CORNELL ! UNIVERSITY LIBRARY GIFT OF Hauck Memorial Fund PELLAGRA > : Sd : i . = 5 os a : : ’ . : 4 i : F - , : i : . . mi 5 i 3 < . ‘ : ° ° : : ree Se eer teat : % * . : . ‘ . s a : : : H . ye . ee : . : 5 : Me . , : ‘. . a ss a . . : ms, . © ‘, . . . 2 : *, : : . : . * ‘ si . . . 4 : *@ . a a . . Epwiva yoo y0-- ner nee | oree, Diagrammatic cross section of the spinal cord of a pellagrin, the parts 1, central canal; 2, column of Clarke; 8, tract of Burdach; 4, tract of Goll; 5, tract of de Lissauer; 6, posterior in red representing the lesions. roots. (Procupiu, after Babes.) See page 145. PELLAGRA HISTORY, DISTRIBUTION, DIAGNOSIS, PROGNOSIS, TREATMENT, ETIOLOGY BY STEWART R. ROBERTS, S. M., M. D. ASSOCIATE PROFESSOR OF THE PRINCIPLES AND PRACTICE OF MEDICINE, ATLANTA COLLEGE OF PHYSICIANS AND SURGEONS, ATLANTA, GEORGIA; PHYSICIAN TO THE WESLEY MEMORIAL HOSPITAL; FORMERLY PROFESSOR OF BIOLOGY IN EMORY COLLEGE WITH EIGHTY-NINE SPECIAL ENGRAVINGS AND COLORED FRONTISPIECE ST. LOUIS C. V. MOSBY COMPANY 1912 V& A QL 24\ REY /4—- RCS 77 CoPpyYRicuT, 1912, By C. V. Mossy ComMPANy Press of C. V. Mosby Company St. Louis dds Ay Qa To THAT LONG LINE oF PHYSICIANS AND SCIENTISTS FROM CASAL THROUGH LOMBROSO TO SAMBON, AND THOSE WHO SHALL COME AFTER THEM WHO HAVE BEEN AND ARE AND SHALL BE STUDENTS OF PELLAGRA, THIS VOLUME IS DEDICATED BY THE AUTHOR, WITH THE HOPE THAT THE DAY IS NOT FAR DISTANT WHEN THERE SHALL ARISE FROM AMONG THEM ONE TO WHOM SHALL BE REVEALED WITH CLEAR AND CERTAIN PROOF THE TRUE CAUSE OF THE MAL DE LA Rosa. PREFACE. This is a book on Pellagra for the student and the practicing phy- sician. It is not merely a discussion of Pellagra, nor is it devoted to upholding any special theory of etiology. At the present time it is impossible to have a book of this size contain the entire data concerning the disease. It is not only im- possible to include all such matter, but it would be also useless. We need the essential facts of the subject—we need to know its pathol- ogy, its diagnosis, and its treatment. There has been entirely too much speculation on Pellagra, and entirely too little investigation of Pellagra. It is a pleasure to express my thanks to all those who have studied and written extensively on the disease. Among these are Casal, the elder Strambio, Jansen, Frapolli, Lombroso, Roussel, Hirsch, Sam- bon, Marie, and the contributors to the National Pellagra Congress of 1910. Other acknowledgments are made throughout the book. I wish to thank Dr. Eugenio Bravetta, of Mombello, province of Milan, for many photographs, and especially for his aid in the study of his pathological sections, for the preparation of which he deserves much credit. I am particularly indebted to Dr. E. M. Green, clinical director of the Georgia State Asylum for Insane at Milledgeville, for per- mission to use his valuable work and classification on ‘‘Psychoses Accompanying Pellagra,’’ and to Dr. 8S. 8. Hindman, pathologist to the same institution, for permission to use his report on the cerebrospinal fluid. The chapter on Alimentary Tract in Pellagra includes the re- searches of Dr. J. Clarence Johnson, of Atlanta, on the digestive system, and I wish to acknowledge my thanks to him for his aid in the preparation of this chapter. My thanks are due to Dr. Charles C. Bass, of New Orleans, for photographs, and to Dr. J. O. Elrod, of Forsyth, Georgia, and to many others for valuable aid. Mrs. M. L. Ragin, my secretary, 7 8 PREFACE, has been of much assistance in the preparation of the manuscript and the index. ; Finally, I wish to express my gratitude to one whose mature wis- dom and kindly approval are always a source of constant help and cnecouragement. Srewart R. Roperts. ATLANTA, Ga., May, 1912. . WORDS OF GOETHE. The following, written by the poet Goethe in his ‘‘Italian Jour- neys ’’ (from Brenner, in the Tyrol, Austria, to Verona, Italy), September, 1786, is of peculiar interest in connection with the now supposed etiology of Pellagra: I know little, if anything, pleasing to say about the people. As soon as the sun rose over the Brenner paths in the Alps I noticed a decided change in their appearance, and especially displeasing to me was the brownish tan color of the women. Their features indicated misery, and the children were just as pitiful to behold; the men are little better, though their general features were regular and good. I believe the cause of this sickly condition is found in the continued use of Turkish and heath corn. The people call the Turkish corn also yellow grain and the heath corn black grain. These are ground, the meal mixed with water, cooked to « thick paste, and eaten in this condition. The Germans across the Alps divide the dough into small pieces and fry it in butter. The Tyrolese, on the other hand, eat it plain, sometimes with cheese on it, but eat no meat the entire year; besides this, they eat fruit and green beans, which they soak in water and cook with garlic and oil. CONTENTS. CHAPTER I. GENERAL CONSIDERATIONS . a 8 : Pronunciation — Typical cases — Definition — Deserinbion — Age — Sex — Inheritance — Contagion — Immunity — Occupation, CHAPTER IT. HISTORY AND GEOGRAPHICAL DISTRIBUTION . Synonyms — History — Geographical distribution — Spain: —_— Ttaly _— France — Egypt — America. CHAPTER IIT. CLASSIFICATION . ‘ a Nel dtp lee, bs. ay A general disease — Other infections in pallars Relation to the seasons — Incubation period — Duration — Duration of a single at- tack — Acute pellagra — Subchronic pellagra — Chronic pellagra — Stages of chronic pellagra — Pellagra sine exanthemate — Pseudo- pellagra. CHAPTER IV. ALIMENTARY TRACT IN PELLAGRA The tongue — Gums — Teeth — Buccal mucosa — Palate — Salivary glands — Pharyngitis — Esophagitis — Stomach and _ intestines — Tissue changes. CHAPTER V. SKIN IN PELLAGRA . Character — Pellagrous slaith — Dimorphous = LGiaxstieation — Loea- tion — Relation to light— Sensory symptoms— Changes in the skin. CHAPTER VI. NERvouS SYSTEM IN PELLAGRA Introduction — Tissue changes in ain and sori — Relation of end lesions and clinical symptoms— Sympathetic nervous system — Cerebrospinal fluid — Examination of cerebrospinal fluid — Pain — Reflexes — Changes in the muscular system — Insomnia — Head symptoms — Neurasthenic state — Mental state — Psychoses accom- panying pellagra. 11 PAGE 17 43 74 107 12 CONTENTS. CHAPTER VII. PAGE OrnerR SYSTEMS AND CHANGES . . . . » 2 . 185 Circulatory system — The blood — Pulse = Blood pressure — No in- fecting agent found— Tissue changes — Lungs — Temperature — Bones — Weight — Genito-urinary system — Urine — Sexual organs and functions — Organs of special sense — Eye — Ear — Taste — Touch — Smell. CHAPTER VIII. DIAGNOSIS AND PROGNOSIS . 204 Diagnosis of pellagra — During the eed. of creas ing the at- tack — During the intermission between attacks — Pellagra sine exanthemate — Prognosis in pellagra. CHAPTER IX. TREATMENT OF PELLAGRA . . 218 Treatment of avail — Improvement — Aesoetaien sudeebious = ~ "Treat ment of disease — Medicinal treatment — Salvarsan in pellagra — Chlorides — Transfusion — Diet — Hygienic measures — Baths — — Climate — Treatment of special symptoms — Dermatosis — Diar- rhea — Stomatitis — Nervous system. CHAPTER X. CAUSE OF PELLAGRA . ; 231 Cause unknown — Many ‘diferent dhestes ibs ‘dhiet eiecien as Pellagra an intoxication — Varieties of corn— Analyses of corn — Corn in Italy — Good corn the cause — Spoiled corn the cause — Argument for and against corn — Pellagra an infection — Patho- logical evidence — Ecological evidence — An insect agent — Simu- lium fly — Argument for and against an infection —Summary of theories — Outlook. ILLUSTRATIONS. Diagrammatic cross section of the spinal cord of a pellagrin . . Frontispiece FIG. PAGE 1 Pellagrous boy, showing dermatitis on hands and face 24 2 Dermatitis on hands of pellagrin 4 : : - . 384 3 Dermatitis on feet of pellagrin 36 4 Map showing distribution of a in the western half of the state of Tennessee . . 54 4a Map showing distribution of pelieeya 4 in the custay half of the stuila of Tennessee . . 55 5 Map showing distribufion of pellanea in tthe tnited States . « .56, 57 6 Pellagrosario at Rovereto, Austria. . . . & 8 @ 65 7 Group of eight boys, all pellagrins .. : me Ge Syl 0 8 Closer view of three of the boys shown in Fig. Tos oe ee ae HO 9 Map showing distribution of pellagra in the world. . . .72, 73 10 Pellagrous boy : By eia le, UB 11 Two Georgia cases, presented by the State Hedlewsen ‘Goumteion . 76 12 Same case as Fig. 11, side view wl aoctes Tal ake Lege! og - . 76 13 Diagram illustrating periods in an attack . . . . 1... (86 14 Pellagra during period of attack 87 15 Diagram illustrating stages of chronic pillage with relation ig liz: ical symptoms . . for te Ss he oe LEY, LOE 16 Intestines, showing atrophy of ag muscles , : Be, ee A 17 Section of liver , ge eo we, ALIS 18 Spleen, showing increase in connective tissue ar . 9 19 Dermatitis on hands. 122 20 Diagram illustrating the development and course of pallggioid fier Matitis « 2 » © # 2 # & 2 3 - 123 21 Insane pellagrin. . . . . . . Holey ae Le 22 Pellagrous dermatitis : : bowe ow a ow AS 23 Dermatitis > 1% ; gee ADE 24 Italian case of senile hans. in nellseee ¢ = «* w « E31 25 Wet form of dermatitis 134 26 Rough hands of a pellagrin as contradbed with the normal hands of a hospital orderly . : ‘ » & 186 27 Italian case of typical dermatitis . ‘ 136 28 Pellagrous dermatitis . . 137 29 Georgia case, showing extoliaiion of the sie following a spring ait: tack . .. ‘ gia Ie el a? ABS 30 Italian case of ainotiolis csi gO GR a ee we ae BD 31 Italian case of alcoholic erythema . . . . . . . . . . 139 13 14 FIG. 32 33 34 35 36 37 38 39 40 41 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 * ILLUSTRATIONS. Close view of the rough skin in pellagra . . . . Pellagrous dermatitis Cortical cells, showing piementary desoneration Cortical cell, showing contraction of the protoplasm . Cells from the spinal cord, showing thickening and contr setan of the neuro-fibrillar net . : Cells from the spinal cord, showing naeel thickening and contrac- tion of the neuro-fibrils . Cell from spinal ganglion, showing iasanentialy destneuaan Chromatolysis and pigmentary degeneration in cells of the cord Same case as Fig. 35, showing chromatolysis and pigmentary de- generation in cells of the cord . : Cells from the cord, showing yellow pigmentation antl deweneratien ; Same case as Fig. 37, showing cells from the cord, with yellow pig- mentation and degeneration . Spinal cord, showing the cellular body entirely fhivadell by yellow globular pigment Spinal cord, showing the vel iertially savaded by yellow globular pigment Cell is invaded in two aipestte intes by yellow siobaline pigment Partial thickening of the neuro-fibrillar net Spinal cord, showing pigmentary granular degeneration Spinal ganglia, showing invasion of the special net or ‘ViuAience’s net. Spinal con, ehowing thickening and eoncdntration of the neuro- fibrillar net * Spinal ganglia, showing changes in the fibrillar net Spinal cord, showing increase in the neuroglia in crossed pyramidal tract a Spinal cord, chowing section of Burdvch’s tract, with several fibers and primary degeneration Spinal cord, showing’section of Burdach’s tract, with numerous fibers in secondary degeneration Pellagrous insanity, showing deviate, on heath w ith exfoliation of the skin . Pellagrous insanity, showing dermatilie on fends ‘ Pellagrous insanity, a dry dermatitis, with exfoliation ee the skin Pellagrous insanity in the scold ‘ 5 Pellagrin, with dermatitis on hands, fonenrind, and altiuens : X-ray illustration of the hands of a female pellagrin X-ray illustration of the hands of a female pellagrin . : Same case as Fig. 60, cee x-ray illustration of the cee re- gion : Pellagrin after recovery erom sitbacle. Pellagra in time of intermission . PAGE 140 141 143 144 144 145 146 147 147 148 148 149 149 150 150 151 153 155 157 159 167 169 173 175 187 194 195 196 210 212 FIG. 64 65 66 67 68 69 70 71 72 73 74 75 76 17 78 79 80 81 82 83 84 85 86 87 88 89 ILLUSTRATIONS. Same case as Fig. 63, showing elbow slightly rough; hands appear normal, but covered with fine branny scales Field of Italian corn, first crop Field of Italian corn, first crop Field of Italian corn, second crop Ear of Italian corn, first crop . Ends of three ears of Italian corn, first eran Method of drying shelled corn in Italy , Corn swept into another kind of building after digiing in tie sun Cakes of yellow polenta . American corn from Georgia . American corn from Georgia . Field of American corn, Georgia One method of gathering and drying corn in Rierten Rail pens without covers, sometimes used for storing siitahncked com in America . Cribs used for diving corn in ‘the. United States Diagrammatic section of a grain of corn Cellular structure of a grain of corn Penicillium, a common mold found on corn . Ustilago maydis, a fungus that causes corn smut Simulium fly and larva Wing of simulium fly, showing qenation : Legs of a chicken showing pellagrous symptoms Legs of a chicken showing similar symptoms to those of chicken in Fig. 85 Bobbin Creek, near Athens, Ga., shes the santinn —— were first found in Georgia . Diagram showing ere weimbertiogd at Dadar Ala., anit the relation of pellagra to streams Diagram showing the relation of pellagra to streams in the a of Cornelia, Ga. . . 2. . . « 15 PAGE 213 237 238 239 240 241 242 243 244 244 245 245 246 246 247 248 250 251 252 252 252 254 255 256 PELLAGRA CHAPTER I. GENERAL CONSIDERATIONS. The manifestations of pellagra are definite only in wide limits. One case may be as different from another case as if each were a different disease. It is well, therefore, for the student of pellagra to note the varying and different symptoms of several typical cases, each case differing in course and severity from the others. PRONUNCIATION. Pellagra is pronounced in the United States in three ways. It is ealled (1) pél’la-gra—e short as in fell, first a short as in am, second a broad as in father, with the accent on the first syllable; (2) pel- 1a’gra—each a long as in fate, with the accent on the second syllable; (3) pel-la’gri—each a broad as in father, with the accent on the second syllable. Dictionaries are presumably correct, but even they differ in the pronunciation of this word. It is an Italian word, originated among the common people of Italy, and was first used in medical literature by Frapolli in 1771 in the phrase, ‘‘morbus vulgo pellagra,’’ meaning ‘‘a disease among the people called pellagra.’’ The name is therefore of peasant origin, and is a union of two Italian words—pelle, meaning skin; agro, meaning rough. The final e before another vowel is dropped, the final o of agro is changed to a; thus pelle agro becomes pell + agra, or the present word pellagra, meaning rough skin. In the Italian language the word is pronounced pél-la’gri, each syllable separately and distinctly spoken, the accent on the second syllable, and each a pronounced broad as in father. This Italian pronunciation differs from all three used in America in that the Italians use J separately in the first two syllables, while in Amer- ica the word is pronounced as if it were spelled with only one I. It is manifestly out of the question to pronounce it as the Italians do, and therefore the word has been Anglicized and is now an Eng- lish word, and to be pronounced according to English methods. 17 18 PELLAGRA. Webster gives pé-li’gri, but prefers pe-la’gra; the Century dic- tionary gives only one pronunciation—pe-la’-gra. Webster’s pref- erable pronunciation is not used at all in this country, and, since both dictionaries give pé-la’graé, and, in addition, the other two related words—pella’grin and pella’grous—are pronounced with the a long and accented second syllable, as pé-la’grin and pé-la’grus, it seems wise to use this altogether natural and easy American pro- nunciation, pé-la’ gra. TYPICAL CASES. One need not expect to find a typical pellagra. It is a disease of many symptoms and of many variations; its only consistency is its inconsistency ; it seems cured and yet recurs; the pellagrin seems to be approaching his end and yet lives for many years; it spreads and is not contagious; the offspring of the pellagrin receives his mark and. yet it is not inheritable; it is not and appears; it is and disappears; it is a morbid entity and yet it contains within itself many lesser morbid entities; it falls with equal right in the sphere of dermatology, neurology, and gastrology, and yet it is a general disease; divers diseases become one, and this one is called pellagra; there is no pellagra—only the pellagrous. The following cases are selected with a view of illustrating differ- ent pictures of the same disease in reference to severity, marked improvement, early death, pellagra in the negro, termination in in- sanity, and general clinical symptoms common to pellagrins. It is well to understand and keep in mind the general picture of the disease, but it is well also to remember that this picture is a com- posite picture, made up of widely different and apparently unre- lated pictures, imposed one upon the other in all imaginable angles, and each individual picture, as well as the composite result, vary- ing in hue and aspect in each case and in every season. No disease is so plain as pellagra in the early spring, and no disease so obscure as pellagra in the same patient in midwinter; a slight indigestion may introduce the pellagrous attack, and the case be so slight in its systemic effect that a month later no apparent traces remain. Case 1. A housewife, aged 48, the mother of nine children, noticed that for the past month she had not been feeling as well as usual. Up GENERAL CONSIDERATIONS. 19 to this time she had always been an exceptionally healthy woman. She married at 17, lived in the mountains of North Georgia until grown, and has lived in the country all her life. She had always done her own work; her labors had been very easy and without complications; no miscarriages, and her menstrual period regular until the last period, which did not appear. Her husband is living, and her children are healthy. About May Ist her appetite began to fail, and there gradually developed a feeling of uneasiness in the stomach, which at times amounted almost to nausea. There seemed to be an increased amount of gas in the intestines, although she did not belch at all. There was no pain in the abdomen or anywhere else, and she at- tributed her trouble to ‘‘biliousness and indigestion,’’ but noticed that her indigestion seemed to continue, whether she ate or not. The uneasiness in the abdomen was neither made worse nor better by food. About this time a diarrhea began to develop, and she would have from four to eight thin stools daily, but did not pass any blood. These movements had a peculiar odor like oats or barley after soaking in water. ; She did not feel very weak, but thought her clothes hung rather loosely, and imagined she was losing a little flesh. About this time she noticed a peculiar discoloration on the back of her hands, and thought at first they were sunburned, though she could not remember being in the sun long enough to have caused this. This color on her hands ended just above the wrists; it did not hurt her, though when she used hot water to wash the dishes her hands seemed tender and sensitive. She had come very near having headache. She had strange feelings in her head, as if something were about to happen, and if she stood up quickly she felt slightly dizzy. Her husband thought she was rather nervous, and she cried easily for seemingly no reason. On examination she gave one the impression of having great weariness, and seemed glad of an opportunity to lie down. The palms of her hands were normal, but on the backs the skin was of a deep sunburn, with a peculiar brown tint added. It was symmet- rical on both hands, extended from above the wrists to about the middle of the fingers, and the skin over the first phalangeal joints was loose and unduly wrinkled. In the middle of the back of one hand the skin was beginning to peel off, leaving a thin new skin 20 PELLAGRA. beneath slightly lighter in color than the old. Her hands looked thin, and the fingers rather long drawn out. Her elbows were rough and the skin loose. Her tongue was without a coat—red, with a few little fissures about the middle; the inside of the cheeks was red and tender, and her whole mouth sore. Heart and lungs negative; abdomen negative, except for the presence of large amount of gas in the intestines. Knee jerks equal and slightly exaggerated; eyes nor- mal; no ataxia, no ankle clonus, or Babinski reflex. Pulse, 90; temperature, 98; respiration, 18. Urine averaged 30 ounces in twenty-four hours; specific gravity, 1.005; no albumen, sugar, or casts; a few blood and epithelial cells. Blood normal, except hemoglobin, 80 percent. Weight, 135. She was put in bed for a few days, and then allowed to sit up TABLE SHOWING THE VARYING CONDITIONS oF CASE 1. Tem- Res- Tem- Res- Date. Hour. pera- | Pulse. | pira- Date. Hour. |pera- | Pulse. | pira- ture. tion. ture. tion. June 6 | 11 a.m.{ 102 Ilf 18 June 20 Sa.m.| 984 80 18 6 1 p.m.} 1013 98 20 20 4 p.m.| 983 88 16 6 3 p.m. | 1023 94 20 21 8 a.m.} 98 80 20 6 6 p.m.} 101 92 18 21 4 p.m.}| 983 82 18 7 8 a.m.|100 90 20 22 8 a.m.| 98 80 18 7 | 4 p.m.} 99 94 26 22 | 4 p.m.} 984 78 18 8 Sa.m.] 98} 90 18 23 8 a.m.] 98 92 20 8 | 4 p.m.} 99 82 24 23 4 p.m.|] 983 72 18 5 8 a.m.} 99 90 24 24 8 a.m.| 984 80 18 9 | 4 p.m.} 983} 100 18 24 4 p.m.] 99 99 20 10 8 a.m.] 974 78 18 25 8 a.m.} 983} 100 22 10 | 4 p.m.} 983 92 14 25 4 p.m.| 993} 100 20 M1 8 a.m.| 98 90 20 26 8/a.m.{ 98 98 16 11 4 p.m.} 99 8+ 18 26 4 p.m.|{ 983 86 18 12 8 a.m.} 99 80 20 27 8 a.m.} 973 82 16 12 4 p.m.| 983 86 14 27 4 p.m.] 993 86 16 13 8 a.m.} 98 96 18s 28 8 a.m.} 983 90 18 13 | 4 p.m.) 983 78 18 28 | 4 p.m.} 99 76 | 20 14 8 a.m.| 98 90 16 29 8 a.m.| 98 82 16 14 | 4 p.m.} 983 86 16 29 4 p.m.} 983 92 16 15 Sa.m.}| 985} 100 16 30 8 a.m.}| 994 80 16 15 4 p.m.} 993 88 16 30 4 p.m.} 99 82 18° 16 8 a.m.]| 984} 100 16 July 1 8 a.m.] 99 88 16 16 | 4 p.m.} 99 98 14 1 | 4 p.m.] 993} 92 18 17 8 a.m.| 98 88 14 z 8S a.m.| 99 88 16 17 | 4 p.m.] 984] 100 16 2) 4p.m.] 99 84 | 18 18 8 a.m.| 983 80 20 3 8 a.m.] 993 88 18 18 4 p.in.} 98 88 16 3 4 p.m.] 994 80 18 19 8 a.m.| 98} 99 20 4 8 a.m.] 983 80 18 19 | 4 p.m.} 99 83 18 GENERAL CONSIDERATIONS. 21 at intervals. Her diet was rather full, with the exception of pastries and heavier vegetables, and she was given milk and albu- mens between meals and at bedtime. Fowler’s solution was given, beginning at 3 drops and increasing gradually to 10, three times a day. She was encouraged, and seemed better on the days her friends and relatives visited her. She grew better rapidly, gained in strength and flesh, and was discharged on the twenty-ninth day apparently in good health and with a gain of 8 pounds. The interne at the hospital marked this case ‘‘cured’’ on the records, much to the displeasure of the head nurse. I heard a month later that the woman was improving, but had at times slight attacks of diarrhea. Discussion of Case 1. This case illustrates the first attack of pellagra in a previously healthy woman of middle age. Notice that she lived in the country, and that digestive disturbances ushered in the attack. Without the bilaterally symmetrical erythema, the diagnosis might have been incorrect. The nervous and cutaneous symptoms were sub- ordinate to the digestive disturbances and the diarrhea. The pulse was fast and the temperature slightly below normal; the urine of low specific gravity. She lost flesh, seemed tired, and appreciated encouragement. The only medicine used was a form of arsenic. Case 2, A widow, aged 30, no children, complains of pains all over her body, and a diarrhea that comes every three months for about three days. Her pains are worst in the waist line. Her family history is negative. In childhood she had measles, whooping-cough, and chicken-pox. She had good health until her husband died in March, 1904, and grief over his death brought on an attack of nervous exhaustion. She had a similar attack three years later. In 1908 she was operated on for appendicitis and a movable right kidney double in size. This right kidney is still very sensitive. She felt bad in the spring of 1908 for two or three months, but im- proved after going to the mountains. This sensation of being weak and run down recurred in the springs of 1909 and 1910. She im- proved each time after going to the mountains, but now, August, 1910, there is a recurrence of these spring attacks, this one more severe than ever before. 22 PELLAGRA. She is constipated at the present time, sleeps poorly, and has a good appetite. Her menstrual period has been irregular, and has not appeared for the last three months. She has suffered two nerv- ous breakdowns in the last six years, both of them occurring in the spring of the year. She is now very irritable and nervous. She is a highly educated woman, and was formerly in the habit of TasLE SHOWING THE VARYING CONDITIONS OF CASE 2. Tem- Res- Tem- Res- Date. | Hour. pera- | Pulse. | pira- Date. Hour. pera-| Pulse. | pira- ture. tion. ture. tion. Sept. 22 8 a.m.| 99 102 18 Oct. 8 | 12 m. 1003] 126 | 24 22 | 4 p.m.| 99 84 20 8 | 4 p.m./101 132 | 24 23 8 a.m.| 98 90 18 8 8 p.m. | 102 134 | 26 23 | 4 p.m.] 99 102 26 8 |11 p.m.]1013) 142 26 24 8 a.m.| 98 98 24 9 3 a.m.| 1024) 140 28 24 | 4 p.m.] 98 96 24 9 8 a.m.| 1013] 1327] 26 25 8 a.m.|] 98 102 24 9 {12 m. 1003] 128 18 25 | 4 p.m.|} 98 70 | 26 9 | 4 p.m.]100 134 | 26 26 8 a.m.| 98 90 20 9 8 p.m. | 102 130 22 26 | 4 p.m.] 99 102 20 9 |10 p.m.] 102 140 | 26 27 8 a.m.| 99 108 20 10 | 2 a.m.}] 1023] 120 22 27 | 4 p.m.] 99 100 24 10 8 a.m.| 1003} 120 | 20 28 8 a.m.| 98 100 24 10 |12 m. 102 134 28 28 | 12 m. 99 108 16 10 | 4 p.m.| 102 130 28 28 |} 4 p.m.| 99 100 18 10 8 p.m./1914] 134 | 26 29 8 a.m.} 99 100 20 10 |12 p.m. | 102 126 26 29 | 4 p.m.| 99 102 20 ll 8 a.m.}| 1013] 140 30 30 | 8 a.m.| 98 100 20 11 |} 12 m. 101 132 28 30 | 4 p.m.] 99 108 20 11 4 p.m.} 101 124 | 30 Oct. 1 8 a.m.| 98 98 18 ll 8 p.m. | 102 120 30 1 4 p.m.| 99 108 22 11 | 12 p.m.} 1014] 126 30 2 | 8 a.m.| 99 130 20 12 2 a.m.| 1003] 120 30 2] 4 p.m.) 99 120 24 12 8 a.m.| 983] 124 22 3 | 8 a.m.| 99 126 24 12 {12 m. 102 112 26 3 | 4 p.m.} 100 130 24 12 | 4 p.m.) 1003} 120 28 4 | 8 a.m.] 99 130 28 12 | 6 p.m.} 103 130 | 34 4 | 4 p.m.] 994] 120 26 12 |10 p.m.} 103 140 32 5 | 8 a.m.} 1013] 128 30 13 1 a.m.| 103 140 19 5 | 4 p.m.] 102 150 28 13 5 a.m. | 104 140 20 6 8 a.m. ] 103 120 24 13 8 a.m.} 104 ait 22 G6 | 4 p.m.| 103 140? 30 13 + p.m. | 103 128 24 7 8 a.m. | 101 128 22 13 8 p.m. 103 140 28 7 |10 a.m./1003] 120 26 13/12 p.m.| 1033] 140 | 32 7 | 4 p.m.] 1014] 150 26 14 2a.m.]1044] ... 22 iC 7 p.m.| 102 148 26 14 8 a.m.]103*] 130 28 8 1 a.m.| 1024] 128 20. 14 |12 m. 104 ee 26 8 8 a.m.}101 120 20 14 9 p.m. 1 Direct transfusion. ? Direct transfusion, 3 Axilla. 4 Patient expired. GENERAL CONSIDERATIONS. 23 reading a great deal. She has noticed a gradual failure in her memory and ability to understand what she reads. At present it is often necessary for her to read the same sentence or paragraph over two or three times before she can understand it, and she has difficulty in remembering even the simplest things. Her weight three years ago was 100 pounds; now 86. She is a tired, nervous-looking woman, with little strength. She gives one the impression of exhaustion and rapidly approaching cachexia. On September 13, 1910, she is nervous and suffers with abdominal uneasiness from no apparent cause that she knows. The entire dorsum of both hands is rough, scaly, cracked in places, especially over the knuckles, and the dorsum of the wrists presents the same appearance, the whole area having a light-russet tint. Over the knuckles the soreness is more severe; a little serum exudes from the raw surface of the fissured skin, and above the erythematous area on the forearms the skin is rough up to and including the elbow on the extensor surface. This erythema and roughness is symmetrical on both sides. Between the fingers on the back the brown tint changes to a pink or red, and the tips of the fingers on the palmar surface seem unusually pink and clean. The skin on the back seems to be peel- ing in places, and a skin lighter in color, but still pigmented, appears beneath. The skin of the erythematous area is rather glistening, thin, and dry, and scales are larger than the bran-like scales of the nonerythematous area above the wrist. The forehead is slightly rough, although not enough to be apparent without very close examination. There is some atrophy of the hands, and the skin is looser than normal. The heart and lungs are negative; gas is present in large amounts in the intestines, and the abdomen has a peculiar appearance as if about to point at the umbilicus. She thinks her hands are swollen at times, especially after a restless, sleepless night. Her reflexes are all exaggerated; no ankle clonus or Babinski reflex. Her mind is noticeably slow and dull; it is an effort for her to answer a ques- tion at all; the introduction of a new subject causes an effort on her part to incorporate it into the stream of her consciousness, and she gives the impression of abject neurasthenia, with a tendency to melancholia. Her height is 5 feet 1 inch. Pulse, 96; temperature, 99.5; urine, 1.005; acid, no albumen or sugar, and the microscope shows 24 PELLAGRA. nothing abnormal. Hemoglobin is 75; reds, 4,602,950; whites, 9,400. Stomach contents after test meal showed 190 ce., free HCl .15 percent; total acidity, .33 percent. Fig. 1.—Pellagrous boy. Dermatitis on hands and face. Austriancase. (After Merk.) The diagnosis is, of course, pellagra of possibly six years’ dura- tion. She is apparently in the stage of cachexia, and the outlook is bad. She became gradually worse; nausea, vomiting, and diar- rhea increased, and pulse rose to 130; temperature, 99.3°. On GENERAL CONSIDERATIONS. 25 October 9th, four days before her death, examination of blood showed hemoglobin of 70 percent; reds, 2,780,000; whites, 6,970. Differential count: polynuclears, 57 percent; lymphocytes, small, 24 percent; large, 16 percent; eosinophiles, 3 percent. Her fever and pulse continued to rise, great quantities of bile-stained fluid were vomited, gas in the abdomen increased, abdomen dis- tended, bowel movements of a quart of pure watery discharge. Dissolution on October 18th, with temperature in axilla of 104.3° just before death. Discussion of Case 2. This is a case of recurrence for six successive years, reaching finally cachexia, with rapid death. The trouble was not diagnosed until two months before her death. The erythema was present in August. The blood showed excess of lymphocytes. The mental symptoms were not as severe as one would have supposed from the physical condition. Rest, treatment, arsenic, and transfusion were of no avail. The rapidity of the pulse was out of all propor- tion to the temperature. During the last month the blood lost red corpuscles rapidly, but the hemoglobin remained nearly the same. Case 3. A married woman, aged 25, with one healthy child 3 years old, was seen on June 24, 1911. Her father died of paralysis at 56, and her mother is living and well, 52 years old. She has always lived within one hundred yards of a branch and half a mile of a ereek all her life, and has eaten corn bread in usual amounts. For the past five years she has been especially nervous at her menstrual period, and she does not think her nervous system is in a good con- dition. During this time her health was bad every spring, extend- ing even into midsummer. During these spring attacks she noticed she grew weak and had some dizzy feelings, but thought she had the ‘‘spring fever.’’ During the spring of 1910, with the usual spring weakness, she had a slight stroke of paralysis; and her whole left side has been of little use in work since. Her menstrual period is regular, but scanty; no pain, except backache at times. She has never had any diarrhea, and is usually constipated. Lately there has been a feeling of dullness in her head, almost headache, and she grows despondent and cries at times. There is evidence of a right hemiplegia, slight hemiplegic gait, 26 PELLAGRA. left knee jerk absent, and slight ankle clonus in left foot. Right knee jerk slightly exaggerated. Her usual weight is 135, but she has lost 8 pounds this spring. She looks weak, though well nourished. Her face is sad. Pulse, 90; temperature, 99.4; tongue slightly coated in middle, sore and red at tip and margins. Blood pressure, 85 mm. One month ago her mouth was sore and raw inside; gums and inside of lips still red; throat red. She has too mtch gas in the abdomen, though her appetite is good, and there has been no nausea. Three weeks ago the backs of her hands grew red, and she thought they were sunburned ; the skin from the middle of the fingers to above the wrists then began to peel off in scales and at times she felt burning sensations in her hands and feet. Her hands now are rough and cracked slightly, of a sepia tint, the finger tips pink and clean. Blood shows hemoglobin 85 percent; urine with a specific gravity of 1.012, otherwise negative. Heart, lungs, and abdomen negative. Discussion of Case 3. This case illustrates a pellagra of probably five years’ standing, no diarrhea, no nausea, and a slight hemiplegia, probably of pella- grous origin. This case might have been diagnosed as a chronic neurasthenic, and indeed I suspected neurasthenia, when I first saw her, from her general appearance. The erythema clinched the diagnosis of pellagra. There was no great inroad made on the general nutrition; even her periods continued. She had probably had the erythema before, though had never noticed it until this last attack. This type corresponds more to the chronic form com- mon in Italy. Notice the burning in her hands and feet. Case 4. A farmer, aged 50, the son of pellagrins, was seen in August. He had an attack of pellagra in the spring of 1910, with a recur- rence the following September. In the spring of 1911 there was a third attack, this time more severe than in the preceding year. Since March he seemed to grow worse rapidly. He lost 40 pounds; his memory became bad, and his mind almost a blank. He was brought to the hospital a month ago suffering with acute confu- sional insanity, difficulty in speech, cachectic, and helpless. His tongue is without a coat, bald, red like a cut beet, and cov- ered with small fissures. The erythema extends from the middle GENERAL CONSIDERATIONS. 27 of the second phalanx half way up the forearm to the elbow on the extensor surface, and around the wrist, meeting on the flexor surface. All this erythematous area is peeling and cracking; the hands are thin and bony; the fingers long and keen. Above the eruption the skin is rough and scaly; this roughness extends up on the shoulders, and even appears on the trunk, forehead, and as scaly patches below and behind each ear. Erythema on ankles, half way up leg to knee; knee rough and scaling. The elbows are exceedingly rough, almost like an ichthyosis. His lower legs some- what spastic, and he is unable to control them. Before he became bedridden he was ataxic; would fall at times, and often stagger when walking. His entire left side presented a striking contrast with the right. On the left he had ankle clonus, Babinski reflex, trophic disturb- ances of the left hand, fingers slightly swollen at the tips; the nails white, thick, long, and swelling at base and beneath, with contractures of fingers—a claw hand. Knee jerks greatly exag- gerated, eyes glassy and staring. He was put in bed and showed marked improvement from the beginning of treatment. He was fed four times daily, chiefly on meats, milk, cheese, salads, a few vegetables. He was given iron, quinin, and strychnin, Fowler’s solution in increasing doses, and occasionally tincture of nux vomica. A month after treatment began he was growing stronger, had a good appetite, and could talk a little, though his ideas were still confused. He will prob- ably continue to improve until next spring, though confirmed dementia may develop. Discussion of Case 4. This case illustrates the rapid onset of cachexia and insanity in a man; trophic changes in the hand; wide distribution of the rough skin; marked improvement after cachexia had begun; ataxia, and spastic condition of lower extremities. The spinal cord was, of course, markedly affected, and the nervous symptoms predominated. Diarrhea was almost absent, yet cachexia developed rapidly. Case 5. A negro woman, aged 52, after a week of rather unusual feeble- ness, beginning about May 1st, went to bed from sheer weakness. She had been healthy and strong, did her own housework and 28 PELLAGRA. washing, and weighed 172 pounds. At times everything seemed to swim before her eyes, and it seemed that her legs would give way under her when she stood or tried to walk. Her mouth was sore, her gums bled, tongue raw, and it even hurt her to swallow water. Diarrhea began and grew worse, and when she went to bed she noticed streaks of blood in the stools. Her hands and feet burned; she had pains in the left back along the middorsal region; and on acéount of a constant feeling of nausea and this rawness in her throat she ate hardly anything. About May 10th she presented a characteristic roughness on the back of the fingers, hands, and extensor surfaces of forearms half way to elbows. On the back of the hands there were several blisters, varying in size from a pea to a quarter and containing serum, occasionally streaked with blood, with an ulcerated base. The dermatitis was symmetrical, and one could not help thinking that the skin was similar to a burn. The roughness was not the usual color of the pellagrous erythema, but presented somewhat the appearance of an old negro’s hand on a cold winter morning. It seemed at certain angles of a dark, ashy gray, and as if the dry skin would shed off in scales if the hands were well washed in warm water. There were patches of dermatitis on each side of the nape of the neck, and at the base of the ale of the nose. The ankles and shins were rough, and at times the feet and hands were slightly swollen. Her feet and hands burned severely at times. Temperature rose to 103.5°, with pulse at 120. Her eyes had a staring, vacant expression, and she looked wild and anxious. Re- flexes all exaggerated, and she lay in bed in a rather stuporous condition. Her mind rapidly failed her, and control was lost of the lower limbs. She seemed a mass of helplessness. Occasionally she grew rigid and half violent, and then relapsed into a stuporous condition. Her urine contained a trace of albumen, with a few hyalin and granular casts. Diarrhea continued until finally incon- tinence of urine and feces developed. Toward the close she de- veloped opisthotonos, though most of the time she was rather quiet and rigid. She died on June 6th, with a temperature of 105, but the fever ranged from 101 to 104 after she went to bed. After death she looked as though she had lost forty or fifty pounds. The rapidity of the disease, its increasing severity until death, gave one the impression that the patient was suffering with an acute infec- tious disease. Diarrhea, temperature, high pulse, prostration, emaciation added evidence confirming this idea. GENERAL CONSIDERATIONS. 29 Discussion of Case 5, This is typhoid pellagra, or the tifo pellagroso of the Italians. The eruption was a wet dermatitis, and the attack grew rapidly worse. Notice the tendency to muscular rigidity and opisthotonos. The kidneys were involved. Stomatitis and anorexia severe. The continued fever distinguished this form. Death in five weeks. DEFINITION. Pellagra is an endemic and epidemic disease, periodic and progressive in its course, and characterized by a series of symptoms involving chiefly the digestive, cutaneous, and nervous systems. GENERAL DESCRIPTION, Pellagra may be endemic in country communities for a century, as in Italy, or suddenly epidemic, as in America. It varies in length from the six weeks’ course of typhoid pellagra to twenty or thirty years, or even longer, of the chronic forms. It finds its chief home in the country districts, and attacks all classes, all ages, and both sexes, but does not attack dwellers in crowded cities. The attack begins usually in the spring and summer mouths, recurring with increasing severity every spring. A sec- ond attack may occur in the late summer or autumn months, with remission of symptoms and improvement during the winter. Its onset is insidious, its attack is periodic, and its course is progressive. The symptoms of the digestive tract are stomatitis, esophageal burning, pyrosis, gastralgia, belching, nausea, gastritis, enteritis, dyspepsia, diarrhea usually and constipation rarely. The chief cutaneous symptoms are a peculiar, bilaterally symmetrical ery- thema, with progressive desquamation and pigmentation, a branny roughness of symmetrical skin areas, occasional serous or bloody blisters, and trophic changes around the nails. The chief nerve symptoms are a chronic neurasthenia, exaggerated reflexes, vertigo, ataxia, spastic and paralytic gaits, palsies, and paralytic strokes; occasional ankle clonus and Babinski reflex. Mental symptoms include sadness, melancholia, dementia, mania, confusional insanity, mutism, murder, and suicide. Emaciation and chronicity go hand in hand. The diagnosis is generally easy, and the prognosis varies 30 PELLAGRA. with the type of the disease and the time treatment is begun. An early diagnosis is important. IS PELLAGRA CONTAGIOUS? Endemic and epidemic diseases spread by contagion or the con- veyance of a disease from one person to another by direct contact, as illustrated by small-pox; by bacterial infection of one person by germs from another, as illustrated by the tubercular infection of a wife from a tubercular husband; by bacterial or protozoan infection through the bite of an insect which acts as host, as illus- trated by malaria and yellow fever by different mosquitoes; by bacterial or parasitic infection through food and water, as illus- trated by cholera and trichina spiralis; by parasites burrowing through the skin, as illustrated by scabies and uncinariasis. As the cause of one disease after another is discovered, the number of diseases officially classified and popularly called ‘‘contagious’’ continues to decrease. Yellow fever a short time ago was always and everywhere considered contagious, and a medical man who would have disputed the contagiousness of yellow fever would have been considered foolish indeed, yet yellow fever is not at all con- tagious and the criminal is a mosquito. Applying this classification to the transmission of pellagra, two facts are clearly apparent—(1) pellagra is not transmissible by contagion from one person to another; (2) pellagra is not trans- missible by infection from one person to another. It is neither contagious from person to person, as smallpox, or infectious from person to person, as tuberculosis. In certain quarters there is ob- jection to the use of the word contagious, but, until the real cause of every disease is discovered, this word is needed. The truth of these two propositions denying the transmissibility of pellagra is amply proved by the following facts: 1. The limitation of pellagra to the rural population. People who live in cities need have no fear of the disease, because pellagra stops at the city gates. Paved streets, high buildings, and crowded populations are not its home. This is one of the outstanding facts of the disease. Because pellagra develops in villages and towns of a few hundred or a few thousand inhabitants does not contradict the immunity of cities. Especially in the southern states these villages are under the same condition of living and environment GENERAL CONSIDERATIONS. 31 as far out in the country. An investigation of many of these so-called city cases will reveal the fact that they contracted the disease in the country, or spent much of their time in rural dis- tricts. 2. The limitation of the disease in many cases to large families or to several families living together under the same conditions of daily life. Alessandrini found 269 Italian families of 1,659 per- sons, and only 274 pellagrins among them, and of these only five families had 2 pellagrins each. One family of 21 members and another of 13 had only one pellagrin in each. 3. The complete immunity of hospitals, asylums, orphan homes, hotels, summer resorts, and all institutions where pellagrins are admitted for temporary or permanent residence. Nurses and at- tendants who stay with pellagrins all the time, physicians who treat them, relatives who live and sleep with them, are all alike immune. At the pellagrosari in Inzago, Mogliano Veneto, and Rovereto, where thousands of cases have been treated, no physician, nurse, or attendant has ever developed the disease. 4. The enormous intercommunication between urban and rural populations, and the absolute failure in any instance of pellagra to develop along the highways and lines of travel, or in cities where exposure in pellagra countries is constant. 5. It is impossible to reproduce the disease by inoculation from the serum exuded from the skin or from the blood and saliva of pellagrins. It is impossible to convey the disease from pel- lagrous wet-nurses to suckling infants in lactation. Here the very food of the infant is secreted from the blood of a pellagrin, and yet there is no record of the transmission of the disease to the infant. Sambon quotes Nardi in a conclusive way: ‘‘ Although several children belonging to the upper classes of this town (Milan) were suckled by women recognized to be pellagrins at the end of lactation, nevertheless, notwithstanding that some of the nurslings have now passed their fifteenth year of age, not one of them exhibits any sign of having contracted the nurse’s disease.’’ I know of no better way to test the contagiousness of the disease than this, and espe- cially since these cases were observed for a period of fifteen years. It is a common observation in medicine that nursing infants are easily affected by a disease or even passing illness of the mother, and the susceptibility of infants to contagious diseases is well known. The contagiousness decreases with age, as illustrated by 32 PELLAGRA. scarlet fever and mumps, and, if there is a remote possibility of contagion in pellagra, it should appear in infants nursing pella- grous milk, and the development of the disease would not be long delayed. It did not develop in such nurslings either during in- fancy or thereafter. 6. In the surgical procedure required for the transfusion of blood from a healthy donor into a pellagrin in the last stages of the disease, open wounds in both are brought in contact, vessel is joined to vessel, and for periods exceeding an hour. The disease is at its height, and, if either contagion or infection were possible, it would be at this time, and yet there has been no development of pellagra in any donor. In the country districts in Italy and in America there is unques- tionably an uncertainty of belief regarding contagion, and a suspi- cion in areas where the disease develops with great rapidity that it is somehow contagious. In an area of less than one-half mile in length along the banks of a small branch and pond near Forsyth, Monroe county, Georgia, 5 cases of pellagra originated. Elrod, of Forsyth, who drove me out to this endemic area, called my atten- tion to the fact that there were no cases between these and the town of Forsyth, nine miles away, and how easy it would be to believe in the contagiousness of the disease if one merely viewed these 5 cases. It is easy in the popular mind to believe that, if a disease spreads in a community, it is therefore contagious, but the medical mind knows how false is this assumption. Pellagra does spread in one of its endemic areas, not because it is contagious, but because the people live in this area under the same conditions and are subject to the same causes of the disease. The point is that a pellagrin can not convey the disease by removing to a nonendemic area, but a well person can contract the disease by moving into an endemic area. It is important that this matter be understood, and the fears of relatives and friends of pellagrins be allayed. I have known a young lady to develop the disease, her friends to forsake her, and her relatives to appear only when necessary and in plain fear of the patient lest they contract the disease from her. Pellagra is bad enough, and the sadness symptomatic of the disease is sufficient, without causing the pellagrin to feel that she is a menace and a source of contagion. It would be different if it were true, but pellagra is not contagious. GENERAL CONSIDERATIONS. 33 WHICH SEX IS MORE AFFECTED? More women than men suffer with pellagra. This is one of the striking features of the disease. A study of groups of cases re- ported by general practitioners in America reveals the constant preponderance of female pellagrins. A few of these taken at random follow: Seven cases, 5 women and 2 men; 24 cases, 14 women and 10 men; 9 cases, 8 women and 1 man; 10 cases, 7 women and 3 men; 18 eases, 18 women and 5 men; or of these five groups, with a total of 68 cases, 49 were women and 19 men. The following groups from the American asylums for the insane report somewhat the same proportion: of Zeller’s 130 cases from Illinois, 75 were women and 55 men; the Cook county institutions in the same state report 26 cases, with 13 of each sex; the East Mississippi Asylum reports 9 cases, 7 women and 2 men; in the Florida Hospital for the In- sane, among 85 women there were 11 pellagrins, and among 240 men only 2 pellagrins. Along the foothills of the Alps in Umbria, Italy, Alessandrini found in one area 254 pellagrins, 192 women and 62 men. In Roumania, of 19,796 cases 9,132 were men and 10,664 were women. Warnock’s report from the Egyptian government hospital for the insane for the nine years from 1901 to 1909 inclusive gives 636 pellagrous admissions, and of these 477 were men with 69 deaths, and 159 were women with 24 deaths. The figures of both Sand- with and Warnock seem to prove that in Egypt at least there are more men than women affected, but their figures are from hospital and asylum sources. In Italy, in 1847, out of 1,503 pellagrins in Venice and Piedmont, 658 were men and 854 women, a proportion of 4 to 5; another group of Italian statistics gives 2,289 men and 2,478 women. Dr. Fritz, at Inzago, in the province of Milan, after an experience of thirty years with the disease believes women always suffer more than men. The proportion of male to female eases in the United States is from 1 to 4 to 3 to 4, depending on the locality ; the average is probably about 2 to 4, as illustrated by Porter’s Florida figures of 33 men and 41 women. Grimm found 111 females and 29 males in three Kentucky counties; and of 189 deaths from pellagra in Texas, 153 were females and 36 males. Nowhere have I found any adequate explanation of the excess of pellagra in women. In Italy it is said that more women have 34 PELLAGRA. pellagra because they work in the fields, but more men than women work in the fields in Italy and for longer periods. Sandwith’s Egyptian cases show more men, and he thinks that it is because the women are not field laborers to the extent that they are in Italy. In America the women, as a rule, are not field laborers, and prob- ably the vast majority of women pellagrins in this country never work in the fields. Some of them pick cotton in the fall for a very short time in the South, but this hardly accounts for the cause. In Italy and the southern states one may see large num- Fig. 2.—Dermatitis on hands of pellagrin. Skin dry, with exfoliation. Note the wrinkles. (After Merk.) bers of women doing the washing for the family in some sheltered swamp cove where a spring arises or beside some running stream. This work takes the women outdoors far more in America than any farm work. Furthermore, men are far greater consumers of corn products than women. It is certain that the prevalence of the disease among females can not be attributed to the additional burden of childbearing. It is as natural for women to bear chil- dren as for men to work, and, what is more important, the same preponderance of females holds in comparing pellagrins of both sexes under 18 years. Women are neither more predisposed nor GENERAL CONSIDERATIONS. 35 less resistant to pellagra than men, and we must look to a greater exposure of women to the active cause of pellagra to account for the greater number of female pellagrins. This matter is discussed further in Etiology, page 263. IS PELLAGRA INHERITED? One of the questions asked of the physician, and one he often asks himself, is whether pellagra is inherited. Heredity is too vast a problem to be dismissed with a ‘‘yes’’ or ‘‘no’’ until one knows exactly in what way the word heredity is used. The under- standing of the heredity of diseases is not as easy as counting chro- mosomes or comparing colors in the offspring of animals. There are aS many opinions on the question as there are writers on the subject, and the answer has depended largely on the opinion of the writer. Another unconscious influence has held sway—more, perhaps, than has been realized. This relates to the theory one accepts as to the cause of the disease. It is obvious that if one accepts the corn theory, and believes the disease due to toxins acting in the same individual for a number of years, it is very easy for him to believe that the same toxin can easily ensconce itself in some organic way in the ovum, reappear in the child, and continue to poison the infant. If one accepts the parasitic theory of the disease, he must either refuse to believe in its heredity or else postulate a new theory based on the idea that the cause is a germ or parasite with which the embryo becomes infected. One asks, if a toxin continues to act for ten years in the body or somatoplasm, why may it not con- tinue to act through the germ plasm; the other refuses to believe the disease inheritable, or believes the embryo may become infected with the unknown organism. Viewed from the accepted idea of modern medicine, a disease is inherited when the child has the disease at birth, as when a syphilitic child is born of syphilitic parents. It begs the question to say that syphilis is not inherited because the embryo was in- fected by the spirocheta pallida during gestation. One or both parents had syphilis, and their child at birth had the disease, illus- trating the direct transmission of disease from parent to offspring. In the sense, then, that the germs or parasites may be contained either in the ovum or spermatozoon, or that the toxins may affect 36 PELLAGRA. these, or may through the fetal circulation and the placenta cause the disease to be present in the child at birth, one may say that pel- lagra is distinctly not inherited. As Sambon well says, there is no record of a child born with the characteristic signs of the disease upon it. Children are born with syphilis, but children are not born with pellagra. The disease pellagra in one or both parents does not reappear as the disease pellagra in the newborn infant. Even Lombroso, who believed firmly in the heredity of pellagra, did not believe the disease appeared in the offspring before the second year, and then not as pellagra, but as pellagra without the Fig. 3.—Dermatitis on feet of pellagrin. ape een: with edema on left foot. (After erk. eruption—pellagra sine pellagra—but we shall see that he mistook the degeneracy caused by pellagra for hereditary pellagra. At this point has originated the difference of opinion and the various beliets regarding its heredity. Pellagra is too recent in America to permit any statistics on heredity, but the family reported by Watson had three children, all pellagrins; both parents healthy, all living under the same conditions, and yet only the children developed the disease. Here healthy children developed pellagra, but, had they been born with a congenital weakness of any organ or feebleness of the entire sys- tem, it is reasonable to believe they would have developed pellagra GENERAL CONSIDERATIONS. 37 or any other disease very much more easily. A pellagrous parent is not a healthy ancestor, and predisposes his offspring to the attack of any widely prevalent disease. Heredity depends on the quality of the sperm, the quality of the germ, and their suitability to each other. Gross errors in either parent tend to reappear in some form in the offspring, and par- ticularly is this true of neurotic errors in the parent. An epileptic or a hard drinker is not apt to produce a child without some flagrant neurosis or mental weakness. The pellagrin suffers not only a chronic neurasthenia, an ever increasing tendency to melancholia, but also actual organic changes in the cord and brain. These organic changes do not appear in the child, but the stigmata of degeneracy do appear. Pellagra is not inherited, but the result of its ravages in the parent is inherited, and appear in the child in the form of dwarfism, deficient development, anemia, various malformations of the skull, asymmetry, bad set ears, mental weak- ness, slow growth, an unusual lack of resistance, and a frailness out of all proportion to age. In addition to pellagra, the parent may also have ankylostomiasis, or be tubercular, syphilitic, or alcoholic, and the degeneracy in the child would thus be increased. Let this continue for two or three generations, and it is natural to find the descendants of pellagrins suffering with the widely preva- lent disease of the community, and increasingly degenerate and pauperized. Pellagra thus becomes a real cause of race degeneracy. These children live under the very same conditions in which their parents developed pellagra, and their very degeneracy is, in turn, an invitation to the disease already widely prevalent. If strong men develop pellagra, frail children will develop pellagra much more easily. The injurious influences are at work, and both parents and children may be attacked at the same time, or children may become pellagrous first and their parents afterward. The excellent table on page 38 prepared by Boudin is worthy of study. The first three groups, with pellagrous parents, give 443 pellagrous children, while the last two groups, with parents well, give 297 pellagrous children, an excess in favor of pellagrous degeneracy and predisposition of only 20 percent. Even this is enough to furnish evidence that adult pellagrins should not marry and add a burden to the race in the form of degenerate children. Dr. Fritz, at Inzago, in the province of Milan, told me that he had noticed that pellagrous children, attacked in early childhood and 38 PELLAGRA. recovering rapidly, often married and had healthy families, with. no pellagrous children. The disease in them did not pass the ini- tial stage or become confirmed, and they were healthy men and women when they married. Parents. Number Pellagrous children. Total married couples. Boys. Girls. children. Father and mother......... 96 116 146 262 Father pellagrous, mother WEIL) cid tiod nace ae Bees 160 64 49 113 Mother pellagrous, father WEL esis consume auaaet aed 175 30 38 68 Father and mother well, two or more children pel- Tagrous: aiiee ica ee esses 43 59 53 112 Father and mother well, only one child pellagrous...... 185 80 105 185 1. Pellagra, as such, is not inherited. 2. The children of pellagrins are apt to be of inferior physique and have stigmata of psychophysical degeneracy. 3. Pellagra is thus a cause of race degeneracy. 4, Adult pellagrins should not marry. AGE. Pellagra may occur at any age. The youngest cases I have found were in infants of 4 and 5 months, and the oldest in a man of 99 and a woman of 102. Casal, Strambio, and Sambon report cases in octogenarians, and Siler found a case of 85 in Illinois, the oldest reported American case. In Egypt, Sandwith did not see any cases under 5, they were rare under 10, and most of the cases occurred in men in the prime of life. He considers puberty in boys a vulnerable time for the pellagrous attack. Sambon found in the country districts of Italy one family of eleven members, the youngest an infant of 16 months, all pellagrins; and a family of seven, the father aged 44, all pellagrins except the 4 months’ old baby. Cases in children from 21, to 10 years of age are found in the United States, but pellagra in infants is certainly not as com- mon as in Italy, or, if so, it is either overlooked or not reported. It is probable that, as the disease is studied in greater detail in the country districts, more cases will be discovered in children. Often in the little ones the erythema is so slight and transient, the other GENERAL CONSIDERATIONS. 39 symptoms not at all severe, that the disease passes unsuspected and unnoticed. This is certainly the case in Italy, and, in addition, the pellagrosari do'not take the younger children and infants. The summary of different groups of statistics from different countries at different times permits a safe conclusion. Potarca collected 17,027 cases of pellagra, and found 13 percent under 20 years, 31 percent between 20 and 40, and 56 percent over 40. Strambio gives 129 cases, with 15 percent under 25, 29 percent between 25 and 35, 67 percent between 36 and 60, and 3 percent over 60 years. Calderini studied 352 cases in 1844, and found 83 of them under 3 years and 55 between 45 and 60. During the years 1905, 1906, and 1907 the pellagrosario at Rovereto, Austria, in the Tyrol, treated 456 cases, with an average age of 3214 years. Of these 456 cases 275 were males, with an average age of 3414 years, and 181 were females, with an average age of 29 years. I have collected 159 cases in the United States, reported chiefly from the country districts of the southern states, and it is inter- esting to note that the average age of these cases is 3214 years, or the same as the 456 cases from Rovereto. This gives 615 cases from America and Italian Austria, with an average lower by 1814 years than the 130 cases from Illinios, with an average of 51 years, reported by Zeller. It is true that the average age of pel- lagrins in any state is lower than the average age of the insane pellagrins in the asylums of that same state; and, while most of the pellagrous area of the Union is not in the vital statistical area, we may assume with reason that the average age of pellagrins is in the fourth decade, and nearer 30 than 40. The Egyptian cases range around 40, while my own cases average 36 years. 1. Pellagra may occur at any age, the average being about 35 years. 2. By far the larger number of pellagrins are between 20 and 40. 38. Age influences neither the severity of the attack nor the course of the disease. IMMUNITY. The question of a natural immunity to pellagra is now merely a matter of observation, and can not be decided until experiment is substituted for observation, and then only after the cause of the disease is definitely known. Physicians and nurses are clearly 40 PELLAGRA. immune to the disease from transmission by contagion. The ad- vocate of the corn theory believes all are immune as long as they do not eat corn, and the advocate of the parasitic theory believes in immunity as long as there is no infection with the parasite. The offspring of pellagrous parents is not immune, for he not only develops pellagra easily, but inherits a proclivity to disease in general. The inhabitants of an area where pellagra is endemic are not immune, because pellagra is there all the time, and individ- uals of their strength and environment constantly develop the disease. Furthermore, it is difficult to believe that a disease which admittedly is unable to confer acquired immunity is to any degree able to permit a natural immunity. Natural immunity is probably always only another name for variation in susceptibility. In- dividuals vary in susceptibility to pellagra as they vary in other diseases, and probably to a greater degree, as evidenced by the rapidly fatal and slowly chronic forms, the failure of certain in- dividuals to develop the disease when living in the same environ- ment, eating the same food, doing the same work, and exposed to the same influences as their brothers and sisters who become pellagrous. An individual may develop pellagra and be cured, or he may have pellagra with a recurrence ten years later. In this latter case there was either a reinfection or a reintoxication after a period of protection conferred by the first attack—a kind of pellagrous vaccination—or the parasites were latent this long period. A latent intoxication for twelve years is to me unthinkable. Parasitic infection permits and rather predisposes to reinfection, especially when the environment continues the same. There is probably neither a natural nor an acquired immunity to pellagra, but there is probably a variation in susceptibility to the disease, and certainly a variation in exposure to the causative agent. For in- stance, even when pellagra is epidemic, the crowded city escapes the disease, as illustrated by Milan, in Lombardy, in the last century. Even in country districts one area may be pellagrous, and another near by free from the disease, and this condition con- tinue for long periods of time. OCCUPATION. At the Ospitale Maggiore, in Milan, pellagra is classified as a disease peculiar to farmers and peasants, just as lead poisoning is GENERAL CONSIDERATIONS. 41 confined to workers in lead. The triple cause of pellagra in the popular mind included this idea as expressed in the axiomatic phrase, ‘‘ Peasant life, poverty, and polenta.’’ That peasants, field workers, and farmers are peculiarly susceptible to pellagra is the opinion of writers in Spain, Italy, Egypt, and Roumania. Our experience so far in America does not agree with this altogether, and a study of Sambon’s Italian Teport: shows facts more nearly similar to conditions in America. J. ©. Johnson, of Atlanta, reports 20 cases of pellagra, with the following occupations: farmers, 2; merchants, 3; lawyers, 1; minister, 1; teacher, 1; salesman, 1; housewives, 10. From this series of 20 cases it will be seen that there are only two who worked in the fields, and that three of the four professions are repre- sented. Consulting articles by different authors who report Amer- ican cases, I find one group of 5 cases, all living in the country, but no farmers or field workers among them; another of 8 cases with only one farmer; of 6 cases one was a farmer and all lived in the country; of 10 cases 1 was a farmer, 1 a lawyer, 1 a ear- penter, and the others housewives. It is probably true that a majority of the adult white pellagrins in America do not work in the fields, nor have I been able to find any record of pellagrous children who did farm work to any extent. What is of vastly more importance is the fact that practically all the pellagrins in America either live in the country districts, or in villages where the conditions and environments are the same as in the country. Procopiu says that pellagra exerts a preference for farmers, but it would be more correct to say that it exerts a preference for those who live in the country or in a rural environment, and this without reference to occupation. Environment, rather than occu- pation, is the predisposing and determining factor. When I told Dr. Bezzola, of Milan, that pellagra occurred among the well-fed and highly nourished individuals in the South as well as among the poor, he expressed his astonishment and said that he even doubted that the disease was pellagra, so firmly was the idea of farmer and poverty as the united host of pellagra fixed in his mind. . The physicians in the country districts of the southern states bear witness to the excess of female pellagrins and the rarity with which they work in the fields. Sambon found pellagra in coachmen, fishermen, priests, shepherds, carpenters, masons, in a shoemaker, and found in one case a hesitancy on the part of some 42 PELLAGRA. physicians to diagnose pellagra because the pellagrin was a cul- tured lawyer. He found in Italy, as is true in America, that members of the wealthiest families have the disease, but all these were rural in their habitations and lives. Of 1,955 deaths from pellagra in Lombardy from 1848 to 1859, the number of country people was 1,853; all the 150 lunatics in the asylum at Modena were from the country; of 148 insane pellagrins only 9 were not peasants, and even these were mostly born of pellagrous parents. About the same proportion holds in Corfu and in Roumania. Sandwith found of 137 cases 88 percent were peasants, 6 mason’s laborers, 4 beggars, 3 boatmen, 2 policemen, 2 brickmakers, 1 potter, 1 servant. I have seen three physicians in Georgia who stated that mem- bers of their families were pellagrous. They were cultured and refined men, and their families were in good circumstances. One mayor of a Georgia village developed the disease and died in a short time. Pellagra is not limited to, nor does it exert a preference for, those engaged in any one occupation. Taking the pellagrous area of the world, it is probable that more farmers will have the disease than those of any other occupation—not because they are farmers, but because pellagra is limited to country districts, and a majority of the rural inhabitants are farmers. Probably a majority of American pellagrins do not work in the fields, but practically all American pellagrins live in a rural area, CHAPTER II. HISTORY AND GEOGRAPHICAL DISTRIBUTION. In nearly every country in which pellagra has developed, the disease was known among the people in the rural districts before it was known in the medical literature of the country. The name pellagra itself was given the disease by the common people and not by a physician. There are about sixty synonyms, which include names given by the people in Spain, Italy, France, Austria, Egypt, and America to the symptom complex known in medicine today as pellagra. Some of these are interesting in that they embody the double idea of symptom and of cause—as, for instance, scottatura de sol (the burning of the sun), which refers, of course, to the dermatitis and to the fact that the sun was at one time considered the cause of pellagra. Another idea conveyed by some of these synonyms is that pellagra at first was not considered as a separate disease, but a condition comparable to erysipelas, to scurvy, and to leprosy. Among the synonyms that originated in Spain are: Spanish Synonyms. Mal de la rosa—sickness of the rose. Mal de Asturias—the disease of the Asturias. This refers to the ancient province of Asturia in Spain, where the disease first originated. According to the redivision of Spain in 1833, this province took the name of Oviedo. Mal del higado—disease of madness. La gala de Saint Agnant, or sometimes written La gala de Saint Ignace—the itch of Saint Ignace. Calor del hidago—burning of the person. Escamadura del hidago—a desquamation of the person. Flema salada—the salty phlegm. This refers to the salty taste occasionally persisting in pellagrins. 43 44 PELLAGRA. French Synonyms. Mal du maitre—the master’s disease. Maladie de la Teste—the disease of Testa, Gironde, France. Pel- lagra originated in France in the vicinity of Teste. Eruption de Lombardie—the Lombardian eruption. Pellagra originated in Italy in the province of Lombardia. Mal de saintes mains—the sickness of the main saints. Mal de Sainte Rose—sickness of Saint Rose. Mauvais dartre—a bad eruption. Italian Synonyms. Mal della spienza—disease of melancholia. Mal del monte—disease of the mountains, Mal del padrone—the master’s disease. Mal del sole—the disease of the sun. Scottatura de sole—the burning of the sun. Jettatura di sole—the evil eye of the sun. Umor salso—the salty humor. Mal salso—the salty disease. These last two refer to the salty taste present in the mouth of some pellagrins. Cattivo male—the wretched disease. Mal della vipara—the disease of the viper. Psychoneurosis maidica—the psychoneurosis caused by corn. Pelandria, pellarela, and pellarina are dialectic corruptions of the ordinary pellagra. The first is used in the rural districts of Pavia. Mal roxo, mal rosso—a blushing disease. Pellis aegra—the rough skin. Risipola Lombardia—Lombardian erysipelas. Lepra Italica—Italian leprosy. Maidica—the corn disease. Malattia della miseria—the disease of the poor. Raphania maistica—the corn shapping. Malattia del insolata di primavera—disease of the sun’s rays in the spring. Calore del fegato—the heat of madness. Salso—salty, biting. Scorbuto mantano—mountain scurvy. Scorbuto Alpino—Alpine scurvy. HISTORY AND GEOGRAPHICAL DISTRIBUTION. 45 Lepra Asturiensis—Asturian leprosy. Elephantiasis Italica—Italian elephantiasis. Referring to the skin in the third stage. Greek Synonym. Greci elephantiasim—Grecian elephantiasis. Roumanian Synonyms. Buba tranjilor—refers to the pimples of the dermatitis on the back of the hand. Rana tranjilor—refers to the roughness with the skin divided up with a supposed similarity to a frog’s skin. Parleala—a burning. Jupuiala—a desquamation. German Synonym. Der Lombardische aussatz—-Lombardian leprosy. Egyptian Synonyms. Inshuf—chapping. Gotar—an eruption in camels and sometimes horses, and given by the fellaheen to the dermatitis in pellagra. Among the synonyms which have become current in the English language are scorbutic paralysis, land scurvy, and Italic scurvy. An interesting fact is the origin of synonyms in the United States. Three are in common use among the people in the southern states, where pellagra is known as ‘‘the corn bread disease,’’ ‘‘corn bread consumption,’’ and ‘‘corn bread fever.’’ A study of these synonyms is very interesting, as it brings out some of the early ideas current concerning the disease. Mixed with these, of course, is an element of fact. Several of the syno- nyms refer to the sun, because in the early days the sun was believed to be the cause, and even now the part played by direct sunlight in the eruption is not clearly understood. Several refer to the mountains, making evident the fact, as is well known, that pellagra is found chiefly in a rolling country toward the foothills of the mountains as well as up in the mountains themselves, where the streams have cut deep and narrow valleys among the hills. There are several references to the salty taste in pellagra and to the fact that pellagra is a disease of the poor. The word scurvy 46 PELLAGRA. as regards pellagra occurs because in the early days in Italy pel- lagra was considered a form of scurvy. Different words relating to heat and burning are, of course, ap- plied because of the sensations of burning often present in the hands and feet. HISTORY AND GEOGRAPHICAL DISTRIBUTION. The history of pellagra resolves itself into the history of the disease and its distribution in the several countries where it has appeared during the last two centuries. Pellagra may be said to have had six epochs, beginning probably about 1700 in Spain and extending to the present time in the United States of America. These six epochs may be called (1) the Spanish epoch, dealing with pellagra in Spain; (2) Italian epoch, dealing with pellagra in Italy; (3) French epoch, dealing with pellagra in France; (4) Austria-Hungarian epoch, dealing chiefly with pellagra in Austro- Hungary, Turkey, Roumania, and Greece; (5) Egyptian epoch, dealing with pellagra chiefly in Egypt and to a lesser extent in other parts of Africa; (6) American epoch, dealing with pellagra in North and South America, but chiefly in the United States. These epochs will be taken in order, and the history and distri- bution of the disease in each country discussed. Spanish Epoch. Pellagra originated in the northern part of Spain on either side of the Cantabrian range of mountains, which form that part of Spain known originally as the Asturias, but which is now on the northern side of the mountains the province of Oviedo and on the southern side the province of Leon. Casal wrote in 1735 in the city of Oviedo a treatise which he called the ‘‘Natural History of the Asturias,’’ and in which what we know today as pellagra was called mal de la rosa—the sickness of the rose. His book was written in Latin, and it is interesting to know that this book has been translated into Spanish and printed in Spain in 1900. I found a copy of it in the British Museum. Thiery, a French physician, was familiar with the contents of Casal’s treatise, and wrote a description of the mal de la rosa in the Journal of Medi- cine of France, 1755, II, 557. Casal’s book was not really pub- lished until 1762. HISTORY AND GEOGRAPHICAL DISTRIBUTION. 4T Townsend, an Englishman, in his ‘‘ Travels Through Spain’’ (vol. I, page 289, published in 1787), in writing of a visit which he made to the hospital at Oviedo, the capital of the Asturias, refers to this mal de la rosa, the first reference to the disease I have been able to find in the English language. Of this hospital he says: ‘“The most remarkable cases were tertians, dropsies, and a disease peculiar to this province called mal de la rosa. This disease is considered a species of leprosy, and descends the sternum nearly to the cartilago xiphoides. Those who suffer with this disease have a peculiar propensity to drown themselves. When the disease is neglected, it terminates in scrofula, marasma, melancholy, and madness. The people among whom it originates eat little flesh in their food; they drink little wine. Their usual diet is Indian corn, with beans, peas, chestnuts, apples, pears, melons, cucumbers; and even their bread made of Indian corn has neither barm nor leaven, but it is unfermented and in a state of dough. Their drink is water.”’ From the province of Oviedo pellagra spread westward into northern Portugal and south into the provinces of Leon, lower Aragon, and Burgos. The second focus of pellagra in Spain seems to have been in the province of Guadalajara, just west of Madrid and in the midst of the Sierra de Guadarrama mountains. The third focus was in southern Spain in the province of Granada, in the midst of the many ranges of mountains in southern Spain. The Academy of Medicine in Barcelona in 1879 made an inves- tigation of the prevalence of pellagra in Spain, and, with certain limitations, according to Hirsch, the following facts may be ac- cepted: The Asturias were the chief center of the disease at that time, and to a lesser degree lower Aragon and Burgos. In fifty villages in the province of Guadalajara 2 percent of the popula- tion were affected. 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[9 3 5, 5 3/7 | |B S a S|2 oy iS B 8 E f 3 ‘VaOVITAd NI SANILSHLNT GNV HOVWOLG JO SISAIVNY 114 PELLAGRA. bulimia, and is not influenced by food. Indeed, the distinguishing characteristic of these sensory symptoms is that they seem to bear no relation to food in any way. Pellagrins with severe gastric symptoms often suffer as much with an empty stomach as with regular diet. As one of them wisely said, ‘‘I have pain in my stomach and indigestion, whether I eat anything or not.’’ With these sensory symptoms, varying in kind and in degree, nausea, and often increased saliva, it is no wonder that choking sensations and difficulty in swallowing are present at times. The pellagrin remarks that he can drink just so much water—to drink Fig. 16.—Intestines showing atrophy of the muscles; increase in the connective tissue; chronic enteritis; hematoxylin-eosin. (By Dr. Bravetta.) any more will choke him, or only so much will run down. The nervous exhaustion marked in the outbreak, added to these sen- sations of choking and burning, with gaseous distention, often causes the complaint that the stomach is full and weighty even when no food or drink has been taken for hours. Cough was present in 11 cases, and one of these was tubercular. With stomatitis and pharyngitis, nausea, and other gastric symptoms, the wonder is that cough is not more common and more violent. Unless a local pulmonary condition is present, it does not persist after the attack is over. ALIMENTARY TRACT IN PELLAGRA. 115 One of the most striking facts in this series of cases is the fact that there seems to be a relation between the lack of hydrochloric acid and the presence of diarrhea. Only 6 had free acid, and, with one exception, diarrhea was absent; in the 14 with absence of hy- drochloric acid there was diarrhea. The diarrhea in the one ex- ception noted was temporary and due to a different cause. Rennin was present in 7 cases, and in those cases with rennin present and the acid absent, Johnson noticed that the ‘‘diarrhea was less fre- quent, less severe, and less persistent.’’ Another striking fact is that in no case with free acid has insanity developed or death fol- lowed in his experience. Two cases had no gastric juice whatever ; in one was pain, frothy saliva, vomiting, diarrhea, and prostra- tion; in the other a persistent diarrhea, with dizziness and ocular symptoms ‘‘without astigmatism.’ Johnson’s argument as to the relation of acid absence and diarrhea is confirmed by the ordinary observation that in pellagrins, when the stomatitis and esophagitis permit, the administration of hydrochloric acid with pepsin has more effect on the diarrhea than the ordinary astringents and diarrhea remedies. Back of the absence of the acid stands another problem—What causes the lack of acid? What causes the involvement of the alimentary tract as a whole? Is it related to the nervous system as an effect, or is it as truly an outcrop of the pellagrous process as the dermatosis or the pellagrous neurosis and organic cord changes. If the diarrhea is the result of gastric failure, is the gastric failure due to a deeper failure of the nerve certers? How much are the sympathetic ganglia in the abdomen involved in all this? Are they primarily affected as Lombroso thought, or is it not rather more in harmony with the facts to consider the sym- pathetic ganglia as the playground and meeting place of two dif- ferent sets of impulses—one arising in the cord as the result of the pellagrous process, and the other in the alimentary tract as the result of the pellagrous process there? One is reminded of the striking statement of Gurd that pellagra is essentially a dis- ease of the epithelial tissues, including the skin epithelium, the alimentary endothelium, and the ectodermically derived nervous system. Out of all these questions and facts emerges one clear conclu- sion—changes in the nervous system in pellagra can not be con- sidered solely responsible for all the symptoms that in an ordinary 116 PELLAGRA. case of neurasthenia are attributed to nerve exhaustion. The stomatitis, indigestion, gastritis, diarrhea, gastralgia, ravenous ap- petite, or refusal of food, thirst, or antipathy to water will of themselves cause dizziness, vertigo, weakness, neurasthenic con- ditions, functional ocular symptoms, and the exhaustion common to constant nausea and occasional vomiting. One recalls how great an influence a single aphthous ulcer has on his feelings, indigestion following a banquet provokes irritability and the blues, diarrhea for a day calls for rest, and the combination and increased severity of all these in pellagra produces a reflex effect on the nervous system and systemic condition that contributes to the facies dolorosa of the pellagrin. The diarrhea usually precedes the dermatitis, but it may occur simultaneously, and Fritz has noticed that it is common for the two to appear together in those whose work keeps them in the sun. It also shows that the diarrhea is the symptom of a systemic morbid process. The diarrhea, stomatitis, and dermatitis reach their cul- mination together during the outbreak. The diarrhea comes grad- ually, lasts about a month all told, disappearing gradually as it came. In Tucker’s 55 collected cases diarrhea was present in 54, with remissions in the diarrhea in 36 cases, and diarrhea alter- nating with constipation in 30 cases. All my cases except one had diarrhea, and, without exception, the more severe the diar- rhea the greater the prostration and exhaustion, and the more apparently severe the pellagra. In some pellagrins the flux is so severe as to merit the title of diarrheic pellagra. The Egyptian eases of Sandwith seem to have less diarrhea than either the Italian or American. Out of 166 cases the bowels in 103 were normal, 9 had slight constipation, 46 with slight diarrhea, and 8 with exces- sive diarrhea. In the height of the spring attack the number of stools in the twenty-four hours varies from six to thirty, ten to twenty being an average. In my own experience the number of stools is in- fluenced neither by rest nor food, and the number is as great in the night as in the day, and often worse from 3 to 9 o’clock in the morning. In the early part of the attack and in the initial stage of the disease the diarrhea is more spasmodic in character and with far more peristaltic activity, so that the patient complains of ab- dominal pain and griping like a colic from indigestion. The stools at this time are thicker, contain more mucous and endothelial cells, ALIMENTARY TRACT IN PELLAGRA. 117 the pellagrous odor is not so pervasive, and the stools do not come so freely as in the latter stages. At this time they may be tinged with blood, though not so commonly as in acute dysentery. They vary from gray and light-brown to green in color. In the later stages of the disease the diarrhea assumes a more serous character, is more persistent, and far less amenable to treat- ment. It is almost a pure watery stool, usually of a light-green color, occasionally almost clear. At this time the acute phase of the disease may develop, and the diarrhea precede the delirium, and foreshadows marasmus and the approach of death. As the serous discharges increase, distention develops and paresis of the intestinal walls occurs. Rectitis, hemorrhoids, and anal fissures add to the cachexia and distress. As a rule, the mild cases do not develop a severe diarrhea, and the diarrhea ceases as the attack recedes. The diarrhea may be the only symptom of the fall ex- acerbation and may last for only a few days; in other cases, after the first spring attack, the bowels are always relaxed, and two to four stools a day common. In the cases with constipation the at- tack is mild and short, and the disease progresses slowly. The life of the pellagrin is prolonged in inverse proportion to the severity and the persistence of the diarrhea. As the disease advances, the entire alimentary tract becomes in- flamed; gastritis, enteritis, colitis, and rectitis are the foundations for gastric and intestinal ulceration, with blood, mucus, pus, and increased putrefaction and fermentation. At this stage indicanuria is common. Absorption is interfered with, and there is an increase in undigested food materials, especially fats, starch granules, plant cells, and muscle fibers. The stools are acid as a rule and gaseous, looking as if they had been whipped, so numerous are the air bubbles. Under the microscope there is an increase in the fat globules, due probably to a decrease in the bile and pancreatic juice. If the stool in pellagrous diarrhea is put in a bottle or graduate and allowed to stand for several hours, it separates into three layers—(1) above is the aqueous portion, serous in char- acter, often colored a light-yellow; (2) below this a thick gray layer composed of mucus, pus, and occasionally blood cells; (3) a heavy layer below, dark-brown or green in color, and composed chiefly of waste matter from the food, or ordinary fecal matter, in which is found clinging mucus that has not separated. J. D. Long in his admirable studies found ammonium and magnesium 118 PELLAGRA. phosphate crystals, fatty acid crystals, calcium oxalate, cholesterin plates, and fungi. PATHOLOGY. The mucosa of the oral cavity presents hyperemia, occasional swelling, ulcerated areas, and infrequently the remains of small vesicles. A favorite spot for the vesicles is on the cheek just an- terior to the pillars. At times the pharynx, palate, and esophagus may be in this same hyperemic condition, with a diffuse ulceration. Fig. 17.—Section of liver; hyperemic; hematoxylin orange. (By Dr. Bravetta.) At the summit of the anterior pillars two cyanosed areas, round or oval in shape, are often found. The tongue presents fissures, absence of its epithelial coat, and engorgement of the veins on the margins and beneath. Ulcers may be present on the tip and anterior lateral margins. The stomach is found normal in position and size, or gastro- ptosis occurs, and I believe more frequently than the records would show, and dilatation is present infrequently. Watson reports a ease in which there was excessive redness of the peritoneal coat noted during a laparotomy. Post-mortem, the organ is rather pale, * ALIMENTARY TRACT IN PELLAGRA. 119 the muscles atrophied, the walls thinned, and the internal walls covered with mucus. In the more acute forms the classic picture of a gastritis is present, with redness of the mucosa and marked ulceration, especially in the pyloric region. The intestinal changes are variable, depending on the length and the severity of the disease. The intestine is usually emaciated and thinned in proportion to the rest of the body, though it is not true that the walls are always atrophied, especially throughout their entire course. As a rule, the intestine is atrophied, brown pig- mentation is often present, and the muscular coat thinner than Fig. 18.—Spleen, showing increase in connective tissue; hematoxylin orange. (By Dr. Bravetta.) normal. Labus thought the intestinal canal was contracted through- out, a point not confirmed altogether by later investigators. With acute cases and enteritis, ulceration may occur at any part of the large or small gut. With ulceration, hyperemia instead of anemia is present in more or less localized sections. Ulcers may form in the duodenum, jejunum, and ileum—more frequently in the last two divisions; ulceration may occur in the large intestine, but most often in the rectum. The mouth and rectum are the most fre- quent areas in the alimentary tract for pellagrous inflammation. The anus is often swollen, discolored, and fissures and hemorrhoids 120 PELLAGRA. are occasionally found. The diarrhea is the cause of these fissures and hemorrhoids, and the resulting irritation. The liver varies from atrophy to hypertrophy; in far the greater number of cases it is atrophied. This is a simple atrophy due to malnutrition, cachexia, and marasmus. The decrease in size may be very marked, even to one-third the original size. The edges are sharp, the capsule wrinkled, and the gall bladder may project. be- yond the lower border, often dilated and engorged with bile. Fatty degeneration, cloudy swelling, or brown atrophy may exist in the liver cells. The liver is frequently tough, and pale like the liver in senile anemia. The pancreas is usually small, tough, and friable. The spleen may be normal, but it is usually atrophied and tough. In his report on case 6 of his post-mortems, Strambio notes the spleen weighed twenty-seven pounds, with no other com- ment. This was probably a malarial spleen, as in all his other cases the organ was normal according to his report. The mesenteric glands are often enlarged. CHAPTER V. THE SKIN IN PELLAGRA. Hebra, in the first volume of his famous work on ‘‘ Diseases of the Skin,’’ classifies pellagra as a skin disease in the group which he describes as ‘‘acute, exudative, but noncontagious dermatosis.’’ He makes a second division which he ealls ‘‘the polymorphous erythemata,’’ and includes pellagra there, believing it to be not an inflammation of the skin alone, but depending rather on a toxic action affecting the whole organism. ‘““The symptoms of the erythematous inflammation of the skin consists in rose or blood-red discoloration, disappearing under pres- sure, and in a slight degree of swelling, caused by serous exudation or edema. In this affection the tension of the skin is inconsid- erable, and little or no pain or itching is complained of. Its course is always acute, and its chief peculiarity is that it generally ter- minates in the absorption of the inflammatory products, followed by deposit of pigment or desquamation of the cuticle. It rarely happens that either vesicles, bulle, or pustules develop themselves in this form of dermatitis; and there is never any deeply seated suppuration, attended with loss of substance, or followed by the formation of cicatrices. The erythematous inflammation involves only the superficial layers of the cutis, while the phlegmonous in- volves the whole skin and the connective tissues beneath.’’ (Hebra.) Howard Fox very wisely believes the red erythema in pellagra to be a true dermatitis, and not a simple erythema. Hebra was of the same mind, and the sooner we come to their belief the better. Fox adds this important statement: ‘‘It would seem quite proper to use the term erythema for the first stage of the disease, which resembles an ordinary sunburn and which lasts only a few days. But it seems somewhat anomalous to speak of the entire eruption as an erythema when the erythematous stage is so comparatively insignificant, while the stage of desquamation is so characteristic and of such long duration.’’ Jn reading a case reported by Turck 121 122 PELLAGRA,. occurs this sentence, and, taken with the statement of Fox, the problem of the skin in pellagra will become easy: ‘‘Within two weeks after the operation these patches increased in extent, and there was a condition resembling in places a dry eczema and in others an erythema,.’’ Here is the clue to the whole matter. The pellagrous skin is dimorphous. It is a dermatitis, which is called also the eruption, the erythema, or the pellagrous exanthem. It is also a dermotagra, or a rough skin, which is called the dry Fig. 19.—Dermatitis on hands. A clear band of skin is shown on left hand where ring was continually worn, and a darker band is shown on ring finger of right hand where ring was occasionally worn, indicating the influence of light. (Courtesy of Dr. C. C. Bass.) eczema or branny skin of pellagra, or the eczematoid condition of the skin in pellagra. With this idea of a double affection of the skin in pellagra, I think we can trace the origin of some of the early synonyms of the disease. In Spain it was called ‘‘mal de la rosa,’’ named from the rose-red inflammation of the hand. In Italy among the common people originated the pellis agra, or rough skin, because the Italians named it from the roughness so markedly apparent above and around the dermatitis and on the elbow and body, and persisting in some cases on the original der- THE SKIN IN PELLAGRA. 123 matitis area. It is a mal de la rosa because it is a rose-red derma- titis; it is a pellis agra because it is a dermotagra or rough skin. The following diagrammatic arrangement permits us to discuss separately the two divisions: : a. Erythema, maculo- papular. 1. a a in- J p, Erythema, vesicles amed. skin. Dermatosis of pellagra- one, baile: i ce. Fissures. dimorphous. 2. Dermotagra, or rough skin. b. Keratoid. . Follicular, a. Eczematoid. c In the majority of cases the dermatosis is a dermatitis of the maculo-papular type with the dermotagra of the eczematoid type. The dermatitis with vesicles and bulle is far less frequent, involves the skin to a greater degree than the first type of dermatitis, and generally indicates a severe pellagrous attack internally. Fissures develop rarely, and the area of inflammation about them is de- pendent on their length and depth. Taking a pellagrous dermatitis limited to the back of the hands and wrists, and a dermotagra around the borders of the dermatitis and extending up the extensor surface of the forearm to and including the elbow as a type, the order of the development is as follows, as illustrated by a diagram from Merk, slightly altered: === B Fig. 20.—Diagram illustrating the development and course of the pellagrous dermatitis. The beginning of the dermatitis is represented by a, when the influx of blood and serum into the dermis is marked; 1 to 2 marks the erythema at the time when the livid red hue is most prominent; b represents the increase in the dermatitis, c its maximum develop- ment, d and e mark the gradual recession of the dermatitis and the erythema. At f the stage of dermatitis may be considered over, and the shedding of the epithelium begins. As the dermatitis re- cedes, the shed epithelium becomes evident, but, what is important, this continues in fine, branny scales, and marks a permanent change 124 PELLAGRA. in the dermatitis area; it becomes hyperplastic, and in a great many cases remains eczematoid, feeling rough and shedding fine scales. This is indicated by g; the line f g does not again coincide with the basal line of skin smoothness, A B, except in mild and rare cases. Above the wrist and occurring with the dermatitis is the typical = - Fig. 21.—Insane pellagrin, with a typical dermotagra in palm of hand. (Courtesy of Dr. Bravetta.) dermotagra. It involves the flexor surface of the forearm and the elbow-joint over the olecranon process. Usually it is eczematoid in character, partaking in appearance and feeling of a dry, scaly eczema; but there is often a noticeable prominence of the hair follicles, and the elbow may be so rough, wrinkled, and laid off in small rhomboid and rectangular areas that it assumes a keratoid condition. This last is especially true in old cases, and is most THE SKIN IN PELLAGRA. , 125 often seen in asylums for the insane. I have seen it both in Amer- ica and in Italy. As Watson very wisely remarks, the dermatitis with vesicles and bulle ‘‘differs only in degree’’ from the maculo-papular type as above. When the vesicles occur, the dermatitis is known as the ‘‘wet’’ form as distinguished from the ‘‘dry.’’ Even this wet form differs very much in severity. The dermatitis may be of the ordinary erythematous type, and a few small vesicles may develop in the center of the back of each hand. These are usually small and discrete, contain serum, occasionally blood-streaked. The epi- XY Fig. 22.—Pellagrous dermatitis; dry form, with exfoliation of the skin. (Courtesy of Dr. Bravetta.) dermis is elevated, serum quickly exudes, and a common Dlister results. It ruptures, the base is raw, heals quickly, and rarely in the mild forms leaves a scar. In the more severe cases the vesicles become bulle, cover the back of the hand; edema occurs, and small vesicles may occur on the fingers. On Siler’s cases 10 percent had the vesicles, and 66 percent of the cases with vesicles died. The presence of blisters indicates usually a severe attack of the disease. Occasionally they become purulent, with a phlegmonous 126 PELLAGRA. involvement of the deeper structures. After rupture, ordinary granular tissue with the small elevations are seen as healing takes place. Hither here or in the more severe dry form, fissures may develop, with gaping and localized inflammation. Favorite seats are between the metacarpal bones, over the knuckles, and between the fingers. The pellagrous dermatosis is a part of the pellagrous process— it is pellagra of the skin. One asks why the skin is affected in pellagra. There is no more an answer to this question than to the other view—why should the skin not be affected in pellagra? Measles begin on the face and scarlet fever on the body; the reason is not clear, and one can only say that it is a characteristic of the disease in question. The rose-red spots of typhoid select the abdomen and the dermatitis of pellagra selects the hands, and the selective action of different diseases on different organs and in different locations is as inexplicable as is the specific action of different pathogenic bacteria. Even with the knowledge that the dermatosis is the skin ex- hibition of the disease, it is well to remember that the internal malady may continue to exist independently of the eruption or of its disappearance. When the dermatosis goes, it does not mean that the pellagra has gone. The eruption does not kill, but pel- lagra does kill. The dermatosis is the least of the dangers to the pellagrin, but the most important of the symptoms to the phy- sician in diagnosis. It is the passkey and the capstone to the correct diagnosis of the disease. In the language of Roussel, it is the ‘‘element decisif dans le diagnostic.’’ The existence of pel- lagra sine exanthemata is relatively infrequent, and in all ordinary cases of pellagra the decisive element is the dermatosis. It may be so slight as to hardly differ from a slight sunburn and last only a few days in its entirety, though the dermotagra on the forearms and elbows usually lasts longer, but this skin involve- ment is the decisive and conclusive element in the diagnosis. In the language of Hyde, it is ‘‘the local expression of a systemic disorder.’’ Eruptions in systemic diseases are common, and, viewed in this broad light, there is nothing remarkable in the presence of the pella- grous dermatosis. Syphilis has an eruption, and in suspected cases the physician may postpone treatment and wait for the appearance of the rash, because it is confirmatory and diagnostic rather than THE SKIN IN PELLAGRA. 127 dangerous. Scarlet fever, measles, smallpox, and rétheln each furnish their peculiar rash and eruption, with its individual char- acteristics, time of appearance, and duration, and pellagra does Fig. 23.—Dermatitis. It is symmetrical, and is called the pellagrous glove. (From Pel- ae lagra Report of the Tennessee State Board of Health.) likewise. As Merk well says, ‘‘the cutaneous symptoms in pellagra are of the same importance from the point of view of diagnosis as in chickenpox, smallpox, scarlet fever, and measles.’’ 128 PELLAGRA. The color of the dermatitis varies according to the stage of the attack and the length of the disease. At the beginning it is the color of red cedar, with a tint of pink added; at the acme of the attack it is the color of red cedar, with a greater and more marked redness; at the decline of the dermatitis it is like red cedar, with a darker tint added. If one takes a smooth piece of the heart of red cedar wood, and compares it with the pellagrous dermatitis, he is at once struck with the similarity and with the fact that the brownish-red color of the cedar is the fundamental color of the various stages of the dermatitis. In the lighter attacks the simi- larity with sunburn is to be borne in mind, and at times in these mild forms the dermatitis is indistinguishable in tint from ordinary pigmentation caused by the sun. In the more severe forms it turns to sepia toward the close, and especially if there have been several previous attacks. On the face there may be a dermatitis with a marked redness, and at times one thinks of a brick-red color or even the lighter hue of terra-cotta. In the dermatitis with vesicles and bulle the redness is more apparent, and in the general development the similarity to a burn first pointed out by Babcock may become evident. These vesicles break and heal, and leave a hard, scabby covering darker than the surrounding skin. During the dermatitis the skin is smooth, glistening and shiny, and may appear tense and very slightly swollen. In the negro the dermatitis is either stark black, like soot or a black hat, or at certain angles a gray tint may be apparent. Marie noticed this gray hue in the Arabs in Egypt. At times this skin in the negro may peel off in large, thick plates, perfectly black in color, and as thick as skin from the sole of the foot of the negro in typhoid. Here the lamelle are hard and dry, and more like plates than pieces of skin. Ecchymosis may appear on the body during the dermatitis or in the dermatitis area after the exfolia- tion has begun. The dermotagra occurs simultaneously with the dermatitis, but usually on the flexor surface of the forearms, elbows, occasionally on the arms, face, and other parts of the body. The branny rough- ness may be in color and appearance similar to a dry, scaly eczema, except there is usually a brownish tint present and the flexor surface of the forearm and the elbow look dirty as if in need of soap and water. The smooth and glistening appearance of the dermatitis area is absent, and dirty roughness persists. On the THE SKIN IN PELLAGRA. 129 elbow, face, knees, and at times on the trunk even, the slight brown- ish tint is absent and only the roughness is noticed, with the shedding of small branny scales when rubbed or scratched. I have seen cases in which the maculo-papular dermatitis, after exfolia- tion and all signs of the inflammation and pigmentation had gone, was succeeded by a persistent dermotagra on the back of both hands and the flexor surface of the forearms. The patient may seem and feel well, and yet on close observation this suspicious dermotagra can often be seen. This is one of the strongest evi- dences presented by the skin in the periods of intermission and when no other symptom remains of the previous dermatosis. Another aid afforded by the skin in the periods of intermission is what Sandwith calls ‘‘the preternatural pinkish cleanliness’’ of the finger tips, and he might have added of the toes also. At times this pink cleanliness includes the palmar surface of all the fingers, and it is especially evident when the arms hang down or when the hand of the pellagrin is put by the side of the hand of a healthy person for comparison. The tips of the fingers seem as clean be- tween the attacks as the back of the hands seem dirty during the attack. This condition is especially evident in the better class of pellagrins. Along with the abnormal pinkness on the palmar sur- face is found the increase in the number of folds or wrinkles over the first interphalangeal joint, and the division of these folds into small areas, which are square, rhomboid, or rectangular in shape, and rather rough. After the attack these folds hang loosely, are increased in number over the usual three to five wrinkles, and, when gently rubbed by the index finger, feel rough. A laborer’s hand may have these rough divisions, but the pinkness of the fingers and reduplication of the folds is absent. Another factor in diagnosis between attacks in regard to color is the mosaic mottling of the back of the hands, and a cyanotic condition of the whole hand when the arm hangs loosely by the side. The same condition prevails after the dermatitis on the foot. One can sometimes examine the hand of a pellagrin during the winter months after the attack of the previous spring, and the pink fingers, mosaic mottling and cyanosis, increased wrinkles and rough areas are of great aid in doubtful cases. I have been able to bring all these symptoms out more clearly by lightly grasping the wrist with my hand and interfering with the circulation. In one case the perspiration burst forth quickly all over the palm of the hand, 130 PELLAGRA. and the cleanliness of the pink fingers was wonderful. The hands of the pellagrin can not be too closely studied. LOCATION. The location of the dermatosis is influenced by the selective action of the disease, by symmetry, and by light or heat. Merk, with the aid of Weiss, collected pellagra statistics in the south of the Tyrol for the years 1905-1907. These observations included 384,072 in- habitants, of whom 4,836 were pellagrins, or 13.4 per thousand; of these, 2,973, or 61.4 percent, presented some of the cutaneous manifestations of pellagra; and 2,179, or 45 percent of the cases, presented the maculo-papular dermatitis. Of these last the follow- ing notations were made: 1,677, or 77 percent, with dermatitis on the back of both hands. 283, or 13 percent, with dermatitis on the back of both hands and on the neck. 164, or 7.5 percent, with dermatitis in rare locations and on the neck. 53, or 2.4 percent, with dermatitis on other parts of the body. This table gives ample proof of the selective action of pellagra on the skin. The back of the hands is the most favorite spot, then the neck; in America the feet, face, and then other parts of the body. To the selective action is added the symmetrical distribu- tion, the dermatitis or the dermotagra usually appearing on bilateral areas simultaneously. There are exceptions even to this simultaneous action. Echols at Milledgeville showed me a female pellagrin in his wards on whose right hand the characteristic dermatitis appeared, and after eight days it appeared on the same area on the left hand. Tucker reports the only other case of this kind I have found in the literature. He gives in his 55 collected eases 44 in which the dermatosis began on the back of the hands and forearms; in 7 on the back of the hands, forehead, and ale of the nose; in 3 on the back of the hands and feet, and in 1 on the back of the hands and neck. The dermatosis remained con- fined to the hands and forearms in 28; hands, face, and neck in 4; hands, face, feet, and neck in 12. In one case the skin was in- volved all over the body, the pellagra universalis. In this form the dermatitis is limited usually to the ordinary sites of hands, face, neck, and feet, and the rest of the body covered with the THE SKIN IN PELLAGRA. 131 eczematoid dermotagra. I saw a case of this kind in Italy at Mombello, and one case in Georgia even more remarkable, as there was a dermatitis on the hands and wrists, between the scapule, and in the sacral region, extending down in the gluteal folds. On the hands the dermatitis usually covers the backs, affecting least the terminal phalanges, and it usually extends from two to four inches above the wrist as the pellagrous glove. The eczema- toid dermotagra then usually extends above to and including the elbow. At times the dermatitis extends as far as the elbow, or it may skip the elbow and reappear on the arm or under the ce ee eat al Fig. 24.—An Italian case of senile hands in pellagra. The skin is dry and wrinkled, and lies over the knuckles in folds. (Courtesy of Dr. Bravetta.) axilla. In advanced or severe cases the dermatitis surrounds the wrist, appearing in triangular form anteriorly as the pellagrous bracelet. The feet, when affected, are covered on the dorsum from the toes to the malleoli, but the dermatitis may extend up the leg for a variable distance, as a rule not above the junction of the lower and middle thirds, forming the pellagrous boot. The knees may be covered, like the elbows, with the keratoid roughness, dirty- brown in color, and the legs may present a mottling anteriorly to the knees. After the dermatitis departs and the epidermis exfoliates, the 132 PELLAGRA. dermotagra persists for a variable period, often permanently. Contrary to Jansen and the Italian writers, it may invade the hand as the keratoid dermotagra. Bravetta had a case at Mombello in Italy. Here the dermotagra invaded the palm from the radial side, advancing under the thumb. This invasion of the palmar surface seems more common in America than in Italy. I have seen several cases where it advanced from the ulnar side, and Zellar in Illinios has seen cases on the soles of the feet, with peeling as in scarlet fever. In negroes the elbows and knees are often covered with persistent ashen-gray roughness, noticeable between attacks. A discrete dermatitis may occur around the lips, or the pella- grous mask may cover the face with exfoliation. The forehead may be affected with the eczematoid roughness, or mingled with these may be the isolated areas of dermatitis. The dermatitis may stimulate the sebaceous glands and produce a temporary seborrhea. This is more common on and around the nose than elsewhere. A symmetrical dermatitis may appear over the malar bones, below and behind the ears, and crescentic ecchymosis, dermatitis, or dermotagrous spots, always symmetrical, develop on the lower and upper lids. The symmetrical areas of dermatitis may appear on the back of the neck, or a crescentic area cover the back of the neck, concavity upward, and thickest in the median line and ex- tending the same distance on both sides. The dermatitis may sur- round the neck with a sternal prolongation, which forms the Span- ish cravat of Casal. Sandwith has seen this in Egypt, and thinks it due to the open shirt-front of the field laborers. Studying many hundred cases of pellagra, one sees either the dermatitis or the dermotagra in locations rarely described, and which Bravetta well calls ‘‘atypical locations.’? These are in the axilla, on the flexor surface of the elbow-joint, the posterior surface of the knee, on the thighs, the scrotum, a dermotagra making a girdle around the hips, and Dr. Greene at Milledgeville showed me a remarkable case in a young negro with a severe dermatitis entirely around the shoulder, covering an area about four inches wide and making a veritable shoulder girdle of dermatitis, coal black in color. After the attack is over, walnut stain effects are occasionally seen on the face on the order of chloasmic spots. This colored area may persist as a permanent pigmentation without any roughness. The perineum, vulva, and anal regions in the female are attacked by the dermatitis, occasionally by gangrene, and even a pro- THE SKIN IN PELLAGRA. 133 nounced keratoid condition may be present. In the more serious cases the dermatitis may extend from the inner surface of the thighs upward and backward to the anus and the gluteal region. An acute vaginitis may be present, with a mucopurulent discharge, erosion of the epidermis, and even sloughing of the tissues. The dermatitis may occur on the folds of the labia majora and minora, but the inflammation of the vaginal mucosa is similar in character to the stomatitis. The dermatitis with vesicles is not infrequent when the hands have the same inflammation, and in these cases sloughing and gangrene may develop in the vulvar region a short time before death. J. Clarence Johnson, of Atlanta, had a case in which the vulva and labia majora were covered with a thick, kera- toid covering, very rough and dry to tne touch. The patient re- covered from the attack, and after exfoliation the vulva was normal. RELATION OF THE DERMATOSIS TO LIGHT. In the early days of pellagra the sun was believed to cause the disease, and it was called mal de la sol, or sickness of the sun. Jansen remarked that the sun was neither hotter nor different in Italy than in other sections of the world where the disease did not exist, and the dermatitis may occur on parts of the body covered by clothing. In those exposed to direct sunlight the dermatosis in pellagra seems to appear earlier in relation to the other symp- toms, and to be synchronous with the diarrhea, whereas in those living indoors the diarrhea or dyspepsia usually precedes the der- matitis. This influence of the sun has been attributed to the shorter or violet rays of the spectrum, known usually as the actinic rays. The work of Aaron would seem to weaken the actinic theory in pellagra, and to cause the belief that the direct heat of the sun was the real influence, with the elevation in temperature of the parts exposed to the sun and of the surface temperature in general as the chief heat factor. Various experiments have been performed with fenestrated gloves. The pellagrous glove itself often extends from four to six inches above the lower border of the sleeves. Bass’ ring experiment (Fig. 19) seemed to show protection from the der- matitis when the parts were not exposed to the sun. This much is certain, and proof that the influence of the solar heat is only a very minor influence—a patient must first have pellagra internally be- 134 PELLAGRA. fore the sun can cause or influence the dermatitis externally. The disease, and not the sun, causes the pellagrous dermatitis. The hair is usually not affected in those developing pellagra during adult life, but in children the hair is often short, thick, and coarse, lacks the usual amount of sebaceous matter, and feels rough. It stands up, and does not respond to combing and brushing as Fig. 25.—Wet form of dermatitis, with sloughing of skin. Unusual lesions in the palms of the hands, due to wringing clothes when washing. The elbows are also affected from pressure when rising from the bed. (Courtesy of Dr. ©. C. Bass.) ordinary hair. In children the hair on the body does not develop normally, but is both scant and short. The perspiration, normally acid, may in pellagra be neutral. Procopiu found it neutral in 20 cases, acid in 2, and alkaline in 3. In Tucker’s 49 cases it was normal in 14, increased in 3, and de- creased in 32. In insane pellagrins it has seemed to me that it THE SKIN IN PELLAGRA. 185 was noticeably increased on the feet and hands, and the more ad- vanced the nerve lesions the more variable the amount of sweat. The odor of the body is increased in certain cases, and this is at- tributed to the fetid sweat. The sebaceous glands of the skin are at times overactive—more pronounced, as is to be expected in young pellagrins. The nails are occasionally affected. They turn white or grayish Fig. 26.—Rough hands of a pellagrin as contrasted with the normal hand of a hospital orderly. (Courtesy of Dr. Bravetta.) white, are thick, and in the spatulate hand are very wide and brittle. This is a rare occurrence, and occurs usually in advanced cases— especially in the insane and following a hemiplegia in old pella- grins. Here it is probably trophic in nature and dependent on the pellagrous process in the nervous system. It is found in the asylums for the insane rather than in pellagrins in private practice. Occasionally the nails fail to receive sufficient nourishment from the blood and actually drop off. Such trophic changes rarely occur in private practice, 136 PELLAGRA. SENSORY SYMPTOMS. The sensory symptoms in ordinary cases consist of either tense- ness or tightness of the skin over the dermatitis areas and in those with vesicles, bulle, and swelling; itching sensations; and, lastly, the most constant and irritating of the three is the burning of the hands and feet, and infrequently other parts. For a few days before the eruption the skin may feel tense and tight as if it were Fig. 27.—An Italian case of (Ghites coon hese the feet during an attack. being stretched or the hand and forearm were swelling. This is of short duration, reaches its maximum at the height of the derma- titis, and recedes rapidly with the exfoliation. In the dermatitis with vesicles—the wet form—the swelling and tenseness may be increased even to a condition of edema in the inflamed parts, with the hands swollen and heavy. After rupture of the bulle, this tightness of the tissues and edema rapidly ceases. The itching is a minor symptom, and patients complain of it THE SKIN IN PELLAGRA,. 137 very little. Sandwith, in his 164 cases, had itching in 71, burning in 8, and in 90 neither symptom was present. In the American cases the percent of burning would certainly rank much higher, and the patients complaining of itching much less. Indeed, one seldom notes itching sufficient to cause scratching to any degree. Whatever actual pruritus exists is apt to be heightened by burning sensations, and it is the heat rather than the itching that causes the discomfort. The burning may occur on the back between the scapule, over the sacrum or coccyx, and it may be intense around the anus and in the perineal region. It may cause insomnia, and 2 OL Mls [Be=* Fig. 28.—Pellagrous dermatitis. Hand swollen and edematous. (Courtesy of Dr. Bravetta.) the patient complains that if the burning would only stop he could sleep without trouble. Warnock thinks there is a connection in the pellagrous insane between the sensations of burning and the well-known complaint of discomfort and delusions of being burnt, of sorcery, and of persecution. The area of burning may become red in the periods of intermission, and in the advanced cases the burning often continues long after the attack has receded. This burning is probably central in origin along with the burning felt in the stomach at the height of the attack. In the advanced neurasthenic stage, with mental failure, the burning causes a de- 138 PELLAGRA. sire for cooling and for water, and many of the suicides by drown- ing formerly common in the Tyrol can be explained in this way. One of my cases had no itching or burning, but developed the most Fig. 29.—A Georgia case, showing exfoliation of the skin following a spring attack. Period of recession. (Courtesy of Dr. J. O. Elrod, Forsyth, Ga.) persistently cold nose I have ever seen. It was cold to the touch, and the patient said the tip seemed changed to a small piece of ice. CHANGES IN THE SKIN. The subcutaneous fat and areolar tissues disappear in proportion to the severity and the length of the disease. In any case with a marked dermatitis there is an atrophy of the skin, with wrinkling and often even folds, so that one is struck with the youth of the pellagrin and the senility of the skin. The hands are those of old people, and the face may look old as a result of the wrinkling and puckering of the brow. By pulling up the skin on the back of THE SKIN IN PELLAGRA. 139 Fig. 30.—An Italian case of alcoholic erythema, due to alcohol and not to pellagra. (Courtesy of Dr. Bravetta.) Fig. 31.—An Italian case of alcoholic erythema, due to alcohol and not to pellagra, and of the same character as Fig. 26. (Courtesy of Dr. Bravetta.) 140 PELLAGRA. the hand, it is loose and there seems too much of it—a condition that Italians call ‘‘pelle elastica.’’ After two or more attacks of dermatitis the skin is permanently atrophied, and the site of the inflammation is covered with a thinned, cicatriform, parchment- like integument—this last being often irregularly altered—and the thinning showing occasionally in stripes parallel with the long axis of the hand. (Hyde.) The skin becomes permanently pigmented and discolored, and there may be a universal bronzing. The eczematoid dermotagra may become permanent in the dermatitis y at 5s : | Fig. 32.—A close view of the rough skin in pellagra, showing areas of exfoliation. Hand swollen and edematous. (Courtesy of Dr. Bravetta.) area as well as in the original site of the roughness on the fore- arm, elbow, and face. The microscopical changes are like those of a mild acute inflam- matory condition, with a degeneration of the upper layers of the dermis. The skin in the beginning of the dermatitis is hyperemic, with an exudate of serum and leukocytes, and with no change in the superficial and terminal nerves. (Harris.) Following the degeneration with the involvement of the connective tissue around the blood vessels, repair begins with an increased cellularity of the dermis, the presence of fibroblasts, pigmentation, eczematoid THE SKIN IN PELLAGRA. 141 scaling and shedding, and with an increase in the lymphocytes and plasma cells. The sweat and sebaceous glands are hypertrophied and enlarged. There is an increase in the number of capillaries, with a corresponding increase in the thickness of the skin in the prickle cells and stratum granulosum. In ulceration the epidermis is absent, and there is loss of substance in the upper part of the Fig. 33.—Pellagrous dermatitis. Hand swollen and edematous. (Courtesy of Dr, Bravetta.) dermis. As atrophy continues, the epithelium dips deeply into the thinned connective tissue. Gurd believes the irritant is in the dermis, with the addition of some predisposing factor. There is an enormous increase in the formation of pigment in the cells, and an increase in the number of chromatophores in the upper dermal layers. The pigmentation originates in both types of cells, and, so far as is known, remains where it originates. CHAPTER VI. NERVOUS SYSTEM IN PELLAGRA. The pellagrin is the warehouse of all the symptoms of neuras. thenia. The very name and presence of the disease causes him to fear and to forebode. The dermatosis gives him a sense of filth and repugnance; the gastrointestinal condition reacts on him both mentally and physically; and added to these are the deeper tissue changes in the cerebrospinal axis, which constitute the organic basis for what is at first a neurasthenia, and which later is the worn-out soil in which spring up tremors, pains, increased reflexes, palsies, paretic and spastic gaits, trophic changes, mental retarda- tion, and finally psychoses of different types, inanition, and death. The pathological changes in the nervous system are definite in varying limits, and their study clears the clinical nerve symptoms of much uncertainty. Like the course of pellagra, these changes in the nervous system are slowly progressive in the chronic forms and rapidly progressive in the acute forms. Progression applies as well to the tissue changes as to the external clinical symptoms. TISSUE CHANGES. The Brain. Gross Changes.—The pia mater and arachnoid are thickened with occasional thickenings of the dura. The piarachnoid may be opaque and milky, with purulent deposits under the arachnoid or hemorrhagic ecchymosis. Osseous plaques may be formed and a typical lepto-meningitis exist. The brain and its convolutions, especially the frontal, show atrophy, and the weight of the brain is decreased in the majority of cases. The brain may be partially or completely edematous or hyperemic, with excess of fluid in the ventricles. It may be anemic, and harder on one side than the other. The cerebellum is either small and hard, or edematous and soft. These gross changes are variable, as shown by the fact that the brain may be either increased or decreased in weight. War- 142 NERVOUS SYSTEM IN PELLAGRA,. 143 nock found the brain weight 1,300 grams, with body weight of 46 kilograms, in an old pellagrin 45 years old, who was ‘‘passive, prostrate, and demented.”’ Microscopical Changes.—The capillaries show pigmentation and fatty degeneration in their walls, and occasional calcareous de- posits. The small arterioles and capillaries are filled with blood and the perivascular lymph spaces dilated. This condition ex- plains the increased fluid found in the ventricles in certain cases. The cortical nerve cells show degeneration, with swelling, vacuoles form, the nuclei and nucleoli are swollen and pushed to one side. Fig. 34.— Cortical cells. Pigmentary degeneration. Method of Cajal. (By Dr. Bravetta.) ‘The granules disintegrate in advanced cases, and the dendrites swell and break. The neuroglia cells, especially around the vessels, swell, and Babes and Sion found small collections of lymphoid cells, but this latter was not confirmed by Harris. There is atrophy of the degenerating cells and also degeneration of the fibrillar structure in the cell body. Harris studied the cells of the cerebel- lum and noted degeneration, atrophy, and at times disappearance of many of the cells of Purkinje. In one instance he found the molecular and granular layers separated by microscopic spaces that. probably existed during life. 144 PELLAGRA. Fig. 35.—Cortical cell, showing contraction of the protoplasm. Method of Cajal. (By Dr. Bravetta.) Fig. 36.—Cells from the spinal cord, showing thickening and contraction of the neuro- fibrillar net, or special net of Marinesco. Method of Cajal. (By Dr. Bravetta.) | = NERVOUS SYSTEM IN PELLAGRA. 145 The Cord. Gross Changes.—These gross changes are not as evident in the cord as in the brain. In acute pellagra an acute meningo-myelitis may be present, with inflammation of the meninges and a superficial edema and softening. The superficial vessels are dilated. Microscopical Changes.—These changes include chiefly degen- eration in the direct pyramidal tract and in the posterior column, including both the tracts of Goll and Burdach. The gray matter ee ee. eS Fig. 37.—Cells from the spinal cord, showing partial thickening and contraction of the neuro-fibrils. Method of Cajal. (By Dr. Bravetta.) and the spinal ganglia are affected to a degree.