEATEIA AND VERATEUM VIEIDE. Although veratria is commercially derived from another source than veratrum viride, it will be convenient to con- sider together their irritant action upon the skin. Veratria, which is rarely used internally, causes, when applied to the skin in the strength of the ordinary oint- ment, sensations of tingling, smarting, and increased heat, not only at the point of contact, but on remote parts of the body. When applied in a concentrated form it is highly irritant, producing erythema, and even pustular and petechial eruptions. Veratrum viride is also irritant to the skin, its local application causing redness and burning. The internal use of veratrum viride sometimes occasions an erythematous condition of the skin attended with sen- sations of pain. Forcke, quoted by Lewin, observed a pustular eruption on the face, most marked around the mouth. The use of the drug hypodermatically is sometimes fol- lowed by painful swellings around the point of puncture, with extensive erythema. Bulenburg witnessed the forma- tion of an abscess in one case. 1 Lascelles Scott had a similar experience with terebene. — T. C. F. VALBEIAN. J. P. Prank describes the occurrence of an attack of urticaria invariably following the ingestion of eau de Seltz. — T. C. P. GENERAL BIBLIOGRAPHY. Alley. Observations on the Hydrargyria, or that Peculiar Eruptive Dis- ease arising from the Exhibition of Mercury. Dublin, 1804 and 1810. Almebas. Sur les Bash ou Exanthemes scarlatiniformes. These de Paris, 1862. Atkinson, I. E. Medicinal Eruptions : a course of three lectures. Mary, land Med. Journ., Baltimore, 1880-1, vii, pp. 313, 337, 361, 385, 409. Baudot, E. Traite des Affections de la Peau. Paris, 1869. Bazin, P. Lecons theo. et clin. sur les Affections cutan. artificielles. Paris, 1862. Beheend, Gr. Lehrbuch der Hautkrankheiten, 2nd ed., Berlin, 1883 pp. 287 — 302. Beheend, G. TTeber ein diffus — Entziindliches Opium-Exanthem nebst Bemerkungen fiber die Pathogenese der Arzneiausschlage. Berl. klin. Wochenschr., 1879, Nos. 42, 43. Beheend, Gr. Zur allgemeinen Diagnostik der Arznei-Ausschlage. Ber- liner klinische Wochenschrift, 1879, No. 47. Bell, Benj. Treatise on G-on. Vir. and Lues Ven. London, 1796, vol. ii. Bebengttieb. Des Eruptions provoquees par l'ingestion des Medicaments. These de Paris, 1874. Bebgebon et Lemaitee. De l'^limination des medicaments par la sueur, et de quelques-unes de ses alterations pathologiques. Archiv. ge"n. de Med., Aout, 1864. Binet. Etude sur la sueur et la salive dans leur rapport avec l'elimination. These de Paris, 1884, No. 139. Bofveeet. Des Sueurs morbides. Th. d'agreg., Paris, 1880. Beooke, H. Gr. On Behrend's Division of Drug Rashes into Specific and Dynamic Groups. Brit. Journ. Derm., Loud., 1890, ii, 313 — 318, and Monatsh. f. prakt. Dermat., Hamb., 1890, xi, 193 — 199. Betjn. Des accidents importables a l'emploi chirurgical des antiseptiques. These agreg., Paris, 1886. Deschahps, J. P. Contribution a l'e'tude des eruptions me'dicamenteuses. These de Paris, 1878. BIBLIOGRAPHY. 539 Devebgie. Traite pratique des Maladies de la Peau. Paris, 1857. Discussion. Intern. Med. Congress, Berlin, 1890. Fabquhaeson, K. Various Forms of Skin Irritations due to the Adminis- tration of Drugs. British Med. Journal, Feb. 15th and 22nd, 1879. Fox, T. C. Contribution to the Study of Drug Eruptions. Brit. Journ. Derm., Lond., 1890, ii, 327 — 336, and Monatsh. f. prakt. Dermat., Hamb., 1890, xi, 245 — 256. Gauchee. Des Eruptions me'dicamenteuses. Bull. Me"d. Paris, 1891, v. 339 — 342. Art. Erytheme, Diet. Encycloped. Geneesk. Courant. Amsterdam, 1882, xxxvi, No. 4. Exanthemata ten gevolge van genees middeln. Gebne, Paui. Des Eruptions cutanees cause"es par les Medicaments. Le Concours Medical, March 17th, 1883. Guebabd. Des Eruptions medicamenteuses pathogenetiques. These de Paris, 1874. Imbebt-Goubbeybe. De Taction de l'Arsenic sur la Peau. Paris, 187 1. Kobneb, H. Ueber Arznei-Exantheme, insbesondere iiber Chinin-Exan- them. Berl. med. "Wochenschr., 1877, No. 22. Lessee, E. Beitrage zur Lehre von den Arzneiexanthemen. Deutsche med. Wochenschr., Leipzig, 1888, xiv, 264 — 267. Lewin, L. The Incidental Effects of Drugs. New York, 1882. Lobby. Tractatus de Morbis Cutaneis. Parisiis, 1777. McLaughlin, T. N. Drug Eruptions. Med. Standard, Chicago, 1890, viii, 61. Montegbe. Bibliotheque medicale, t. xlv, 1814. Mobel-Lavallee. Eiude gen. sur les Roseoles. Gaz. des Hop., Aout, 1887. Mobbow, P. A. On Drug Exanthemata, &c. New York Med. Journal, March, 1880. Pifbabd, H. G. Materia Medica and Therapeutics of the Skin. New York, 1 88 1. Eateb. Traite theor. et prat, des Maladies de la Peau. Paris, 1828. Ricobd. Bull. gen. de The"rapeutique, t. xxii, 1842. Skxbnevski, A. Drug Exanthems. Med. Obozr. Mosk., 1888, xxix, 469—474. Thibiebge. Le90n sur les Eruptions medicamenteuses. Ann. de Med. 1892. Teousseau, A. Sudoral Exanthemata, in Lectures on Clin. Med. Van Hablingen. Medicinal Eruptions. Archives of Dermatology, Oct., 1880 (copious bibliography and recital of many interesting cases). Weiss. Des Exanthemes toxiques. Wien. med. Presse, xxiii, 1884. White, J. C. Dermatitis "Venenata : an Account of the Action of External Irritants upon the Skin. Boston, 1887. Wing, E. Dermatitis medicamentosa. Chicago M. J. and Exam., 1888, lvii, 3. Zeissl. Ueber Arzneiexantheme. Wiener med. Wochenschrift, 1880, xxx, p. 768. 540 BIBLIOGEAPHT. ACIDUM BENZOICUM— SODII BENZOAS— FRIAR'S BALSAM. Pox, Tilbuby. The Lancet. London, 1874, vol. ii, p. 195 (Friar's Balsam). Hampeln. Petersburger med. Wooh., No. 3, and Berlin, klin. Wochen., No. 12, 1881. Rohe, G. Maryland Med. Journal, 1885, June 15th, p. 91. Vanini. Giorno Ital. Mallat. Ven. e del Pelle, 1885, iv, p. 193. ACIDUM BOEACICUM— SODII BORAS. Bbuzelius. Cin. Lan. and Clinic (Schmidt's Jahrb.), July 21st, 1883, and Hygeia, 1882. Coelett, W. T. Journ. Amer. Med. Assoc, Dec. 27th, 1890. Febe, C, et Lamt, H. N. Iconog. de la SalpStriere. Paris, 1889, ii, 305, pl.i. Gowees. The Lancet. London, Sept. 24th, 1881. Johnson. Nordisk Medicin. Arkiv, 1885, Band xvii, No. 9. Liveing. Handbook of Skin Diseases, 5th ed., p. 424. Modadewko. St. Petersburg Medicin. Wochenschrift. Molodenkow of Moscow (quoted Lancet, May 6th, 1882). Stille and Maisch. The National Dispensatory. Philad., 1880, p. 1309. Welch, Geo. T. N. T. Med. Record, Nov. 3rd, 1888, p. 532. ACIDUM CARBOLICUM. Ball and Le Neve Postee. Lancet, June, 1885 (warts). Beown. Brit. Med. Journal, Oct. 10th, 1885, p. 694. Bbttn, M. These de Paris, 1886. 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Wochensch., 1888 ; and Deutsche med. Woch., xxxv, 709, Jan. 31st, 1889. FiJEST. Internat. klin. Eundsch., Nos. 48, 49, 1891. Hutchinson, Jonathan. Archiv. Surg., p. 177, 1889. BIBLIOGRAPHY. 565 LbIiOIE. Inter. Med. Congr., Berlin (discussion on drug eruptions). Mebkel, Cr. Munch, med. Woch., 1889, No. 26, 449. Schottbn. Therap. Monats., 1890, iv, 187, and Dec, 1888. SULPHUR. Baudot. Traite des Affections de la Peau, 1869, p. 157. Bazin. Lee. theor. et clin. sur les Affect, cut. artif., 1862, p. no. De Schweinitz. Philadelphia Med. Times, Jan. 27th, 1883. Fox. The Lancet. London, 1867, i, p. 443. Bates. Traite theor. et prat, des Mai. de la Peau, 1835, p. 262. Tbotjsseau. A Treatise on Therapeutics, 1880, vol. iii, p. 290. TANACETUM. Poeteb. New York Medical Journal, Oct. 15th, 1881. THAPSIA. BtANCHET, C. Pharmaceut. Journ., 1880 (from Montpellier Thesis). Mabtin. Bull. gen. de Therapeutique, 1868, p. 170. Touenadbe. These de Paris, 1879, No. 224, 4to, p. 48. Tbotjsseau. Treatise on Therapeutics, New York, 1880, vol. i, p. 272. TURPENTINE— TEREBBNB. Beeengtjieb. These de Paris, 1874. Bbochin. Gazette des H6pitaux, Feb., 1879, p. 99. BtJBTZEFE. Reported in Brit. Journ. Derm., 1891, p. 397. Feibes, Ebnst. Brit. Journ. Derm., 1889, No. 7. GrABliAND. The Lancet. London, May 22nd, 1886, p. 1005 (terebene). Gatjchee. Maladies de la Peau, p. 253. Mobel-Lavaxlee. Ann. de Derm, et de Syph., 1891. VALERIAN. Feank, J. P. Epitom, vol. iii, p. 11. VERATRIA— VERATRUM VIRIDE. Eulenbueg. Die Hypodermat. Injectionen. Berlin, 1875, p. 278. Fobcke. Physiolog. u. Therapeut. Untersuch. iiber d. Veratrin. Hanover, 1837. Ringee. Handbook of Therapeutics. New York, 5th ed., p. 378. INDEX. Acetanilide (antifebrin), 415, 542 Acidum arseniosum, 425 benzoicum, 400, 540 boracicum, 401, 402, 540 carbolicum, 403, 540 chrysophanicum, 405, 540 nitricum, 408, 540 phosphoricum, 518, 563 picricum, 408, 541 pyrogallicum, 408, 541 salicylicum, 409, 541 tannicum, 413, 541 Aconitum, 413, 541 Alcohol, 414, 541 Ammonii bromidum, 440 iodidum, 486 piciatum, 541 Amygdala amara, 414, 542] Anacardium, 414, 542 Aniline, 415, 542 Antifebrin, 542 Antimonium, 416, 417, 542 Antipyrin, 417, 543 Araroba, 405 Argenti nitras, 42 1, 544 Arnica, 422, 544 Arsenicum, 425, 545 Atropia, 437, 547 Ava or Kava, 436 Balsam, Friar's, 540 Balsamum Peruvianum, 436, 547 Belladonna, 437, 547 Benzoate of soda, 400, 540 Benzoin, 400 Benzole, 440 Bibliography, general, 538 special, 540, et seq. Bichromate of potash, 521 Borate of soda, 401, £40 Borax, 401, 540 Boric acid, 401, 402 Bromine and bromides, 440, 548 pathogeny, 450 pathological anatomy, 448 tests for, 450 treatment, 45 1 Burgundy pitch, 519, 563 Calx sulphurata, 452, 549 Cannabis indica, 453, 550 Cantharis, 453, $50 Capsicum, 455, S5° Carbolic acid, 403, J 40 Cardol, 414, 542 Castor oil, 512, 562 Chinolin, 4SS, 55° Chloral, 455, 550 diagnosis, 461 eruptions from, 456 pathogeny, 460 tests for, 461 treatment, 462 Chloralamide, 462, 551 Chlorate of potash, 524, 564 Chloroform, 462, 551 INDEX. 567 Chromates, 427, 523 Chrysarobin, 405, 540' Cinchona et quinise sulphas, 463, 551 diagnosis, 470 eruptions from, 463 pathogeny, 470 tests for, 471 treatment, 472 Cinchonidia, 554 Classification, 364 Cod-liver oil, 512, 562 Condurango, 472, 554 Conium, 472, 554 Copaiba, 472, 554 Croton oil, 512, 562 Cubebs, 472, 554 Dal, 478 Digitalis, 476, 554 Drug eruptions, characteristics, 364 classification, 364 definition, 362 diagnosis, 395 etiology, 369 history, 361 idiosyncrasy, 371 pathogenesis, 373 prophylaxis, 397 symptomatology, 388 treatment, 397 Dulcamara, 477, 555 Dyes, 426, 427, 523 Eczema mercuriale, 361 Ergot, 478, SSS Etiology of drug eruptions, 369 Perrum, 479, 555 Eriar's balsam, 400, 540 Guar ana, 479 Guaiacum, 479, 555 Gurgun oil, 479 Hydrargyria, 361, 480, 482 Hydrargyrum, 361, 427, 479, 555 Hyoscyamus, 485, 557 Idiosyncrasy, 371 Iodine and iodides, 486, 557 diagnosis, 504 eruptions from, 486 pathogeny, 501 tests for, 504 treatment, 505 Iodoform, 506, 560 Ipecacuanha, 510, 560 Lead, acetate of, 520, 564 carbonate of, 520, 564 Iiithii bromidum, 440 Mercury, 427, 479, 555 Morphia, 513, 515, 562 Mustard, 532, 565 Nitrate of silver, 421, 544 Nitric acid, 408, 540 Nux vomica, 510, 562 Oleum cadini, 511,562 dipterocarpi, 479 morrh.ua,>, 512, 562 ricini, 512, 562 santali flavi, 512, 562 terebinthinse, 535, 566 tiglii, 512, 562 Opium, 513, 562 Pathogenesis of drug eruptions, 373 Phenacetin, 518, 563 Phosphorus, 518, 563 Picrate of ammonium, 408, 541 Pimpinella, 519, 563 Pix Burgundica, 519, 563 liquida, 519, 563 Plumbum, 520, 564 Podophyllum peltatum, 521, 564 Poison ivy eruption, 526 treatment, 529 Potassii bichromas, 521, 564 bromidum, 440, 548 chloras, 524, 564 iodidum, 486, 557 Prophylaxis, 397 Pyrogallol, 408, 54 1 568 INDEX. Quinise sulphas, 463, 551 Resin, $25, 564 Rhubarb, 525, 564 Rhus diversiloba, 564 toxicodendron, 564 venenata, 564 Rue, essence of, 565 Salicylate of soda, 541 Santal, 512, 562 Santonate of soda, 531, 561; Santoninum, 531, 565 Sheep-washing, 429 Sinapis, 532, 565 Sodii benzoas, 400, 540 boras, 401, 540 bromidum, 440, £48 iodidum, 486, 557 salicylas, 409, 541 santonas, 531, 565 Stramonium, 532, 565 Strychnia, 510, 562 Sulphide of calcium, 452, 549 Sulphonal, 533, 565 Sulphur, 452, 533, 566 Tanacetum, 534, 566 Tannic acid, 413, 541 Tansy, 534, 566 Tar, 519, 563 Tartar emetic, 416, 542 Terebene, 535, 566 Tests for antimony, 417 Tests for antipyrin, 420 arsenic, 417 boric acid and borax, 402 bromine and bromides, 450 cantharides, 454 carbolic acid, 405 chloral, 461 chrome compounds, 523 chrysophanic acid, 407 copaiba and cubebs, 476 iodine and iodides, 504 iodoform, 506, 509 mercury, 483 opium and morphia, 517" pyrogallic acid, 409 quinine and other cinchona prepa- rations, 471 salicylic acid and salicylates, 412 turpentine and terpenes, 537 Thapsia, 535, 566 Treatment, 397 of argyria, 42 1 bromide eruptions, 45 1 carbolic acid, 405 iodide eruptions, 505 pyrogallic acid, 409 Turpentine, 535, 566 Valerian, 537 Vanadium, 427 Vanilla, 415 Varnishes, rhus, 528 semecarpus, 414 Veratria,537, 566 Veratrum viride, 537, 566 CLINICAL AND ETIOLOGICAL RESEARCHES PSOEIASIS. LUDWIG- NIELSEN, SECUNDABAEZT IK" THE VESTEE HOSPITAL, COPENHAGEN. , TBANSLATED BY EEANK H. BAEENDT, M.D.Lond., E.E.C.S.Eng. CLINICAL AND ETIOLOGICAL RESEARCHES IN PSORIASIS. 1 The nature of the efflorescence. — Hyperemia is the first thing we notice clinically in the development of an efflores- cence ; the production of scales is a later feature. In addi- tion to the frequent brown pigmentation seen especially after arsenic treatment, 2 leucoderma has sometimes ap- peared in the site of the efflorescence. This has also been observed after arsenic and large doses of iodide of potassium. The spots of leucoderma are usually quite small, but in some patients the patches are extensive, and have persisted un- changed for some months (at least six months). Localisation. — The distribution of psoriasis in 862 cases was as follows : — On the trunk, extremities, and head, 489 times ; on the trunk and extremities, 197 times ; on the ex- tremities only, 113 times; on the extremities and head, 53 times ; on the head only, 5 times ; on the trunk and head, 4 times ; and on the trunk alone, only once. Thus we see that limitation of the eruption to the trunk only is very rare indeed, and it is probable that this soli- 1 The present paper is an abridged extract of a larger work (' Contribution to our Knowledge of Psoriasis,' Copenhagen, 1892, pp. 204, fifty-seven histories of cases, with index of literature), which I compiled during my three years' tenure of office as Secundararzt at the General Hospital in the Department for Skin and Venereal Diseases (Prof. Haslund), from 927 cases of psoriasis (616 patients), extending over a period of twenty-five years, and from forty-three private patients in the practice of Prof. Bergh. . 3 In a case of Addison's disease dark brown pigmentation persisted after the spontaneous disappearance of the eruption. 572 NIELSEN ON PSORIASIS. tary case was one of eczema seborrhceicum. A few cases of psoriasis confined to the trunk are recorded by McCall Anderson. This circumstance is valuable in differential dia- gnosis, especially in the case of syphilis. Volse and (or) plantae were attacked in 7 per cent. (65 times) of all cases (927), and in 8*9 per cent. (55 patients) of the 616 patients ; but in 78 cases (66 patients) where we ourselves noted the smallest efflorescence this localisa- tion was still more frequent, viz. 15 times (13 patients), or in i9 - 2 per cent, of cases and in 19*7 per cent, of patients. This is much more often than is commonly stated; of course syphilis was most carefully excluded. In one case only where the diagnosis of psoriasis seemed certain was the eruption confined to the palms and soles. On reference to the litera- ture of psoriasis only two cases are recorded (Angel and Neumann) where the eruption was thus limited for some years, and afterwards appeared in the usual regions. The volae and plantse were most frequently attacked where the eruption was very extensive or of the inveterate type. Sometimes, however, when it was slight or the first attack, these regions were involved. In two patients the palms and soles were attacked every time. The number of males pre- dominated — 54 males, 11 females, — possibly because of their greater exposure to mechanical irritation. Thus, in one patient who always carried his stick in the left hand, that palm was more affected than the right. The soles and palms were attacked 3 1 times simultaneously, the palms alone 24, the soles alone 10 ; both palms or both soles were most frequently affected. The diagnosis is not so difficult as is usually stated. It differs from syphilis especially in desquamation beginning in the centre of the efflorescence, the abundant formation of scales, and the very slight infiltration. Its course is similar to psoriasis in other regions. Psoriasis of the nails occurred 8 times (7 patients) among 78 cases (66 patients), io - 2 per cent, of cases and io*6 per cent, of patients. It was most frequently seen in extensive and old-standing (Ps. inveterata) psoriasis, and in the majo- rity of cases the hands and and feet were implicated ; the nail folds, palms, and soles likewise, but not invariably so. Males were most often attacked. There is nothing charac- NIELSEN ON PSOEIASIS. 573 teristic in psoriasis of the nails, and there is no case on record where this -was the sole localisation, and none is known ■where the eruption appeared afterwards in the usual regions (cf. psoriasis volse et plantae). The punctated condition of the nails is very frequent and characteristic (also seen in syphilis and eczema). It usually occurs in the finger-nails, and appears to be due to an affection of the matrix. Disease of the bed of the nail, with accumulation of scales under the nail extending from before backwards, is not uncommon, either alone or accompanied by the first-mentioned condition. The nails are also liable to other nutritive disturbances — atrophy, desquamation, and total detachment with subse- quent regeneration. Psoriasis of the nails is amenable to treatment, and follows the course of psoriasis in other regions. The glans penis and inner surface of the prepuce are not infrequently attacked (balanoposthitis psoriatica) . The spots are sharply defined, red, glazed, and almost free from scales. Psoriasis started from the genitals in one case only. Of 270 cases of psoriasis of the head (and usually of other regions), face and scalp were attacked 127 times, scalp alone 104 times, face alone 39 times. That luxuriant growth of hair that has been noted sometimes was not observed. Psoriasis of mucous membranes was never seen. Causes of localisation. — The general symmetrical distribu- tion and the usual sites of the eruption support the view of external irritation symmetrically applied, e. g. pressure and iriction of the clothing, irritation due to the occupation and habits of the patient, and the scratching from itching, 1 — com- 1 The relationship has often enough heen pointed out, as is seen in the sites of predilection (elbows, tubercle of tibise, shins, scalp, and sacral region). Several of our patients offered further examples of this connec- tion. One suffering from kyphoscoliosis showed the eruption particularly well marked over the prominence of the spine. Another had psoriasis chiefly in the sacral region and over the prominences of the shoulder-blades ; a third on his left knee, which he used . most whilst working ; a fourth over the left trochanteric region, on which side he always lay in bed; a fifth had the eruption more marked in the left palm than in the right, as he always carried his stick in the former ; &c. In women the furrow caused by fastening the garments round the body is a favourite site. Scratch- marks are often attacked by psoriasis. 574 NIELSEN ON PSORIASIS. pare the causes of symmetry in scabies, in the dermatomy- coses, &c. The assumption that the symmetry of psoriasis is the expression of some nerve-influence is no doubt purely theoretical. The beginning and development of psoriasis. — The initial localities (in the first attack) are most often the extremities, viz. 130 times out of 182 cases. Of this number 130, the elbows, knees, and legs are especially stated to have been the seat 87 times, and then the scalp 18 times out of the 182 cases. Although atypical in its development, various groups may be described, but with sundry connecting links. Out of 181 cases (first attack) the disease began 70 times (38"6 per cent.) as a few scattered spots, which remained practically un- changed for at least six months (often several years) without further extension. Eighteen of these patients never had an extension of the psoriasis, often of many years' standing, and it is perhaps not rare to find the disease limited to a small area. The localisation of these permanent patches was oftenest on the extremities, especially on the elbow and (or) knee 45 times, several times on one side of the trunk, 13 times on the scalp, and once only on the face. Successive or quite acute outbreaks occurred in 1 1 1 cases (61 "3 per cent.). In 36 of these the eruption spread extensively in from five days to four weeks. The single exacerbation (or isolated outbreak) and the inter- relationship of exacerbations (or separate outbreaks). — Although an exacerbation of psoriasis follows no definite rule and then ceases, and although a remission may be very incomplete, or even partly coincide in point of time with a fresh attack, nevertheless fairly distinct exacerbations or isolated attacks may be recognised. The initial localisation of later attacks appears on the whole to be the same as in the primary attack. In 65 cases where no efflorescence of former attacks remained, the ex- tremities (elbow and knee specially noted 18 times) were first attacked 47 times, the scalp 5 times, the trunk 5 times, and various regions simultaneously 8 times, Owing to the influence of the predilection sites on localisation, the initial localisation and subsequent distribution of the eruption in NIELSEN ON PSORIASIS. 575 different outbreaks frequently recur in the same order in the same individual. Further, the method of progress of psoriasis was generally the same as in the primary attack — in not a few cases it was acute : it followed no definite rule in the different outbreaks in the same patient. The localisation of the fully developed eruption was fre- quently partially the same in the various exacerbations. Besides the predilection sites, the occupation and habits of the patient as well as the pigmentation after previous attacks may determine the site of new efflorescences. But apart from these factors, and without any other apparent cause, psoriasis often recurred in the same regions (sometimes in more unusual ones — face, genitals, palms) in the same indivi- dual without regard to severity of the eruption or the length of interval between it and previous ones. Conversely, in some individuals the more usual sites for psoriasis — scalp, back, and in two patients the elbows and knees — regularly escaped, though the outbreaks were frequent and severe. The distribution of the eruption in the different attacks in the same individual appears to follow no regular course. Universal implication of the skin without any healthy areas intervening has only been seen in psoriatics suffering from dermatitis exfoliativa, pityriasis rubra, herpetide exfoliative, 1 &c. These differ clinically so much from psoriasis that they must be viewed as forms of dermatitis, often of varying pathogenesis, which complicate psoriasis, and into which psoriasis may pass. Such cases which may result from irri- tating treatment are also relatively frequent (comparing my own cases with the literature of the subject) in patients suffering from chronic alcoholism and chronic rheumatic joint affections. These diseases may be of importance in connection with dermatitis in psoriatics. It is, however, a Somewhat rare affection, but liable to relapse. A universal eruption (or almost so, with only a few healthy skin islets on the volae, plantse, and face), with the charac- ter of dermatitis exfoliativa, occurred once or oftener in 5 1 Psoriasis acuta vel ps. scarlatiniformis cannot be sharply defined from herpetide exfoliative in psoriasis on account of the transition forms, as French writers, especially Brocq, state. 576 NIELSEN ON PSORIASIS. out of 520 psoriatics (779 cases). In 6 other cases the eruption was less extensive, but of the same character. Males were most frequently attacked by such a dermatitis ; the 5 patients were all males (29 — 44 years of age, one 66 years old). Of the 6 that were less affected 2 were females (33 and 37 years of age). At least 4 out of the 11 patients were addicted to alcoholic excess, and got delirium tremens ; one suffered from relapsing joint disease (chronic rheuma- tism) and heart disease (v. infra). The dermatitis sometimes came on earlier, sometimes later in the course of the psoriasis, without apparent cause, and tolerably acute. The general condition was good, and no rise of temperature was observed. The eruption disappeared rather quickly (from twenty-four days to two months) on treatment, having previously existed at most three months in one patient. On some occasions, during the involution of this universal eruption, ordinary psoriasis guttata appeared. One patient appeared to have had two universal outbreaks before ; another — an alcoholic with chronic rheumatism — had several serious attacks of psoriasis, having partly the cha- racter of dermatitis exfoliativa ; and lastly, a heavy drinker had had seven such universal eruptions. The appearance and the special character of the exacerba- tion are sometimes modified by the application of local irri- tants, e. g. irritant medicaments, or by the complication of other skin affections, or of general cachectic conditions (scurvy, syphilis, &c). In some outbreaks infiltration, red- ness, and formation of scales were remarkably slight (psori- asis pityriasiformis) without apparent cause. Psoriasis in- veterata, which presents quite opposite characteristics, appears rarely during the early stages of the disease, or as a first attack. It rarely occurred among our patients in a typical form, and was unaccompanied by any general disturbance. Sometimes psoriasis inveterata is met with in those suffering from chronic rheumatic arthritis (v. infra). Duration and course of the exacerbation. — The average duration of treatment of outbreaks of psoriasis, cured with large doses of iodide of potassium up to 50 grms. .daily (about 7714 grs.) 1 was in 27 adults 38'7 daysj in 13 chil- 1 The treatment of psoriasis with large doses of potassium iodide by NIELSEN ON PSORIASIS: 577 dren (under 15 years) 61 l g days; and with arsenic in con- junction with, various externalremedies (most frequently baths and tar preparations) was in 47 adults 52-3 days, in 9 chil- dren (under 15 years) 90 days. It is possible, had arsenic been pushed, that the cure would have been as quick as with potassium iodide. From observation of our patients it may be stated as a general rule, the average duration of treatment was much longer in the case of children than in that of adults. This inference is not only obtained from the above figures, but also from the following statistics based on other methods of treatment (external remedies alone, and the internal adminis- tration of carbolic acid, &C.). 1 Thus the duration was in 107 adults 47*3 days ; in 28 children (under 15 years), 747 days. Further, out of 1 1 o patients where treatment lasted at least three months and over, 2 1 were under ten years, 42 between ten and twenty years, and 47 above twenty years. On the other hand, of 55 patients where the eruption disappeared in the course of a month and under, there were only 2 under ten years, 8 between ten and twenty years, 45 above twenty years. Psoriasis often disappeared remarkably quickly in alcoho- lics, probably because they were deprived of alcohol when in the hospital. The general condition of the patient was as a rule undis- turbed ; in a few cases only subjective febrile symptoms were stated to have been present at the onset of the eruption. Elevation of temperature was, however, never observed. No disturbance of the bodily functions occurred ; e. g. the urine showed nothing abnormal, with the exception of a few cases where chronic nephritis was present, and once with diabetes mellitus. In most cases the eruption was accompanied by itching — > generally speaking very slight, occasionally severe. In uni- versal outbreaks (dermatitis exfoliativa) constant chilliness without accompanying fever was sometimes observed. Haslund (' Vierteljahressch. fur Dermat. und Syphil.,' xiv, 1887, pages 708-9). 1 Only oases have been used where no incidental complications required treatment. 37 578 NIELSEN ON PSORIASIS. Among our patients there was no affection present that could be regarded as a true complication of psoriasis. On the other hand, it was frequently met with in conjunction with other diseases (v. infra). Herpes zoster, occasionally arising during treatment by arsenic, 1 must be mentioned, apparently caused by this drug, as well as a peculiar dryness and lustreless aspect of the skin of the palms (observed but once) . During the treatment with potassium iodide, painful cutaneous and subcutaneous nodes, somewhat resembling erythema nodosum, but chiefly much larger (almost the size of an orange), developed in two patients — in one on two occasions he was thus treated. Besides these, several other more usual drug rashes were observed. The entire course of psoriasis is quite atypical. In certain cases the disease lasts for years, sometimes for life, confined to the predilection sites. Exacerbations may cease at any period of its course, or even the psoriasis may disappear com- pletely. We must, however, not ignore the possibility of a fresh outbreak. In some patients exacerbations occurred regularly once or twice a year for a series of years, frequently at definite periods. Sometimes long remissions or apparently complete intermissions 3 take place. The duration of the re- missions varied : from one to five years, 49 times ; from five to ten years, 10 times ; and from ten to thirty-two years, 8 times. Sufficient observations have not been made in order to determine how far remaining patches of psoriasis may influ- ence a relapse. Lang's cases, treated with parasiticides till completely cured, favour the idea of such an influence ; un- fortunately their number is too small. Forty-eight of our patients suffered from psoriasis with or without treatment from twenty or more up to fifty years. Only two of these, who had frequently been treated, suffered from psoriasis inveterata, and only a little over one third 1 " The Appearance of Herpes Zoster during the Administration of Arsenic," by Ludwig Nielsen, ' Monatsh. f. prakt. Derm.,' xi, 1890, No. 7 (translated by the New Sydenham Society). 2 On the parasitic theory of psoriasis we regard true intermissions in the light of complete recovery followed by re-infection. NIELSEN ON PSOB1ASIS. 579 had a very extensive eruption. Thus psoriasis, as a rule, shows no tendency to get materially worse even in untreated cases. On the other hand, in patients suffering from alco- holism and chronic rheumatism it is generally aggravated, and conversely intercurrent affections accompanied by pro- found disturbance of nutrition may be beneficial to, or even cure the disease (v. infra). II. Etiology of Psokiasis. Sex. — Out of 520 patients suffering from psoriasis, 314 were males, 206 females — 60*4 per cent, and 39/6 per cent, respectively. From a compilation of various statistics, out of a total of 2439 patients, 1482 were males and 957 females — 6o*8 per cent, of males and 39^2 per cent, of females, a proportion of 3 to 2. %£Age. — Psoriasis is stated to have begun in 548 cases (325 males, 223 females) — Before 15 years Between 15 and 20 years 20 „ 30 „ 3° » 4° » 4° » 5° » 5° » 6o » 60 „ 70 „ Thus psoriasis began 241 times in childhood (under 15 years), *. e. 44 per cent., and only in 27 per cent, during the fiftieth year and upwards. Its appearance in the first five years of life was rare ; one case only occurred in the second year : its frequency culminated between the fifth and fifteen year. It then diminished up to the twentieth year, and kept on decreasing materially during the succeed- ing decennia, exceeding the synchronous decrease in vital statistics. The percentage was — 241 times 86 >> 123 » 59 a 24 j> 11 >> 4 >> 580 NIELSEN ON PSORIASIS. Under 15 years Between 15 and 20 years 20 31 3° 30 >) 40 40 }> 50 50 JJ 60 60 >> 70 Males. Females 32-6 . 60-5 14-8 . 17*0 28-3 • i3"9 I5"i • 4'5 5-8 . 2-3 2-8 • "9 •6 "9 The percentage of girls was almost double that of boys. From the twentieth year and upwards the excess of males was more than double that of females. Bearing in mind, however, that the proportion between men and women attacked by psoriasis is as three to two (v. supra), in order to state the relationship more exactly the percentage of males should be trebled, and that of women only doubled. This would considerably diminish or even abolish the dif- ference in childhood between the two sexes if the element of uncertainty be taken into consideration. After the twentieth year, during, the following decennia this difference becomes greater than the percentage calculation shows. Among adults, therefore, the percentage of males attacked by psoriasis, as also the absolute number, are much greater than those of females. Neither social status nor any special occupation could be shown to have any influence over the manifestation of psoriasis. As regards heredity, the result of our inquiries in 306 individuals showed that 218 times the patient was the only sufferer in the family, and that 88 times (28*8 per cent.) other members were also attacked. Out of the 306 individuals, the disease was directly hereditary 45 times (147 per cent.), in- directly only 7 times ; 32 times, two or more brothers and sisters suffered ; and lastly, in four cases details were not forthcoming. In 13 cases, besides psoriasis being directly hereditary, it was also present in several of the brothers and sisters of fhe patients. It is very uncommon that all the children of one family should be attacked. Out of 320 children in 52 families (varying from 2 to 13 children in each family), where one or NIELSEN ON PSOEIASIS. 581 more children had psoriasis, the disease affected 82. No rule of sequence for the evolution of outbreaks in point of time can be demonstrated among brothers and sisters, and they often get psoriasis at varying ages. The earlier mani^ festation or treatment of the disease, in contradistinction to syphilis, has no influence on its possible transmission to chil- dren. Psoriasis appeared more frequently in childhood where there was direct heredity than where this was absent. Out of 43 patients whose parents or grandparents had had psori- asis, 24 were attacked before the fifteen year (55*8 per cent.) and 3 after the thirtieth year (6 - g per cent.). Out of 191 patients where the family history was free, 68 were affected before the fifteenth year (35*6 per cent.) and 40 after the thirtieth year (20*9 per cent.). At present there is no proof to show that the origin of psoriasis in several members of the same family should be ex- plained by heredity ; it may just as well at least be ascribed to contagiousness. Relation of psoriasis to, and its complication with, other diseases. — Wehave not beenable to confirm the statement that psoriatics are endowed with particularly strong and healthy constitutions or an unusually fine skin. The statements of other writers to this effect are undoubtedly exaggerated. If other diseases appear during psoriasis, they may either influence the skin disease or in turn be influenced by it. The relation of psoriasis to joint affections has in recent years received considerable attention from French writers, although this had been pointed out previously. Space will allow us only to mention very briefly the cases of joint troubles that occurred among our patients. Two individuals had gonorrheal synovitis, and three acute rheumatism (one heart disease). None of these joint affec- tions bore any relation to psoriasis. Five patients, of whom three were alcoholics, suffered from fugitive, afebrile — or almost so, highest temperature being 38° C. (ioo'4 F.) — rheu- matic arthritis of one of the larger or smaller joints, without any relation to psoriasis, which showed nothing, remarkable beyond simultaneity. 582 NIELSEN ON PSOEIASIS. It has been especially stated that a certain relationship exists between psoriasis and chronic joint disease. One patient had chronic arthritis of the knee ; and another (male> aged fifty-nine), with very slight psoriasis, suffered from arthri- tis deformans which began after the former. In neither case could any relationship be traced, and similarly in three other patients (all males, between fifty-three and sixty-five years of age) with chronic rheumatism or arthritis deformans, which had at least in two cases begun before psoriasis, in one as acute rheumatism. This patient had at the same time pyelo-nephritis, bronchitis, and emphysema. Psoriasis, which had lasted several years (seven to fourteen years) in the three patients, presented this relationship, inasmuch as it was of the inveterate type, and in two of them very extensive. Lastly, in three other patients exacerbations of psoriasis are said to have been contemporary with joint troubles. One of them (male, aged thirty-two) had chronic rheumatism which had begun twelve years before as acute rheumatism, and six years before psoriasis. The eruption was accompanied by loss of the finger-nails, and was very extensive. The second patient (male, aged fifty-five) had arthritis deformans which began two years after psoriasis of some nine years' standing. It was, especially at first, very extensive, and of the inveterate type ; he also suffered from renal colic. Lastly, the third patient (male, aged forty-two), with psoriasis of nineteen years' standing (during the last ten years he had several exacerbations yearly, and was treated some twenty-six times in the hospital), had several serious outbreaks of psoriasis, partly of the character of derma- titis exfoliativa, once almost universal. He suffered from frequent relapses of chronic rheumatism of some ten years' duration. He had heart disease, and was a heavy drinker (delirium tremens). In opposition to the view which French writers (Besnier, Brocq, &c.) hold concerning the relationship of psoriasis and joint affections, none of our patients furnished evidence of a neuropathic origin for the joint troubles, except in so far as arthritis deformans is generally regarded as neurotic. 1 1 Bourdillpn, in a paper on * Psoriasis and Arthropathy,' Paris, 1888, cites a fair number of cases of psoriasis (thirty-six) where joint and nerve NIELSEN ON PSOEIASIS. 583 On the other hand, from a comparison of our cases of chronic joint trouble (chronic rheumatism and arthritis deformans) with those published by foreign, especially French writers, it appears that psoriasis very frequently but not invariably develops severely, and often assumes the character of derma- titis exfoliativa or psoriasis inveterata. Moreover the exa- cerbations of the skin and joint disease often, though not always, coincide, and both diseases may become aggravated in the same patient in the course of years. These points have also been insisted upon by French writers. But since both affections are liable to frequent exacerbations at definite periods of the year, no great stress should be laid upon their simultaneous occurrence. In most cases the joint affections began after psoriasis, corresponding to the different periods of life respectively in which they are generally met with. From the number of cases where joint affections were present in the 616 individuals (927 observations), we are unable to conclude that arthropathies are frequently seen in psoriasis. The absence of figures showing the frequency of joint diseases in non-psoriatics, for the purposes of com- parison, renders this point still more difficult of decision. We must further add that such patients are just those that more frequently come under observation, owing to the ex- tensive character of the eruption. The approximate state- ment of Besnier and Doyon about the frequency of " arthropathic psoriasis," 1 namely 5 per cent., not a little exceeds that derived from our patients. affections besides some other complications were present. Without going into any details of the cases he tries to show that psoriasis and these diseases should he regarded as dependent upon the nervous system. 1 'Pathology and Treatment of Diseases of the Skin,' by M. Kaposi, 2nd edit., translated with additions by Besnier and Doyon, vol. i, p. 554. "We are unable to accept this statement and its implied significance in the light of our own cases ; a critical analysis of the literature of psoriasis renders its correctness, to say the least, very doubtful. According to our researches the relationship between psoriasis and arthropathy cannot be stated more precisely than the clinical connection mentioned in the text. Moreover a similar relationship is frequently found between other skin affec- tions and joint troubles (eczema seborrhceicum, lichen ruber, primary dermatitis exfoliativa, &c). Further, we consider Besnier's "psoriasis douloureux" {v. Bourdillon, loc. cit., p. 81) open to grave doubts. After 584 .NIELSEN ON PSORIASIS. Relation of psoriasis to acute diseases. — Like many other skin diseases (lupus, scabies, favus, &c.), psoriasis may recede or even disappear during intercurrent febrile affections (e. g. once with pleurisy and twice with typhoid fever). In one patient psoriasis was of many years' standing, and very intractable to treatment. Such cases are scattered up and down in the literature of psoriasis. This coincidence is, however, by no means regular. In a few cases psoriasis appeared for the first time im- mediately after an acute illness (scarlatina, measles, typhoid fever, erysipelas, and pleurisy). Gazenave has recorded a case where psoriasis attacked the recent pits after smallpox. Here, again, it was probably only an accidental coincidence. Relation of psoriasis to chronic diseases. — Psoriasis may disappear in chronic wasting diseases (cancer, diabetes, &c), and not recur (F. Hebra's case of recurrent haemoptysis). Even this is not without exception, for psoriasis persisted in two of our patients who had incipient phthisis, and in another with cancer of the breast. On the other hand, we have never seen or read of psoriasis in advanced phthisical patients. Chronic bronchitis, chronic nephritis, chronic gastro- enteric catarrh, chlorosis, and other chronic affections exerted no influence over psoriasis. Three of our patients had had ague. Poor's statement that malaria frequently occurs in psoriatics must depend upou the circumstance that his cases came from a malarious district (Hungary), and consequently were simply examples of coincidence. Just as we were unable to find any ground for a neuro- pathic origin of joint troubles in psoriatics, so we are unable to confirm from our cases the statement made by some writers (especially Polotebnoff and Bourdillon) that the nervous system was so frequently implicated as to admit of all it is not remarkable that patients submitted to frequent and daily baths (to which they are unaccustomed in the majority of cases) should at times complain of lumbago, stiff neck, and other indefinite rheumatic pains. The altered conditions of the skin would probably predispose to such affections. This has also been our experience with psoriatics, and it occurs in other diseases under similar treatment. In this connection acute sore throat appeared no less than thirty-three times. Twice only was true neuralgia noted. NIELSEN ON PSORIASIS. 585 a, possible relationship between it and psoriasis. On the contrary (Prof. 0. Lange and others), neuro-pathologists write that psoriasis seldom occurs in their practice. With the exception of a few cases of herpes zoster (during the administration of arsenic — v. supra), neuralgia is said to have occurred twice (ulnar and sciatic nerves). Affections of the cerebro-spinal system among the 616 psoriatics were as follows : — syphilidophobia with insanity occurred once, epilepsy four times, epileptiform attacks (due to alcohol), three times, hysteria once, disseminated cerebro-spinal sclerosis once, syphilis of the brain and spinal cord twice : and vertigo twice in one of the latter, doubtless due to arterial degeneration. These various diseases sometimes appeared before or after psoriasis without any apparent connection. Chronic alcoholism undoubtedly aggravates long-standing psoriasis ; the most extensive and recurrent cases of psoriasis are most often met with in heavy drinkers, and alcoholism certainly favours the development of universal attacks (der- matitis exfoliativa, v. supra) . In some alcoholics, however, psoriasis is but slight, and not specially liable to relapses, so that the rule is not without exception. As mentioned above, in some cases psoriasis disappeared rapidly when the alcohol was withdrawn. Relation of psoriasis to diseases with shin eruptions. — Psoriatics do not appear to be less prone to other skin affections, and although this is questioned (F. Hebra and Neumann), it has been seen in individuals with prurigo (Neumann) and with ichthyosis (van Haren-Noman) . Those cases are particularly interesting from a diagnostic, etio- logical, and prognostic point of view where a local combina- tion of psoriasis and other eruptions exists (which is, how.- ever, not unusual in other skin affections). Psoriasis either attacks or starts from the site of a disappearing efflorescence of another skin disease, and vice versa where the psoriasis efflorescence is the site or starting-point of the new skin disease. Of the cases in which psoriasis was secondary to another skin affection, those are most interesting where psoriasis appeared for the first time. In two of our patients psoriasis 586 NIELSEN ON PSORIASIS. (first outbreak) is said to have attacked the site of erysipelas. In three cases recorded by Biart, 1 psoriasis (first outbreak, and no hereditary predisposition) began in the regions most attacked by scarlatina. Cazenave's case of psoriasis (first outbreak, no hereditary taint) after smallpox 3 has been already mentioned. Those cases are very remarkable where psoriasis appeared for the first time after vaccination at the seat of inoculation. Neither of Eohe's patients had had psoriasis ; there was no hereditary predisposition, and animal lymph was used. In one of them the vaccination did not take ; but from eight to nine days later a spot of psoriasis appeared in the site of inoculation, and a few days after numerous others elsewhere. In the other case it developed after the vaccine scab had fallen in the hyperasmic area, and shortly afterward the efflorescence generalised. Hyde is said to have seen a similar case. Piffard gives a similar history of a case where psoriasis first appeared on the site of inoculation ; the vaccination with animal lymph was also unsuccessful. "Wood saw two sisters both vaccinated successfully with animal lymph, in whom psoriasis for the first time broke out after the pustules were healed : a brother had psoriasis. s Chambard 4 records also a case of psoriasis (first outbreak) where it manifested itself after vaccination with animal lymph, in a child whose parents were quite healthy. Gaskoin 6 says he has seen six cases of vaccination where psoriasis began at the site of inoculation during the healing process ; and Campbell 6 also mentions a case under similar circumstances. In individuals who have previously suffered from psoriasis it is not uncommon to find it complicating other skin diseases, e. g. retrogressive eczema (Neumann, &c.) twice (among 1 Mentioned in ' Annal. de Derm, et de Syph.,' 1883, p. 721. 2 " Squamous Affections of the Skin ; Psoriasis ; Lepra vulgaris," ' Annal. des mal. de la Peau et de la Syph.,' vol. i, 1844, p. 99. 3 Of several of these cases which were seen in North America (viz. Eohe's, Hyde's, Piffard's, Wood's) we have only been able to see the refer- ence in 'Annal. de Dermat. et de Syph.,' 1883, p. 720. 4 ' Annal. de Derm, et de Syph.,' 1885, p. 498. 5 ' On Psoriasis or Lepra,' 1875, p. 49, and appendix. 6 ' Archives of Dermatology,' July, 1877. NIELSEN ON PSORIASIS. 587 other patients), seborrhoea congestiva faciei once, erythema nodosum two cases (in one, perhaps, it was a first attack of psoriasis), herpes zoster once, and urticaria (Cazenave), &c. In others the psoriasis was primary, and the other shin diseases were secondary. Such are those rare cases where an irritated psoriasis efflorescence has become the seat of infective processes (erysipelas, lymphangitis, and formation of multiple pustules in one of our cases). In other cases psoriasis has assumed an eczematous character as a result of irritation of the shins and other isolated regions (psoriasis eczemateux of Devergie, and psoriasis arthritique of Barm) . Eczema seborrhoeicum must be carefully differentiated in such cases. It is, perhaps, more correct to speak of an artificial eczema or dermatitis complicating psoriasis. The appearance of the former on the legs is ako favoured by the greater chronicity of the psoriasis eruption, as well as by the itching due to the sluggish condition of the circu- lation (varix) . Of course the inflammatory agents (probably micro-organisms) which we assume to be the cause of pso- riasis may themselves be responsible for the increased irri- tation (Unna). On the other hand, we cannot assume, as Campbell does, that there is a close connection between psoriasis and eczema. Dermatitis exfoliativa occurring in the course of psoriasis may be regarded as more closely allied to eczema. In several cases the skin, especially that of the scalp, forehead, face, at times chest and back, shows dirty yellow greasy scales, and in other places the typical efflorescence of psoriasis. These and similar characters not infrequently seen in syphilis should be rather viewed as a combination of psoriasis and eczema seborrhoeicum, as Unna proposes. The localisation of papular syphilides on psoriasis patches has been mentioned by Dornig and Neumann. In two of our patients grouped ulcerative syphiUdes appeared at the margin of extensive patches of psoriasis. The former dis- appeared on treatment with mercury ; the latter remained uninfluenced (as in Neumann's two cases). The exanthe- mata also show a predilection for psoriatic areae (variola, Kaposi). In one case keloid (Purdon) has been observed in patches 588 NIELSEN ON PSOEIASIS. of psoriasis. Those rare cases where a psoriasis efflorescence has been the starting-point of malignant neoplasms are of im- portance from a prognostic point of view, e. g. mycosis fun- goides d'Alibert (Pick and De Amicis) and epithelioma (one case Cartaz, two cases White, one case Hans von Hebra) . In Hebra's and White's cases there were numerous firm wart-like growths, which developed in the patches of psoi'iasis on the extremities, and especially the hands. In fact, they formed the precursory stage, lasting some time before their malignant character set in. In all these cancer patients psoriasis had existed for many years, and none of them were particularly young, as often is the case with cancer developing from lupus (Ludwig Nielsen) . Only in one of our cases was there cancer (of the breast) which apparently had no local relation to psoriasis. Cancer occurs so rarely in psoriatics that no " rapport de succession " can be traced between the two diseases. Relation of psoriasis to external irritation. — Transient mechanical irritation may cause psoriasis as well as the per- sistent application of irritants. Kobner's case is well known with localisation of psoriasis in excoriations, the bite of a horse, and tattooing. Other cases are recorded where pin- scratches, the marks made by wet cupping, scraping with Volkmann's spoon, the pressure of a bandage, and even finger-nail scratches, have been followed by psoriasis. In many cases efflorescences may be produced at will (psoriasis factitia) in a psoriatic by scratching the upper layers of the epidermis (Kobner's experiment) . This was tried in forty- two of our cases ; fifteen yielded a positive, twenty- seven a negative result. In almost all of them the psoriasis was still developing ; the few times the scratch was made during subsidence of the eruption no result followed, and the same happened in those patients under treatment, although the experiment had succeeded before. In one case where the arm and chest were scratched, the former gave a positive, the latter a negative result. All the patients except two (both with a negative result after scratching) were treated with large doses of iodide of potassium. A positive result was first noticed in some eight to ten days ; slight punctiform efflorescences of psoriasis appeared in the scratch-mark itself, NIELSEN ON PSORIASIS. 589 and later on they became confluent. The experiment appa- rently only succeeds, as Kaposi and Hashmd observe, when the psoriasis is progressive, and in certain cases only. On the other hand, if the psoriasis is stationary or retrogressive it fails. Kobner has found this experiment. useful in distin- guishing psoriasis from squamous syphilides, as efflorescences never appear after scratching in syphilitic patients. In a few cases psoriasis began for the first time after and at the site of mechanical irritation, in two cases after wet cupping (Veiel, Bazin), in one case under the pad of a truss (Kopp) with extension during the following weeks ; in four of our patients after and at the site of injury. The data in this respect are somewhat defective. Chemical and thermal irritation can also produce psoriasis efflorescences — blisters (one of our patients), sinapisms, cau- terisation with caustic potash or argentic nitrate, burns (one of our patients), at times lotions, Turkish baths, &c. On some occasions the primary attack of psoriasis has occurred after such irritation — after the application of iodine to a contused knee with subsequent extension of the eruption (Wutzdorff), around a burn on the arm with subsequent extension, and in a recent scar from a burn on the forehead (Bngelsted). In one of our patients (a healthy male about twenty, without any hereditary taint) the first outbreak occurred on the neck immediately after the application of hot fomentations for a sore throat. For eight days the psoriasis was confined to the face and neck, but after a warm bath numerous spots of psoriasis appeared all over the body in the course of a few days, though the patient was now well. This relation of psoriasis to irritation, which is intimately connected with its appearance after the different exanthe- mata, is also observed in other skin diseases (urticaria, eczema, lichen ruber, lupus, dermatomycoses, &c), if not quite in the same manner. Relation of psoriasis to physiological conditions. — No close connection has been observed among our female patients between psoriasis and menstruation. At times it disappears during pregnancy. Balmanno Squire has especially drawn attention to this fact. One of our patients stated that she was free from psoriasis during each of her five pregnancies. 590 NIELSEN ON PSORIASIS. On the other hand, in some cases exacerbations have occurred, or psoriasis has been uninfluenced during the whole of preg- nancy. Lactation has pretty regularly aggravated the erup- tion in some cases (McOall Anderson and Henry), but this does not point to any relationship between the two, as McOall Anderson and Wutzdorff seem to think. If there is any explanation at all, it is rather that pregnancy exerted a tem- porary favorable influence in such cases, and when over psoriasis relapsed. Relation of psoriasis to mental emotion. — In several cases (Fournier, Heube, Leloir) acute psoriasis has appeared, usually after an interval of a few days, in consequence of severe shock, more rarely of anger. It has also been ob- served after more persistent mental disturbance. Such cases French writers especially have insisted upon as showing a causal connection between mental disturbance and psoriasis. But as it is only a question of temporary coincidence there is no clear proof, but only a possibility of the existence of such a relationship ; in any case, it is of no value etiologically. No such evidence could be obtained in those cases where we made careful inquiry. Relation of psoriasis to the seasons. — It is not uncommon to find that psoriasis of some years' duration, in a certain part of its course, regularly undergoes exacerbations and remissions at certain seasons. One of our patients (a male, aged thirty- seven) had, when twenty years old, extensive psoriasis which disappeared on treatment with baths, but reappeared regularly every spring and autumn, though in a slighter degree. When he was thirty he had typhoid fever in the autumn, and had no psoriasis that season ; it, however, re- curred the following years at the same seasons. Fifty-six of our patients stated that they had almost regularly suffered from outbreaks at certain times of the year. The exacer- bations took place most frequently in the spring, viz. 30 times (in conjunction with the autumn 12 times), in the autumn 10 times (excluding the previously mentioned 12 times), in the summer 10 times, and in the winter 6 times. One case only is mentioned where a remission in the spring thus bearing out the above statement. This was a patient who had psoriasis for twenty-two years which dis- NIELSEN ON PSORIASIS. 591 appeared regularly at the end of March (before the bathing season), and remained away the whole of the summer. The remission was stated to have occurred twice only in the autumn, n times in the winter, and 22 in the summer. In ten cases the remission occurred during sea bathing, and conversely in one patient psoriasis was always aggravated by it. There is no doubt, therefore, that a certain connection does subsist between psoriasis and the seasons, it being always worse in spring and in autumn. In two sailors psoriasis always improved when they were in hot climates. The geographical distribution of psoriasis. — Psoriasis is usually stated to be pandemic. It is, however, questionable whether, according to Hirsch, the affections described under the various names of gune in Polynesia, daud in Assam, curuba among Brazilian Indians, are really psoriasis. Among negroes psoriasis is said to be rare (Morison) ; among Jews, on the other hand, frequent (Balmanno Squire). In very northerly latitudes it is not infrequent ; thus in Iceland (Pinsen) out of 513 cases of skin disease 42 were psoriasis (8" 1 per cent.) ; scabies alone was more frequent (46 per cent.). The proportion of cases of psoriasis to those of other slcin diseases. — Prom a compilation of statistics collected from several of the larger towns in Europe we found that out of 15,376 cases of skin disease there were 993 cases of psoriasis, i. e. 6*5 per cent. The proportion, therefore, of psoriasis to other skin diseases was as 1 to 15. Similarly the gross statistics in North America (J. White) show that out of 58,617 cases of skin disease there were 1924 cases of psoriasis, i.e. 3'28 per cent. Thus it would appear that psoriasis occurs more frequently in Europe than in North America. Prom a study of statistics psoriasis stands close in point of frequency to the most common parasitic skin diseases (dermatomycoses and zoonoses), and together with these (and acne) come next to eczema. 592 NIELSEN ON PSORIASIS. III. Pathogenesis op Psoriasis. Psoriasis as an eruption of a constitutional disease or of a specific blood infection. — None of the various theories about psoriasis suffice to account for its pathology. Accordingly psoriasis has been viewed as the expression of an assumed dia- thesis (dartrous, rheumatic, &c.), or as a definite constitutional disorder (syphilis, malaria, &c), or as an infection of the blood with a specific organism {Penicillium glaucum, " epider- midophyton," " Lepocolla repens "). Still certain clinical and etiological relations, which have been pointed out from time to time by various authors, may be adduced in favour of the theory that psoriasis is a constitutional disease, or at any rate a chronic infective disorder, as Kopp supposes. Among such conditions the following may be distinguished : — the diffuse and at times acute character of the eruption; its development and frequent relapses, possibly due to the effects of internal treatment; the appearance of psoriasis in several members of the same family (direct and indirect trans- mission) ; its relation to acute diseases (typhoid fever), and the influence of other irritants (the poison of syphilis and variola). Finally psoriasis may appear after injury and vaccination, starting from the seat of lesion where the specific virus has effected an entrance into the blood. None of the above conditions are conclusive ; in fact, they may be used in support of other theories of psoriasis. Inoculation experiments made with scales of recent psoriasis, which Destot 1 carried out on his own person, gave the following results. In fourteen days an ordinary pimple appeared at the site of inoculation in the right upper arm, and three distinct spots of psoriasis appeared over the elbow. He had never previously had, nor was there any hereditary predisposition to, psoriasis. As, however, the psoriasis did not manifest itself at the site of inoculation — in this the only case in human beings where inoculation was successful — this fact may be used in favour of the above theory. Unfortu- 1 Destot and Augagneur, " Inoculability of Psoriasis," ' Mem. et Compt. rend, de la Soc. des Scienc. Med. de Lyon,' vol. xxix, 1889, 2nd part; 'Compt. rend.,' 1890, pp. 131-3, 215-16. NIELSEN ON PSORIASIS. 593 nately, so far, this experiment stands alone ; and besides, the exact details of the inoculation were not stated. The cardinal objection to the general infection theory of psoriasis is the conspicuous absence of those clinical charac- teristics which mark infective diseases. Psoriasis is in fact, in its whole nature, a shin disease pure and simple; no psoriatic affection of mucosas has been demonstrated which might support this theory, just as little as there are no patho- logical changes in other organs that could be considered of the nature of an irruption of a specific virus comparable to the eruption on the skin. In short, as already mentioned, there are no complications that have a direct relation to psoriasis. The disease is unaccompanied by fever ; in a few cases (v. supra) slight subjective disturbances were stated to have been present, but these probably depended upon individual idiosyncrasy : an actual rise of temperature was never demonstrated. Finally, the general health does not suffer, as some writers have stated. Sometimes in cases of psoriasis inveterata, and more particularly in those with a character of dermatitis exfoliativa the general health is affected ; but this is probably due to the universal implica- tion of the skin, and not to the psoriasis as such, for we find similar disturbances of the general health when a local skin disease (e. g. favus) generalises. Hence, in spite of the apparent support certain conditions lend to such a view, it is improbable that psoriasis is a con- stitutional disorder. Psoriasis as a neuropathic disease. — Whilst several earlier writers (Tilbury Fox, Weyl, Lewin) have viewed psoriasis as a neuropathic affection from the symmetrical distribution of the efflorescences, its appearance after pregnancy, &c, Polotebnoff 1 has recently brought forward fresh evidence in support of this view, insisting on the presence of joint affections in psoriatics. In fact, his statements do not differ materially from those of Bourdillon. Both these observers have found that psoriasis is only seldom inherited (3 out of 64 cases), but nervous affections are of frequent occurrence in the relations of the patient. According to them, psoriasis is seldom the chief process, a 1 "Psoriasis," 'Monatsh.f. prakt. Dermat.,' supplement 1, i89i,pp. 141-2. 38 594 NIELSEN ON PSOEIASIS. neurotic tendency is transmitted, and the psoriasis is one of the manifold signs of the disease — a vaso-motor neurosis. Polotebnoff says he has found various forms of nerve disturb- ance in psoriatics, and, like Bourdillon, includes joint affec- tions. Certain objective nerve phenomena have also been emphasised. Rendu found in some cases of psoriasis circinata blunted sensation, and more or less definite analgesia even in healthy skin regions. Polotebnoff discovered analgesia in two psoriatics (alcoholics) : in one it only lasted a day ; in the other it was confined to isolated patches and their immediate vicinity. The application of electricity yielded very varying results. Among other points, the relation of psoriasis to mental emotion has been put forward as well as its chronic course, with tendency to frequent spontaneous remissions, the remedial action of arsenic, and the symmetry of the eruption. Several other French writers (Besnier, Doyon, Brocq) assume a certain relationship between psoriasis and the ner- vous system, based upon their views of athropathies in general. As regards these various considerations, as we have already mentioned, in none of our patients was any nervous affection shown to be at all frequent, and on the whole, only very few clinicians have been able to support the neuropathic theory. Even after examination of those of our patients who had joint troubles we could not make out any connec- tion between psoriasis and the nervous system (v. supra). The relation of psoriasis to mental emotion is but based on an accidental periodicity, and this very same point has been ad- duced in favour of a similar relation in the case of favus and pityriasis versicolor, in which there can be no doubt whatever about a purely accidental coincidence. Moreover the various disturbances of sensation observed by some writers in psori- atics may in part be referred to the infiltration of the skin and to other complications (alcoholism and other neuroses), without any special relation to psoriasis, as they are often met with in regions free from efflorescences. In several cases where we specially looked for such a connection we were unable to find any evidence at all. Many of the points Polotebnoff adduces appear to rest on physiological considerations as much as on anything else, e. g. acceleration of the heart's action through psychic and physical disturbance, difference NIELSEN ON PSORIASIS. 595 of temperature of corresponding regions of the body, hyperi- drosis of the axilla, &c. In short, there is scarcely an organ in which he has not found some vaso-motor disturb- ance in psoriatics. The usual symmetrical distribution of the efflorescences is so common in skin diseases of diverse origin — even parasitic (scabies and extensive pityriasis versi- color) — that this fact can scarely be used in support of the neuropathic theory of psoriasis. It is strange that Poloteb- noff regards psoriasis as seldom hereditary, for most writers, including ourselves, have found heredity of weight as an etiological factor. None of the above considerations seem to claim our adhe- sion to this theory, which certainly does not accord with the slight influence psoriasis has on the general health, with its chronic and indeterminable course, or even with the bene- ficial effects of arsenic at times. On the other hand, purely local treatment gives better results than arsenic ; the rela- tion of psoriasis to the seasons, the favorable influence at times of acute and chronic diseases, and its more frequent manifestation in males — especially after the twentieth year, although previous to this age there is no material differ- ence in the two sexes — do not appear to bear out this theory, according to which we should expect the mucosae as well as the skin to be affected. Again, although the relation of psoriasis to external irritants is regarded reflex in charac- ter, it is still inexplicable why an interval of a week should elapse after the application of Kbbner's experiment before there is any sign of efflorescence in the scratch-mark. Still less does this theory explain those cases in which psoriasis, with no hereditary taint and after totally insignificant ex- ternal causes, especially after vaccination, even when unsuc- cessful, manifested itself some days afterwards at the seat of inoculation. Bourdillon's statement that a thickening and shedding of the epidermis often result from nerve lesions proves nothing, for the simple reason that psoriasis is of quite a different nature ; besides, no one has recorded a case of psoriasis appearing after a nerve lesion. From none of the numberless examinations of the nerves in psoriasis patches (Leloir, Vidal, Neumann, Kromayer, &c.) has any pathological evidence been forthcoming that will support such a theory. 596 NIELSEN ON PSORIASIS "We may conclude, therefore, that a neuropathic origin for psoriasis is not probable. Psoriasis as an idiopathic affection. — Several of the older writers (Cazenave) regarded psoriasis as a substantive disease of the skin, often hereditary, and sometimes acquired only after certain profound changes in the skin due to other diseases, e. g. infectious diseases. F. Hebra and 0. Simon apparently entertained this view, and compared the hereditary character of psoriasis with the black skin of the negro and congenital nsevi. Kobner's experiment — psoriatic efflores- cences appearing at the site of irritation — forced the older authors to admit a predisposition on the part of the skin — a psoriatic diathesis to develop psoriasis under various ex- ternal and internal causes. According to Kobner, this diathesis was often hereditary, sometimes acquired, and might remain latent for an indefinite period. In this way he accounted for the sites of predilection, the temporary results of local treatment, and the great tendency to recurrence. Later on, Wutzdorff developed this theory, always assuming a congenital predisposition of the skin. This theory rests only on the relation of the disease to irritation (external and internal), and on its assumed here- ditarinees. There are several grounds for objection to it. For there are diverse forms of irritation, varying in intensity, that play an important part in the evolution of skin diseases of widely different origin (urticaria, lichen ruber, syphilis, variola, scabies, favus, &c), and therefore no great weight need be attached to such a causal relationship to psoriasis. This skin diathesis, further, is not peculiar to psoriasis, for these patients may get other skin diseases (eczema, derma- titis), and, as a rule, are just as susceptible to other skin affections as other people. Further, the hereditariness of psoriasis is not proved, and even in the light of the most favorable statistics such an hereditary disposition does not obtain even in half the cases on record. The fact that psoriasis, in spite of repeated traumatism even in hereditary cases, occurs as a rule only several months after birth, can only be referred, like the long periods of remission, to some unknown latent condition. This theory does not explain the punctiform and late appearance of the efflorescence in NIELSEN ON PSORIASIS. 597 Kobner's experiment, the scattered macular eruption, the growth of the rash, &c. Thin, who supports Kobner's theory, rather accounts for the peripheral growth of the eruption by an infective process spreading to the neighbour- ing cells. This theory distinctly approaches that of local parasitism. The weak point is that we know nothing of the nature of the skin proclivity to such parasitism. We can only state that the patient who has or gets psoriasis shows this proclivity. This diathesis is not, therefore, unlike the diathese dartreuse which is regarded as conditioning psoriasis. Psoriasis as a parasitic affection. — Some of the older writers have hinted at this supposition, but it was Lang who first formulated it. In the first place l he showed from its clinical characters a similarity to other know dematomycoses ; then s he found the presence of a presumed fungus (epidermi- dophyton) constant in psoriasis scales. Lastly, 3 he published remarkably favorable results of antiparasitic treatment, though carried out in very few cases. These statements of Lang's gave rise to a series of investigations upon the nature of the fungus ; some (Bklund, Beissel, Wolff) yielded positive, others (Neisser, &c.) negative results. De Matei, on the other hand, discovered a micrococcus which he con- sidered was the cause of psoriasis. These researches, how- ever, fell to the ground when Eies demonstrated that the presumed fungus of Lang was an artificial product. Since then no other specific micro-organism has been found. Attempts have been made by inoculation experiments on animals i and man to verify the parasitic theory. After inoculating rabbits, efflorescences resembling psoriasis ap- peared in some cases (Lassar, Tommasoli) in other cases ; 1 " An Attempt at a Classification of Scaly Affections according to their Clinical Characters," ' Vierteljahressch. f . Derm. n. Syph.,' 1878, pp. 433-44. 2 " Preliminary Communication of a New Discovery in Psoriasis," ibid., 1879, PP- 2 57-63- 3 " The Treatment of Psoriasis," ibid., 1880, pp. 473-85 j cf . " Psoriasis " in Volkmann's ' Collection of Clinical Essays,' No. 208, 1881, pp. 1765-88. 4 It is very doubtful whether psoriasis ever occurs in animals. Several veterinary pathologists (Prof. Bang, Friedberger, Frohner) state they have never observed it in domestic animals. In some instances (HSring, Hafner, Janzer, Tenholt) of accidental communication of psoriasis from animals to man it would appear that it was, after all, herpes tonsurans. 598 NIELSEN ON PSORIASIS. where rabbits and guinea-pigs were used, the result was always negative (De Amicis, Ducreyi Campana, and others). The result was always negative in man (Alibert, Wutzdorff, De Amicis, Ducrey, Hammer, Block) except in Destot's case mentioned above, which, however, as he represents, can neither be used for nor against the theory of psoriasis being a local parasitic disease. These experiments in man have not been numerous, although the methods have been various — inoculation with the blood, scales, and actual transplantation of the skin of a psoriatic. So far nothing has resulted from them to bring the question of parasitism nearer solution. On the other hand, we are not justified in laying aside this theory for the want of agreement with parasitic or, at any rate, undoubtedly infectious skin diseases. For, in spite of numerous researches, we have not been hitherto success- ful in demonstrating the micro-organism in certain con- tagious forms of alopecia areata, as well as in several other apparently parasitic affections, e.g. eczema seborrhceicum. If psoriasis be caused by some form of schizomycetes sparsely distributed and difficult to differentiate (cf. de Matei), and not by one of the hyphomycetes, we have in lupus an example of the difficulties that beset such a discovery. Moreover all of us are well acquainted with analogous difficulties in successful inoculation with other well-known dermatomycoses ; e. g. pityriasis versicolor, where inoculation has succeeded in very few cases indeed (Kobner, Huble). In fine, the general clinical and etiological characters of the disease can only be relied upon in support of this as in other theories, as Lang originally showed. The last-named writer lays particular stress upon the identity of the form and growth of the efflorescence in psori- asis with those of other dermatomycoses — its punctiform origin, its peripheral growth with sharply defined margin, its circinate and gyrate configuration, and its resemblance when diffuse to pityriasis versicolor. The various changes in the skin may be readily explained by the slow or speedy growth of the fungus, the stationary condition of certain psori- asis patches, and the varying development of others; further, the acute exacerbations with scattered efflorescences may be NIELSEN ON PSORIASIS. 599 accounted for by the dissemination of the fungus. In these particulars psoriasis is in complete harmony with other der- matomycoses. No other theory accords so well with the distribution of the eruption, now in grouped aggregations, now as satellites to extensive patches, or again in a serpiginous form, due to the confluence of contiguous circles. Lang accounts for the sites of predilection by referring to the natural characters of the skin which favour the develop- ment of the fungus. The skin over the elbows, knees, and shins is frequently thickened, somewhat rough and furfu- raceous. External irritation (pressure and friction of the clothes, &c), which goes to produce such a condition of the skin, has always a most important bearing on the localisation of psoriasis as well as in other parasitic diseases, if not to quite the same extent. However, the localisation of these diseases is not always the same, probably because the different (anatomical and physiological) characters of the skin, i. e. the soil, are determined by the different regions (flexor and extensor surfaces), and, above all, by varying conditions of life. Thus favus (P. Hebra, Kaposi), besides attacking chiefly the scalp, may also like psoriasis, and unlike dermatomycosis circinata, affect the extensor aspect of the extremities and the trunk. Symmetrical distribution of the eruption occurs in well-recognised parasitic diseases (scabies, dermatomycosis circinata) just as definite as in psoriasis, and is readily explained by anatomical and physiological con- siderations which offer a similar soil for the development of the organism in connection with the usual bilateral external causes of irritation. The nails are attacked by mycoses just as by psoriasis, and, as Lang points out, the diseases are analogous (cf . Kaposi, &c.) . The palms, according to Lang, are as rarely affected with psoriasis 1 as with other dermato- mycoses, and the mucosae are never attacked. 2 Psoriasis must, therefore, be regarded as a purely local affection ; and, just as is the case with other dermatomycoses, no internal 1 As above mentioned, this localisation is not after all so seldom as is usually stated, and the same may possibly hold good in Triehophyta palmse (cf. ' Monatsh. f. prakt. Derm.,' 1887, No. 23, abstract from "Congress in Pavia," Pellizari). s Kaposi has seen a remarkable and unique case of favus where the autopsy showed favus foci in the mucosae of the oesophagus and stomach. 600 NIELSEN ON PSORIASIS. disease can be shown to have any share in its causation. From a pathological point of view no objection can be urged against this theory, and in respect to sex and age nearly similar conditions hold good for psoriasis as for favus and dermato- mycosis circinata. The difference in point of frequency of the sexes affected with psoriasis is probably due to the greater exposure of males to infection. Favus also occurs more in males than in females. Lastly, psoriasis resembles other dermatomycoses in its irregular distribution, in its relation to the seasons, and in its relative frequency com- pared with other diseases of the skin. Among circumstances apparently antagonistic to this view Lang cites heredity, which he rather regards as a predisposing factor. It is well known that the transmissibility of a para- sitic disease, under the ordinary conditions of life, depends on the nature of the soil, i. e. the skin, and varies greatly in different people even under the same conditions. But as psoriasis occurred most frequently in the patient in whom there was direct heredity, and somewhat less so in two or more of the same offspring — circumstances which do not of themselves support the hereditary character of the disease — we may also assume that there is a predisposition on the part of the skin (a more suitable soil for the develop- ment of the fungus) which is inherited, and may possibly be not of infrequent occurrence. In fact, we assume exactly those conditions which we believe to exist in the integument of a person liable to any parasitic affection. As regards the second and equally important factor in parasitic skin diseases, viz. the source of infection, it is close at hand where parents or relatives of the patient are affected with psoriasis. As already mentioned, it begins much more fre- quently in those children where the disease is in the direct line of descent than in others. If it is really a question of infection, and not heredity, we ought then to meet with cases where the parents have been attacked after the children — a possibility which has hitherto never received any considera- tion. In one of our patients actually the mother had psoriasis for the first time long after the daughter. But as psoriasis manifests itself more frequently in early age, such cases must always be few and far between. NIELSEN ON PSORIASIS. 601 It has been urged against the parasitic theory that no case is on record where infection took place between indivi- duals living under the same conditions and not related, e. g. between married persons. Lang refers this circumstance to the absence of skin predisposition, and cites in evidence of this the exceeding rarity of infection of pityriasis versicolor, where actually the fungus abounds in the superficial layers of the epidermis. Even in favus where several members of the family use the same comb and brush, they have escaped infection. 1 Further, Lang thinks that once attention has been drawn to the question of infection, such cases will pro- bably be found ; but if psoriasis be viewed a priori as non- parasitic, cases illustrating a possible etiology of infection will be either overlooked or explained away. In spite of neglect of observation we have been able to collect several cases in which infection was probable. At the Congress of 1884, held in Copenhagen, Dr. Unna communicated a case where three children without any family history developed psoriasis in quick succession, shortly after a nurse suffering from it had been engaged. Among our private patients a similar case occurred, but only one child was affected. In six of Poor's cases 2 (66 hereditary cases) psoriasis was present in both parents, and in one of our cases both maternal grand- parents had the disease. Hammer 3 records a case where father and daughter were treated at the same time for a primary attack of psoriasis from which the mother and aunt had suffered for some time. One of McCall Anderson's 4 patients was attacked with psoriasis whose wife had suffered for years from the disease. Aubert 6 relates two cases where the husband had psoriasis and the wife developed it later on. A patient of Augagneur's 6 suffering from trade eczema deve- loped psoriasis in the eczematous region, have occupied a 1 This has frequently heen pointed out in the Annual Eeports of the General Hospital, Copenhagen. Formerly, indeed, the infectiousness of favus was explained hy heredity (Alibert). * ' Schmidt's Annual,' vol. lxxviii, 1878, p. 148. 3 " Psoriasis Vulgaris," ' Transactions of the Medical Clinic,' Wurzhurg, vol. ii, 1886, pp. 404-5. 4 ' Psoriasis and Lepra,' 1865, p. 37. 5 " Discussion on the Inoculability of Psoriasis," Destot and Augagneur, loc. cit., p. 132. 6 Ibid. 602 NIELSEN ON PSORIASIS. bed in the hospital for four months between two psoriatics. Similarly another patient showed psoriasis on the site of an artificial dermatitis. As these cases are adduced in sup- port of the parasitic theory, we must assume that psoriasis appeared then for the first time, although it is not expressly stated. Lastly, Dr. Beissel 1 gives particulars of two brothers who went on their travels together, and of two cousins who occu- pied the same bed, where psoriasis appeared for the first time shortly after. These cases are perhaps of not so much value, on account of the relationship of the patients ; more- over the grandfather of the two cousins suffered from psori- asis. The patients themselves sometimes state they have caught the disease. One of our patients maintained he had got psoriasis — first attack on the shins — through wearing the trousers of another man suffering from it ; such statements naturally should be received with caution. All the above cases of infection are proportionately few in number ; still, in conjunction with the other circumstances stated above, they throw doubt upon the theory of heredity, and certainly urge us to further researches in this direction. Lang explains the presence of psoriasis appearing some- times at the seat of irritation by inoculation on a soil that has thus been suitably prepared. He cites the analogous instance of the dissemination of the dermatomycoses through scratching (favus, Aubert). Inoculation of irritated or pre- viously diseased regions (eczema) may be presumed to be much easier in parasitic diseases when not only the para- sitic elements are present in the efflorescences, but actually scattered over the healthy skin, e. g. in a case of extensive favus (Kaposi). Where scratch-marks are the sites of the eruption, which are not rare in psoriasis, and are often seen in ecthyma and impetigo contagiosa (Fox), it is only natural to conclude that the nails have effected the inoculation. But what renders this more probable is Kobner's experi- ment, which, strange to say, Lang does not sufficiently accentuate. The scratching is quite superficial, does not extend to the dermis, and no bleeding takes place. The effloi'escence only appears during the evolution of psoriasis, 1 ' Aix-la-Chapelle as a Health Eesort,' 1889, p. 130. NIELSEN ON PSORIASIS. 60S and not always then, especially when several scratches are made. The spots appear in the course of eight to ten days, never later ; they are punctate and situated in the scratch itself. These circumstances, particularly the manifestation after a tolerably definite period of incubation, 1 seem to show that an actual inoculation 3 has occurred. It is not probable that psoriasis should appear in this way were it related to a general blood infection. Kobner never succeeded in pro- ducing psoriasis efflorescences in syphilis ; and certainly no other theory of pathogenesis affords so natural an explana- tion of this phenomenon. In those infrequent cases where psoriasis was manifest for the first time in irritated arese (wet cupping, compresses, &c. — v. supra), or in regions already diseased, and where no " hereditary taint " was present, the parasitic theory offers the most reasonable solution. This holds good particularly in those case where a primary attack of psoriasis supervenes on vaccination (v. supra). The efflorescences appear at the site of inoculation, either after the detachment of the seat or in the course of a few days in cases of unsuccessful vaccina- tion, and subsequently spread acutely. In two cases at least Rohe expressly states that there was no history of psoriasis. It may be objected that animal lymph was used, and that 1 Kobner (' Klin. u. experim. Mitth. aus d. Derm. u. Syph.,' Erlangen, 1 864, p. 23) discovered on inoculation of human beings with Trichophyton tonsurans that the eruption appeared in four to five days, in rabbits about eight days. Several days also were required for the development of Aehorion Schonleinii. s If this theory be correct we should not expect any efflorescences to develop if Kobner's experiment is conducted under rigid antiseptic pre* cautions. We have performed Kobner's experiment in three different ways on some few occasions. The methods were carried out on the same patient. In the first method scales were rubbed into the scratch ; in the second this was not done ; in both the skin was previously rendered antiseptic, and steri- lised cotton wool applied. The third method was carried out without any antiseptic measures except the after-application of a pad of antiseptic wool. The result was negative in all three methods. Further experiments may of course be successful, but isolated positive results do not prove anything, for even under ordinary circumstances an efflorescence is only developed in one of two simultaneous scratches. Such experiments must be carried out in large numbers in patients preferably not undergoing treatment, and where , the psoriasis is in the evolution stage. 604 NIELSEN ON PSORIASIS. psoriasis scarcely occurs in calves. The source of infection, however, cannot always be traced, as Hager 1 has shown in epidemics of herpes tonsurans (or impetigo contagiosa) which appeared at the site of inoculation immediately after vaccination with animal as well as human lymph. As the liability to parasitic skin affections varies with different persons, so probably in the same person transient, and especially (persistent) disturbances of nutrition of the shin must largely influence this proclivity. Lang sees in this circumstance, as Kobner previously stated, an explanation of the curative influence which other diseases accompanied by profound tissue change or by fever exert over psoriasis. After cessation of such disturbances the eruption usually returns. Parasitic diseases like favus, scabies, are analogous examples. It is not uncommon for dermatomycoses like psoriasis to disappear spontaneously. Prom such a standpoint we may account for the retrocession of psoriasis during pregnancy, its return during lactation, as well as the influence which alteration in the habits of life often exerts over the disease. As regards the deteriorating effects of alcoholism and rheumatism on psoriasis, we shall not be far wrong in maintaining that the skin is rendered more suitable for the development and growth of the organism, just as we rightly assume that certain conditions increase and certain others decrease its sensitiveness. Against Lang's theory it has been urged that psoriasis may disappear upon internal treatment only. Lang makes the remark that in such cases the arsenic, even in such small quantities, in the blood may act antiparasitically, 2 as is the case with large doses of iodide of potassium, thus rendering the skin no longer a favorable medium for the propagation of the organism. Moreover internal treatment alone is not by any means successful, and it is almost always combined with external measures, which are nowadays regarded as the most reliable. Brocq 3 states that formerly internal treat- 1 "Animal Lymph and Herpes Tonsurans," 'Berl. klin. Wochenschr.,' March 5th, 1888, p. 197. 2 Unna (' Vierteljahresschr. f. Derm. u. Syph.,' 1880, p. 550) puts forward the same supposition in a case of psoriasis gyrata cured externally with an ointment of vaseline containing potassium arsenite (1 in 30). 3 ' Treatment of Diseases of the Skin,' 1890, p. 704. NIELSEN ON PSORIASIS. 605 merit was everything, whereas to-day it has fallen into dis- repute. The most effective external remedies are indeed those we view as antiparasitic in action — chrysarobin 1 and tar preparations. Lang especially has employed antipara- sitic remedies, laying particular emphasis on the method of application and retaining the patients in hospital some time after all trace of psoriasis has disappeared. The results of his treatment were materially better as regards permanency of cure and absence of relapse than those obtained by the usual methods, where, as a rule, not so much importance is attached to the complete disappearance of every efflorescence before the patient is discharged. Further, psoriasis is stated by other writers (Devergie, Brocq, Eichhoff, Schultz) to be much less liable to relapse after external treatment when every trace of it has been removed. But satisfactory in- vestigations in this direction have still to be made. Meanwhile the constant tendency to relapse and the implied incur ability of psoriasis militate against this theory ; but, as Lang pertinently remarks, pityriasis versicolor, as is well known, is most frequently subject to relapses even after repeated treatment. Bienstock 3 believes that it is quite possible that infective fomites exist on the sound — and there- fore untreated skin — and cause the relapse. He therefore con- siders it advisable, as is done in the dermatological clinic in Breslau, to submit the whole skin to treatment with mild salicylic acid and /3-naphthol ointments for several weeks after the psoriasis has been cured. In certain cases the occasional return of psoriasis to the same regions after long intermission, and apart from the predilection sites, may pos- sibly be accounted for by the persistence of spores (in the epidermic layers ?). Hardy makes this assumption in dermatomycoses, which recur after weeks' or even months 5 apparent cure.' The most probable reason of these constant relapses, according to this view of its pathogenesis, is that treatment has never been carried out so thoroughly as in cases 1 Bienstock sees in the curative action of chrysarobin, pyrogallic acid, and anthrarobin a further proof of the parasitic nature of psoriasis. These drugs absorb oxygen, and so bring about the death of the fungus. 2 "Therapeutics of Psoriasis," Inaugural Dissertation, Breslau, 1888, pp. 34-5- •606 NIELSEN ON PSORIASIS. of known parasitic disease. No great weight has been attached to the importance of removing every trace of psoriasis, of keeping the patient under observation for some time after, as in favus, and certainly not of disinfecting the ■clothes, bedding and toilet articles (brushes, comb, &c), as is the generally followed routine method with scabies and favus. Lang, who relegates the skin proclivity to the back- ground, does not accentuate the importance of such details. Another feature, and one which has hitherto escaped notice, is the not infrequent presence of psoriasis in other members of the family, and the liability to reinfection owing to the assumed existence of the parasite apart from the skin in a susceptible patient. These considerations are in themselves sufficient to explain the frequent relapses, a characteristic which is almost indispensable to the correctness of the theory, even where there have been complete intermissions, lasting in some cases for many years. Of course it is still open to question whether these are really intermissions, or not, after all, remissions with a few persistent spots in the predilection sites that may have escaped notice. Hence we should not lay it down as an absolute rule that psoriasis is incurable, and, as Lang states, cases of definite cure have been recorded ; on the other hand, in the light of the above-mentioned statements about intermissions of several years' duration, no great value should be attached to such records. Although we have no real proof for the parasitic theory, still Lang's statements, which we are in a position to confirm and materially to supplement, establish its probable correct- ness, be the causes either hyphomycetes or schizomycetes. In reviewing the other theories of psoriasis it is evident that several important points remain either inexplicable, or their solution is sought in various dubious relations between psori- asis and other diseases. The pathogenetic theory which in comparison with others best meets the arguments is that of psoriasis being a general infectious disorder. It must, therefore, agree in its main features with local parasitism. The fact that there are not many adherents to this view is probably explained by the non-success of researches for the micro-organism, the firmly rooted impression of heredity, NIELSEN ON PSORIASIS. 607 and the incurability of psoriasis. On the other hand, suffi- cient weight is not attached to the condition of the nutritive medium, i. e. the skin, when the question of parasitism arises. For not only does this condition vary in different persons, but even in the same person, and depends neces- sarily on tissue change as a whole, and its effects may be quite unlooked for. These circumstances have not been sufficiently studied hitherto. Were it not that the parasite in pityriasis versicolor is well known, as Lang has more than once pointed out, more objections could be urged against the parasitic causation of it than in the case of psoriasis. The chief practical result of this theory is the employment of energetic antiparasitic treatment (especially chrysarobin, tar preparations, &c, in conjunction with baths) applied locally as Lang recommends. Internal treatment (arsenic and iodide of potassium) must be viewed under certain con- ditions only as an auxiliary measure, and possibly as expe- diting cure. At all events, every trace of eruption should be got rid of, and, as Bienstock advises, the whole skin itself should be afterwards treated, and the patient kept under observation for some time. In order to prevent any possible reinfection, the clothes, bedding, and all articles that might harbour fomites should be thoroughly disinfected. Even then in cases where the patient's relations suffer from the disease, and are living under the same roof, reinfection may take place unless they are submitted to similar treatment. It is only when the treatment and precautions used in recog- nised parasitic diseases are employed that we may expect to cure psoriasis definitely, and without any chance of relapse. INDEX. Although a tolerably detailed Index to Dr. Morrow's paper on Drug Erup- tions has already been given (see p. 566) yet it has been thought it might serve the reader's convenience to give here a brief General Index to the contents of the volume as a whole. Acetanilide (antifebrin), 415, 542 AchobioV, 65 Acidum arseniosum, 425 — bensoicum, 400, 540 — boracicum, 401, 402, 540 — carbolicum, 128, 403, 540 — chrysophanicum, 405, 540 — nitrioum, 408, 540 — phosphoricum, 518, 563 — picricum, 408, 541 — pyrogallicum, 51, 408, 541 — salicylicum, 68, 409, 541 — tannicum, 413, 541 Acne, 70 — treatment of, 83 Acne bosacea, 23 — treatment of, 83 Aconitum, 413, 541 Agab, 66 Alcohol, 414, 541 Alcoholism, 101, 585 Ammonii bromidum, 440 — iodidum, 486 — picratum, 541 Amygdala amaea, 414, 542 anacabditjm, 414, 542 Anemia, universal, 1 — local, 4 Angionettboses, 38 — cases of, 42 — classification, 44 Aniline, 415, 542 Antibebbin, 542 Antimonittm, 416, 417, 542 Antipxbin, 417, 543 APHTHB, 48 Ababoba, 405 Aegenti niteas, 421, 544 Aenica, 422, 544 Absenicitm, 167, 296, 425, 545 abtebial nebte appabattts, 11 Asthma, bronchial, 100 Ava or Kata, 436 Balsam, Friar's, 540 BALSAMUM PeBUVIANTTM, 436, 547 Baths, 295 Belladonna, 437, 547 Benzoate op Soda, 400, 540 Benzoin, 400 Benzole, 440 Bibliogbapht, general, 538 — special, 540, et seq. blcheomate op potash, 521 Boeate op Soda, 401, 540 Bobax, 401, 540 Bobic acid, 401, 402 Bbomine and beomides, 440, 548 pathogeny, 450 pathological anatomy, 448 tests for, 450 treatment, 451 Bubgundx pitch, 519, 563 39 610 INDEX. Calcium sulphide, 71 Calx sulphubata, 452, 549 Cannabis indica, 453, 550 Canthabis, 453, 550 Capsicum, 455, 550 Cabbolic acid, 128, 403, 540 Cabbol sublimate ointment, 61 Caebon monoxide, 173 Cabdol, 414, 542 Castob oil, 512, 562 Catabbh, bronchial, 101 Chinolin, 455, 550 Chlobal, 455, 550 — diagnosis, 461 — eruptions from, 456 — pathogeny, 460 — tests for, 461 — treatment, 462 Chlobalamide, 462, 551 Chloeate oe potash, 524, 564 Chlobopobm, 462, 551 Choleka, 2, 19 Chbomates, 427, 523 Chtsabobin, 51, 80, 104, 405, 540 Cinchona et quinlje sulphas, 463, 551 — diagnosis, 470 — eruptions from, 463 — pathogeny, 470 — tests for, 471 — treatment, 472 Cinchonidia, 554 Classipication, 364 Cocain, 71 Cod-liveb oil, 512, 562 Cold, 5, 15, 24 Cold ceeam, 78 Condubango, 472, 554 Conium, 472, 554 Copaiba, 472, 554 cobona veneeis, 54 Ceoton oil, 512, 562 Cubebs, 472, 554 Cyanosis, 23 Dal, 478 Deematitis herpetiformis, 182 — bullosa, 190 Deematitis erythematosa, 187 — multiformis, 194 — papulosa, 193 — pustulosa, 191 — vesiculosa, 188 For Table of Contents see 178 Debmatology, contributions to, 152 — anatomical and physiological, 152 — histological and bacteriological, 162 — miscellaneous, 164 — pathological, 154 — therapeutical, 158 Digestion, 100 Digitalis, 476, 554 Dbug ebuptions, characteristics, 364 — classification, 364 — definition, 362 — diagnosis, 395 — etiology, 369 — history, 361 — idiosyncrasy, 371 — pathogenesis, 373 — prophylaxis, 397 — symptomatology, 388 — treatment, 397 Duloamaba, 477, 555 Dyes, 426, 427, 523 Eczema mercuriale, 361 — paste for poor, 77 — seborrhoicum, 132 — treatment, 74 Elephantiasis pilabiosa, 26 Endabtebitis oblitebans, 9 Ebgot, 478, 555 Ebgotine, 3 Ebysipelas, treatment of, 89 Eeythemata, 20, 41 Etiology of drug eruptions, 369 Fayus, varieties of, 64 Peebum, 479, 555 Ploba deematolosioa, 135 Peiae's balsam, 400, 540 Fungi, epidebmic, cultivation of, 132 Pueunculosis, treatment, 87 Giant-cells, 146 Qlyceeine jelly, 76 INDEX. 611 Granuloma fungoides, 316 Guarana, 479 Guaiacum, 479, 555 gurgun oil, 479 hemophilia, 33 Hemorrhage, 30 Heeees zobteb, 578 — during arsenic administration, 167 — synopsis of cases, 174 Hot water, 72 Hydrargyria, 361, 480, 482 Hydrargyrum, 361, 427, 479, 555 Hyoscyamus, 485, 557 Hyperemia of skin, 10 — relaxive, 18 — obstructive, 22 Iohthyol, 51, 69, 83, 295 — use in internal diseases, 99 Idiosyncrasy, 371 Impetigo herpetiformis, 179 INFECTIVE DISEASES, acute, 3 Inflammatory fungoid neoplasm, 317 Inunction, 79 Iodine and iodides, 486, 557 — diagnosis, 504 — eruptions from, 486 — pathogeny, 501 — tests for, 504 — treatment, 505 Iodoform, 506, 560 Ipecacuanha, 510, 560 ' Itching, sensation of, 299 Joint affections, 581 Lanolin, 91 Lead, acetate of, 520, 564 — carbonate of, 520, 564 Lepra tuberosa, 50 Leucoderma, 571 Leucoplakia, 48 Lichen acuminatns, 58 — obtusus, 60 — planus, 60 — ruber, 59 Lingua geoghaphica, 47 Lithii bromidum, 440 Lupus, 128, 145 — treatment, 85 Lymphademe cutanee, 317 Maize, damaged, 347, 352 Mast-cells of Ehrlich, 149 Mercury, 427, 479, 555 Mioro-organisms, staining, 140 — methods, 143 Morphia, 513, 515, 562 Mustard, 532, 565 Mycosis fungoide, case of, 317 — description of plate, 340 Nails, 111, 572 Nerves of skin, 113 Nerye-endin&s, 106 Nervous disease, 584, 593 Nitrate of silver, 421, 544 Nitric acid, 408, 540 Nux vomica, 510, 562 (Edema, mechanical, 25 — inflammatory, 29 Ointment soaps, 95 Oleum cadini, 511, 562 — caryophylli, 128 — dipterocarpi, 479 — morrhuae, 512, 562 — ricini, 512, 562 — santali flavi, 512, 562 — terebinthinse, 535, 566 — tiglii, 512, 562 Onychin, 111 Opium, 513, 562 Organs of reinforcement, 305 Pain, sensation of, 309 Palm, circular exfoliation of, 46 Paralysis, 6 Pastes, 78 Pathogenesis of drug eruptions, 373 Pellagra, Berger on, 341 — 353 — contagiousness, 346 — etiology, 347 — heredity, 345 — organs affected, 345 612 INDEX. Pellagra, pathological anatomy, 346 — prognosis, 351 — prophylaxis, 352 — stages, 344 — theory of, 347 — treatment, 351 Pebspibation, 122 Phenacetin, 518, 563 Phlegmasia dolens, 26 Phosphorus, 518, 563 Picbate of ammonium, 408, 541 Pigment of skin, 117 Pimpinella, 519, 563 Pix Burgundica, 519, 563 — liquida, 519, 563 Plasma-cells, 145 — of Waldeyer, 149 Plasteb-mulls, 75, 81, 91 Plumbcm, 520, 564 Podophyllum peltatum, 521, 564 Poison, ivy eruption, 526 — treatment, 529 Potassii bichromas, 521, 564 — bromidum, 440, 548 — chloras, 524, 564 — iodidum, 486, 557 Powder bag, 73 Prickle cells, 108 Prophylaxis, 397 Pbueittts, 299 pselaphesia, 306 Psoeiasis, complications, 578 — course, 574 — duration, 576 — etiology, 579 — frequency, 591 — geographical distribution, 591 — localisation, 571 — nature, 571 — palmaris, 56 — pathogenesis, 592 — relation to other diseases, 581 external irritation, 588 physiological conditions, 589 mental emotion, 590 the seasons, 590 — theories, 592, et seq. — treatment, 80 Purpura, 33 Pyrogallol, 80, 408, 541 Qunnrai sulphas, 463, 551 Raynaud's disease, 7 Refbigebating ointments, 92 Resin, 524, 564 Resoecin, 51, 71 Rheumatism, 101 Rhubabb, 525, 564 Rhus diversiloba, 564 — toxicodendron, 564 — venenata, 564 Rosacea, 100 Rue, essence of, 565 Sailors' skin, 150 Salicylate of soda, 541 Salve-mulls, 74 Santal, 512 Santonate of soda, 531, 565 Santoninum, 531, 565 Scratching, 312 Seborrhea, 99 Sensation, common and special, 301 Sensoby- organs, evolution of, 302 Sheep-washing, 429 Sinapis, 532, 565 Skin, anatomy of, 106 — therapeutics of, 68 Smallpox, 18 Soaps, medicated, 95 Sodii benzoas, 400, 540 — boras, 401, 540 — bromidum, 440, 548 — iodidum, 486, 545 — salicylas, 409, 541 — santonas, 531, 565 Stramonium, 532, 565 Strychnia, 3, 510, 562 Sulphide of calcium, 452, 549 Sulphonal, 533, 565 Sulphur, 294, 452, 533, 566 Sycosis, hyphogenic, 62 — coccogenic, 63 — bacillogenic, 63