V Class Book. &pgliffi .. COPYRIGHT DEPOSffi J PELLAGRA Diagrammatic cross section of the spinal cord of a pellagrin, the parts in red representing the lesions. 1, central canal; 2, column of Clarke; 3, tract of Burdach; 4, tract of G-oll; 5, tract of de Lissauer; 6, posterior roots. (Procupiu, after Babes.) See page 145. '■" PELLAGRA HISTORY, DISTRIBUTION, DIAGNOSIS, PROGNOSIS, TREATMENT, ETIOLOGY BY STEWART R. ROBERTS, S. M., M. D. 4 ASSOCIATE PROFESSOR OP 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 ^ Copyright, 1912, by C. V. Mosby Company Press of C. V. Mosby Company St. Louis £ CI.A314932 ' ■) 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. S. S. 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. 0. 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 encouragement. Stewart R. Roberts. 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 Yerona, 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 a 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. PAGE General Considerations 17 Pronunciation — Typical cases — Definition — Description — Age — Sex — Inheritance — Contagion — Immunity — Occupation. CHAPTER II. History and Geogeaphical Distribution 43 Synonyms — History — Geographical distribution — Spain — Italy — France — Egypt — America. CHAPTER III. Classification 74 A general disease — Other infections in pellagra — 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 107 The tongue — Gums — Teeth — Buccal mucosa — Palate — Salivary glands — Pharyngitis — Esophagitis — Stomach and intestines — Tissue changes. CHAPTER V. Skin in Pellagra 121 Character — Pellagrous skin — Dimorphous — Classification — Loca- tion — Relation to light — Sensory symptoms — Changes in the skin. CHAPTER VI. Xeryous System in Pellagra 142 Introduction — Tissue changes in brain and cord — Relation of cord 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 12 CONTENTS. CHAPTER VII. PAGE Other Systems and Changes ,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 period of onset — During the at- tack — During the intermission between attacks — Pellagra sine exanthemate — Prognosis in pellagra. CHAPTER IX. Treatment of Pellagra 218 Treatment of avail — Improvement — Associated infections — 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 different theories — Two chief theories — 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 34 3 Dermatitis on feet of pellagrin 36 4 Map showing distribution of pellagra in the western half of the state of Tennessee 54 4a Map showing distribution of pellagra in the eastern half of the state of Tennessee 55 5 Map showing distribution of pellagra in the United States . . .56,57 6 Pellagrosario at Rovereto, Austria 65 7 Group of eight boys, all pellagrins 70 8 Closer view of three of the boys shown in Fig. 7 ....... 70 9 Map showing distribution of pellagra in the world 72,73 10 Pellagrous boy 75 11 Two Georgia cases, presented by the State Hookworm Commission . 76 12 Same case as Fig. 11, side view 76 13 Diagram illustrating periods in an attack 86 14 Pellagra during period of attack 87 15 Diagram illustrating stages of chronic pellagra with relation to clin- ical symptoms 97 16 Intestines, showing atrophy of the muscles 114 17 Section of liver 118 18 Spleen, showing increase in connective tissue 119 19 Dermatitis on hands 122 20 Diagram illustrating the development and course of pellagrous der- matitis 123 21 Insane pellagrin 124 22 Pellagrous dermatitis 125 23 Dermatitis 127 24 Italian case of senile hands in pellagra 131 25 Wet form of dermatitis 134 26 Rough hands of a pellagrin as contrasted with the normal hands of a hospital orderly 135 27 Italian case of typical dermatitis 136 28 Pellagrous dermatitis 137 29 Georgia case, showing exfoliation of the skin following a spring at- tack 138 30 Italian case of alcoholic erythema 139 31 Italian case of alcoholic erythema 139 13 14 ILLUSTRATIONS. FIG. PAGE 32 Close view of the rough skin in pellagra . . 140 33 Pellagrous dermatitis 141 34 Cortical cells, showing pigmentary degeneration 143 35 Cortical cell, showing contraction of the protoplasm 144 36 Cells from the spinal cord, showing thickening and contraction of the neuro-fibrillar net 144 37 Cells from the spinal cord, showing partial thickening and contrac- tion of the neuro-fibrils 145 38 Cell from spinal ganglion, showing pigmentary degeneration . . 146 39 Chromatolysis and pigmentary degeneration in cells of the cord . . 147 40 Same case as Fig. 35, showing chromatolysis and pigmentary de- generation in cells of the cord 147 41 Cells from the cord, showing yellow pigmentation and degeneration . 148 42 Same case as Fig. 37, showing cells from the cord, with yellow pig- mentation and degeneration 148 43 Spinal cord, showing the cellular body entirely invaded by yellow globular pigment 149 44 Spinal cord, showing the cell partially invaded by yellow globular pigment 149 45 Cell is invaded in two opposite places by yellow globular pigment . 150 46 Partial thickening of the neuro-fibrillar net 150 47 Spinal cord, showing pigmentary granular degeneration . . . . 151 48 Spinal ganglia, showing invasion of the special net or Marinesco's net 152 49 Spinal cord, showing thickening and concentration of the neuro- fibrillar net 153 50 Spinal ganglia, showing changes in the fibrillar net 155 51 Spinal cord, showing increase in the neuroglia in crossed, pyramidal tract 157 52 Spinal cord, showing section of Burdach's tract, with several fibers and primary degeneration 158 53 Spinal cord, showing section of Burdach's tract, with numerous fibers in secondary degeneration 159 54 Pellagrous insanity, showing dermatitis on hand, with exfoliation of the skin 167 55 Pellagrous insanity, showing dermatitis on hands 169 56 Pellagrous insanity, showing dry dermatitis, with exfoliation of the skin 173 57 Pellagrous insanity in the aged .175 58 Pellagrin, with dermatitis on hands, forearms, and elbows . . . 187 59 X-ray illustration of the hands of a female pellagrin 194 60 X-ray illustration of the hands of a female pellagrin 195 61 Same case as Fig. 60, showing x-ray illustration of the cervical re- gion 196 62 Pellagrin after recovery from attack - . 210 63 Pellagra in time of intermission 212 ILLUSTRATIONS. 15 FIG. PAGE 64 Same case as Fig. 63, showing elbow slightly rough; hands appear normal, but covered with fine branny scales 213 65 Field- of Italian corn, first crop 237 66 Field of Italian corn, first crop 238 67 Field of Italian corn, second crop 239 68 Ear of Italian corn, first crop 240 69 Ends of three ears of Italian corn, first crop 241 70 Method of drying shelled corn in Italy 242 71 Corn swept into another kind of building after drying in the sun . 243 72 Cakes of yellow polenta 244 73 American corn from Georgia 244 74 American corn from Georgia 245 75 Field of American corn, Georgia 245 76 One method of gathering and drying corn in America 246 77 Rail pens without covers, sometimes used for storing unshucked corn in America 246 78 Cribs used for drying corn in the United States 247 79 Diagrammatic section of a grain of corn 248 80 Cellular structure of a grain of corn 250 81 Penicillium, a common mold found on corn 251 82 Ustilago maydis, a fungus that causes corn smut 252 83 Simulium fly and larva 252 84 Wing of simulium fly, showing venation 252 85 Legs of a chicken showing pellagrous symptoms 254 86 Legs of a chicken showing similar symptoms to those of chicken in Fig. 85 255 87 Bobbin Creek, near Athens, Ga., where the simulium larva? were first found in Georgia 256 88 Diagram showing pellagrous neighborhood at Dadeville, Ala., and the relation of pellagra to streams 258 89 Diagram showing the relation of pellagra to streams in the town of Cornelia, Ga 259 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 called (1) peTla-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- la'gra — each a long as in fate, with the accent on the second syllable ; (3) pel-la/gra — 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 Avord. 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 -j- agra, or the present word pellagra, meaning rough skin. In the Italian language the word is pronounced pel-la'gra, 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 I 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 pe-la'gra, 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 pe-la'gra, and, in addition, the other two related words — pella/grin and pella/grous — are pronounced with the a long and accented second syllable, as pe-la/grin and pe-la/grus, it seems wise to use this altogether natural and easy American pro- nunciation, pe-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 1st 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 w T ere 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- ture. Pulse. pira- tion. Date. Hour. pera- ture. Pulse. pira- tion. June 6 11 a. m. 102 114 18 June 20 8 a. m. 981 80 18 1 p. m. 10H 98 20 20 4 p. m. 98,1 88 16 6 3 p. m. 1021 94 20 21 8 a. m. 98 80 20 6 6 p. in. 101 92 18 21 4 p. m. 981- 82 18 7 8 a. in. 100 90 20 22 8 a. m. 98 80 18 7 4 p. m. 99 94 26 22 4 p. m. 981 78 18 8 8 a. in. 98,1 90 18 23 8 a. m. 98 92 20 8 4 p. m. 99 82 24 23 4 p. m. 981- 72 18 9 8 a. m. 99 90 24 24 8 a. m. 98,1 80 18 9 4 p. m. 98-1 100 18 24 4 p. m. 99 99 20 10 8 a. m. 971- 78 18 25 8 a. m. 981 100 22 10 4 p. m. 981 92 14 25 4 p. m. 991 100 20 11 8 a. in. 98 90 20 26 8 a. m. 98 98 16 11 4 p. m. 99 84 18 26 4 p. m. 981 86 18 12 8 a. in. 99 80 20 27 8 a. m. 97-1 82 16 12 4 p. m. 981 86 14 27 4 p. m. 991 86 16 13 8 a. in. 98 96 18 28 8 a. m. 981 90 18 13 4 p. m. 98-1 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. 98,1 86 16 29 4 p. m. 98-1 92 16 15 8 a. in. 98-1 100 16 30 8 a. m. 99,1 80 16 15 4 p. m. 99-1 88 16 30 4 p. m. 99 82 18 16 8 a. m. 981- 100 16 July 1 8 a. m. 99 88 16 1G 4 p. m. 99 98 14 1 4 p. m. 994 92 18 17 8 a. m. 93 88 14 2 8 a. m. 99 88 16 17 4 p. m. 981 100 16 2 4 p. m. 99 84 18 18 8 a. m. 981 80 20 3 8 a. m. 99,1 88 18 18 4 p. in. 98 88 16 3 4 p. m. 991 80 18 10 8 a. m. 981 99 20 4 8 a. m. 98-1- 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 tAvo 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 Table Showing the Vaeying Conditions of Case 2. Tem- Res- Tem- Res- Date. Hour. pera- ture. Pulse. pira- tion. Date. Hour. pera ture. Pulse. pira- tion. Sept. 22 8 a. m. 99 102 18 Oct. 8 12 m. 100* 126 24 22 4 p. m. 99 84 20 8 4 p. in. 101 132 24 23 8 a. m. 98 90 18 8 8 p. in. 102 134 26 23 4 p. m. 99 102 26 8 11 p.m. 101* 142 26 24 8 a. m. 98 98 24 9 3 a. m. 102* 140 28 24 4 p. m. 98 96 24 9 8 a. in. 101* 132 2 26 25 8 a. m. 98 102 24 9 12 m. 100* 128 18 25 4 p. m. 98 70 1 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. in. 102 140 26 27 8 a. m. 99 108 20 10 2 a. m. 102* 120 22 27 4 p. m. 99 100 24 10 8 a. m. 100* 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. in. 101* 134 26 29 8 a. m. 99 100 20 10 12 p. in. 102 126 26 29 4 p. m. 99 102 20 11 8 a. m. 101* 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 11 8 p. m. 102 120 30 1 4 p. m. 99 108 22 11 12 p. m. 101* 126 30 2 8 a. m. 99 130 20 12 2 a. m. 100 1 120 30 2 4 p. m. 99 120 24 12 8 a. m. 98* 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. 100* 120 28 4 8 a. m. 99 130 28 12 6 p. m. 103 130 34 4 4 p. m. 99i 120 26 12 10 p. m. 103 140 32 5 8 a. m. 101* 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 22 6 4 p. m. 103 140 1 30 13 4 p. m. 103 128 24 7 8 a. m. 101 128 22 13 8 p. in. 103 140 28 7 10 a. m. 100* 120 26 13 12 p. m. 103* i40 32 7 4 p. m. 101* 150 26 14 2 a. in. 104* 22 7 7 p. m. 102 148 26 14 8 a. in. 103 3 130 28 8 1 a. m. 102|- 128 22 14 12 m. 104 26 8 8 a. in. 101 120 20 14 9 p.m. 4 1 Direct transfusion. 2 Direct transfusion. 3 Axilla. * 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 cc, free HC1 .15 percent ; total acidity, .33 percent. . ,. / ^H •if " - ks Mf ^ ^fe «£ f 1 ^ |PI I |. V ml ■ 'iw''"'a'( ¥ lit 5 - wH' -' ' •JaB ; tik * A- u^fil •S-. .M^M r ^bm! Si ®| 5 <>''?..V>'-» i >f;<*.ji fef !®5 Hf *^;\">' v. t , * • V i &*C '■'I'ji^y^k^ 1 * « ,»4 , *' I '.•^,";''* •»*":". " "F J * 1^*' &»• n « ' • **^*y :: p,- rJBW***."^ • v, . r *; > ^Hj^RSxS&fflREsf^H^r ««*. iJiuUH HA9U ■ ■ \> Kir V- • • . .* - " X. P&l ; .*■.' • •*. - '""W -' tl w ft \* k; ' • V; *' . . >y fry •.,)*•'<. ir "'' ' 0! , '* '' 1 K'iC* • •- 'H. ' 'v. . fv ■'''.' , \<&\\ : S '•> ' ! J V " . * v i '• V.> **' ->-" ■ ■'-■- '"* ■'V'vxSWv '.'. * 'u '•'■' t! y<» '■ '• ■ ' V '. .*-*. ,.■• ' "^. ■;*■ ■- v " ." .*. §' j:f '' i~r o" ' 5 \%) WW! >'; ; *.' "f\*^ ( , -,v-'- ' l ' .••'.* .-'_ . r-w •*& il i\ i$tf&\\ :•• > .S,:' *"; A «r''. * Fig. 1. — Pellagrous boy. Dermatitis on hands and face. Austrian case. (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 13th, 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 creek 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 much 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 account 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 alae 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 months, 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 cases, 13 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 cases 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. (After Merk.) Note the wrinkles. 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 Avith 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. Skin peeling, with edema on left foot. (After Merk.) 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 beliefs 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 ankjdostomiasis, 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 well 160 64 49 113 Mother pellagrous, father well 175 30 38 68 Father and mother well, two or more children pel- lagrous 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 2y 2 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 32% years. Of these 456 cases 275 were males, with an average age of 34% 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 32% years, or the same as the 456 cases from Rovereto. This gives 615 cases from America and Italian Austria, with an average lower by 18% 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. 3. 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 report shows facts more nearly similar to conditions in America. J. C. 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 car- 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. Mai de la rosa — sickness of the rose. Mai 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. Mai 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. Mai 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. Mai de saintes mains — the sickness of the main saints. Mai de Sainte Eose — sickness of Saint Rose. Mauvais dartre — a bad eruption. Italian Synonyms. Mai della spienza — disease of melancholia. , Mai del monte — disease of the mountains. Mai del padrone — the master's disease. Mai 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. Mai salso — the salty disease. These last two refer to the salty taste present in the mouth of some pellagrins. Cattivo male — the wretched disease. Mai 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. Mai 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. Graeci 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 Avith 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. Gofar — 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, Boumania, 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. 47 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 : 1 '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. The other provinces chiefly affected at that time were Cuenca, Navarra, Zaragoza, Zamora, and Galicia. A few cases were found in all the other provinces in Spain. Since that time the number of cases has decreased and the severity of the disease has greatly lessened. From a report of the Fourteenth Inter- national Medical Congress, held in Madrid in 1903, it appears that only twenty cases were observed in the Asturian districts where the disease first became known. There has been a marked decrease in the number of cases since 1900. Nearly all of the twenty cases above mentioned terminated by death of the infected person, largely 48 PELLAGRA. on account of lesions of the spinal cord. It is stated that the rapid decrease of the pellagra has been due to the general im- provement in hygiene, food, and cleanliness among the laboring classes. For these facts concerning the present history of the dis- ease I am indebted to Consul General Morgan, of Barcelona, Spain. There are probably more cases in the province of Madrid than in Oviedo at the present time. Spain, topographically, is a rolling, mountainous country, con- sisting of hills, narrow mountain valleys, and swift-running streams. In those portions poorly watered a system of irrigation is used which dates from the Roman and Moorish periods. The chief cereals in order are wheat and barley, oats and rye. Corn is cultivated in all the provinces, but not to a great degree. Indian corn began to be used in Spain probably in the sixteenth century, and was doubtless brought there by the Spanish explorers from the West Indies and South America. The chief fact of impor- tance in the history of pellagra in Spain is that it nourished for nearly two centuries, and then for some reason since 1900 has ceased to exist to any great degree. Italian Epoch. Pellagra next appeared in northern Italy. Sambon has investi- gated at great length the time of this appearance, and from the evidence presented it was certainly prevalent there in the year 1720. Dr. Bava said in 1781 that it has been known in the Ligurian mountains for over sixty years, and that it proceeded in the same order and manifested itself and grew with the same symptoms. Taraghi says the disease was noted before 1730 in the vicinity of Sesto Calende, on Lake Maggiore, just north of the present city of Milan. In these earlier days the oldest peasants said their an- cestors spoke of it as mal rosso and mal della rosa, according to Alvera quoted by Sambon. Frapolli was the first to use the word pellagra, a name which originated among the peasants themselves. It is altogether probable, considering the later history of the dis- ease and the fact that it has always seemed to have been present in a country a number of years before its discovery by the pro- fession, that pellagra existed in northern Italy as early as 1700. The history of pellagra since its appearance in Italy has been largely its history in that country. Despite the fact that it first appeared in Spain, more cases have appeared in Italy than any- HISTORY AND GEOGRAPHICAL DISTRIBUTION. 49 where else in the world, and that country may rightfully be called the home of the disease. Pellagra has existed in forty-four out of the sixty-nine provinces in Italy. Dividing Italy into northern, central, and southern por- tions, the disease first appeared in the compartments of Piedmont, Lombardy, and Venetia, which form northern Italy. It then spread gradually southward, but always tended more to the east than to the west, and has always seemed to avoid the Genoan lit- toral. In addition to the three compartments already mentioned, it has nourished in Liguria and Emilia ; passing southward then into central Italy, it appeared in Tuscany, Marches, Umbria, and Latium, and to a small degree in Rome, Abruzzi, and Molise. It has avoided the southern compartments of Apulia, Campania, Basilicata, and Calabria. On the whole, however, pellagra has shown a constant tendency to extension southward. It has avoided the insular possession of Italy, and, strange to say, does not seem to have appeared in Corsica, Sardinia, and Sicily. The following tables show in table No. 1 the deaths from pellagra from 1898 to 1905 inclusive; table No. 2, the number of pellagrins in the entire kingdom of Italy as taken by four different censuses; and table No. 3, the number of pellagrins enumerated in the chief regions of Italy according to the last three censuses. Table No. 1 — Mortality. Years. Deaths from pellagra. 1898 3,987 1899 3,836 1900 3,788 1901 3,054 1902 2,376 1903 2,647 1904 2,363 1905 2,359 Table No. 2 — Census of Pellagrins. First census ( 1879 ) 97,855 Second census ( 1881 ) 104,067 Third census ( 1899 ) 72,603 Fourth census ( 1905 ) 55,029 Notice the constant decrease since 1881. 50 PELLAGRA. Table No. 3 — Pellagrins in the Different Nations by Census. Regions. 1881. 1889. 1905. Piedmont 1,328 1,223 1,012 Liguria 56 30 56 Lombardy 36,630 19,557 15,746 Venetia 55,881 39,882 27,781 Emilia 7,891 4,617 3,357 Tuscany 924 1,125 1,137 Marches 406 920 1,426 Umbria 872 5,103 4,250 Latium 32 146 195 Abruzzi and Molise It will be noticed from these tables that the chief seats of pel- lagra have been Piedmont, Lombardy, Venetia, and Emilia. Pel- lagra seems to have originated in the district of Milan, then in Brescia, Bergamo, and Lodi, and then around Lake Como, Cre- mona, Mantua, and Pavia, so that by 1800 it covered practically all of Lombardy (Hirsch). In Venetia it appeared at Udine, far to the east of Milan and to the right of the Austrian Tyrol. In 1787 the naturalist and poet Goethe, in his Italian journey from Verona, speaks of seeing patients with pellagra. In Piedmont and Liguria it has never developed to any considerable degree, and this is strangely true of Liguria. In Tuscany it appeared as early as 1785, but has not shown any marked increase in the last three censuses. Hirsch as early as 1885 stated: "Pellagra in Tuscany in more recent years has established endemic centers in the upper valley of the Arno, in Volterna around Lucca and Pisa, and among the hills near Florence. The disease appeared in Emilia about the same time that it appeared in Tuscany, though seven times more prevalent in the latter." In the last twenty -five years the disease has extended southward into the regions of Marches, Umbria, and Latium, and has been strikingly prevalent in Umbria. Now, according to Hirsch, as pellagra has extended into southern Italy, the cases in the earlier seats of the disease have increased — as, for instance, the history of pellagra in Lombardy shows that in 1839 there were 20,282 pellagrins; in 1856, 38,777; and in 1879 there were 40,838 out of a total urban and rural population of 3,653,941, or 11.2 pellagrins per one thousand. In 1889 the cases show a decrease to 19,557, and a further decrease in 1905 to 15,746. The census of pellagra in Italy can not be relied on as more than approximately accurate. The total evidence, however, seems to show that at the present time there are about 50,000 pellagrins HISTORY AND GEOGRAPHICAL DISTRIBUTION. 51 in the kingdom. The number of deaths per year shows a con- tinued decrease, so that there are probably less than 2,000 deaths per year from the disease, and that there are admitted into the asylums per year between 75 and 100 insane pellagrins. Certainly in Piedmont, Lombardy, and Venetia the disease is showing a rapid decrease, both in the number of cases and in the severity of the individual case. I found a good illustration of this fact at the Ospitale Maggiore in Milan. In former years several legacies were left to this hospital, the income from which was to be used in the treatment of pellagrins. The number of cases in the district of Milan and even in the adjacent country around the city had de- creased to such an extent that there were practically no cases and no demand for help. It is probable that in the course of the next twenty-five years pellagra in northern Italy will cease to exist to any extent. This is in harmony with the history and almost com- plete extinction of the disease in Spain. The Italian government, in view of the plague prevalency of the disease, has taken various measures in an attempt to stamp it out. These measures have all been based on the idea that the cause of pellagra is in some way connected with Indian corn. Therefore in Italy corn is the official cause of the disease, and various measures and institutions for the relief and treatment of pellagrins have thus originated. One of the most famous of these was the law of 1902, and, while this law has certainly not been well en- forced, there is a difference of opinion as to whether the decrease in the number of pellagrins has been due to what application this law has had or to other unknown causes. In Spain no preventive measures have been taken, and yet the disease has shown a greater decrease than in Italy. Sambon quotes Professor Sanarelli, under secretary of state for agriculture, in regard to this law and its results as follows : ' ' Not- withstanding the application of the law of July 21, 1902, for the prevention and cure of pellagra; notwithstanding the assiduous propagandism and the increasingly active endeavors of the pro- vincial pellagra commissions ; notwithstanding the great subsidies made by the state ; notwithstanding the locande sanitarie, the ex- change for bad maize, the dispensation of free salt, the encourage- ments given for the promotion of wheat cultivation, the teaching of sound agrarian principles, and many other direct or indirect meas- ures excogitated by private initiative and by the government to effi- 52 PELLAGRA. ciently fight against pellagra, this disease in Italy does not show any tendency to decline in a satisfactory measure. "It is true that in these last years the general death rate from pellagra has gradually diminished, and that at first sight this marked improvement might appear to be due to the application of the law of 1902. But in comparing either the number of pel- lagrins or the number of deaths from pellagra in the three years 1900-02 — that is to say, before the application of the law — with those of the three following years, 1903-06, one finds that all these figures do certainly indicate a gradual, progressive improvement, but an improvement which takes place in more or less the same proportions. A legitimate doubt, therefore, arises as to whether it be right to ascribe the gradual decline of pellagra throughout the kingdom to the measures contained in the law of 1902." The history of pellagra in Italy includes a reference to the measures used by the government to prevent the disease. Among these are the inspection of corn and the discovery and destruction of damaged grain. Some such measure as this was first authorized by the authorities in Venice in 1776. Efforts have been made to destroy damaged grain, but this law has been neither observed nor enforced. Practically all methods for the detection of damaged grain have failed. Sambon states that out of 44 Italian provinces affected by pellagra only 2, Venice and Padua, have a pellagro- logical inspector, whose duty it is to prevent the sale and con- sumption of damaged corn. Dr. Bresadola inspects corn at Ro- vereto, Austria. Efforts have been made to exchange sound corn for damaged corn, but this has been limited to one district in the province of Brescia. The royal law of 1884 tended to encourage the construction of plants for the drying of corn on the idea that corn spoiled and caused pellagra because it was gathered before it was dried. I have never been able to understand the necessity for these drying plants, because the Italian sun, like the Egyptian sun, is very warm, and what corn I had opportunity to examine in September and October was certainly dry and well seasoned. These drying apparatuses have never been used to any great ex- tent. For a short time in Milan and Coma rural bake-houses were established which aimed to be model bakeries, cooperative in plan, and to cook good, cheap, wholesome wheat and corn bread. They were not patronized and were not useful to any degree. Sporadic and spasmodic efforts have been made to abolish the HISTORY AND GEOGRAPHICAL DISTRIBUTION. 53 late varieties of corn on the idea that corn reaching maturity in the autumn in forty to sixty days was immature and unhealthy. In regard to this it may be said that the second crop of corn in Italy is certainly not as large or as well developed as the first crop, but whether this second crop has anything to do with pel- lagra is a matter of serious doubt. In the Austrian Tyrol there is no second crop of corn, and yet nowhere on the earth has the disease been fiercer in type. The law of Italy requires what is known as the notification of cases, or, as understood in America, the law requires the physician to report cases of pellagra when first diagnosed, just as the law in the states requires contagious diseases to be reported. For many reasons, economical and in- tellectual, this report of new cases is neither accurate nor honest. Sambon (Progress Report, page 37) discusses this matter in full. Other measures include free meals to poor pellagrins for periods of not less than forty days twice every year. As Sambon wells states, this aims both to cure and prevent the disease, but the re- sults do not seem to bear out the statistics. By thus giving away food the law is imposed upon, and often the poor and ignorant who are not pellagrous are fed. In other cases these locande sanitarie are so far from the homes of the pellagrins that they are unable to reach them. The pellagrosario is an institution estab- lished as a pellagra hospital. Only those who are pellagrous are admitted, and they are lodged, fed, and treated at an expense borne jointly by the local province and the national government. The first pellagrosario was established at Legnano, in the province of Milan, in 1784 by authority of Joseph II. of Austria. For some reason it was discontinued after four years, but during that time the elder Strambio was physician in charge and here made his fame. At the present time the pellagrosari at Inzago, Citta di Castello, Mogliano, Veneto, and at Rovereto in the Austrian Tyrol are the most important. At all these the inmates are decreasing from year to year, and, as Dr. Bresadola remarked to me at Ro- vereto, ' ' soon the building will have to be used for other purposes, because there will be no more pellagrins." See page 65 for an illustration of the pellagrosario at Rovereto. French Epoch. Pellagra in France was first known through a report made by Hameau to the Society of Medicine in Bordeaux in 1828. He 54 PELLAGRA. HISTORY AND GEOGRAPHICAL DISTRIBUTION. 55 >> *S 5=^ > O.rt 03 05 03 «? bjo"£ rf 05 .^ p, 03 £ 2 » .3 j=-° n -4-^ bD 02 O! >> *? 05 03 ■^H 02 -TJ 05 03 02 030 03 ^ 05 o * w £, T3 03 ^-3 .5 03 05 £ 3 _(B O 03 rH 11 OJD 05 M -" *o O 03 ^ 1H ^^ h w « ^ £ 2 e3 o3 05 ° H j-^ 03 05 fi E"l 05 -T-T3 ft^! w -+^ 03 .^ ^02 rvoj +j-p 03 ■h3oS 03 5 "el M to 2 O c H 03 5"5 03^ 2 sit 2 fl 05 O 3h — 03 V t-i Jh 05 O 03 £ m ° » J-C 03 C4H q 03 03 03 ' — ' 05 in rf O ,53 fe Sh 03 -*> ^ 05 -*> i« r- s-e ,£ 03 £ X ^ ^ 02 « O O 03 O ■+^ U *^ ^ 03 "£ P* 02 03 03 S ^ ft (OS 61 s O w ^ t, 03^ 03^ 03 05 +3 bJD _ «S * l ~ l 03 & -^ 03 2^ 05 = t-i _, O! O £ pj « * ■ S ■— ' o 03 2 03 03 ^^! i»^ 02 - £ 0! °=ft ^ «t-i 03 ~ 02 O 03 O •43 c S'r3 a* Oj 05 0! ^S ■ O .S 03 03 03 ■P id C ^ u 03 fH co 03 cj c5 'r52 02 W r-i ~*-"T- 03 CJO 2 p 2 02 "^ >< 5 ^ «(-( ft C ^ 0) i8 05 02 »x 2 5 c ?h c l # S « ° 5 05 2- * ° bi X 03 - _, Eh > > 2 ^ 03 l> C s h O U -♦^ -*^> =+-( 56 PELLAGRA. Tig. 5.< — Map showing distribution of pellagra in the United States. HISTORY AND GEOGRAPHICAL DISTRIBUTION. Note predominance in the southern states — sporadic elsewhere. 58 PELLAGRA. found the disease in La Teste de Buch, in the southwestern part of Gironde, a province of southwestern France bordering the Bay of Biscay. The disease was later found to have extended over the area known as the Landes, which lie to the south of Gironde. More cases developed in the latter than in the former department ; further south, in the valleys and hills of the Basses Pyrenees, in the department of Hautes-Pyrenees, and further eastward toward the Mediterranean in the Pyrenees Orientales. North of the Pyrenees around Toulouse and in the department of Aude endemic centers developed. Later, cases drifted into Paris, and sporadic cases, according to Hirsch, were found in the department of Seine- Oise, Marne, Allier, Maine-Loire, Ille-et-Vilaine, and Rouen. Pel- lagra existed in the regions south of Bordeaux from the time it was first observed by Hameau in 1818 for about fifty years, but since 1890 it has practically been an extinct disease, though during the last quarter of the last century a few cases w T ere admitted to the asylums for the insane. At the present time pellagra is not indicated in the French health statistics, and, if there are any isolated cases developing among the Pyrenees, they are either over- looked or not reported. The region in southwest France, where pellagra formerly flour- ished, is among the hills and valleys at the foot of the Pyrenees mountains. It extends then northward along the coastal plain; it is a country intersected and cut in all directions by flowing streams. The Landes was formerly a very unhealthy country, and the novel "Maitre Pierre" was written to show the unhealthiness of this region before it was drained. A French proverb refers to the ravages of pellagra in this area : "Taut que Lande sera Lande, La Pellagra te demande." "As long as the Landes are the Landes, Pellagra will demand you." The cause of the disease in this country was laid to many things, as air, water, food, millet seed, rye, maize, sardines, and salted eels. Corn is still cultivated in the Landes, the Basses Pyrenees, and adjacent departments in southwestern France. This area is just across the Pyrenees mountains from Spain and to the northeast of that country. HISTORY AND GEOGRAPHICAL DISTRIBUTION. 59 Austro-Hungarian Epoch. The Austro-Hungarian epoch includes the distribution and his- tory of pellagra in that area extending from the Austrian Tyrol on the west, Poland on the north, southward and eastward to Bes- sarabia, Turkey, and Greece. The Austrian Tyrol lies to the north of and between Lombardy and Yenetia, and the development of pellagra here is principally an extension in point of time from these two regions. In 1875 to 1905 cases were numerous and severe, but at present show a decrease in number and in severity. I saw some of these pellagrins at Rovereto, a town in the Tyrol, at the foot of the Alps. Pellagra crossed the Transylvania Alps, which separate Hungary on the west from Roumania on the east, and appeared in the latter country about 1830. The elder Theodori assigned its first appearance to the year 1833, and the first patient was admitted in the hospital in 1846. It has continued to spread and increase in Roumania, which is divided into the two compart- ments of Moldavia and Wallachia. Felix, according to Hirsch (1878), estimated that there were 4,500 pellagrins in Roumania, not quite 1 per thousand of the whole population. Since that time the disease has constantly increased, and it is estimated that out of a population of 5,000,000 there are probably 75,000 pellagrins. Berger in 1888 found in the district of Gradisca, where he lived, 790 pellagrins, 1.2 percent of the population. This district is in the western part of Austria, on the Italian frontier. It would seem that in the last twenty-five years the disease has constantly tended to decrease in the western part of Austria and to increase in the eastern part. It will be noted, too, that both of these areas are mountainous sections, the surface rolling in character, and in both sections corn is raised. According to Benjamin Triller (Thesis, Paris, 1906) the disease is also increasing in Servia and Bulgaria. Cases have been reported from Poland, southwestern Russia, Croatia, Dalmatia, Servia, Bosnia, and Herzegovina. Consul General G. Bie Ravendel investigated for me the preva- lence of the disease in Turkey, but found it so rare — comparatively unknown — that little definite information could be obtained. The disease is probably more prevalent in the rural sections of Turkey than has been known or reported. In Greece at the present time it is a rare disease, and is certainly not increasing. According to Consul General Gates, Athens, Greece, a case is occasionally re- 60 PELLAGRA. ported, but chiefly from Thessaly in the mountains of northern Greece. Contrasting these two countries, Turkey and Greece, in respect to corn, it is found that in a good year in Turkey the corn crop amounts to from 140,000 to 160,000 tons, and in a bad year from 30,000 to 40,000 tons. On the other hand, in Greece, accord- ing to Consul General Gates, the amount of corn raised is neg- ligible, the principal crops being wheat and barley. The island of Corfu is off the western coast of Turkey, across the Adriatic from Italy. Information about pellagra in this island is furnished by Thypaldos. According to him the first appearance of the dis- ease was in 1839, but it became rather endemic in character, and in 1867 it prevailed in twenty-seven out of one hundred and seventeen rural communes in the island, the cases representing about 3.2 percent per one thousand of the population. Egyptian Epoch. Pellagra was first discovered in Egypt by Prunner, and he de- scribed it in 1847 under the heading "Leproses" as follows: "Pellagra is sporadic in Egypt, and such as we have studied it in Milan. We have seen three cases of it among the peasants, one of whom presents today, twelve years after our first seeing him, a brownish exanthem, paresis of the upper limbs, with re- traction and muscular atrophy." Up to the time of Sandwith this is the only reference made to the disease, except one by Dr. A. Figari Bey, who writes of a venereal disease in lower Egypt with "a kind of leprous pellagra." F. M. Sandwith, while at work on a paper on hookworm disease in 1893, became aware that some of his patients among the peasants, to use his own words, "were suffering with dermatitis, bald tongue, diarrhea, pains in the back, alteration of the knee jerk, insomnia, and melancholia, all symp- toms which could not legitimately be attributed to the anemia caused by the hookworm. ' ' It is, therefore, apparent that Prunner was right, even though so eminent an authority as Hirsch said that his description "does not by any means correspond to pellagra." The disease has, therefore, been in Egypt certainly for nearly seventy years and probably longer. It is far more extensive in Egypt, as outlined by the studies of Sandwith and Warnock, than has been supposed. The latter speaks of finding "scores" of pel- lagrous children. HISTORY AND GEOGRAPHICAL DISTRIBUTION. 61 According to Sandwith, pellagra in Egypt extends as far south as Assouan, or the tropic of cancer, latitude 24 degrees north. In 1897, 178 cases were admitted to the Cairo hospital and the home of 164 determined. Of these 37 came from upper Egypt and 127 from lower Egypt. Sandwith adds these two sentences: "The peasants in upper Egypt eat chiefly millet or sorghum vulgare, and not maize. The disease is said to be absent in Luxor, where no maize is eaten, but I saw several cases there. ' ' In 1891 Myles found it among the Arabs at Tokai on the Red Sea. In Egypt, as else- where, it is a country disease, and rare in such Egyptian cities as Port Said, Suez, and Alexandria. There is no polenta eaten in Egypt. Corn was brought from Syria into Egypt about 1840, and the peasants eat the variety called the camel's tooth, which is sown in July and ripe in November and December. According to Triller the disease has been found in Tripoli and in Tunis. Sandwith, during the South African war, found two cases among the lunatics at Robben Island, Cape Town, and he had previously recognized a third case in London which had been imported from South Africa. Physicians practicing in South Africa told Sandwith that they had never seen the disease in that section, but the two cases he found at Cape Town show that it exists there to a degree. Dr. W. M. Eaton, medical director of Rhodesia at Salisbury, Africa, states that "this disease has not been recognized in the territory." The meager facts at hand regarding the distribution and ex- istence of pellagra in Africa show that it is found at Cairo, in the parallel of latitude 30 degrees north, and at Cape Town, on the extreme of the African continent, latitude 34 degrees south. A further study and investigation in Africa would probably show a far wider distribution. I questioned very carefully in London the general agent of the African territory of Rhodesia, who is very familiar with the habits, customs, diseases, and foods of the people in that country, and, though I failed to gather from his very thorough description any evidence of the existence of the disease in Rhodesia, his opinion is borne out by Dr. Eaton quoted above. This is very interesting, too, in view of the fact that Rhodesia is an enormous corn-growing country. The samples shown me in London were the finest and largest ears, with the largest grains, I have ever seen. Two cases of pellagra have been reported as originating in the British Isles, but there is some difference of opinion as to whether 62 PELLAGRA. the diagnosis was correct. At the meeting of the British Medical Association in 1898, Sandwith exhibited to physicians from India photographs of the Egyptian pellagrins, and three of these recog- nized the disease as existing in India. I have searched the records of the Indian medical congresses, bnt failed to find any reference to the disease. Dr. W. H. Jefferys, the coauthor of Jefferys and Maxwell 's ' ' Diseases of China, ' ' wrote me in response to an in- quiry as to the existence of pellagra in China: "My colleague, Dr. A. W. Tucker, suggested a long time ago that we should make a special point of looking out for pellagra in our Shanghai (China) clinic, and we did so and have never seen a case. Our clinic is a very large one, and represents Chinese from almost every province of the republic. Many of these pa- tients are not, of course, of the farmer class, so they bear little on the subject. "The Chinese eat practically no corn. I think this is a correct remark for all China. They grow a little for the use of foreigners in the treaty ports. "I have been misled far too often, and become very conservative about predicting that a disease does not exist in China, and, there- fore, I can not make such a statement. I can tell you, however, positively that pellagra has never been reported from China. Yet even that does not mean much, for I do not think that the average surgeon or physician would recognize pellagra unless on the lookout for it, or unless its great prevalence as a disease should force his attention. ' ' I have not been able to find any records of the existence of pel- lagra in Australia. Dr. Hubert M. Hewlett, of Fitzroy, Victoria, Australia, has been on the lookout for the disease in that continent, but has so far failed to find any record of it or any case of the disease. My friend, Mr. D. P. Mitchell, a mining engineer of Australia and a gentleman of exceptional powers of observation, told me that the disease was unknown there. American Epoch. This epoch includes the history and distribution of the disease in the western hemisphere, and naturally falls into two divisions: 1. Pellagra in North America, including Mexico, Panama, and the West Indies. 2. Pellagra in South America. HISTORY AND GEOGRAPHICAL DISTRIBUTION. 63 1. North America. — Pellagra was first discovered and reported in America in 1864 by Dr. John T. Gray, of Utica, N. Y. A second case was reported verbally at the same time by Tyler, of Summerville, Mass. There have been speculations as to pellagra existing among the soldiers during the Civil War, but this is a matter of doubt. In 1883 Sherwell, of Brooklyn, reported a case in an Italian sailor, and in 1889 Bemis, of New Orleans, diagnosed a case of pellagra in that city. From all the evidence it is probable that the disease existed in the Carolinas and in Georgia in the early eighties, though the cases were not diagnosed as pellagra and the disease itself was unknown. Sherwell reported another case in New York in 1902. These cases thus far referred to seem to have been sporadic or imported cases, but it is probable that the number of cases of pellagra in the United States has been increasing since 1890, and that the disease has existed in the United States since 1880. It is interesting to know that Sandwith, in Egypt, while study- ing hookworm disease, discovered pellagra in that country in 1893. At this time he suspected the existence of pellagra in America, thinking that it "might exist unrecognized in the South, and at one time I requested my friends to put me in communication with the poorest folk of the maize-eating district. I was referred to a settlement in eastern Virginia for pauper negroes, but on investi- gation I found that the inmates lived in stone houses on pork rations, and I came to the conclusion that the word poverty repre- sented no condition in America which could compare with the misery of the impoverished peasants of Italy, Roumania, or Egypt." Seven years later, while in South Africa, Sandwith saw two cases of pellagra and again suspected the disease in the United States. The real beginning of the history of pellagra in North America and the discovery of the present epidemic began just as the real discovery of pellagra in Egypt began — by the study of hookworm disease. H. F. Harris, of Atlanta, reported "A Case of Hookworm Disease Presenting the Symptoms of Pellagra." In 1907 George H. Searcy reported an epidemic of pellagra at the Mt. Yernon, Alabama, asylum for negroes. This epidemic existed during the years of 1906 and 1907. Babcock and Watson diag- nosed the disease at the state hospital for the insane at Columbia, S. C, and their report marks the beginning of widespread interest in the disease in North America. In 1908 they studied the disease 64 PELLAGRA. in Italy, and identified American and Italian pellagra as one and the same disease. Their reports aroused the attention of physi- cians throughout the country, and to them is due the arousal of the attention of the profession in the southern states. Assistant Surgeon C. H. Lavinder, of the United Hospital and Marine Service, studied the malady, and later Captain J. F. Siler and Captain Henry J. Nichols, of the medical corps of the United States army. Under the auspices of the State Board of Health of South Carolina a conference on pellagra was held in October, 1908, and a national conference on pellagra was held in South Carolina at Columbia in 1909. Surgeon C. H. Lavinder, Dr. J. W. Babcock, J. J. Watson, Zeller of Illinois, and Bass of New Orleans have written many articles on the disease, which have been helpful to the physicians in this country. Pellagra in America has increased very rapidly, especially in the southern states and in the Mississippi valley, during 1908 to 1911, and it is probable that the spring of 1912 will show an influx of new cases. The type of the disease so far has been more severe, more acute, of shorter duration, and higher mortality than in Italy, Roumania, or Egypt. The percentage of males is less in proportion than in Italy. For example, in the state of Tennessee, out of 316 cases 214 were females and 102 males, and in three counties in southeastern Kentucky out of 140 cases 111 were females. The map on pages 72 and 73 shows the distribution of pellagra in North America. Much of the area where pellagra is endemic is not in the official registration area, and many of the statistics are merely estimates. The United States Census Bureau for 1910 re- ports 368 deaths from the disease in the bureau's registration area, and of these 71.5 percent were females. This, however, does not nearly represent the number of deaths in that year in the United States from the disease, since most of these occur in the country districts and are not reported at all, either to country, state, or national authorities. The census gives 69 deaths as occurring in Atlanta, Ga., more than occurred in any other city in the United States. As a matter of fact, hardly any of these cases originated in the city of Atlanta, but most of them came from the smaller towns and adjacent rural districts, and should really be classified as imported cases so far as the statistics of the city of Atlanta are concerned. The states of the Union, according to reports received in HISTORY AND GEOGRAPHICAL DISTRIBUTION. 65 '-%««*£ *-=- -'-"-- r,r-r. _ _ _ _ _ • - - II [ ) < i ijjn. j / . t a U u [ ■ i B5 I jill 1 .'.'I p^ 1 1 1 j| n f| « ** a ''Lrndtf"^ ~"^*3k. V , *L. ,,, 1 1 'I Fig. 6. — Pellagrosario at Rovereto, Austria, with the Alps in the background. A govern- ment institution for the treatment of pellagra, and only pellagrins are admitted. Dr. Probitzer is the director of the institution. This place was visited by the author in October, 1911. November, 1911, as to the prevalence of pellagra in them, are here given : Pellagra in the States. 1. Maine „. . » . 1 case in the state hospital for the insane. 2. New Hampshire. . . .No cases reported. 3. Vermont 1910, 2 cases in Addison county; both fatal. No cases since. 4. Massachusetts 1910, 3 cases. No report since. 5. Connecticut No cases. 6. Rhode Island 1910, in insane hospital, 7 cases, with 4 deaths; 2 males and 2 females. All these insane. 7. New York 1911, 2 cases, with deaths. These were imported cases. 8. New Jersey 1910, 1 case; 1911, 1 case in Somerset county. 9. Delaware No cases reported. 66 PELLAGRA. 10. Pennsylvania January, 1911, to November 1, 1911, 8 new cases. 11. Maryland To January 1, 1911, 11 cases; from January 1, 1911, to October 1, 1911, 8 cases. Of the 1911 cases, 7 died and 1 showed improvement; 6 were white and 2 were colored; 6 females and 2 males. The case that improved was a negro girl 5 years old. 12. Dist. Columbia 1911, 2 cases; 1 death. 13. Virginia 1910, 350 cases. During 1911 there were not as many, but no estimate. 14. West Virginia 1 case. 15. North Carolina. ... 1911, during the first eight months there were 69 white and 40 colored deaths reported to the State Board of Health from pellagra from a registration area with a population of 348,057. This area in- cludes all towns of over 500 inhabitants. Estima- ting the mortality at 20 percent, we have a total number of cases in North Carolina of 545. 16. South Carolina .... Estimated, 1,000 cases. 17. Georgia Estimated, 2,500 cases. 18'. Alabama Disease increasing. Estimated, 2,000 cases. 19. Mississippi Disease increasing. Estimated, 2,000 cases. 20. Florida At the close of 1910, 99 cases reported. Estimated, 250 cases. 21. Louisiana In June, July, and August, 24 deaths were reported. Estimated, 500 cases. 22. Kentucky Estimated, 500 cases. Specially prevalent in the mountain counties in the southeastern part of the state. Assistant Surgeon R. M. Grimm found 140 cases in the three counties of Whitley, Knox, and Bell. 23. Tennessee Pellagra prevails in sixty-seven out of the ninety- six counties in the state; 316 cases in these coun- ties. Out of the sixty-seven visited, number of cases in the state estimated, 500. (See Report of Pellagra Commission appointed by the Tennessee State Board of Health.) 24. Texas July, 1911, 33 deaths from pellagra, and 35 deaths in August. Estimated, 1,500 to 2,500 cases. 25. Arkansas Disease increasing. Conservative estimate, 1,000 cases. 26. Kansas First 10 months of 1911, 8 cases; 2 fatal. Disease increasing. 27. Missouri Estimated, 10 cases. 28. Oklahoma September 30, 1911, 19 cases and 13 deaths. 29. Nebraska No cases reported. 30. Ohio February, 1910, 1 case at Ironton, O.; May, 1911, 1 case at Cortland, O. HISTORY AND GEOGRAPHICAL DISTRIBUTION. 67 31. Illinois 1909, 192 cases, all in hospitals for the insane; 1910, 78 cases in hospitals and 5 outside; 1911, 48 cases in hospitals and 9 outside. Report of special com- mission to be published in 1912. 32. Indiana 1 case reported, with death. Insane hospitals have been carefully searched for the disease, but no cases found. 33. Iowa 1910, 3 cases; 1911, 1 case. 34. Wisconsin 'No cases originating in the state ; 1 case in spring of 1911 in Milwaukee and 2 deaths in September, 1911, but these 3 cases contracted the disease in the southern states and went north Avith the hope of obtaining relief. 35. Michigan No cases reported. 36. Minnesota No cases reported. The state institutions, especially * the hospitals for the insane, have been carefully searched and no cases found. 37. North Dakota No cases reported. 38. South Dakota No cases reported. Probabty present, but not identi- fied. 39. Montana No cases reported. 40. Wyoming No cases reported. 41. Colorado ..Previous to July, 1911, no cases reported. In July, 1911, 5 cases reported, and in August, 1911, 4 cases. 42. New Mexico No cases reported. 43. Idaho No cases reported. 44. Arizona To November 1, 1911, 3 deaths reported in the terri- tory; 8 cases unofficially reported in 1910. No new cases in 1911. 45. Utah No cases reported. 46. Nevada No cases reported. 47. Washington A sporadic disease, with 3 cases, reported. No cases in the asylums for the insane. 48. Oregon 1 case reported, and this a patient coming from one of the coast counties in Washington. Case rapidly fatal. 49. California First case reported in 1909, only 4 cases reported all told, with 2 deaths in 1910. There are probably more cases in California. From these figures, out of the forty-nine states, including the District of Columbia, pellagra has originated and prevailed in thirty-three. This count of thirty-three does not include a state like Oregon, for instance, where pellagra was imported, but did not originate within the state. It is apparent that the disease ex- tends from Maine to California, and that there is a skip in that 68 PELLAGRA. tier of states beginning with Montana on the north, extending southward through Idaho, "Wyoming, Utah, Colorado, Arizona, and New Mexico. The disease, however, reappears in the three Pacific coast states, but does not seem as yet to have originated in Oregon. It is interesting also to note the presence of the disease in Illinois and its extreme rarity in Indiana and Ohio. Again, Wisconsin, Min- nesota, and the Dakotas are a nonpellagrous territory. The disease, therefore, may be classed as sporadic in the New England and middle Atlantic states, epidemic in the southern states, and sporadic again on the Pacific coast. It is probable that there are 10,000 cases of pellagra in the United States at the present time. These statistics were furnished by the different State Boards of Health throughout the country. 1 have collected by means of return postal cards more detail facts concerning the distribution of pellagra in the state of Georgia. Topographically, this state may be divided into three sections. The northern, hilly and mountainous; the middle third, hilly, rolling country; and the lower third, flat. Pellagra is least prevalent in the southern part of the state and the number of cases increase toward the north. There extends across the state from Columbus through Macon to Augusta on the eastern border a line which is presumed to divide the northern hilly portion of the state from the southern portion, which partakes more of the nature of a coastal plain, and by far the majority of these cases originate north of this fall line. Counties in the Northern Third of the State. County. Cases. Deaths. Condition. Polk 75 25 Disease increasing. Gordon 20 3 Disease increasing. Clark 200 1 50 2 Disease increasing. Fannin 12 4 Disease increasing. Stephens 10 2 Disease not increasing. Habersham 50 45 Disease increasing. White '. 8 3 Disease increasing. Cobb 15 153 Disease increasing. Madison 12 6 Disease not increasing. DeKalb 150 50 Disease increasing. 1 Two hundred cases in three years. 2 With possibly 50 deaths. 3 Fifteen deaths in last three years. HISTORY AND GEOGRAPHICAL DISTRIBUTION. 69 Middle Thied of State, County. Cases. Deaths. Newton 5 6 Muscogee 100 25 Henry 14 Cla} T ton 3 Monroe 30 12 Meriwether 10 Taliaferro 4 45 Greene 25 5 Heard 5 5 Condition. Disease not increasing. Disease increasing:. Disease increasing. Southern Third of State. County. Cases. Deaths. Colquitt . 2 Worth 6« Berrien 5 Dodge None Decatur 6 8 Pulaski None Burke None Randolph 10 39 Coffee None Condition. 4" Disease increasing. 2. Mexico. — The mortality statistics for the city of Mexico for the eleven years 1900 to 1910 give 1 death from pellagra, which oc- curred in the sixth district of the city in 1909. The physicians and hospitals for the city of Mexico have not had any cases. A death from pellagra occurred in the city of Monterey, Mexico, in 1910. This patient was a physician who formerly lived in the United States, but he probably developed the disease in Mexico. Dr. George McDonald, Avho formerly lived in Mexico in the section around Monterey, told me that since coming back to the states he remembers three cases in his practice in Mexico who were strangely diseased, but that he is convinced now that they were cases of pel- lagra. The disease has prevailed quite extensively in Yucatan, a province in the southern part of Mexico. Pellagra developed there 4 No cases at present. 5 Four deaths in last three years. 6 Probably 20 cases in the county. 7 Four deaths in 1910. 8 Six cases in last few years. 9 Three deaths in last three years. 70 PELLAGRA. Pig. 7. — Group of eight boys, all pellagrins. (Photograph by the author on the steps of the pellagrosario at Inzago, near Milan, Italy.) Fig. 8. — A closer view of three of the boys shown in Fig. 7. HISTORY AND GEOGRAPHICAL DISTRIBUTION. 71 between 1882 and 1891, and was very prevalent in 1907 and 1909. Ganmer is probably mistaken when lie says that from 8 to 10 percent of the population are affected with the disease. Pellagra has, therefore, existed in the city of Mexico, Monterey, and Yucatan, and it is probable that an investigation of the disease in Mexico would show that it is more prevalent than is supposed, especially in the northern and central parts. There is no positive evidence as to the existence of the disease in Central America, but Dr. John L. Phillips, under date of November, 1911, writes: "Pellagra was first diagnosed on the Isthmus of Panama in October, 1909. Since then we have had 32 cases, with 16 deaths." These statistics were collected by Dr. Phillips in the sanitary division of the Isthmian Canal Commission and are accurate. Pellagra probably prevails, therefore, through- out Central America in all that region north of Panama. The disease is also found in Jamaica, and occasional cases develop in Cuba, Porto Pico, and many cases occur in Barbados. 3. South America. — The existence of pellagra in South America is doubtful. Information regarding cases in Peru, Brazil, and Argentina is lacking, but one would not be surprised to find the disease more widespread in South America than evidence shows. I have searched the reports of the congresses on sanitation of the American republics, but I have failed to find any reference to or mention of pellagra. It is probable that the disease exists in Colombia, Venezuela, and Ecuador, though much positive infor- mation is needed for all this continent. Fig. 9. — Map showing distribution of pellagra in the world. ^ Pellagra not reported. Pellagra sporadic — few cases. Pellagra prevalent. ,A ^ C E 4? - v> Note relatively small pellagrous area. CHAPTER III. CLASSIFICATION. Pellagra is a general disease, and in our nomenclature it should be classed as such. It is a systemic disease, and not a system disease; a disease of the whole organism, and not a disease of any one system of organs. It is net a skin disease, because it also affects and produces organic changes in the nervous and gastro- intestinal systems. It is not a disease of the nervous system, be- cause it affects the cutaneous and digestive systems. It affects the nervous system as much as, if not more than, the digestive system, and therefore it can not be classified as a gastrointestinal disease. In Italy it is somehow preferably placed in dermatology, probably because the skin symptoms are so noticeable and have received so much attention. Up to 1884 the Royal College of Physicians of London classified it as a skin disease, but since 1896 it has found a home among general diseases. It is no more a skin disease than syphilis or typhoid fever, though both of these have eruptions which help to confirm and to decide the diagnosis; it is no more a gastro- intestinal disease than yellow fever or tuberculosis, though both of these involve the abdominal organs; it is no more a nervous disease than sleeping sickness or leprosy, though both of these involve the nervous system seriously. Pellagra leaves its mark everywhere — on bone and parotid gland, cord and intestine, skin and stomach. It is a general disease, with a systemic pathology. OTHER INFECTIONS IN PELLAGRA. The tissues of a pellagrin offer fertile soil and little resistance to infection by bacteria, protozoa, and worms. Pellagra draws generously on the natural reserve force of all the organs, and it is natural to find several infections associated with the disease. The advance of tropical medicine has shown that the pellagrin is fre- quently a hospitable host to more than one parasite, and that the cachectic power of pellagra is aided by the blood extracting power -74 CLASSIFICATION. 75 of several varieties of worms. Harris, studying ankylostomiasis, first discovered pellagra in Georgia, and Sandwith had the same experience in Egypt. The first record I can find of the presence of parasites in a pellagrin is in the elder Strambio's work on "De Pelagra." In case 9, at autopsy, he records "20 lumbrici in stomach and 7 in esophagus." I have been surprised at the similarity in distribution of pellagra, uncinariasis, and malaria; and, since other intestinal parasites and protozoa are common in temperate and tropical climates along r - '•- . i * * *•*«%«, % „ M\ » w ■ '^BBJ KT#: : , g|H ***' W m 1 n Fig. 10. — Pellagrous "boy. Very stupid, with vacant expression ; body thin and gaunt. (Photograph by the author in Italy in 1911.) with these diseases, pellagra is found associated with as many as three infections in the same patient. Pellagra by itself is serious enough, but pellagra associated with other infections endangers the patient far more. Pellagra diffused throughout the system, and hookworm inside removing constantly "the blood thereof which is the life thereof," causes darker clouds to rise on an already clouded prognosis. Amebic dysentery is found throughout the tropics and in parts of the temperate zone ; in the United States it is the most common variety cf all dysenteries. Pellagra involves the whole gastrointestinal tract, and, of course, would tend to increase an 76 PELLAGRA. infection with amebas, and an amebic infection would tend to cause the pellagra to make greater inroads. Much attention has been given to amebic infection in pellagrins in the United States, but Fig. 11. — 'Two Georgia cases, presented by the State Hookworm Commission. The smaller boy, aged 4 years, has had pellagra two years, and is also infected with hookworm ; dry, wrinkled skin on hands, feet, and legs; marked diarrhea, rather constant; in- continence of urine and feces when picture was made ; anxious, drawn, old-age expression of face ; marked physical weakness and mental apathy. The larger boy, aged 7 years, has had same duration of symptoms, though less severe ; skin eruption is slightly worse than that of the smaller boy; there are epithelial and blood cells in the feces, and the hookworm disease is present. Fig. 12. — Same case as shown in Fig. 11. Side view, showing the protruding abdomen. the prevalence ot amebic dysentery in this country, plus the recur- rent inflammation of the mucosa in pellagrins and the general lowered resistance, tends to explain the association of the two infections. CLASSIFICATION. 77 The following interesting table from Sandwith's Egyptian cases shows uncinariasis and bilharziosis in pellagrins during 1895, 1896, and 1897 : Not Remain- Cured. Relieved, relieved. Died. ing. Total Pellagra and uncinariasis... 50 184 18 8 23 283 Pellagra, uncinariasis, and bilharziosis 19 99 3 9 24 154 This is a general death rate of 4.3 percent after deducting the cases still in the hospital, 6.9 percent for patients attacked by all three diseases, and only 3 percent for patients attacked by only two diseases. It seems that the additional infection by bilhar- ziosis doubles the danger and the death rate. Of course the treat- ment of uncinariasis is far easier and more satisfactory of the two associated infections, and even a pellagrin shows marked improve- ment after the hookworms are gone. Willetts, formerly pathologist to the Georgia State Sanitorium, examined the feces of 500 unselected insane negro females, and of these 35 were pellagrins ; of the total number 250, or 50 percent, were infected with some form of intestinal parasite ; of the 35 pellagrins, 14, or 20 percent, were so infected. Trichuris and ascaris predominated in the whole number, and strongyloides and uncinaria in the pellagrins. Strongy- Trichuriasis. loides. Uncinaria. Hymenolepis. 40.2 18.2 11.8 0.2 Number examined. 500 Infections. Ascaris 250, or 28.2 50 percent Number of these pellagrins 35 14, or 8.57 40 percent 17.14 25.71 20.0 2.86 Pellagrous children especially are apt to have hookworm and pinworm infections. The former may occur in pellagrins having only a mild attack, but hookworm disease is to be considered an enfeebling factor in pellagra, and some of the symptoms attributed to it — as anemia, emaciation, and weakness — may, in part at least, be due to the worms. This also applies to malaria, alcoholism, syphilis, tuberculosis, frequent pregnancies, surgical operations, or any condition of disease or stress that lowers resistance and invites prevalent disease of any kind. It is plainly true that with all the 78 PELLAGRA. members of a family equally exposed to the cause of pellagra, ex- isting infections present in certain debilitated individuals act as predisposing factors to pellagra, and these individuals will develop the disease more easily than their strong and healthy relatives ; and, vice versa, once pellagra is developed, other infections will more easily gain a foothold. Favus seems to have a preference for the scalps of Egyptian pellagrins. The physician often observes in poor children a paleness and lack of color and vivacity, due not to food nor to any disease, but to an absolute lack of food; it is the cachexia of indigence, and in endemic pellagrous districts predis- poses to the disease. Nichols' researches at the Peoria (111.) Asylum for the Insane enabled him to prepare the following very interesting table on protozoan infection in pellagrins, and to compare it with nonpella- grous inmates and soldiers in the Philippines. Pellagrous Nonpellagrous Soldiers in inmates. inmates. Philippines. Number examined 88 101 454 Negative 14.7 percent 51.4 percent 48.8 percent Amebse 37 11 16 Flagellates (alone) 20 12 34 Encysted protozoa (alone).. 27 24 Percent of cases with protozoa 85 48 51 The excess of protozoan infection in pellagrins is here very noticeable, being 37 percent greater than in the nonpellagrous in- mates, and 34 percent greater than in the soldiers living in the tropical Philippines and subject to far greater changes in diet and variations in climate. Babcock and Lavinder found protozoan in- fections in pellagrins in South Carolina, and I have observed amebae in a highly cultured woman with pellagra of several years' duration. The diarrhea in her case was persistent and more pro- nounced than any diarrhea I have seen. On autopsy of 18 of the pellagrins included in the above table, Siler and Nichols found ulcers in the colon in 12, or 66 percent, and 1 pellagrin "died of peritonitis following a perforation of an amebic ulcer;" 2 had tubercular ulceration and 1 trichinosis. In 1 case oxyuris eggs were found, but no uncinaria. Siler and Sambon, working together in Italy, found ankylos- toma duodenale, which is the European species of hookworm corre- sponding to the necator Americanus of Stiles, the most common CLASSIFICATION. 79 intestinal parasite in Italian pellagrins. Pisenti and Mandolesi state that those pellagrins who present the most severe anemic and oligemic symptoms "were those who presented the greatest number of hookworm eggs in their feces." Pellagra causes anemia, but the profound anemia in pellagrins necessitates the examination of the feces for hookworm ova. In the southern states it should be the first step in the treatment of pellagra. Besides the hookworm, Sambon found ascaris lumbricoides, trichuris trichiura, oxyuris vermicularis, cercomonas hominis, ameba coli, and in one case the ova of hymenolepis nana. Strongy- lcides intestinalis is also found in Italy as well as necator Ameri- canus. Summarizing the varieties of intestinal parasites found in pellagrins in Egypt, Italy, and America gives the following results : America. Italy. Egypt. Ameba coli -\- Ankylostoma duodenale iSTecator Americanus -\- Trichocephalus hominis -{- Oxyuris vermicularis -|- Cercomonas hominis — Hymenolepis -)- Schistosomiim — Bilharziosis — Strongyloides -(- Flagellates '. -(- Trichina spiralis -j- — ' — Ascaris lumbricoides -j- -\- — The plus mark (-|-) indicates presence, and the minus mark ( — ) indicates absence. Some forms marked absent are probably pres- ent, but not reported. Intestinal parasites in pellagrins deserve a more detailed study, and its importance in treatment will become more apparent in view of the wide distribution of hookworm disease in the southern states. Either disease produces lassitude, weak- ness, dwarfism, anemia, emaciation, senile and wrinkled skin, dizzi- ness, headache, gastralgia, stupid expression, and mental inertia. Pellagra is more susceptible of treatment after removal of hook- worm infection. Both diseases are rural in origin, common among farmers, and with the same general geographical distribution ; often to be found aggravating each other in the same individual, and their association may be expected in many cases. + + + + + + + + + — + — — + — + + — + + 80 PELLAGRA. RELATION OF PELLAGRA TO THE SEASONS. Pellagra is a disease which avoids the winter. It usually first appears in the spring and early summer; it may reappear in the same patient in the autumn months of September or October, but usually it omits the autumn advent, hibernates during the winter, and recurs the following spring. In Italy the majority of the spring attacks occur between the middle of March and the middle of May, with extremes of invasion as early as February and as late as June. The autumn invasion recurs during September and October, with extremes of an early limit in August and a late limit in November. The latitude of 40° cuts the pellagrous area of Italy into northern and southern halves. The pellagrous area of Egypt is cut by the latitude of 26° north, and therefore is about 1,000 miles south of the Italian area. The spring attack occurs from November to March ; the majority of the cases make their advent and reach their acme during January and February. Few cases recur during the summer. The Egyptian climate is far more tropical than either the European or American, and January more nearly corresponds to spring in the latter two countries. In North America the pellagrous area is included be- tween 25° and 45° north latitude, though by far the greatest num- ber of pellagrins live in the belt on either side of the line 35° north latitude. In Florida the spring invasion may occur as early as December and January, as in the case reported by Randolph; coming north into south Georgia, the spring attack may begin in February, and the farther north the later the seasonal attack. These represent the early appearances of the malady, but as a rule the greater number of cases in the southern states occur in April, May, and June. What is most surprising and apparently different from the usual cases described in the Italian and French literature is that the onset in America varies from January in Florida to late October, and one case is reported as recurring in November. I have seen cases whose onset included every month in the year except November, December, and January. One reason for this is the mild climate in the South, with only two or three months that could be counted severe, and even then the severity is not continuous. Again, spring advances in this large country gradually, so that a 200-mile trip produces quite a change in climate and in the time CLASSIFICATION. 81 of advent of the seasons. As a rule, pellagra is synchronous with spring, recurring earlier in the year if the winter is mild and spring early, and later if the winter is severe and the spring late. Of 45 cases collected by Tucker of Virginia, 4 cases began in the summer, 4 in the spring, 2 no time given; of the 45 who gave the months, 2 began in January, 2 in February, 10 in March, 9 in April, 7 in May, 9 in June, 4 in August, 1 in October, and 1 in November. It is important to remember that there are greater variations in the time of the first onset than in the time of the subsequent attacks. In America the first invasion of the disease may come in any month from late February to October, with an occasional case in January or November, but the recurrences are more periodic and uniform, and come with a vernal regularity. Case 3 in Chapter I (page 25) illustrates this uniform recrudescence in the spring. The autumn recurrences are practically limited to September and October, a more narrow limitation than obtains in the spring, and the autumn attack probably in a majority of cases fails to appear. One of the essential elements in the knowledge of the disease is the ability to diagnose pellagra in the fall or winter, when the disease concels itself in the winter sleep. I have seen one case, about to recur in October, where the prodromes of epigastric uneasiness, slight diar- rhea, vertigo, and weakness recurred, but no dermatitis, and in a few days the woman seemed strong and well. It is probable that if the disease in this case had taken deeper root and been more advanced, there would have been a typical autumnal recurrence. INCUBATION PERIOD. The period of incubation of a disease includes the time between the intake of the poison or the infecting agent and the actual onset of the disease. This incubation time consists of two stages: (1) the stage immediately after the infection or the intoxication, in which there are no external symptoms, as in the two to four days following the exposure of a child to scarlet fever; (2) the stage of prodromes, during which symptoms appear which are premoni- tory of the disease, as the appearance of sore throat before the actual onset of scarlet fever. The determination of the incubation period is not difficult when the cause of a disease is well known, because then the time of infection or exposure can be accurately ascertained. It is altogether different in pellagra, for the simple 82 PELLAGRA. reason that we do not know the cause, and therefore the incubation period is more or less a matter of a priori reasoning and specula- tion. Furthermore, the prodromal symptoms differ so widely in degree and in kind that even now the initial symptoms, not to mention the initial symptom, are still a matter of dispute. The prodromal symptoms vary from constipation to diarrhea, vertigo to dermatitis, and slight stomatitis to actual nausea. It is evident that if an infant is born healthy, and develops pellagra during early infancy, the incubation period is slightly less than its age. Pellagra in a 5-months' infant previously healthy indicates an incubation period of less than five months. Further- more, if a disease habitually makes its appearance in the early spring both in its first and subsequent attacks in the same individ- ual, it is evident that the exposure to the intoxicating or infecting agent must be near the early springtime, or the intoxicating agent must be strangely and unaccountably cumulative at this time. In- fants are peculiarly susceptible to intoxications, as indicated by milk poisoning, and to infections, as indicated by the various infective diseases common to childhood. I have not been able to find in America pellagrous infants under one year, with one exception, but Sambon found infant pellagrins in Italy, and their ages reduce the previously estimated time of incubation. One infant was born in an Italian jail and nursed by its mother until 5 months old; it was then taken away and given to peasants living in the country. It developed pellagra in two weeks, or at 5y 2 months old. Another infant was born in Novem- ber, and taken into the fields about the middle of March; it de- veloped the pellagrous dermatitis in May. One of these developed the disease about April 1st and the other about May 15th. The incubation period in intoxications, such as meat and mushroom poisoning, ergotism, ice cream, and canned goods, is short, varying from twelve hours to a week, and usually near twelve hours — longer, of course, in ergotism. The time of incubation in infectious diseases is notably short, as in typhoid, cholera, malaria, smallpox, and influenza. Considered either from the history of the two in- fants given, or intoxications and infections in general, there is reason to believe the incubation period in pellagra varies from two weeks to two months, and probably nearer two weeks. Another reason that complicates our knowledge of the disease is the insidious onset of pellagra. It insinuates itself into the system, CLASSIFICATION. 83 and even an intelligent pellagrin hardly knows from the prodromal symptoms how or when it started. Sandwith in Egypt, and Lud- wig Merk studying in Austria and Italy, believe the incubation period to be from seven to nine months. Sandwith believes the poisoning due to corn from the previous year's crop, and the incuba- tion probably as long as twelve months. The corn crop is harvested in Egypt in November and December, and the majority of Egyptian pellagrins begin their eruption in January. He does not think sufficient fungi or poison could de- velop in this time to cause pellagra, and therefore makes the criminal out of the previous year's crop. This reasoning appears incorrect in view of corn as a cause. Incubation is considered to end with the dermatitis, and, as fever is practically absent in the initial attack of pellagra, the erythema marks the close of the prodromal symptoms, and usually the definite onset of the disease. There may be no prodromal symp- toms, and the dermatitis ushers in the attack. DURATION OF PELLAGRA. The duration of pellagra depends on the severity of the symp- toms and the rate of progress of the disease. It is a chronic disease as a rule, but it occurs as an acute disease occasionally, and mid- way between these is a third form of moderate length. It is better to say that it is a disease of relatively long standing, whether the attack be acute or chronic. For instance, the acute form may last six weeks or three months, but this is unusually long for the aver- age acute attack of a disease. Classified according to time, three types are found: 1. Acute Pellagra. — Malignant pellagra characterizes this at- tack. It lasts from one week to three months, and progresses rapidly to a conclusion. Fatal as a rule. It is also called typhoid, florid, tetanic, or fulminating pellagra. 2. Subchronic Pellagra. — Lasts not over two years and ends in death or recovery. Two subdivisions : (a) Mild Subchronic Pellagra, or Convalescent Pellagra. There are one or two mild attacks, ending in recovery without sub- sequent recurrence. Pellagrous Italian boys, after one or two mild attacks, may develop into healthy men, and be accepted as soldiers in the Italian army. 84 PELLAGRA. (b) Severe Subchronic Pellagra, or Cachectic Pellagra. From the first attack there is rapid emaciation, the symptoms are pronounced, and cachexia comes quickly. There are no intermis- sions as in the chronic form, and death ensues in two years or less. 3. Chronic Pellagra. — This is the usual type in point of time, and it may last from three to thirty years, recurring regularly each spring or at longer intervals. It is mild and slowly pro- gressive. It may end in apparent recovery, in insanity, or in death. Patients with this type are often not incapacitated from work, and may be apparently healthy during the seasonal intermissions of the disease. Pellagra is too variable a disease to permit hard and fast lines of classification, and, as in nearly all diseases, different types grade insensibly into each other in actual practice. The chief features of the acute form are its rapid onset, high fever, and quickly fatal ending, but acute pellagra may terminate in either the severe sub- chronic pellagra or even the chronic form. The chronic form may occur for three successive years, disappear from external appear- ances, only to reappear in from three to six or ten years. In the same patient the disease may appear for several successive seasons, and then disappear for an equal time or longer. There are problems that arise from this behavior of pellagra that are at present unsolved. Does reinfection or reintoxication account for the chronicity of pellagra? Is there a latent pellagra that explains its disappearance in a patient pellagrous for a number of years, or does reinfection account for the reappearance of the disease? Malaria is a disease which may appear as a result of long-standing latency, or as a result of reinfection. An individual moving from a malarial area to a more healthy center may for one or two springs have a malarial attack due to a latent infection, with subsequent improvement in health. He may return to the endemic malarial area and have a reinfection. Pellagra offers a stronger evidence of latency than malaria, for it is certainly latent from season to season, as it appears in the spring and disappears until the following spring, even if the patient is removed from the en- demic area and no longer eats any of the products of maize. Since it is latent from season to season, it is reasonable to believe that it is latent for longer periods. Jansen, in 1788, saw the disease in Milan, and, referring to the end of the spring attack, writes : "The patients, however, are not now to be considered well; the CLASSIFICATION. 85 disease hides itself, but is not eradicated, for no sooner does the following spring return, then it quickly reappears." Strambio says pellagra, concealed after several successive seasonal attacks, "is a snake in the grass.' 7 There is no reason for doubting the fact that reinfection recurs, and especially is this true if residence in an endemic center is continued. Strambio, in 1787, found the length of the disease from onset to death in 10 pellagrins — 7 men and 3 women — averaged five years and seven months, ranging from three months in the lowest to twenty years in the highest. Sambon found octogenarians in Italy who had "donned the pellagrous bloom since childhood." I have found one North Carolina case with a clear history of duration of about twenty years, and, while the disease has been epidemic in the United States for an unknown period, probably not longer than twenty years, many physicians can make a backward diagnosis of pellagra in former patients with a course of from fifteen to five years. In Egypt the peasant pellagrin or fellah does not apply for treatment at the government hospital until he is too weak to earn bread, or until emaciation is present and cachexia is threatened. Of Sandwith's 162 hospital cases the average time they were ill be- fore entry was two years; in 36 there was illness of less than one year, and 9 were ill for five years and longer. Siler investigated the number of previous attacks among pellagrins in Illinois, and found of 104 cases 25 percent had suffered three previous attacks, 52 percent two previous attacks, and 23 percent only one previous attack. My own cases in private practice average about three and one-half years. It is probable that the average length of the disease in Italy is between five and ten years, and in America and Egypt about five years. DURATION OF A SINGLE ATTACK. This ranges from the mild and often unnoticed attack in an infant, lasting a week, with an erythema hardly discernible, to the severe subchronic attack, which lasts from the initial onset to death, or from six months to two years. By an attack is included the premonitory symptoms, the dermatitis, with accompanying digestive disorders, and the gradual disappearance of the objective signs of the disease. The subsequent emaciation, weakness, and neuras- thenic condition are to be considered the results of the attack, rather 86 PELLAGRA. than a part of it. A single typical spring attack, lasting from six weeks to three months, consists of three essential elements: (1) onset of the attack, (2) the outbreak of the attack, (3) the reces- sion of the attack. A diagram will render the wisdom of division into these different periods clearly evident. The line a b does not coincide with the base line A B, indicating the lesions from the single attack. 1. Onset. — This period includes the prodromal symptoms, which begin toward the latter part of the period of incubation, and corre- sponds to the preerythematous stage noted by many writers. Its duration varies, but, as a rule, five to thirty days are the limits, with a probable average of fifteen days, or from two to three weeks. Outbreak. 4 ' c e Si H °U. -B Fig. 13. — Diagram showing periods in an attack. This period of onset may be altogether absent, and the dermatitis be the first symptom. Its severity is usually proportionate to the severity of the period of outbreak, and it, of course, closes with the advent of the outbreak. It is the period of minor symptoms, whose aggregate would lead both patient and doctor -to use the word "bilious" or "spring fever." There is lassitude, general malaise, slight mental and physical inertia, lack of appetite, epigastric uneasiness, bulimia, coated tongue, occasional relaxation of the bowels, and a systemic desire to rest. At this stage the tongue, though coated, may present red, slightly swollen and occa- sionally cyanosed papillae on the tip or edges, but no ulceration or buccal pain. It is a period of pathological introspection rather than of an objective disease. A burning sensation in the stomach, or on the hands or feet, is strikingly suspicious, and the occurrence of this group of symptoms in the spring in a patient in the country, especially if in an endemic pellagrous area, should make the physi- cian both silent and careful. 2. Outbreak. — This period of outbreak closes the period of onset, and ushers in the objective symptoms that make pellagra so easy of diagnosis at this time of culmination of the single attack. The biliousness of the patient has become the pellagra of the physician. CLASSIFICATION. 87 The lassitude and malaise, the desire for rest and quiet, the mental and physical inertia, are now noises in the ears, vertigo, weakness in the lower extremities, occasional headache, increased reflexes, conversation is slow, the usual vivacity and force of the mind are Fig. 14. — Pellagra during period of attack. Typical wrist band, raw tongue, and erup- tion on face. (By Dr. O. C. Bass.) subdued and low, and depression has taken the place of the normal happiness of life. The backs of the hands are covered to a greater or less degree with a symmetrical dermatitis resembling a sunburn in the lighter attacks, and a sunburn with the tint of a full ripe 88 PELLAGRA. plum in the more severe attacks. Above the redness and around the borders the skin is rough ; the elbows over the olecranon process are rough; there may be with this some roughness or dermatitis en parts of the face, neck, forehead, feet, and knees. There is an undue sensitiveness to sunlight or heat of any kind, slight pains in the abdomen occur, the pulse is faster, and fever is absent. The digestive symptoms of the onset are now really evident. The lips are red, the saliva is increased, and the tongue is smooth and of a beety nakedness ; the papillag are red and prominent, the tip and edges are raw in small areas; the soft palate, fauces, and throat are red and tender, and the esophagus seems in the same condi- tion. There is actual diarrhea, with a peculiar odor to the stools, a sense of nausea develops, gas increases in the intestines, and one is reminded of an acute gastroenteritis. The facial expression is one of anxiety, the neurasthenic element arrives, and it is evident that some flesh has been lost. The patient is suddenly and tem- porarily a neurasthenic, with accompanying cutaneous and gastro- intestinal symptoms. 3. Recession. — The period of outbreak continues from one week to a month, and, as the symptoms that characterize it begin to lessen, the period of recession has begun. The patient feels bet- ter, pains disappear, and appetite returns. The buccal and lingual areas return to their natural state, except the covering of the tongue seems strangely slow and delayed. The throat heals, and acid foods can be swallowed without burning. The stomach feels natural, digestion improves, the number of stools decreases and again assume their normal consistency. The dermotagrous area desquamates, and the skin becomes smooth. The erythematous area on the back of the hands desquamates in larger scales, and a cleaner, lighter skin, slightly pigmented perhaps, appears beneath. The ends of the fingers seem unusually pink and clean, and the sensa- tions of burning depart. The face assumes its wonted brightness, and. cheerfulness takes the place of depression and sadness. The step again becomes elastic, and the sense of well-being and strength returns. The pellagrin thinks he is well. Pellagra, unlike a garment, is not made to pattern, and these symptoms are subject to great variation. These manifold symp- toms vary in their order, in number, in association, and in severity. The first symptom may be the dermatitis, and for the first few seasons it may be the only noticeable symptom. There may be a CLASSIFICATION. 89 dermatitis and malaise, with entire absence of gastrointestinal symptoms. The skin may itch and burning sensation be absent. The attack may be so slight that it interferes with neither work, sleep, nor strength ; or so severe that the first attack is malignant pellagra and death comes quickly. The dermatitis, instead of dry, may be of an exudative type, with vesicles, rupture, and ulceration. Constipation may occur and diarrhea be absent even in the period of outbreak. The neurasthenic element may be absent, weight may remain as usual, and good spirits instead of depression be the rule. Appetite may continue as usual, or even be increased to greediness. Thirst may increase, or there may be a repugnance to water. Lassitude, dermatitis, and the tongue without a coat are the rule. ACUTE PELLAGRA. The idea involved in the phrase "acute pellagra" is threefold: (1) it includes a pellagrous attack which is severe in its symptoms and prostrating in its effect; (2) temporary, limited, and not chronic in time ; and ( 3 ) characterized by a fever, with extremes of 101 u to 105°. These three ideas of severity, brevity, and fever caused the unfortunate term "typhoid pellagra" to be applied to this acute pellagra. Typhoid fever is one disease, and pellagra is another disease, and the two rarely occur together in the same individual. Procopiu and "Watson each report two cases of typhoid in pellagrins, and even here it would be more correct to say that these pellagrins had typhoid fever complicating their pellagra, rather than to call the association of the two diseases typhoid pella- gra. In this acute pellagra as it occurs the bacillus typhosus is not present, and the disuse of the term typhoid would be a gain in the nomenclature of pellagra. The term "acute pellagra," as now applied to three conditions which occur, is (1) a primary acute attack of pellagra; (2) an acute attack in the course of the disease — sudden, severe, and febrile in its manifestation; (3) a terminal state of chronic pella- gra, with prostration, convulsive seizures, fever, diarrhea, and emaciation. It seems hardly consistent to call the terminal stage of a most chronic malady the acute form of the disease, and a similar inconsistency arises when acute pellagra develops in the course of the chronic form. To be consistent, acute should apply only to 90 PELLAGRA. the primary attack, malignant in its nature. Pellagra is not noted for consistency, and acute pellagra includes all three conditions mentioned above. Each of the three is similar in symptoms and in duration, but each differs in the time in which it appears in the course of the disease. Classified according to time of appear- ance, they are as follows : Acute pellagra. Malignant pellagra. 1. Primary acute pellagra, first attack. 2. Secondary acute pellagra, developing suddenly in usual chronic form. 3. Terminal acute pellagra, ending cachectic stage, and fatal. The duration of acute pellagra ranges from two weeks to three months; a duration of less than two weeks is extremely rare. It is sudden in onset, and the patient goes to bed at once. Prostra- tion seems out of proportion to the fever, and the pulse is high in proportion to the fever, wherein it differs notably from typhoid fever. Rarely is the pulse lower than 120, often it runs to 130, and higher as death approaches. The heart is not enlarged, and the sounds seem humdrum and low; the fever is continuous, with- out any regular morning and evening variations. The pulse is small, often irregular. Procopiu calls it a filiform pulse. The coat of the red tongue is gone, and fissures cover the dorsal surface, a true dissecting glossitis. Stomatitis, pharyngitis, gastroenteritis, and rectitis are usually present. A serous diarrhea, stubborn and persistent, is more frequent in the terminal acute type, with an accompanying emaciation, which ends cachexia and ushers in marasmus. Added to the difficulty in swallowing is dyspepsia, nausea, aversion to food and often to drink; prostration, loss of vital and muscular power, a fetid perspiration, and a peculiar pellagrous odor increase the general despair. The skin takes on a deeper hue, approaching lividity, and there may be the typical dermatitis and rough skin. Petechias may develop in the skin, bedsores on the supporting areas, trophic changes in the nails, wrinkled forehead, and rapid mummification. Instead of immobility and permanent dorsal decubitus, tetanic and meningeal symptoms arise, which are probably due to an advance of the pellagrous process in the cord and brain, with inflammation and exudate in some cases on the meninges and the cortex. Tremors, tetanic tossing to and fro, CLASSIFICATION. 91 convulsions, opisthotonos, emprosthotonos, localized muscular con- tractions, delirium, mutterings, mania, depressive states, and hal- lucinosis mark the departure of the intellect. Toward the last, incontinence of urine and feces may develop. The urine is probably increased, excepting the rare cases with uremic symptoms. The specific gravity is low ; hyalin and granular casts, with occasional corpuscular elements, and albumen are often present. The course of the attack is rapid, death the rule, and temporary recovery the exception. Such a patient never recovers from pellagra, but recovery from the attack may grant a tem- porary respite. Terminal acute pellagra is always fatal. Differential diagnosis and post-morten findings will be found in appropriate sections. (See page 208.) SUBCHRONIC PELLAGRA. Convalescent Pellagra. This is the least serious of the forms of pellagra. In itself it is proof that a pellagrin may recover permanently from the disease and that treatment is really worth while. Fritz, at Inzago, called my attention to this type of the malady and to its evanescent tendency. In his thirty years' experience he had often observed children who developed pellagra to the extent of a mild dermatosis and dyspepsia, and after not more than two years of pellagrous symptoms, usually one year, recovered, grew into healthy men and women, and never afterward had any pellagrous symptoms what- soever. One of his patients, a boy, gained forty pounds in three months. This is true in Italy and in Roumania, and as the disease advances in America, and its different degrees of severity become more apparent, evidence will accumulate as to the convalescent form. Fritz 7 cases among the men married and raised large fami- lies, and that with no pellagra among their children or any stigmata of pellagra. The women married and bore children, often large families, and with no miscarriages. The boys, on reaching man- hood, stood the rigid physical examination, were often accepted as soldiers in the Italian army, and became strong men and good soldiers. Under this division come also many of the cases that Sandwith found when he examined 352 presumably healthy men and boys in eleven different villages in Egypt, and found 127 of them suffering with unmistakable signs of pellagra. 92 PELLAGRA. Pellagra may be so mild that the pellagrin suffers no inconven- ience and is unaware of the presence of any disease whatsoever. Infants and young children develop the disease and present to the mother no signs of sickness, play and run as usual, and eat and sleep as well as ever. Pellagra varies as much in its severity as in its mass of symptoms, and one to see convalescent types of pella- gra has only to visit the various pellagrosari in Italy. In Amer- ica this subchronic type is extremely rare as compared with Italy, but, as time goes on, the extreme virulence of American pellagra will probably decrease with an increase in the number of cases of the convalescent type. Convalescent pellagra does not advance beyond the stage of ini- tiation. It is the pellagra of dyspepsia and dermatosis, with the practical absence of all the neurasthenic symptoms. It is well known that the initial stage may last in chronic pellagra for ten years, but in the present form even the initial stage is not far ad- vanced. The cause of pellagra fails to gain a foothold, its tendrils do not take root in the body soil, and after one or two vernal at- tempts it surrenders. Weight is the great mass symptom of pella- gra, and here there is no emaciation and often no loss in weight. The metabolic processes proceed as usual, appetite continues, sleep is good, and work is not interfered with. Young people are most often affected with this type, and their natural reserve force and resisting power help to ward off the disease. Youth is the best medicine in pellagra. The dermatitis is mild, rarely extends far above the wrist, comes quickly and goes quickly, leaving no objective change in the skin. The wet form never occurs in this type. The dermotagra is nearly always limited to the flexor surface of the forearm and to the elbow. The forehead may occasionally show a little branny roughness, but no dermatitis. The buccal mucosa is not very tender, though it is nearly always slightly red. The tongue does not have the entire nakedness, ulceration, and fissured glossitis of the more severe forms. It does not pain the patient to swallow, and diges- tion is rarely interfered with to any extent. For a day or two, rarely longer than a week to any extent, does diarrhea exist. The bowels are rather relaxed than loose, and constipation is often present; in many of this type no change occurs in the action of the alimentary canal of which the patient is aware. In two weeks to a month all signs of the disease are gone, and the health is as CLASSIFICATION. 93 good as ever. There may be one or two recurrences, but of no greater moment than the first attack. Anemia is not pronounced, weakness is not felt, and recovery is without incident. Cachectic Form. Strambio must have had this type in mind when he spoke of continuous pellagra. It is true that cachectic pellagra does have periods of remission, but they are so slight M ^Mt both physician and patient feel that the disease is still actively ; . peent. There is. really no level in cachectic pellagra, and down-g Uj is the rule. There is no up-grade, because the patient does d til et better. The first attack is inordinately severe, even fever of hjj|( or less may be pres- ent, the pulse quickly rises to 100° and i ifcc, and the digestive symptoms are pronounced. The lips are red, often cracked and painful, and in one case I saw there was a continuous herpes on the lips. The tongue is red, with small ulcers on the tip and margins, and papillae are prominent, and the circumvallate papillae begin rising almost to the dignity of warts in their size and firm- ness. The soft palate, fauces, pharynx, and buccal mucosa are red, inflamed, and on the anterior pillars is occasionally a livid, cyanotic area which seems on the eve of ulceration. Indigestion, nausea, actual vomiting, diarrhea that is continuous, though not as severe as in the acute types, abdominal distention, gastralgia, and epigastric weights are so many separate blows on the general nutri- tion, and gradual loss of weight and emaciation introduce cachexia. After the first attack the patient is thin, cachectic, a profound neurasthenic, discouraged, mental activity gone, and despair and tears are moods in his neurasthenia. The essential difference in this form is the absence of any real period of intermission. The attack continues, and the loss of weight gradually increases. The dermatitis may disappear, leaving a pig- mented area in its trail. On careful examination the dermotagra remains on the elbows, flexor surface of the forearm, and even on the arms and shoulders, especially if in the primary attack the skin involvement had this area. The mouth rarely entirely heals, and, even if it appears well, in another week a new wave of in- flammation sweeps over the mucosa of the oral cavity. The tongue never resumes its normal coat and state; on its tip and margins are red areas, and the papillae are more or less prominent. Fre- quently the gums are red and tender, and toward the latter stages 94 PELLAGRA. recede, with a collection of putrefactive material on the gum edges, giving the appearance of the mouth in Riggs' disease. As a rule, the abdomen is flat, and in one case of a woman of 34 a typical boat-shaped abdomen was present even in the periods of active diarrhea. There may be burning in the feet, occasional nights of insomnia, and the temperature may rise to 101°, with five to ten stools daily for a week, and dissolution appear near. The fever and diarrhea abate, sfd the former ability to sit up and even walk may return. After jure of the severe weeks the cachexia and gen- eral debility are mor , -Apparent, listlessness increases, the emotions come more to the sun ace, recurring attacks of erythema may de- velop, and the approa;' h. of death nears usually without pronounced symptoms of insanitj/' Sunken eyes, wasted face, keenly drawn fingers, and skin and bones represent what six to twenty-four months ago was a healthy, vigorous man or woman. I saw one case of this course in a girl of 8 years. At different times fever is present in this type, but not of the severity or length of the acute type. In women there is amenorrhea as a rule. It should be remembered that in a spring attack, with a cachexia resulting in midsummer, the recurrence in September or October of an autumn attack may close the scene, though occasionally the patient may last through the winter until the following spring or summer. Even in midwinter the evidences of the disease are still present on the tongue, hands, and gums, with weakness, emacia- tion, and neurasthenic cachexia. This rapid course of the disease is more common at the present time in America than in Italy, though I am convinced from a study of the literature that this cachectic type was also common in Italy about the close of the eighteenth century. This type is chronic pellagra, with the omis- sion of the stages of dyspepsia and neurasthenia, and with the early onset and rapid course of the stage of cachexia. CHRONIC PELLAGRA. Before one can understand pellagra he must have a general con- ception of the disease from its inception to its termination. It is a chronic disease, and, as time passes, the malady tends to progress. It is one thing to know pellagra at the acme of the spring attack, but it is another matter to comprehend the disease with its remis- sions and intermissions, its conglomeration of variations in season CLASSIFICATION. 95 and out of season, and the fact that, once firmly fixed in the system, the periodic attacks are vernal links in the chain of a steady pro- gression toward cachexia, insanity, and death. Jansen, of Leyden, in his monograph on pellagra written in 1787, accents this idea in his definition: "An endemic disease usually manifesting itself first in the spring by rose-colored spots on the back of the hands, disappearing in winter, but which almost always recurs the follow- ing year full of more serious symptoms- at length attended by melancholia, mania, and convulsions; with exceptions here and there, it causes death." Jansen wrote his work in Latin,, and his description of the disease, splendid as it is, was improved by the excellent translation made by Chevalier, which appeared in the Tiondon Medical Review and Magazine in May, 1799. Chevalier's comments and transla- tion constitute the first article in the English language on pellagra. This article takes into account the progressive element in chronic pellagra, and from it as a basis the different stages of the chronic form become apparent. I give Jansen 's delineation of the clinical course in full, for I have found nowhere else in the literature so classic a description. About the month of March or April, when the season invites the farmers to cultivate their fields, it often happens that a shining red spot suddenly arises on the back of the hand, resembling the common erysipelas, but without much itching or pain, or indeed any other particular inconvenience. Both men and women, boys and girls, are equally subject to it. Sometimes this spot affects both hands, without appearing on any other part of the body; not uncommonly it arises also on the shins, sometimes on the neck, and now and then, though very rarely, on the face. It is also sometimes seen on the breasts of women where they are not covered by the clothes, but such parts of the body as are not exposed to the air are seldom affected, nor has it ever been observed to attack the palm of the hand or the sole of the foot. This red spot elevates the skin a little, producing numerous small tubercles of different colors; the skin becomes dry and cracks, and the epidermis some- times assumes a fibrous appearance. At length it falls off in white furfu- raceous scales, but the shining redness underneath still continues, and in some instances remains through the following winter. In the meantime, except- ing this mere local affection, the health is not the least impaired; the patient performs all his rural labors as before, enjoys a good appetite, eats heartily, and digests well. The bowels are generally relaxed at the very commencement of the disease, and continue so throughout its whole course. All the other excretions are as usual, and in females the menses return at their accustomed periods and in the proper quantity. But what is most surprising is that in the month of September, when the 96 PELLAGRA. heat of summer is over — in some cases sooner, in others later — the disorder generally altogether disappears, and the skin resumes its natural, healthy appearance. This change has been known to take place as early as the latter end of May or June when it has been only in its earliest stage. The patients, however, are not now to be considered as well; the disease hides itself, but is not eradicated. For no sooner does the following spring return, but it quickly reappears and generally is accompanied with severer symptoms. The spot grows larger, the skin becomes more unequal and hard, with deeper cracks. The patient now begins to feel uneasiness in the head, becomes fearful, dull, less capable of labor, and much wearied with his usual exertions. He is exceedingly affected by the change in the atmosphere, and impatient both of cold and heat. Nevertheless, he generally gets through his ordinary labor, with less vigor and cheerfulness indeed than formerly, but still without being- obliged to take his bed; and he has no fever, his appetite continues good, and the chylopoietic viscera perforin their proper functions. When the pel- lagra has arrived even at this stage, the returning winter nevertheless com- monly restores the patient to apparent health ; but the more severe the symp- toms have been, and the deeper root the disease has taken, the more certainly does the return of spring reproduce it, with additional violence. Sometimes the disease in the skin disappears, but the other symptoms remain notwith- standing. The powers of both the mind and body now become daily more enfeebled; feverishness, watchings, vertigo, and at length complete melancholy super- vene. Nor is there a more distressing melancholy anywhere to be seen than takes place in this disease. On entering the hospital at Legnano I was aston- ished at the mournful spectacle I beheld, especially in the women's ward. There they all sat, indolent, languid, and with downcast looks, their eyes expressing distress, weeping without cause, and scarcely returning an answer when spoken to; so that a person would suppose himself to be among fools and mad people, and indeed with very good reason, for gradually this melan- choly increases and at length ends in real mania. Many, as I had opportunity of observing in this hospital, were covered with a peculiar and characteristic sweat, having a very offensive smell, which I know not how better to express than by comparing it to the smell of moldy bread. A person accustomed to see the disease would at once recognize it by this single symptom. Many complained of a burning pain at night in the soles of their feet, which often deprived them of sleep. Some are affected with double vision, others with dementia, others with visceral obstructions, others with additional symptoms. Nevertheless, fever still keeps off, the appetite is unimpaired, and the secre- tions are regularly carried on. But the disease goes on increasing, the nerves are more debilitated, the legs and thighs lose the power of motion, stupor or delirium comes on, and the melancholy terminates in confirmed mania. In the hospital at Legnano I saw both men and women in this maniacal state. Some lay quiet, others were raving and obliged to be tied down to the bed to prevent them from doing mischief to themselves or others. In almost all these the pulse was small, slow, and without any character of fever. One woman appeared to have a slight degree of furor uterinus, for at the sight of men she became CLASSIFICATION. 97 merry, smiled, offered kisses, and by her gestures desired them to come toward her. Some were occupied in constant prayers, some pleased them- selves with laughter, and others with other things. But it was remarkable, as Moscati observed, that all who were in this stage of the disease had a strong propensity to drown themselves. They now begin to grow emaciated, and the delirium is often followed by a species of tabes. A colliquative diar- rhea comes on, which no remedy can stop, as has also been observed in nos- talgia. Sometimes in pellagra the diarrhea comes on before the delirium, and the delirium and stupor mutually interchange with each other. The appetite often suddenly fails, so that the sick will sometimes go for nearly a week without tasting food. Not uncommonly it returns as suddenly, so that they eagerly devour whatever is offered them, and this even at times when they are horribly convulsed. The convulsions with which they are attacked are most shocking to see, and are of almost every kind; catalepsy is frequent, which has been described by writers. I saw one girl in bed who was violently distorted by opisthotonos every time she attempted to rise; some are seized with emprosthotonos, and others with other species of tetanus. At length syncope and death close the tragedy, often without any symptom of fever occurring throughout the whole course of the disease. STAGES OF CHRONIC PELLAGRA. The course of chronic pellagra can best be represented and under- stood by a diagram, with the dermatosis as the common basis, since it is common to all three stages and is the one objective symp- tom that connects the varying pictures of dyspepsia, neurasthenia, and cachexia. Dermatosis of Pellagra. Degree of initiation. 2. ; < 3. Degree of \ J Degree of confirmation. ( J desperation Stage of dyspepsia — Stage of neurasthenia — Stage of cachexia. The Dermatosis of Pellagra. (a) Dermatitis or erythema; (b) dermotagra or rough skin. Fig. 15. — Diagram showing stages of chronic pellagra with relation to clinical symptoms, The time of a single pellagrous attack was divided into period of onset, outbreak, and recession, while the course of chronic pella- 98 PELLAGRA. gra includes a far greater length of time divided into relatively long stages. Periods in the single attack are to be distinguished from stages in the chronic course ; the period refers to a short time and the stage to long duration, involving the idea of continuance. To a certain extent these stages are as abitrary in their separation and limitation as are the three periods in the recurrent single attack. Each stage in chronic pellagra consists of recurrent at- tacks of activity and times of intermission, or inactivity of the pellagrous advance. The node of the jointed reed represents the attack in the spring, and the internode the intermission between attacks. The internode is longer than the node, and the inter- mission longer than the attack. To carry the figure further, the ten-foot cane is divided into proximal, middle, and distal parts, each in turn formed of several nodes and internodes. Chronic pellagra is divided into degrees of initiation corresponding to the clinical stage of dyspepsia, the degree of confirmation correspond- ing to the clinical stage of neurasthenia, the degree of desperation corresponding to the clinical stage of cachexia, and each of these three degrees or stages consists of periodic attacks and interperiodic intermissions. To use Cabot's phrase, the presenting symptom in the initial stage is dyspepsia, the presenting symptom in the confirmed stage is neurasthenia, and the presenting symptom in the desperate con- dition of the late chronic pellagra is cachexia. These stages lap like shingles on a roof, and, while it is no great matter for the physician to tell which stage confronts him in the pellagrin, it is altogether difficult to know when and where one ends and the next stage begins. The fundamental idea in chronic pellagra is progres- sion, and these stages are epochs in this progress. It is natural that they should vary very much in time, but as a rule the duration decreases from first to last ; the dyspeptic stage may last for fifteen years, and then be short of its full development. A symptom that is temporary in one stage may become permanent in the next and of increasing intensity. Temporary neurasthenia often appears in the attack of the first stage, but permanent neuras- thenia is the marked symptom of the confirmed degree. Diarrhea is temporary in the dyspeptic time, longer in the neurasthenic stage, and practically continuous in the shorter cachectic forms. Emaciation presents itself in the attacks during the second stage, but there is usually a gain in weight in the intermission following ; CLASSIFICATION. 99 emaciation is, however, constant in the cachectic time and of dis- tressing permanency. In America these facts are not so evident because here the disease is as yet more strikingly temporary in time and severe in its aggregate symptoms, and therefore the pre- senting symptoms of the different stages and the evolution of a symptom through the course of the disease is less apparent. Never- theless, each stage of chronic pellagra is an aggregate of more or less well-defined symptoms, and the course of the disease progresses by the evolution and increasing intensity of these symptoms. The initial stage marks the beginning of the disease, and years may elapse before the disease gains appreciable foothold. Several years may elapse without an attack, and then suddenly a more severe attack develops, with the subsequent appearance of the neu- rasthenic stage. Indeed, the confirmed degree may be less serious than the initial degree, and the feebleness of the supposed on- coming cachexia never develop. Instead of progressive seriousness, there may occur a progressive lessening of the symptoms. The symptoms of the first and second stages may occur at the same time, and, as very frequently happens, the second and third stages seem to be identical. In this country the initial stage and simple dyspepsia in many cases fail to appear, and the first spring attack ushers the pellagrin into a state of confirmed neurasthenia. In older pellagrins one is often called upon to distinguish differ- ent diseases and their effects from a superimposed pellagra with its inroads, and, while the diagnosis of the different diseases may be easy, the relative effects are difficult. The following case illus- trates this: A white man, 58 years old, developed in 1909 a severe attack of articular rheumatism. He was in bed for three months and re- covered from the attack, but with hypertrophic arthritis in both ankles. He had been a farmer, but, on account of his feebleness, went to work in a cotton mill in a small town. In August of 1911 he developed a typical pellagra, with dyspepsia, dermatitis, but practically no dermotagra. I saw him in November, and, from his description of his pellagrous attack and present symptoms, I judged the attack was mild and initial in degree. He was a neurasthenic of a most confirmed type, his heart sounds were weak, and a blowing mitral alternated with a loud aortic regurgitant. He had evidently suffered with a late endocarditis of rheumatic origin from the weakness and evident roughness of all the valvular 100 PELLAGRA. sounds. Severe arteriosclerosis was present, and his urine showed hyalin and granular casts, with a large amount of indican. The evolution, in order, was probably arteriosclerosis, aortic insuffi- ciency, Brightism, rheumatism with chronic arthritis, endocarditis, and pellagra over it all. He looked as if cachexia was imminent, and yet the pellagrous attack was mild, and it would be impos- sible to state accurately the part pellagra played in causing his condition, or to what degree the pellagra had attained. According to him, this was the first attack, but earlier attacks may have been so slight that they were not noticed, or the lowered vitality fol- lowing rheumatism and endocarditis may have floated a latent pel- lagra. 1. Initial Degree — Stage of Dyspepsia. — Duration, from one to twenty years. It consists of one or two attacks in the year ; usually the spring attack is persistent, and the autumn attack is not con- stant. With two yearly attacks, the progress of the disease is faster, and the duration of this stage shorter. The attack has been described, but in this stage it tends to be mild, and may last but a week, and averages from four to six weeks. It may be so mild as to pass unnoticed, and this may occur several years in succession before it is severe enough to arouse the suspicion of the patient. The dermatitis in the first few years may be con- sidered a sunburn, especially in those cases in which the general health is unimpaired, and the usual work and play are not inter- fered with. The appetite is good, except in the height of the at- tack in the marked cases. In the majority of pellagrins the bowels tend to relaxation, more during the attack and less in the inter- mission, but constipation occurs, and often the bowels may be normal throughout the early part of this state. Dyspepsia, bulimia, gas in the intestines, are usually present at various times, and especially during the beginning of the spring attack. The dys- pepsia is apt to be more noticed than the dermatitis. Belching occurs, the pellagra tongue as heretofore described, occasional abdominal pain, and perhaps weakness and vertigo, especially in the attack. After the attack and during the fall and winter the skin is frequently apparently normal, and often one is unable, except on very close observation, to note any evidence that the dermatitis has ever been present. At times, and more frequently after several attacks, the dermatitis area is slightly darker and more pigmented than normal, and the elbows a little rough. CLASSIFICATION. 101 Weight may continue as usual, with the loss of a few pounds during the annual attack, which, however, is quickly regained. During the summer, fall, and winter, with the absence of the au- tumnal recurrence, health and spirits are good, and the spring malaise considered natural and to be expected as peculiar to the patient's constitution. At one time of the year the patient feels bad, but he may think this is due to spring and not to disease. Toward the close of this stage, in America from three to five years as a rule, symptoms of neurasthenia begin to creep in, less work is done, headache comes, the spirits lack buoyancy, and the walk is not so rapid and elastic. Mental activity lessens, and the mild malady of the first stage begins to be succeeded by the more con- firmed degree of the neurasthenic time. 2. Confirmed Degree — Stage of Neurasthenia. — Duration, from one to ten years ; in America usually less than five years. The attacks of this stage differ from those of the dyspeptic stage, in degree rather than in quality, and in the aggravation of the symptoms of the first rather than the introduction of new symp- toms. The attacks are certainly more severe, last longer, recovery from them is slower, and their permanent results strike deeper into the mental and physical strength. In the language of Mayr in Hebra's Treatise, "the fresh symptoms which now present themselves do not concern the eruption, but rather indicate the progress of the internal malady." The cutaneous involvement pursues a beaten track throughout the course of chronic pellagra, while the new symptoms refer to the greater involvement of the nervous system and the appearance of symptoms which are signs of this new and more serious turn of the disease. Here one is tempted to ask what part of the new symptoms is due to organic changes in the nervous system and what part to the aggravation of the condition of the alimentary tract and the resulting effect on the general nutrition. The great difference in the two stages is not in the attacks in the spring or fall, but in the marked differ- ence in the pellagrin between the attacks. In the intermission of the dyspeptic stage he is apparently and practically well; in the second stage he is a confirmed neurasthenic all the time, and his normal metabolism begins to waver. The attack is more severe, and in the intermission he is more feeble. Loss of flesh is permanent, the forehead becomes wrinkled, the senile face is in evidence, the body is bent, and the walk is aged; 102 PELLAGRA. he leans on a stick; at times he staggers and his legs are drank. "Weakness of the muscles is evident, fatigue comes after little exer- tion, and between attacks the condition of the pellagrin reminds one of Beard's description of a neurasthenic in his "Nervous Ex- haustion:" "Unwonted and unaccustomed muscular exercise is especially irksome to neurasthenic sufferers. They can do very well in an ordinary routine, but stepping out of this routine, and attempting something new to them, they quickly become wearied. The very narrow margin of muscular force is soon exhausted. This applies to both nervous and muscular exhaustion." Later in this stage develop tremor, cramps, contractures, cataleptic and epileptic states, tetanic movements, tendencies to fall in all direc- tions, uncertainty in all things. The tongue in the attacks is more inflamed, stomatitis more se- vere, even for a few days it may interfere with swallowing ; nausea, pyrosia, intense bulimia, real gastralgia, recurrent epigastric pain that brings the gastric crises of tabes to mind ; drooling saliva during the attack and occasionally during the intermission; in- creased number of stools during the attack, with a moldy odor; abdominal distention increased after eating, voracious appetite or refusal of food; a diarrhea that alternates with a constipation, or that continues intermittently, or even persistent constipation, tenesmus, gastritis, enteritis, and rectitis that vary in severity and in persistency. Both Strambio and Roussel considered the sudden attacks of diarrhea or vomiting that occur at this stage to be due to spasmodic phenomena arising from the nervous system. The pulse is more rapid, running often in the intermissions from 80 to 100; dyspnea may develop, and occasionally slight dropsy, though these are not common in America. The reflexes are usually permanently exaggerated, vertigo, headache, heavy-headed- ness, drawing feelings in the back of the neck, pain in the back to one or the other side of the dorsal spine, and all or any of these absent at times ; and, like a neurasthenic, a sense of well-being and health alternates with nerve exhaustion and all the symptoms of the nervous dyspeptic. The mind loses its cunning ; no more is it the active human mind. Little tasks become like mountains, and the pellagrin is more content to sit and rest than to walk and work. Like Napoleon in his last days, he prefers rest to all the thrones of Europe. CLASSIFICATION. 103 The hand is now no longer a normal hand. Even in the inter- missions its back is pigmented, the wrists are dark with a brownish- red color, and occasionally it has rounded to the front; the elbows are rough and the skin over them becomes thick; the knees are rough likewise, and even the feet and shins are sometimes darker than normal. Areas of dermatosis of the face or neck are now unusually dry and branny, and one often involuntarily thinks of dry, scaly eczema. The finger and toe tips seem pink and clean; the face rather reddish like a faint blush, or of a darker bronze like that of a bronzed diabetic. One man had this red hue over his back and between the anal folds. The hands, legs, and feet burn at times to despair, itching may alternate with burning, and the physician is asked to ' ' give a remedy that will stop this burning and let me sleep." The skin over the hands cracks, and is loose and wrinkled like the senile skin. The recurrent dermatitis has left an old man's hand. The urine is usually acid; the specific gravity may be normal, but is often lowered, and, according to Procopiu, gives in some cases the diazo reaction. The amount of urine is increased, with occasional traces of albuminuria and a few casts. Sight begins to fail, and reading is troublesome to the eyes and burdensome to the mind. The neurasthenic is naturally a sad person, and de- spondency, fear of water or attraction to it, desire to suicide, days of melancholia and despair, mark the wane of the mind, oncoming cachexia, and insanity. 3. Degree of Desperation — Stage of Cachexia. — Duration, from one to five years, usually short. Dermatosis and dyspepsia char- acterize the initial time; dermatosis, indigestion, neurasthenia, and feebleness the confirmed time, and all these, with prostration, cachexia, and insanity added, occur in the degree of desperation. Death may occur early, or insanity develop and the pellagrin, with his pellagrous insanity and some cachectic symptoms, live many years. It is well to understand that pellagrous insanity may occur in the neurasthenic stage as well as in the last stage. Insanity in pellagra may come at any time. To walk through any asylum for the insane in the southern states and see the pel- lagrins is ample proof of this. At Mombello, in Italy, I saw two pellagrins with manic-depressive insanity, who weighed probably 160 pounds each, were well and strong physically, and yet whose minds were gone in the initial stage. Dr. Green showed me at the 104 PELLAGRA. Georgia asylum a negro of this type, who looked well nourished enough to do a day's work. Invalidism is the rule here. Paralysis, paraplegia, and hemi- plegia occur, though anesthetic areas are rare. Ankle clonus and the Babinski reflex may be present, and absence or presence of knee jerks. The delirium and diarrhea may alternate. Diarrhea may become blood-streaked, mucus is found in the stools, and a serous diarrhea, unyielding to any treatment, end in death. The hands are exceedingly thin, petechias may occur, and discolored spots as if the flesh had been bruised; the muscles atrophy and the subcutaneous fat is gone. Bed sores may develop, there is incontinence of feces and urine, and the gradual onset of acute terminal pellagra, with high fever and death. The discussion of pellagrous insanity will be found in the chapter on "Nervous System," page 171. PELLAGRA SINE EXANTHEMATA. I have in this month seen the patient described as Case 1, on page 18. The skin symptoms were absent, and only a long expe- rience with pellagrins would permit one to suspect a past pellagrous dermatosis. The pellagra tongue was present and occasional diar- rhea, Strambio believed that the skin symptoms could be absent during the entire course of chronic pellagra, including even in the spring attack, and to this condition Strambio gave the name of pellagra sine pellagra. He applied this phrase to the permanent absence of skin symptoms in pellagra, and not to the temporary absence during the annual intermission following the annual at- tack. Girelli, of Brescia, cited a case with violent pellagrous symptoms of twenty years' standing and no dermatosis. Roussel cites two cases. The phrase is misleading, and, literally translated, is "pellagra without pellagra." I have substituted for this a plainer phrase, and one that means just what it is intended to mean — pellagra sine exanthemata, or pellagra without the exanthem. Strambio 's phrase means pellagra without pellagra, whereas he meant that a marked pellagra does exist, but no skin involvement. It is prob- able that this condition does exist, but that it is very rare. The exanthem is coincident with the attack, as the erythema of scarlet fever is coincident with its attack; the pellagrous exanthem marks CLASSIFICATION. 105 the exacerbation time of pellagra, and in this time it can certainly be absent and the internal malady be present. It is probable that a more careful study of the skin will show a pellagrous dermotagra in these cases, with absence of the dermatitis. A sharp distinc- tion is to be drawn between these, for in the past the attention has been focused nearly altogether on the dermatitis. I have under observation at this time a female pellagrin who, I know, has pel- lagra, and yet there has never been a dermatitis, but a noticeable dermotagra exists in the region of the elbows, on the flexor sur- face of the forearm, and at variable times on the back of the hands. When her tongue and diarrhea grow worse, the dermo- tagra increases. Harris describes three cases of pellagra sine ex- anthemata in the American Journal of the Medical Sciences for May, 1911. One should be very careful, and hesitate a long time before he makes a diagnosis of this form. I would prefer to ob- serve such a patient several months before reaching a conclusion in my own mind. In the meantime treatment for pellagra could be instituted if the pellagrous evidence was weighty. PSEUDO-PELLAGRA. It was an unfortunate day when Roussel applied the term pseudo-pellagra to pellagra. There is no pseudo-pellagra. Real pellagra is hard enough for a patient to suffer and for the phy- sician to treat, and the use of pseudo in regard to the disease is unwise. A disease is either pellagra or it is not pellagra, and there is no middle ground. Pseudo-pellagra is not pellagra; it i> some other disease. Pellagra is pellagra, and there is nothing false about it. Roussel applied the term more in derision of imagined and arbitrarily constructed groups of symptoms, which he called unites factices, in patients not pellagrous. Billod believed in pseudo-pellagra, and executed many marked diagnostic flounders ; Hardy confused pellagra and alcoholism; sporadic pellagra was unexplained and called pseudo-pellagra ; pellagrins who had never eaten corn in any form, but who had pellagra, were called pseudo- pellagrins. Because a confirmed alcoholic has a few nerve or di- gestive symptoms that pellagrins have is no reason to call him a pseudo-pellagrin. "When pellagra invades a country for the first time, inexperience on the part of some and fear on the part of others inclines to confusion in a few cases as to just what does 106 PELLAGRA. constitute the pellagrous syndrome, and occasionally the diagnosis of pellagra is made without evidence and incorrectly. Referring to these conditions in France and the different maladies called pellagra and pseudo-pellagra, De Jeanne wrote: " These are mala- dies differing widely among themselves, and all of them differing widely from endemic pellagra, not only in the etiology, but also in the nature and concatenation of the symptoms." CHAPTER IV. THE ALIMENTARY TRACT IN PELLAGRA. In Edmond About 's novel, "Maitre Pierre," whose scenes are laid in the Landes in France, and which was published in 1844, the heroine says of pellagra: "It commences in the stomach and soon reaches the surface like a noxious weed which nourishes rankly everywhere." When the cause of pellagra is fully known, the reason for the extensive involvement of the gastrointestinal tract will become evident. As a rule, the symptoms that arise here are the earliest, the most persistent, and the most dangerous of all the pellagrous symptoms ; and of these pellagrous symptoms, diar- rhea holds the red flag, and reminds one of Lauder Brunton's statement that "diarrhea destroys more lives than any other dis- ease." The two great causes of gastrointestinal irritation are (1) those which concern the food and (2) those which concern the organism, and in the latter class pellagra is found. I am disposed to believe that for some reason the gastrointestinal tract should blame the nervous system for much of its condition in pellagra. Goodhart, quoted by Allbutt, writes : " It is no great exaggeration to say that there are only two forms of indigestion — that produced by overeating and drinking, and that due to a failure of the nervous power." The nervous power fails, and the gastrointes- tinal condition keeps pace with this failure.. These symptoms involve the oral cavity — always the tongue, the pharynx, the esophagus, the stomach, the large and small intestines, the salivary glands, the liver, pancreas, and spleen. There are organic and functional changes, and both to a marked degree. Stomatitis, ptyalism, glossitis, pharyngitis, esophagitis, gastritis and dyspepsia, enteritis and ulceration are in one sense the different and separate diseases whose union with variations present the ex- tensive pathology of the digestive system. With a few slight changes, Lauder Brunton's description of dyspepsia applies to the mass of symptoms of indigestion in pellagra : i l Briefly, the symp- toms of dyspepsia are a furred tongue, a bad taste in the mouth, 107 108 PELLAGRA. want of appetite or even loathing of food, vomiting, oppression in the chest, weight at the epigastrium, pain, distention, flatulence, acidity, eructations, pyrosis, constipation or diarrhea." THE TONGUE. The condition of the tongue is the most constant and most im- portant diagnostic symptom furnished by the digestive system. During the onset of the attack it is furred and coated, and the patient has occasional anorexia and bad breath. As the outbreak occurs, the lingual epithelium is lost, the tongue becomes red, is slightly swollen, and the tip and anterior lateral margins are first affected and then the back. Irregular fissures form in the middle and on the lateral margins; these sometimes cross the tongue and descend the sides like the outline of a cross section of an empty shoe box turned upside down. This stage is a dissecting glossitis. The true pellagra tongue is a tongue without a coat, the beet tongue — the "bald" tongue of Sandwith. Aphthous ulcers may develop on the tip and margins, and their rawness causes pain in eating. As the attack recedes, the tongue for a long period may present a few red papillae scattered over the tip, and the epithelium may never return with its characteristic thickness. This redness of the tongue is due to inflammation, and for a time after the attack the tongue may present a paleness due to anemia. This pallor is out of all proportion to the previous red- ness and fissured condition. The tongue improves as the attack recedes and inflames as the attack approaches, reaching the greatest inflammation at the acme of the outbreak. In the severe cases it is often tremulous, usually thick and beefy, and occasionally pointed. Occasionally the papillae may be dark at their tips, due probably to swelling with cyanosis. Sandwith 's 163 cases had tip and edges naked and red in one-half the number, one-fourth com- pletely denuded of epithelium, and only 5 had a coated tongue; 37 were normal except for anemic pallor. Of 121 patients with tongue either completely or partially denuded on leaving hospital, 45 returned as normal, and 38 remained partially denuded. As a rule, during the onset the tongue is coated, then gradually loses its coat, and the papillae at tip appear red and prominent; during the outbreak the tongue is red, fissured, and its coat gradually reappears as the attack recedes. During the periods of interims- ALIMENTARY TRACT IN PELLAGRA. 109 sion the tongue may be strangely clean, unless one thinks of pel- lagra. It is well to remember that after surgical procedures in septic cases the tongue may be naked, red, and swollen, with ac- companying stomatitis; and in uremia the tip of the tongue may be similar to the pellagrous tongue. Acute alcoholism presents the inflamed tip, prominent papilhe, and tender margins. GUMS, TEETH, BUCCAL MUCOSA, PALATE. Between attacks the gums are usually normal, but during the outbreak the gums are inflamed in common with the rest of the oral mucosa. They are tender, often spongy and easy to bleed, as in scurvy; around the lower incisors this condition is most noticeable. The teeth are not affected, and in one series out of 166 pellagrins 120 had sound teeth. Pellagrins usually can mas- ticate well, and with them the teeth do not in any way influence the gastrointestinal condition. The poison arises within in pel- lagra. Between the attacks, except in the subchronic cachectic form where there is no real intermission, the buccal mucosa is usually normal. During the outbreak stomatitis is present, and reaches its acme at the culmination of the dermatitis and the glossitis. At this time the outer border of the lips are dry, and, in the severe cases, of a cyanotic hue ; the inner border of the lips and cheeks are red, tender, raw, and swollen, and this inflammation extends over the buccal mucosa to such an extent that eating and swallowing are difficult, and even weak acid drinks are so painful and burning that they can not be taken. Occasionally Stenson's duct opens into a pit, instead of on the surface, on account of the swollen mucosa. Aphthous ulcers are common, and occasionally small blisters arise on the inside of the cheeks, which, when burst, leave the membrane dead and pale. These small bulla? are espe- cially noticeable as the period of recession begins. At this time the mucosa exfoliates, and is thrown off in macerated strands. In the very mild attacks the mucosa is only red and may be tender for a few days, but it lacks the velvety rawness of the severe forms. The latter half of the palate, including the uvula, the anterior and posterior pillars of the fauces, may be either red in the lighter attacks, inflamed on the anterior pillars, with scattered pin-point 110 PELLAGRA. areas in the more severe attacks, and entirely raw, very red, and even ulcerated on the anterior pillars in the severe forms. The uvula may become edematous, sag, and add to the general pharyn- geal discomfort. Posteriorly the inflammation is neither as severe nor as uniform as anteriorly in the region of the labial frenum. Evidences of the oncoming stomatitis are first found anteriorly around the frenum, and it persists longer there. The actual stomatitis does not last longer than two weeks as a rule, and may cause inconvenience for only two or three days. As the attack recedes, the increased saliva decreases, the edema departs, the epithelial coverings regenerate, and the mouth feels and appears normal. SALIVARY GLANDS. Ptyalism is a variable symptom, depending on the degree of stomatitis present, and on an unknown factor in that a few cases present during the attack an almost continuous drooling of saliva from the mouth and an increased expectoration in the intermis- sions. One old lady of 60 years had a constant flow of saliva for three weeks, and then, when up and feeling well, stomatitis gone, she would have to spit about every fifteen minutes during her waking hours. Just why this extraordinary symptom should con- tinue I do not know. The increase synchronous with the stomatitis is primarily a reflex stimulation of the salivary and mucous glands, but it is also influenced by the hyperemia, degeneration, and in- flammation of the buccal mucosa. There is another factor than the stomatitis, because many pellagrins with severe stomatitis have only a small temporary increase in the saliva. There is present in these cases an abnormal chemical reaction of some kind, as proved by the fact that the saliva may be acid instead of alkaline. Taste may be disagreeable, and even salty or briny, giving rise to the Italian synonym of pellagra salso and umor salso, or salti- ness and salty phlegm. I saw one patient who had a drooling saliva for more than a month, and who died from exhaustion. Swint and Echols at Milledgeville showed me two female pellagrins, insane, dementia precox type, who were up and walking around with a constant production of thick, ropy strands of saliva flowing to such an extent that their garments were wet all the time. It has seemed that in those cases where the saliva was markedly in- ALIMENTARY TRACT IX PELLAGRA. Ill creased the diarrhea was less, and with decreased saliva there was an increase in the severity of the diarrhea. It seems that the body in pellagra is trying to get rid of something, and either diarrhea or salivation may remove it. Sandwith fonnd 6 out of 151 cases with a bilateral enlargement of the parotid gland. It occurs in children with the bald tongne, and dermatosis on face, ears, and neck. The parotitis is painless, and, like mumps, does not proceed to suppuration. "With the dermatitis at its height on the hands, the epitrochlear glands may become enlarged; and with the cutaneous involvement on the face and neck, through the lymphatics, the parotid gland may similarly enlarge. Certainly a far different process is present, because in mumps there is a tendency to a decrease in the saliva. The pel- lagrous saliva, increased in amount, is deficient in solids, and con- tains microscopically enormous numbers of enlarged flat epithelial cells, with debris from the tongue, teeth, and buccal mucosa. The parotid gland in the sheep secretes saliva continually, and a similar ability is certainly present in a few pellagrins, leading to the belief that the pellagrous toxin must influence the salivary center in the medulla, as all three pairs of salivary glands are affected. PHARYNGITIS AND ESOPHAGITIS. Inflammation of the pharnyx and esophagus is simply a con- tinuation of the pellagrous process. As the stomatitis grows worse, the sensation of rawness in the throat and esophagus increases, and also the pain in swallowing. I have seen a female pellagrin at- tempt to drink an orange albumen and complain that "it burns all the way down." The esophagitis can not be caused by the condition of the gastric juice, because the acidity is decreased and gastric regurgitation would therefore play no part. The throat and esophagus grow worse as the stomatitis increases, and better as the stomatitis improves. These symptoms exist only during the attack, and cause inconvenience chiefly during the period of outbreak. During recession, regeneration and healing of the mucosa is rapid. STOMACH AND INTESTINES. In these organs arise such symptoms as gastralgia, epigastric pain, bulimia, nausea, vomiting, gaseous distention, diarrhea, en- 112 PELLAGRA. teritis, colitis, and rectitis. Burning in the stomach or pyrosis is a variable symptom, present chiefly during the period of outbreak. Nausea is common and actual vomiting absent in the milder cases ; during severe attacks vomiting is a common symptom. The pel- lagrin sums up his gastrointestinal symptoms as sore mouth, in- digestion, and diarrhea. Of these indigestion, lack of appetite, coated tongue appear first, next the diarrhea, and lastly the sore mouth. Even with those patients who say that the dermatosis is first, careful and patient questioning will reveal a week or a few days of heaviness in the stomach, gas, belching, occasional nausea, and that disease known far and wide as "biliousness" may have preceded the dermatitis. J. Clarence Johnson, in his 1911 paper before the American Gastroenterological Association, pre- sents the analysis of 20 cases and relates the analyses of the stomach contents, the position of the stomach, the diarrhea, to each other and more general symptoms. This table (page 113) adds much new information to the condition of the stomach and intestines in pellagra, and on the relation between the secretion of hydrochloric acid and the diarrhea. Summarizing the important details of this valuable table, the stomach was normal in position in 11 cases, ptosis present in 4, and atony in 5 ; nausea was present in 15, vomiting in 7, indi- cating a common experience that vomiting is rather the exception and present only during the severe cases, or during the acme of the outbreak. I have never seen it except in bed-ridden pella- grins, and in fatal cases the vomiting is often an accompaniment of the diarrhea. Only 3 of the 20 cases failed to have pain in the stomach, the gastralgia so accented by Procopiu and Triller. The three sensory gastric symptoms in pellagra are pyrosis or burning, gastralgia or a real gastric hurt, and bulimia or the hungerache. The pyrosis is rather the most chronic symptom of the three, often preceding the other gastric symptoms and per- sisting during the winter when the others have disappeared. These burning pains are probably referred pains, having a common cause of origin with the well-known fiery sensations in the hands and feet. I can not believe that they arise in the stomach from any gastric condition, but are rather due to cord involvement and impulses reflected through the sympathetic ganglia. The gastralgia may arise without known cause, persist for a few days, and disappear. It is rather more chronic than the ALIMENTARY TRACT IN PELLAGRA. 113 PS o < w Ph Q S o H fa o Mouth and hands Palms of hands Face and hands Face, hands, mouth Hands and mouth Hands Hands, arms, legs Face and hands Hands, arms Hands Hands, arms, face, mouth, body Hands, wrist, mouth Hands, arm, mouth Hands, wrists Hands, mouth Hands, mouth Hands, mouth Hands, mouth Hands, arms, mouth Hands U0pBUIUIBX9 [1309^ •AVig^uasA'p puB Bgqjj'BTp A^uipjo ut punoj ^on Suiq}0^[ li39ui ^saj, 00 » .2 >> .2 .2 >> ^ >> .2 psgdripip(dg2g22gdgggg3g, 0Q % s 1 § | § g | 1 1 g (j rt .S .h .3 .h O .3 S H (S S eS S S H r^)c3 .h >h h fi S S S ^ cS h ,8 r h - h h O rj •£ uopBjUQ; MM • M M • . M* M • • m' M «2 aa ^a^^^^aaa^-^^aa a ;>» A\io}siq snoiAajd Neg. Neg. Indig'n Neg. Indig'n Indig'n Neg. Indig'n Neg. Rheum. Indig'n Diarrh. Diarrh. Indig'n Indig'n T. B. Neg. Indig'n uoi^ednooo Farmer Housewife Merchant Farmer Lawyer Housewife Minister Housewife Housewife Teacher Merchant Housewife Salesman Housewife Housewife None Housewife Housewife Merchant Housewife X9g aSy 1 ^NOlOOlOWCONDONHTlit-NgCOl-N 1 eiOMTfCOWOTtiWWWMlOMBMNW^ia | HOMTfiflot'OOfflOHNw^ioe^cgoS o PM bfl ^H •« OS ESH X! N c fl p) O rt 3 rt o O m en *a ■ ■■■■-, 1 i ■•-'. " &&3Pt*m^ --'^^"•'■fl. 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 centers? 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 Grurd 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 f acies 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 cases 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 case 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: Bravetta.) hematoxylin orange. (By Dr. 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 calls "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, bullae, 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." In 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.' 7 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 Pig. 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. 5.) 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: Dermatosis of pellagra- dimorphous. 1. Dermatitis, or in- flamed skin. 2. Dermotagra, or rough skin. "a. Erythema, maculo- papular. <; b. Erythema, vesicles and bullse. c. Fissures. a. Eczematoid. b. Keratoid. c. Follicular. 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 bullae 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 / 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. Bravetta.) (Courtesy of Dr. 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 bullae "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- Fig. 22. — Pellagrous dermatitis ; dry form, with exfoliation of the skin. Dr. Bravetta.) (Courtesy of dermis is elevated, serum quickly exudes, and a common blister 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 bullae, 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. Either 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 rotheln 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, lagra Report of the Tennessee State Board of Health.) (From Pel- 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 bullae 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 lamellae 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 IX 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 cases 44 in which the dermatosis began on the back of the hands and forearms; in 7 on the back of the hands, forehead, and alae 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 scapulae, 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 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. Sand with 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. 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, 135 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, bullae, 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 typical dermatitis, showing the feet during an attack. (Courtesy of Dr. Bravetta.) 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 bulla?, 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 3, 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 scapula?, over the sacrum or coccyx, and it may be intense around the anus and in the perineal region. It may cause insomnia, and 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 Fig. 32. — A close view of the rough skin in pellagra, showing areas of exfoliation, swollen and edematous. (Courtesy of Dr. Bravetta.) Hand 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. Bravetta.) (Courtesy of Dr. 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. - , ■' *.«* *• t 4* 1 i 1 i 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 Fig. 37. — Cells from the spinal cord, showing partial thickening and contraction of the neuro-fibrils. Method of Cajal. (By Or. Bravetta.) and the spinal ganglia are affected to a degree. A tabular sum- mary follows : 1. Tracts. — The tracts of Goll and Burdach show degeneration and a profuse proliferation. These tracts are pale compared with the rest of the cord. Occasionally degenerate roots entering in lumbar region can be traced up into the dorsal region. There may be degeneration of the posterior roots and an increase in the con- nective tissue around these roots, with occasional thickening of the arteries. The degenerate areas in stained preparations show like small spots of ink spattered all over the posterior column. 2. Direct Pyramidal Tract. — There is more or less degeneration 146 PELLAGRA. and scattered areas from which the nerve fibers have disappeared. Occasionally swollen axis cylinders are fonnd. (Spiller.) 3. Gray Matter.-^-There is pigmentation of the cells of the anterior and posterior horns. The recticulum of many of the cells is clearly evident, and the fibrils appear contracted and the cell smaller. The degeneration in the cells of the posterior horns ap- pear degenerated from the cervical region downward, and espe- cially are the cells in Clarke's column affected. Spiller found cells in the anterior horn in the lumbar region degenerate, the cell body swollen, the nucleus displaced to the periphery, dendrites gone, and Fig. 38. — Cell from spinal ganglion. Pigmentary degeneration. Method of Cajal. (By Dr. Bravetta.) intense chromatolysis. Bravetta, of Mombello, showed me slides with an increase in the neuroglia elements, and others with sclerosed and isolated masses of gray matter, indicating the chronic nature of the process in the cord. Bravetta showed pigmentation and degeneration in cells in the spinal ganglion. Spiller found the capsules of the cells in the ganglia in the lumbar region showed much proliferation of the lining cells, and, like Bravetta, the nerve cells presented a marked degeneration. The Nissl granules also disappear in some of the cells of the medulla, and there occurs in such cells a yellow pigmentation. (Bravetta.) Pigmentation, NERVOUS SYSTEM IN PELLAGRA. 147 swelling of the body of the cell, disappearance of the dendrites, chromatolysis, and displacement of the nucleus peripherally sum- marize the changes in the gray matter. Dejerine reported a case with degeneration in the nerves on the back cf the hand, but the patient was a chronic alcoholic instead of a pellagrin. In general, it may be stated that the peripheral nerves are normal, Bravetta in all his researches found the nerve fibers Fig. 39. — Chromatolysis and pigmentary degeneration in cells of the cord. Method of Nissl. (By Dr. Bravetta.) WW* ^ > Fig. 40. — Same cr.se as shown in Fig. 39. Chromatolysis and pigmentary degeneration in ceils of the cord. Method of Nissl. (By Dr. Bravetta.) intact. Spiller studied the sciatic nerve and found the nerve fibers normal, but the connective tissue of the nerve and the intima of the vessels were proliferated. Whatever sensory changes exist in pellagra find their cause in the spinal ganglia and the cord, and not in the nerves, as in an ordinary neuritis. The process in the cord is chronic. The Marchi method often shows in the posterior column sclerosis, but no degeneration. Six out of eight of Tuc- 148 PELLAGRA. zek 7 s cases showed the sclerosis chiefly in the dorsal region, and this may account for the pain in the back so often complained of by pellagrins. The chief anatomical lesions in the cord are the degenerations in the posterior column and in the direct pyramidal Pig. 41. — Cells from the cord, showing yellow pigmentation and degeneration. Method of Donaggio. (By Dr. Bravetta.) Fig. 42. — Same case as shown in Fig. 41. Cells from the cord, showing yellow pigmen- tation and degeneration. Method of Donaggio. (By Dr. Bravetta.) tract in the lateral column. This distribution of degenerative changes resembles ataxic paraplegia, but in the latter the cellular changes in the horns and the menin go-myelitis is absent. The tissue changes in the cord are important, viewed both from their relation to clinical symptoms and to the ultimate cause of NERVOUS SYSTEM IN PELLAGRA, 149 pellagra. Mayr in Hebra *s work says : ' ' The science of patholog- ical anatomy has as yet contributed nothing toward the explana- tion of this mysterious malady." Spiller has commented on this point more fully than any other authority in nerve pathology, and it is well to note carefully his conclusions. "It is evident from the brief abstracts of the foreign repre- sentative papers treating of the pathology of pellagra that there Fig. 43. — Spinal cord. The cellular body is entirely invaded by vellow globular pig- ment, and passed through by few thin fibrils, which form a net. Neurofibrillar method by Donaggio. (By Dr. Bravetta.) Fig. 44. — Spinal cord. The cell is partially invaded by yellow globular pigment. De- generation of the nucleolus, perinuclear membrane, and long fibrils. Xeuro-fibrillar method by Donaggio. (By Dr. Bravetta.) is a difference of opinion in regard to the systemic or nonsystemic appearance of the degeneration in the spinal cord. This is a mat- ter of some importance, as a toxic degeneration is more likely to be nonsystemic. In the two cases I have studied the degeneration was diffuse. Indeed, from my own experience I have come to be- lieve that, with the exception of Friedrich's ataxia, there are few disorders causing a truly combined systemic disease of the spinal cord. The degeneration observed in anemia is not systemic, but 150 PELLAGRA, NERVOUS SYSTEM IN PELLAGRA. 151 in the cases I have studied (quite a large number) it has invariably been a diffuse process. It is more intense than I have observed in pellagra, but not of an essentially different character. The nerve cells, however, are much more affected in pellagra than in anemia. "Writers seem to agree as to the pronounced degenerative changes in the cells of the anterior horns of the spinal cord and of the cortex of the cerebral hemispheres in pellagra. It appears from the first case reported in our paper that the moderate degeneration of the pyramidal tracts predominate clinically over the apparently more intense alteration of the cells of the anterior horns, so that exaggeration of the patellar reflexes was present. Fig. 47. — Spinal cord. Pigmentary granular degeneration. Method of Cajal. (By Dr. Bravetta.) "The view has been expressed (Long) that the thickening of bone about the intervertebral foramina, possibly more in the cervical region, may be a cause of the symptoms. Unfortunately, only the extreme lower part of the cord in the cervical region in case 1 was obtained, but posterior and anterior roots from this region, cut separately, show no distinct degeneration, even by the Marchi stain. Had these roots been implicated in the intervertebral thickening, degeneration would have been detected in them. I have found no indication of root degeneration in the thoracic or lumbo-sacral region, and the alteration of the posterior columns, at least below the eighth cervical segment, is clearly en- dogenous, as it is also m the piece of thoracic cord obtained in the second case. 152 PELLAGRA. "I must conclude, so far as a study of these two cases permits, that pellagra does not always produce — if, indeed, it ever does pro- duce — a truly systemic disease of the central nervous system, but that the degeneration is caused by some toxic or infectious sub- stance affecting all parts of the cerebrospinal axis, producing cellular degeneration and diffuse degeneration of nerve fibers in Fig. 48. — Spinal ganglia ; outlines irregular, net. Method of Cajal. Invasion of the special net or Marinesco's (By Dr. Bravetta.) the posterior and antero-lateral columns. It is not difficult to ex- plain the mental symptoms when cortical degeneration is so intense as may occur in pellagra, and as is seen in the brain I have studied ; and the insanity in this disease seems to be of a toxic or infectious character. ' ' RELATION OF CORD LESIONS AND CLINICAL SYMPTOMS. The most striking summary of these changes is given in Hyde's article on Dr. Bassoe's work. I have used this classification as a working basis in pellagra cases, and find it admirable. There are three types of cord lesions, considered clinically and related to the cord tracts chiefly affected. I give Hyde 's account : (a) Probable Pyramidal Tract Degeneration — Case 1. — Demented male epi- leptic, aged 37 years, admitted April, 1902, previously at a poor farm and another state hospital. Insane for nineteen years. Diarrhea and erythema of the hands during the past summer. The hospital record mentions in- creased tendon reflexes and positive Babinski sign on August 31, 1909. Ex- amination on October 10th revealed increase of all tendon reflexes without NERVOUS SYSTEM IN PELLAGRA. 153 clonus; inconstant Babinski and Oppenheim signs; pupils react to light. There is a slight swaying in Romberg's position, but the patient walks well and the heel-knee test is as good as can be expected in a demented subject. A note was made on October 31st that he had had stomatitis and diarrhea for several weeks, and lost forty pounds in weight. Fig. 49. — Spinal cord. Thickening and concentration of the neuro-fibrillar net. Nucleo- lus enlarged and irregular. Method of Cajal. (By Dr. Bravetta.) (b) Posterior Column Degeneration — Case 2. — An elderly demented woman developed characteristic skin lesions in August, 1909. Ataxia is so marked that she can not walk or stand alone. The wrist, elbow, knee, and ankle reflexes are lost. No Babinski sign. Xo involuntaries. Pupils normal. Characteristic erythema of the hands and face when examined on October 10th. (c) Combined Degeneration — Case 3. — A woman, aged 50 years, was ad- mitted in November, 1908, with a history of having been insane for fourteen months. On admission she was fairly well nourished and the tendon reflexes 154 PELLAGRA. were normal. The psychosis was melancholia of involution. On August 27th the wrist and elbow reflexes were recorded as normal; the knee reflexes as increased. No Babinski sign at that time. On October 10th she was ema- ciated, with severe stomatitis and diarrhea. The wrist jerks and the left elbow jerks were absent; the right elbow jerk, weak. Knee and ankle jerks absent. Inconstant Babinski sign on the right side; normal flexor response on the left side. The pupils react rather sluggishly to light. She died on the following day. No necropsy. It seems probable that the pyramidal tracts were first involved, causing increased knee reflexes. Later, the posterior col- umns degenerated sufficiently to abolish nearly all of the tendon reflexes. Sympathetic Nervous System. The study of the sympathetic system has been done by R. Brugia, of Bologna, and summarized by Antonini. 1. In all insane pellagrins the sympathetic nervous system is injured and the changes are extensive in all its component parts. 2. The ganglia of the cervical region and the abdomen are affected differ- ently, according to the extent of the common forms of the pellagrous psychoses or of acute pellagra. 3. In the prevailing forms there is hyperplasia of the connective tissue, with sclerosis, a constriction of the vessels, a reduction in the number of nerve cells with atrophy, and a pigmentation plainly visible; in these at times there is a form of hypertrophic degeneration. 4. In the acute relightings of the pellagrous process the particular ele- ments present entirely different appearances. Only rarely is atrophy seen. Instead there occurs a turbid swelling of the cytoplasm, a central and periph- eral chromatolysis, complete absence of the chromatic granules, and a variety of lesions in the nucleus and the nucleolus ; in the supporting tissues a diffuse infiltration with leukocytes, a proliferation of endothelium and the formation of capillaries, circumscribed hemorrhages, points, and areas of softening. 5. In every case, and more particularly in the chronic forms, the lesions are greater in the abdominal ganglia, both centrally and cortically. 6. With the degeneration of the abdominal sympathetic there occurs acetonuria and the paretic diarrhea so frequent in insane pellagrins; while the lesions of the cervical sympathetic contribute in great part to cause the characteristic erythema, with the habitual dryness of the skin and the changes in the pupils. The conclusions in the last paragraph require further investiga- tion for their confirmation. The extent of the part played by the sympathetic system in pellagra is not yet determined. CEREBROSPINAL FLUID. 1 am indebted to Dr. S. S. Hindman, pathologist to the Georgia State Asylum, for permission to use the results of his work on the spinal fluid in pellagrins. These patients came from the wards NERVOUS SYSTEM IN PELLAGRA. 155 of Dr. W. J. Cranston, who did all the punctures, and the work was done under the direction of Dr. E. M. Green, clinical director. The table on page 156 shows the results of these counts in detail and the averages at the foot of each column. Chemically the fluid is acid in reaction, twenty-three of the twenty-five cases are positive to the butyric acid test, and all of the twenty-four specimens tested Fig. 50. — Spinal ganglia. Changes in the fibrillar net : changes in the nucleus. One may see the different phases of degeneration in the cell. Only one cell normal. Neuro- fibrillar method of Donaggio. (By Dr. Bravetta.) reduce the copper sulphate solution. The average number of cells to the cubic millimeter is 35, and the percent of the cells in a differential count follows. In four cases taken in the intermission period between attacks Hindman found the total cell counts at 30, 17.7, 6.6, and 4. This is quite a decrease as compared with an average count of 35 during the outbreak of the attack. Further, in two of these four cases 156 PELLAGRA. c3 ft > !!!!.'!; °° '!!! w ® .' .' .'.''"'.'""" .' r-i .' '. '. .' 06 pq re u C5 in I© 05 t> CO (M CO CM r-i CM in to Tf o oo co w h rinNw'oNnad IO N N H H tl H i-l bo re es y C0C5 >r-l o Q < rl < o w Pm O O ce o P3 o p PR H Ph W O P4 M H P3 H o Ph o o M «4 co «j res O I OO CM' 05 - 00 CM* O rH "*' CO Nrl H H r-i 1-1 T« CO <^> <^ tC co re rt >3 OCJ 2 CO rH Q) co bo rt - h O CDrH > re .-c oj a u Ph fi co cm cm Ph ' • CM CO IM . . o m cm CO (M . CO CM CM CM t- CO •<* CM CM co' co i-I oo m' oo oo „, 1— I CO "^ co co w bo rt tS u <0 rH > > +J Tj H fl >> .* ,' 03 « CO (M uj •<* ^ ^ O ^3 ft 00 b- ^ t> ^ CO CO ri ce CO CO o CO m cm Ph Ph Ph th co _ N m CO cm' T* od i-tCDT-HCOOin-^ CM cori^^WNoi^inio cc CO M 4) CM CO -P W Pi TH r-1 ^' H CM CM ^ rH CM tH m' th m' thJ csj rj? tH H CM m (M t- (M CM CO CM* CM CO* cmco in ■<# co oo t> co cxi co in" in th co' oo' r> co © HirtlOWCOCOCOriCO CO » 2 co en bo TO CD CM CO rl Ph Ph ft O ^ c > CO > CD > CD > CD > CO > • CO • > CO > CD CD > CO > • CO CD > CD > CD > co > CD > CD > CD > CD > to > +=> +a +a 43 -*3 -*-3 '■+3 -«- +J +3 -*-3 . += += -t- -»— +3 ^~ += -t- +a CO CO CO CO CO CO • co 111 co CO VI . CO CO co ■ji EC c/. CO Cfl CO oooooooo o o O O o OOOOOOOOOo PhPhP^PhPhPhPhPm ! fn Pi Ph Ph ft .fliPHrHPHP-iPHPHPHpHrH .S > CO cj bfi ft CO co C CM CM Ph CDCDCDCDCDa>CDCDCD o NERVOUS SYSTEM IN PELLAGRA. 157 the butyric acid test was only very weakly positive, and in the other two it was actually negative. Comparing Hindman's table with the results obtained in other diseases, excess of lymphocytes is present in syphilitic meningitis and syphilitic disease of the nervous system, in tabes and general paresis. Purves Stewart found in fifteen tabetics the average count Pig. 51. — Spinal cord. Increase in the neuroglia in crossed pyramidal tract. Weigert's method. (By Dr. Bravetta. ) per cubic centimeter was 125 cells. In tabes and general paresis the spinal fluid often reacts positively to the butyric acid test. In meningitis there is an excess of the polynuclear cells, except in the later stages, when the lymphocytes may be increased as compared with the early stages. In a case of syphilitic meningitis reported by Batten in Allbutt's System the lymphocyte count was 92 158 PELLAGRA. percent. In tubercular meningitis there is often a lymphocytosis. The spinal fluid in pellagra is evidence that the pellagrous process includes in its advance organic changes in the nervous system, and that in general these changes are part of a chronic disease, as evi- denced by the association of the lymphocytes, whereas acute organic diseases of the nervous system are associated with an increase in the polynuclear elements. In pellagra the lymphocytes are increased both in the blood and in the cerebrospinal fluid. * • «B $, >*4 ■5i^.*40MHl '-"'" | ■■j Fig. 76. — One method of gathering and drying corn in America. (Courtesy of Professor Fain, College of Agriculture, Athens, Ga.) Fig. 77. — Rail pens without covers, sometimes used for storing unshucked corn in Amer- ica. Corn on the ear. (After Hartley, Farmers' Bulletin 313, United States De- partment of Agriculture.) lations and is practically absent from cities. "Why should the same corn cause pellagra in the country and not in the city? 4. The numerous prophylactic measures — such as the inspection of corn, the drying of corn, the maturing of corn — have had no effect on lessening the prevalence and the severity of the disease, as illustrated by Spain, where practically no preventive measures have been taken and where the disease is nearing extinction due to unknown factors, and contrasted with Italy, where many pre- ventive measures have been taken and where the disease still exists over wide areas. CAUSE OP PELLAGRA. 247 5. The topographical relations of the disease to streams and the persistency of its endemic areas are not explained by the corn theory. 6. The disease occurs in persons who do not eat corn or who have eaten it but rarely. The attacks of pellagra continue to recur in a pellagrin longer after he has ceased to eat corn. Fig. 78. — Cribs used for drying corn in the United States. Crib shown is 240 feet long, divided into bins 6x8 feet to facilitate drying of the corn. (After Hartley, Farm- ers' Bulletin 313, United States Department of Agriculture.) 7. It is true that fungi cause such diseases as ringworm, acti- nomycosis, and the various mycetoma, but none of these resemble pellagra. This is evidence against the fungus theory of the disease. IS PELLAGRA AN INFECTIOUS DISEASE? A broad view of infection is given by Professor Kitchie in his article on the pathology of infection in Allbutt and Rolleston's ' ' System of Medicine : ' ' The study of infection in its widest and most scientific sense is almost coterminous with, the study of the effect of any foreign living agent when it gains a foothold, and especially when it multiplies in the animal body. Another great truth has also emerged in modern times in the recognition of the fact that, notwithstanding the variety of clinical types produced by different agents, there is a great unity in the morbid processes set up. We must, therefore, in taking a broad view of the subject, be prepared to account for observed facts and to recognize common processes in such varied con- ditions as the following: 1. The action of parasitic fungi and bacteria in such diseases as favus, septicemia, tuberculosis, diphtheria, enteric fever, etc. 2. The action of parasitic protozoa in such disease as malaria, tsetse-fly disease, etc. 248 PELLAGRA. 3. The action of what for the present are called "ultramicroscopic" living agents in such diseases as pleuropneumonia and foot-and-mouth disease in cattle, and probably yellow fever in man. 4. The action of parasites of unknown character, though probably belong- ing to one or the other of the last three groups, which are in all likelihood associated with such disease as smallpox, scarlet fever, hydrophobia, measles, etc. 5. It is a question whether certain phenomena associated with the presence of parasitic worms in the body ought not properly to be classed along with the phenomena of undoubted infections. These five propositions refer to the cause of that great group known in modern medicine as infectious diseases, and, if pellagra belongs to this group, its cause must come under one of these con- Fig. 79. — Diagrammatic section of a grain of corn, a, skin; b, germ; c, endosperm. (After Woods, Farmers' Bulletin 298, United States Department of Agriculture.) ditions of infection. The body of the pellagrin must, therefore, contain either living parasitic bacteria or fungi, which are the specific causes of pellagra and of no other disease ; or the pellagrin contain within his body parasitic protozoa or ultramicroscopic living agents or parasites of unknown character, causing diseases trans- missible by contact ; or, lastly, the body of the pellagrin must con- tain worms which act as specific cause of the disease. Now, it is necessary that the evidence which goes to show that pellagra is an infectious disease be presented in two ways : First, are the morbid processes carried on in the body of the pellagrin similar, in the widest sense, to the morbid processes characteristic of other known CAUSE OF PELLAGRA. 249 infectious diseases, such as syphilis, malaria, sleeping sickness, hookworm disease, tuberculosis? This is the evidence from within the body, and may be called the pathological evidence of infection. Second, the evidence afforded from without the pellagrin, such as his relation to his environment, climate, temperature, home, stand- ing and running water, age, sex, occupation, and the history of the disease in one country for a long period of time. This may be called the relational or ecological evidence of infection. The dis- covery of the protozoan or bacterium which causes this disease is necessary before any absolute scientific proof can be given. (a) The Pathological Evidence That Pellagra is an Infectious Disease. 1. There is a relative increase of the lymphocytes. Other proto- zoan diseases — as syphilis, kala azar — show a similar increase in these cells. Trypanosomiasis, or sleeping sickness, has a lymphatic infiltration of the brain with the mononuclear cells. 2. Pellagra shows a marked increase in the lymphocytes of the cerebrospinal fluid. 3. Pellagra shows at certain stages a marked leukocytosis, similar to the lukocytosis in malaria, which is a protozoan disease. 4. Pellagra, syphilis, kala azar, malaria, and sleeping sickness are all alike benefited by arsenic. 5. The nervous system is involved centrally as in syphilis, kala azar, and trypanosomiasis. These show an affinity for the spinal cord. Leprosy, an affinity for the peripheral nerves, and pellagra, like leprosy, has peripheral nerve formications, burning, numbness, pain. 6. Pellagra, like malaria, shows a complete absence of eosino- philia. In pellagra as many as a thousand leukocytes may often be counted without the occurrence of a single eosinophile cell. 7. Diarrhea is a characteristic of infective diseases, rather than a chronic intoxication, as illustrated by cholera and the choleraic or the algid form of malarial fever as contrasted with the constipa- tion of chronic alcoholism or beriberi. 8. Like hookworm disease, pellagra produces eye changes and often causes the formation of cataracts. These cataracts are prob- ably due in hookworm disease to toxins elaborated by the worms and circulating in the blood and lymph for long periods. An in- fection may exist in pellagra with a similar elaboration of toxins. 250 PELLAGRA. (b) Ecological Evidence of Infection. 1. Pellagra occurs in tropical and subtropical climates where infective diseases, and especially diseases caused by parasitic pro- tozoa and parasitic worms, are prevalent. Wherever pellagra occurs, malaria and hookworm disease are to be found, and nearly always amebic dysentery. 2. Pellagra is not characteristic of climate in the northern sec- tions of the world, where the winter seasons are extremely long. 3. Pellagra is a rural disease, and develops on farms and in homes whose environment is rural. It is not a city disease. >a Fig. 80. — Cellular structure of a grain of corn, a, skin; b, endosperm, consisting of (c) aleurone cells and (d) starch cells; e, membrane. 4. Pellagra is more common in females than in males, and espe- cially is this true in America. Both eat the same food, and a food poison affects both sexes equally. There is a reason for the pre- dominance of female pellagrins, due in all probability to the fact that they are more exposed to the infecting agent. 5. Children six months of age develop the disease in country dis- tricts. It seems more reasonable to believe the development of the chronic disease in an infant of this age to be due to an infection aris- ing from without than to poison in ordinary food given it infre- quently and in very small quantities. 6. Pellagra bears a direct relation to the seasons in all countries where it exists. This is characteristic of infective protozoa and dis- CAUSE OF PELLAGRA. 251 eases like malaria, and is probably due to the more or less fixed life span of the parasite. Intoxications are not seasonal in their relations. 7. Parasites, especially protozoa, are active in the spring, sum- mer, and autumn, and inactive in the winter. Pellagra is active in the spring, summer, and autumn, and latent in the winter. 8. Infective diseases are widespread over the earth, as illustrated by such widespread diseases as tuberculosis, malaria, and syphilis. If pellagra is not an infectious disease, it is the only disease due Fig. 81. — Penicillium, a common mold found on corn. A, mycelium, with numerous branching sporophores bearing conidia ; B, apex of a sporophore enlarged, showing branching and chains of conidia. (Coulter, after Brefeld. ) to the ingestion of a poison formed in a grain that has so wide a distribution on the earth, is so chronic in its nature, and so per- sistent in its endemic relations. 9. Infectious diseases are epidemic in character — as cholera, and endemic in character — as malaria. Pellagra is epidemic, as illus- trated by its recent invasion of America. It is endemic in char- acter, as illustrated by the fact that it exists in one mountain valley for a hundred years. Dr. Louis W. Sambon, an Italian physician, who lived formerly in the city of Milan, graduated in medicine at Naples and later 252 PELLAGRA. moved to London, where he is the present lecturer in the London School of Tropical Medicine, first advanced the theory that pella- gra is an insect-borne disease similar to sleeping sickness, malaria, and yellow fever. The evidence of this fact chiefly relates to the topographical relations of pellagra. Fig. 82. — Usailago maydis, a fungus that causes corn smut. A, staminate flowers of Indian corn, attacked by ''smut''; B, mycelium, showing the beginning of spore formation; G, ripe spore (X600) ; D, germi- nating spore, developing a promyce- lium, with sporidia, E. (Campbell, after Bref eld.) Fig. 83. — The simulium fly and larva. (After Comstock.) Fig. 84.- — Wing of simulium fly, showing venation. 1. Pellagra is a disease of place. It occurs in restricted areas in a country where it is endemic. Sambon found numerous illustra- tions of this in Italy, and Lavinder, with Sambon, was "frequently impressed with the statements of practitioners in pellagrous sections that all of their cases come from this or that restricted locality. ' ' The disease is found in an area, as a rule, at the foothills of CAUSE OF PELLAGRA. 253 mountainous regions in areas traversed at frequent intervals with small streams. The vast majority of pellagrins in all the countries of the world where pellagra exists live in such areas. Now, in such areas in one of these mountain valleys many cases of the disease may originate, while no other cases may exist for miles around this valley. One of the most remarkable facts brought forward by Sambon as a result of his researches in Italy is that these endemic centers remain the same for a century. This is evidence in favor of the view that the disease is spread by an insect. He found that the present distribution of pellagra in the province of Bulluno is the same as that observed by Xecchinelli in 1818 and Odoardi in 1776. Taking these three dates— 1776, 1818, and 1910— "the dis- ease affects the very same places along the valleys of the river Piade." 2. Pellagra originates chiefly along streams and water courses. Sambon first pointed this out in Italy, and, following his example, I have found the same condition to exist in the southern states. The following table illustrates the relations of thirty-five pellagrins in Georgia to streams : Number of Number. Pellagrins. Residence. 1 3 Swamp, three streams. 2 3 Swamp. 3 1 In 50 yards of stream. 4 1 Location wet and swampy. 5 2 In 14 mile of stream. 6 1 Unknown. 7 1 In i/4 mile of standing water. 8 1 In % mile of branch. 9 1 Between two streams. 10 1 In 14 mile of pond and stream. 11 1 In 300 yards of branch. 12 1 On Chickamauga creek. 13 1 In 220 yards of creek. 14 1 In 300 yards of creek. 15 1 In 14 mile of creek. 16 1 On stream. 17 1 On stream. 18 1 Resided on pond 5 years. 19 1 Between two springs and fresh branches. 20 1 In 1 mile of stream. 21 1 In 250 yards of stream. 254 PELLAGRA. Number of Number. Pellagrins. 22 23 24 25 26 27 28 29 30 Residence. In 200 yards of stream. 12 years in 100 yards of stream. 15 years in 100 yards of stream. In 1 mile of stream. In % mile of stream. In 30 yards of stream. On sea coast. In city. In 100 yards of stream. Fig. 85. — Legs of a chicken showing pellagrous symptoms produced by feeding maize spoiled by inoculation with a specific bacterium. (By Dr. C. C. Bass.) CAUSE OF PELLAGRA. 255 Fig. 86. — Legs of another chicken manifesting similar symptoms to those of chicken in. Fig. 85. (By Dr. C. 0. Bass.) A single illustration from Sambon will suffice : It is a well-known fact among the peasants themselves that in pellagrous districts the disease is far more prevalent and severe in those who live quite close to a stream than in those who dwell at some distance from it on the neighboring heights. At Trestina (Citta di Castello), a place I visited in the company of Professor Centonze and Dr. Sediari, two peasants, Tommaso Paronni and Emidio Caracchini, told me that some years ago they used to 256 PELLAGRA. live by the Torrent Nestore, but that, owing to the severity of the disease, they had been obliged to abandon their houses near the stream and take refuge with their respective families on the Trestina hill. There are places on the Nestore, on the Minimella, and on a thousand other brooks and creeks where healthy newcomers invariably contract the disease. On several oc- casions I have seen families all the elder members of which were pellagrins, while the two or three youngest children were not, owing to the fact that the parents had removed from a pellagrous to a healthy locality before the birth of the latter. Fig. 87. — Bobbin Creek, near Athens, Ga., where the simuliuni larvae were first found in Georgia by Professor J. M. Reade. The larvaa are abundant on the rocks, where the water is swift. (Photograph by Professor J. M. Reade.) In July, 1911, Dr. L. B. Morse, of Hendersonville, N. C, became interested in the relation of pellagra to streams, and found in four cases in his community the disease originated while the patients were living near streams. Assistant Surgeon R. M. Green found the same conditions to exist in three counties in southwestern Kentucky, and regarding the 140 pellagrins which he found in these counties he writes as follows : CAUSE OF PELLAGRA. 257 On account of the topography of the country, the most suitable locations for homes are along the streams, and consequently a large percentage of the inhabitants live along water courses. In every instance where I was able to visit the pellagrins at their homes I found them living within 500 or 600 yards from a stream. A number of them were living in houses situated liter- ally on the banks of the streams. Fig. 88 shows an endemic pellagrous area in Dadeville, Ala. The stream in the center flows between the houses, those on the right being 200 yards away and situated on a hill. No cases de- veloped here. The houses to the left of the stream each contain pellagrins, which have developed while living in these houses. The family inhabiting house No. 2 moved away, and Mrs. A., who lived in the hilly portion of the town and was perfectly healthy, moved in. In a short while she developed the disease. These three homes are situated on a gentle slope just 75 yards away from the stream. One-half mile to the left a negro cabin was situated prac- tically on the stream. A negro woman and her daughter lived here, both developed the disease, and both died. It seems that the endemic area in this community was in the valleys trenched by these two streams, and the families that lived to the right on high ground were exempt. I know of no better evidence than is afforded by this simple illustration. I am indebted to Dr. J. Clarence Johnson for it and to his assistant, Dr. John Fitts, who made the sketch. J. O. Elrod, of Forsyth, Ga., showed me a similar endemic area in Monroe county. This endemic area w T as a valley in rolling mid- dle Georgia land, trenched by an ordinary small creek. Five cases of pellagra developed in this valley — one an old man, one a man of 40, two white women, and one negro woman. Fig. 89 shows the relation of a pellagrin to a stream in the village of Cornelia, Ga. In this case the patient had lived in a house for a great num- ber of years, and the disease originated here and here the patient died. While in Franklin, N. C, in the summer of 1910, I studied the premises and surroundings of a pellagra patient, a woman, who had recently died. The house bordered the road in front, and behind a branch of rapid mountain water ran within fifty feet of the back porch. On the right of the house was a perfect swamp, and the stream marked out a narrow mountain valley — exactly the same topographic conditions found in Italy by Sambon. K. H. Beall (Journal of the American Medical Association, 258 PELLAGRA. 1^ to $uu6ou©d ^o soujoj-i 45 °tH as o o cS-2 En '-3 - M O ^ ra * a SI -2 a *£ CD f-l CD _, S «2 *> o o oi 2-=! * Pi -*> ^ I O c3 8«n '""'3 CD H 03 ^45 u O 1) P O CD °45 2~ CD ■*» 0) x5o9 CD . ** o 2 © ® £ M h O O CD r ° rt CD -uEH ■§>«* « ft 2 « s M g« . 03 ^'-S CD^ rj ,_ CD CO J q* &!)«„ bC M ^03 o Pi C3 gjS * £ CD to ^3 x CD O § =3 s CD 2 03^^ cS-g *h cd ;; &JD CDTi ^ a 18 H pj iS H T * --^ -p! \ ■* PI . « oo o -£.£ P 60 CAUSE OF PELLAGRA. 259 5 980- o\ £ 2 og Oj_w ft 260 PELLAGRA. November 18, 1911) is the only author I have found who disagrees with the relations of pellagra to streams. He studied 54 cases, and found that 4 lived in one-half mile of a stream; 9 lived from one- quarter to one-half mile; 41 lived at least one mile; 2 lived eight miles ; 4, ten miles ; 1, twelve miles ; 1, fifty miles, and 1 sixty miles from any overground collection of water — a general average of over four miles. INSECT CARRIER. Pellagra is not contagious, but spreads probably through the agency of its insect carrier as malaria or yellow fever are spread by insects. Alessandrini agrees with Sambon that pellagra in Italy is endemic along the borders of the streams, though he believes the cause to be a species of nematode worms of the genus filarida3. He ad- vanced this theory in 1910 in opposition to the corn theory, but it has neither been proved nor has it developed followers. From the foregoing it is evident that the same conditions in by far the larger number of cases prevail in the United States. Again, pellagra is rural and not urban. I was impressed with this at the hospital for the treatment of rickets and other deformities of the city of Milan. This very charitable institution sends out over the city every morn- ing and collects the deformed children of the poor, keeps them in the hospital all day for treatment and while their parents are working. I was told that in all their experience they had not found any of these children with pellagra, and yet their food is poor and certainly not any better than the food furnished the children in the rural districts in Egypt and Italy, where pellagra is common among children. It is evident that there is something in the country which is not in the city, and which is the cause of the disease. It is further evident that this something probably originates in or along streams, or standing water. Pellagra is not contagious, avoids the winter, develops in the spring and autumn, recurs and continues to redevelop at these same seasons. Pathological evidence affords reason for the belief that the disease is protozoan in origin. For all these reasons it is evident that pellagra is probably due to the agency of an insect of some kind. Sambon believes this insect to belong to the genus simulium. The following is a brief descrip- tion of this fly : CAUSE OF PELLAGRA. 261 The simulium fly is one of the order diptera, or two-winged flies ; family simuliidge, with the one genus simulium, having many species. Of these Sambon found three species in Italy — simulium reptans, ornatum, and pubescens, chiefly the last. The two chief species in America are simulium venustum, or black fly, the great biter of the northern woods ; and simulium pecuarum, the southern buffalo gnat. This buffalo gnat causes the death of many mules and domestic animals. It is found along the tributaries of the Mississippi, through the state of Mississippi, possibly all of Arkan- sas, in Kansas, in Tennessee, Kentucky, and parts of Missouri, Illinois, and Indiana. Since 1850 this buffalo gnat has killed many thousand domestic animals. They appeared in the Mississippi valley as early as 1818, and in 1884 killed in Parrish, La., 300 head of stock in one week. They do not seem to appear every year in damaging numbers, but are always more numerous in time of flood. Sambon notes that in Italy the greatest number of pellagra cases occur in the flood and overflow years. Two crops of the insects emerge from the streams each year — one appearing from February to April, and the other from Septem- ber to December. The eggs are laid, when possible, in streams of rapid, shallow water, as in an ordinary branch or creek. Rock, leaves, and brush in the water are good places. They hatch in about eight days to a larva, passing in about four weeks into the pupa stage, and emerging in three weeks, after having spent the pupa stage in the bottom of the stream, as the mature two-winged fly or gnat. The Cambridge Natural History, vol. 6, page 477, defines the simulium or sand fly, or buffalo gnat, as "small obese flies with humped back, rather short legs and broad wings, with short, straight antennas, destitute of setse; proboscis not projecting; will probably prove to be nearly cosmopolitan. ' ' In Great Britain these flies do not increase to an extent sufficient to render them seriously injurious, but their bite is very annoying. Simulium columbaczense has caused great loss among the herds on the Danube. They prefer brisk and lively streams, as in rapids above the waterfalls, but have been found in sewage water. Further information about these flies can be found in the "Proceedings of the Boston Society of Natural History," Hagen, 1880, pages 305 to 307; American Entomologist, Osten Sacken from Verdat, vol. 2, page 229. De Geer's Memoirs (vol. 1, page 328) says they attack large, smooth 262 PELLAGRA. caterpillars, sucking blood, and Verdat has found them sucking honey dew from the aphidae. Osten Sacken (Berliner Entomolo- gische Zeitschrift, bd. 37, 1892) says the males love sunshine and swarm high in the air ; females remain at lower levels, and perhaps only females bite. F. M. Howlett, article on Indian Sand Flies, Congress of Medicine, Bombay, India, 1909. Dr. J. Cheston Bradley, assistant professor of entomology, Cornell University, was bitten by a simulium fly in the hotel at Clayton, Georgia, in the summer of 1911, and later, on a tramp up the mountains, found himself attacked again. He did not develop the disease, of course, but the point is that people in the pellagrous area are bitten by the simulium fly, and yet previous to 1911 this fly had never been reported from Georgia, and until Dr. Bradley was bitten it was not even known in that section that man was sub- ject to their attack. For the following reasons Sambon believes this insect to be the carrier of the disease: (a) Simulium, so far as we know, appears to affect the same topographical conditions as pellagra. (b) In its imago state it seems to present the same seasonal incidence. (c) It is found only in rural districts, and, as a rule, does not enter towns, villages, or houses. (d) It explains most admirably the peculiar limitation of the disease to agricultural laborers, a limitation which nothing else can explain in a satisfactory manner. (e) It has a wide geographical distribution, which seems to cover that of pellagra, although certainly exceeding it, in the same way that the distributional area of the anophelinae exceeds that of malaria, and the range of stegomyia calopus that of yellow fever. (f ) It is known to cause severe epizootics in Europe and America. (g) Other similarly minute blood-sucking diptera, such as phlebotomus papatassi and dilophus febrilis, are strongly suspected of being propagators of human diseases. The evidence so far in favor of the simulium is circumstantial evidence. So far as is known, where pellagra exists the simulium fly exists, but there are many species of this fly, and the question arises which one of these species is, or are all of them, the insect carrier. There are five species of the simulium in the Austrian Tyrol. There are many species in America, but the evidence thus far adduced is far stronger in favor of an insect as the carrier of CAUSE OF PELLAGRA. 263 the disease than it is definite in favor of the simulium as the carrier. Sambon's argument and later evidence for an insect is very rea- sonable. Whether it is the simulium fly or not remains a problem. As pointed out by Chilton Thorington (Virginia Medical Semi- Monthly, July 21, 1911), the mosquito is to be borne in mind. It is not known whether a certain species of mosquito is common to all pellagrous areas, but certainly it should be determined whether the mosquito has any relation to the disease. The members of the genus ceratopogon of the family chirononiidas include the small midges commonly known as punkies. It should be determined whether these have any relation to the disease, as they, too, are blood-sucking and man-biting flies. Finally, Beall, formerly re- ferred to, has called attention to the fact that on account of the predominance of females in America it is reasonable to believe that they are more exposed to the disease. Of those males who developed pellagra in his series the majority of them were either under 20 or over 50, and, like the women, spent most of their time at home. The predominance of females is greater in this country than in Italy or Roumania, and Beall believes this to be due to the fact that the insect w T hich causes the disease is one common to homes in the endemic districts and which bites during the day. If it were a night-biting insect, males and females would be equally attacked. This affords further evidence in favor of the necessity of investi- gating the mosquito as a probable cause, and the punkies. Objections to the Theory that Pellagra is an Infection. 1. The failure to find in the blood, or in the tissues and body fluids, any parasites or specific bacteria. 2. The failure to reproduce the disease when the blood of a pellagrin is injected into the body of a healthy person or into monkeys. Objections to the Theory that the Simulium is the Carrier of the Disease. 1. The failure to find in the simulium any protozoa or specific bacteria. - 2. The inability so far to reproduce the disease when simulium flies are permitted to suck the blood from individuals suffering 264 PELLAGRA. with pellagra and to then bite monkeys, as illustrated by the work done by the State Board of Health of Kansas. 3. Lack of evidence to prove that blood-sucking flies other than those of the genus simuliidse may not be the carrier of the disease. At the present time further discussion of the cause of the dis- ease is to no purpose. If we knew the cause, it could probably be stated in a sentence — certainly in a page. Pellagra is either an infection or an intoxication — it can not be both. It can not be caused by the poisons of both corn and protozoa. Mizell, of At- lanta, has advanced the theory that cotton-seed oil and other oils are the cause, but so far no evidence — either chemical, physiolog- ical, or economic — has been advanced in favor of his idea. Bass, of New Orleans, like Lombroso, has fed chickens on spoiled corn and caused changes in the epidermis of the leg (Figs. 85, 86), even as Lombroso did before him, but that this is pellagra in the chicken is hardly probable. Would a continued diet of spoiled wheat, or spoiled oats, or spoiled buckwheat not cause a similar condition? Sambon's theory that pellagra is an infection has produced a profound impression. It is probable that the majority of physi- cians in Italy lean toward the corn theory. They have heard or been taught nothing else for a hundred years. It is probable that the majority of the physicians in the southern states lean away from the corn theory — certainly bear toward it the relation of the open mind. Many of them believe it to be an infectious disease, and I am inclined to this belief. The experiments now being carried on in the state of Kansas by Dr. S. J. Hunter (Journal of the American Medical Association, February 24, 1912), in which sand flies bite pellagrins and then are permitted to bite guinea pigs and monkeys, should bear some fruit. One of these monkeys so bitten became sick and developed fever. He was autopsied, and his nervous system is now being studied. Whether this experiment will result in anything is unknown, but it is at least along the right line. The advocates of corn have had a hundred years, and have not made out their case. Sambon's theory is but two years old, and is be- ing investigated. It behooves the Zeists to agree among themselves as to what it is in corn that causes the disease, and until this is done the burden of proof for the corn theory rests on them. It behooves Sambon and his followers to prove that pellagra is an infectious CAUSE OF PELLAGRA. 265 disease, and to locate and name both the insect which acts as host to the parasite, if it be an insect-borne disease, and to find the protozoan or the bacterium which causes the disease. Both ideas can not be true. No theory is true which is not in accord with the facts. Until one of these two theories is proved or both dis- proved, the majority of physicians will bear to the question a relation of waiting. They have their opinions and are waiting for proof. The history of pellagra in other countries for the past two cen- turies warrants the belief that the United States is facing a long period during which the disease will prevail and in which many thousand human beings will become its victims. Little children will yield themselves to its insinuating and mysterious grasp ; strong men will become weak, and no longer able to render service as citizens; its mark will be left on the offspring of pellagrin mothers ; and especially through the southern states its ravages and its memory will exist side by side in every rural community. It has already fastened itself on the spinal cord, and its poisons flow in the blood of probably as many as ten thousand human beings in the states today. American medicine has given to the race the serum for the treatment of meningitis, and has discovered the in- sect carrier of yellow fever. There is reason to believe Ameri- can physicians will finally settle the problem of the cause of pel- lagra by the discovery and the proof of the toxin or the parasite which causes the disease. The corn theory is a century old and unproved — the infection theory of Sambon is new and unproved. Until the cause is definitely known, the wisdom of prophylactic measures is in doubt, and the hope of more satisfactory methods of treatment is delayed. In the language of a European physi- cian, "pellagra has appeared in America, and no doubt in America the true cause of the disease will be discovered. ' ' INDEX. Abortions in pellagra, 200 Acidity of urine, decrease in, 197 Acute pellagra, 83, 89 duration of, 90 primary, 89, 90 secondary, 89, 90 terminal, 89, 90 Africa, distribution of pellagra in, 61 Age in relation to pellagra, 38 Albuminuria, 198 Alcoholic dermatosis, diagnosis of pellagra from, 207 Alimentary tract in pellagra, 107 Alkaline urine, 198 Amebic dysentery in pellagrins, 75 Amenorrhea, 199 America, distribution of pellagra in, 62 history of pellagra in, 62 Analysis of cases of psychosis, 178 of corn, 234 of stomach and intestines, 113 of urine, 197, 198 Anemia, 187 Anesthesia, 203 Ankle clonus, 163 Ankylostomiasis in pellagrins, 75 Antisepsis in treatment, 221 Arsenic in treatment, 220 Ascaris in pellagrins, 77 Atoxyl in treatment, 221 Atrophy, muscular, 164 Australia, distribution of pellagra in, 62 Austro-Hungary, distribution of pel- lagra in, 59 history of pellagra in, 59 B Babinski reflex, 163 Bacteria on corn, 241 Bass' experiments on chickens, 264 Bath in pellagra, 227 Bilharziosis in pellagrins, 77 Blood, changes in the, 185 count, 185 differential, 185, 186 pressure, 189 267 Bones, 192 softening of the, 192 Bracelet, pellagrous, 131 Brain, gross changes in the, 142 microscopical changes in the, 143 tissue changes in the, 142 Buccal mucosa in pellagra, 109 Buffalo gnat, 261 cause of pellagra, 262 Burning in pellagra, 137 C Cachectic pellagra, 84, 93 Cachexia in chronic pellagra, 103 Cacodylate of soda in treatment, 220, 222 Cases, typical, 18 Cataracts in pellagra, 201 Cause of pellagra, 231 corn as, 232, 239, 241 good, 239 spoiled, 241 simulium fly as, 262 Census of pellagrins by states, 65 of pellagrins in Georgia, 68 of pellagrins in Italy, 52 Central America, pellagra in, 71 Cerebrospinal fluid, 154 examination of, 156 Changes in direct pyramidal tract, 145 in gray matter of cord, 146 in the blood, 185 in the brain, 142 gross, 142 microscopical, 143 tissue, 142 in the cord, 145 gross, 145 microscopical, 145 in the kidneys, 199 in the muscular system, 164 in the skin, 142 in tracts of Goll and Burdach, 145 Chickens, Bass' experiments on, 264 Children, pellagra in, 38, 82, 250 China, distribution of pellagra in, 62 Chlorides in treatment, 224 Chronic pellagra, 84, 94 degree of desperation in, 98, 103 268 INDEX. Chronic pellagra — cont'd. Jansen's delineation of clinical course, 95 pathology of, 118 stages of, 97 dyspepsia in, 98, 100 neurasthenia in, 98, 100 Circulatory system, 185 Classification of pellagra, 74 Climate, 227, 250 Clinical symptoms, relation of cord lesions and 2 152 Cod liver oil in treatment, 223 Color of finger tips, 129 of hands, 129 of skin, 128 Contagiousness of pellagra, 30, 31, 32 Convalescent pellagra, 83, 91 Cord, changes in the, 145 gray matter of, 146 gross, 145 microscopical, 145 Corn, analysis of, 234 as cause of pellagra, 232, 239, 241 good, 239 spoiled, 241 as diet, 226 bacteria on, 241 fungi on, 241, 242 history of, 233 in Italy, 237 inspection of, in Italy, 52 theory, objections to, 245 varieties of, 233 Cramps, 165 Cutaneous symptoms of pellagra, 29 D Definition of pellagra, 29 Degeneracy, pellagra cause of race, 37 table showing race, 38 Dementia precox type of psychosis, 174, 176 Dermatitis, 123, 125, 128 color of, 128 diagnosis before, 206 symmetrical, 132 treatment of, 228 Dermatosis of pellagra, 97, 123, 126 location of, 130 pellagrous, 208 relation of, to light, 133 treatment of, 228 Dermotagra, 123, 124, 128 Description of pellagra, general, 29 Diagnosis, 204 before dermatitis, 206 during attack of pellagra, 207 early, 206 Diagnosis — cont'd. of alcoholic dermatosis from pel- lagra, 207 of erythema multiforme from pel- lagra, 208 of eczema from pellagra, 208 of sunburn from pellagra, 207 in the intermission between at- tacks, 209 without eruption, 212 Diarrhea, 112, 116, 229 Diet, 225 corn as, 226 between attacks, 225 during attack, 225 Differentiation of skin conditions, 207 Digestive symptoms of pellagra, 29 Distribution of pellagra, geographical, 46 in Africa, 61 in America, 62 in Australia, 62 in Austro-Hungary, 59 in China, 62 in Egypt, 60 in France, 53 in Georgia, 68 in Greece, 59 in Italy, 48 in Mexico, 69 in North America, 63 in Roumania, 59 in South America, 71 in Spain, 46 in Tennessee, map showing, 54, 55 in the world, map showing, 72, 73 in Turkey, 59 in United States, map showing, 56, 57 Duration of acute pellagra, 90 of pellagra, 83 of single attack, 85 Dyspepsia in chronic pellagra, stage of, 98, 100 Lauder Brunton's description of, 107 E Ears in pellagra, 202 Ecological evidence of infection, 250 Eczema, diagnosis of pellagra from, 208 Egypt, distribution of pellagra in, 60 history of pellagra in, 60 Egyptian synonyms of pellagra, 45 Endemic, pellagra, 252 English synonyms of pellagra, 45 Environment in relation to pellagra, 41 INDEX. 269 Erythema multiforme, diagnosis of pellagra from, 208 Esophagitis, 111 Etiology of pellagra, 231 Examination of cerebrospinal fluid, 156, 158 Exanthemata, pellagra sine, 104 Eye in pellagra, 201 F Families, large, limitation of pellagra to, 31 Farmer, pellagra in, 26, 42 Fever, 191 Field laborers, pellagra in, 34 Filiform pulse, 189 Finger tips, color of, 129 Fowler's solution in treatment, 220 France, distribution of pellagra in, 53 history of pellagra in, 53 French synonyms of pellagra, 44 Fungi on corn, 241, 242 G Gastric symptoms, 112 General considerations, 17 paralysis type of psychosis, 174, 177 Genito-urinary system, 197 Geographical distribution of pellagra, 46 Georgia, census of pellagrins in, 68 pellagra in, 68 German synonyms of pellagra, 45 Glands, salivary, 110 Glove, the pellagrous, 133 Goll and Burdach, tracts of, 145 Gray matter of cord, changes in, 146 Greece, distribution of pellagra in, 59 history of pellagra in, 59 Greek synonyms of pellagra, 45 Gums in pellagra, 109 H Hair in pellagra, 134 Hands, color of, 129 Hearing in pellagra, 202 Heredity in pellagra, 35, 36, 37 History of corn, 233 of pellagra, 46 in America, 62 in Austro-Hungary, 59 in Egypt, 60 in France, 53 in Greece, 59 History of pellagra — cont'd. in Italy, 48 in Mexico, 69 in North America, 63 in Eoumania, 59 in Spain, 46 in Turkey, 59 Hookworm disease, 63 in pellagrins, 75, 77 Housewife, pellagra in, 18 Hydrochloric acid, lack of, 115 Hy drothorax, 191 Hygiene, 227 Hymenolepis in pellagrins, 77 Hyperesthesia, 203 Immunity, 31, 39 acquired, 40 natural, 40 Incubation period, 81 Indigestion in pellagra, 112 Infection, description of, 247 ecological evidence of, 250 of pellagra, 30 pellagra an, 232, 247 theory, objections to, 263 Infections of pellagra, other, 74 Infectious, pathological evidence that pellagra is, 249 Infective exhaustive type of psychosis, 173, 175 Inheritance of pellagra, 35 Insanity in pellagra, 171, 172 pellagrous, 172, 173 treatment of, 230 Insect carrier, 260 Insomnia, 166 Intestinal parasites in pellagrins, 79 Intestines in pellagra, 111 analysis of, 113 Intoxication, pellagra an, 232 Involutional melancholia type of psy- chosis, 174, 177 Italian synonyms of pellagra, 44 Italy, census of pellagrins in, 49, 50 corn in, 237 distribution of pellagra in. 48 history of pellagra in, 48 mortality of pellagra in, 49 prevalence of pellagra in, 49 Itching, 136, 203 treatment of, 228 Jansen's delineation of clinical course of pellagra, 95 270 INDEX. K Kidneys, changes in, 199 Knee jerks, 163 Latency of pellagra, 40, 84, 205 Leucorrhea, 200 Light, relation of dermatosis to, 133 Limitation of pellagra to large fam- ilies, 31 of pellagra to rural districts, 30 Location of dermatosis, 130 Lungs in pellagra, 190 M Mai de la rosa, 43, 122 Malaria in pellagrins, 75 Manic depressive type of psychosis, 174, 176 Map showing distribution of pellagra in Tennessee, 54, 55 showing distribution of pellagra in the world, 72, 73. showing distribution of pellagra in United States, 56, 57 Married woman, pellagra in, 25 Medicinal treatment, 220 Man, pellagra in, 33 Menstrual period, 199 Mental symptoms, 29, 168, 211 summary of, 181 Metrorrhagia, 199, 200 Mexico, distribution of pellagra in, 69 history of pellagra in, 69 Microscopical examination of cerebro- spinal fluid, 158 Monkeys, experiments on, 264 Mortality in America, 215 in Italy, 49 Muscular atrophy, 164 system, changes in, 164 N Nails in pellagra, 135 Negro woman, pellagra in, 27 Nervous symptoms, 29, 211 summary of, 180 system, 142 sympathetic, 154 treatment of, 230 Neurasthenia, 142, 169 in chronic pellagra, stage of, 98, 101 sexual, 200 Noguchi reaction, 190 North America, distribution of pel- lagra in, 63 history of pellagra in, 63 O Occupation in relation to pellagra, 40 Onset of pellagra, 86 diagnosis during, 206 Outbreak of pellagra, 86 Pain, 161 Palate in pellagra, 109 Panama, pellagra in, 71 Parasites in pellagrins, intestinal, 79 Parasitic theory of pellagra, 35 Pathological evidence that pellagra is infectious, 249 Pathology of chronic pellagra, 118 Pelle elastica, 140 Period of onset, 86 of outbreak, 86 of recession, 88 Perspiration in pellagra, 134 Pharyngitis, 111 Physicians, pellagra in, 42 Pregnancy in pellagra, 200 Prevalence of pellagra in Italy, 49 in Spain, 47 in United States, 65 Prognosis, 214 in America, 215 in asylums, 216 Pronunciation of pellagra, 17 Proportion of sex affected by pellagra, 33 Protozoa in pellagrins, 78 Pseudo-pellagra, 105 Psychosis, analysis of cases of, 178 dementia precox type of, 174, 176 general paralysis type of, 174, 177 infective exhaustive type of, 173, 175 involutional melancholia type of, 174, 177 manic depressive type of, 174, 176 senile dementia type of, 174, 177 unclassified type of, 174, 178 Psychoses accompanying pellagra, 171 Ptyalism, 110 Pulse, filiform, 189 rate, increase in, 188 E Race degeneracy, pellagra cause of, 37 table showing, 38 INDEX. 271 Recession of pellagra, 88 Reflex, Babinski, 163 Reflexes, 162 Roumania, distribution of pellagra in, 59 history of pellagra in, 59 Roumanian synonyms of pellagra, 45 Rural disease, pellagra a, 250 districts, limitation of pellagra to, 30 S Saliva, increased flow of, treatment of, 230 Salivary glands, 110 Salty taste in pellagra, 110 Salvarsan in treatment, 223 Seasons, relation of pellagra to, 80, 250 Senile dementia type of psvchosis, 174, 177 Sensory symptoms, 136 Sex in relation to pellagra, 33 Sexual functions, 199 neurasthenia, 200 organs, 199 Simulium as cause of pellagra, 262 fly, 261 theory, objections to, 263 Skin, changes in the, 138 color of, 128 condition, differentiation of, 207 in pellagra, 121 Smell in pellagra, 202 Soamin in treatment, 221 Sodium cacodylate in treatment, 220 Softening of bones, 192 Sore mouth in pellagra, 112 South America, pellagra in, 71 Spain, distribution of pellagra in, 46 history of pellagra in, 46 prevalence of pellagra in, 47 topography of, 48 Spanish cravat, 132 synonyms of pellagra, 43 Specific gravity of urine, 198 decrease in, 197 Stomach, analysis of, 113 in pellagra, 111 Stomatitis, treatment of, 229 Streams, pellagra originates along, 253 Strongyloides in pellagrins, 77 Subchronic pellagra, mild, 83, 91 severe, 84, 93 Sun, relation of dermatosis to, 133 Sunburn, diagnosis of pellagra from, 207 Susceptibility to pellagra, 40 Sympathetic nervous system, 154 Symptoms, clinical, relation of cord lesions to, 152 cutaneous, 29 digestive, 29 gastric, 112 mental, 29, 168, 211 summary of, 181 nervous, 29, 211 summary of, 180 sensory, 136 special, treatment of, 228 treatment of, 219 Synonyms of pellagra, 43 English, 45 Egyptian, 45 French, 44 German, 45 Greek, 45 Italian, 44 Roumanian, 45 Spanish, 43 T Table showing census of pellagrins by states, 65 showing census of pellagrins in Georgia, 68 showing census of pellagrins in Italy, 49, 50 showing mortality of pellagrins in Italy, 49 showing race degeneracy, 38 Taste in pellagra, 202 Teeth in pellagra, 109 Temperature, 191 Tennessee, map showing distribution of pellagra in, 54, 55 Tifo pellagroso, 29 Tissue changes in the brain, 142 in the cord, 145 Tongue in pellagra, 108 Touch in pellagra, 202 Tracts of Goll and Burdach, changes in, 145 Transfusion of blood, 32 in treatment, 224 Transmission of pellagra, 30 Treatment, 218 antisepsis in, 221 arsenic in, 220 atoxyl in, 221 cacodylate of soda in, 220, 222 chlorides in, 224 cod liver oil in, 223 Fowler's solution in, 220 medicinal, 220 of dermatitis, 228 of dermatosis, 228 272 INDEX. Treatment — cont'd. of diarrhea, 229 of increased flow of saliva, 230 of insanity, 230 of itching, 228 of nervous system, 230 of special symptoms, 228 of stomatitis, 229 of symptoms, 219 of vertigo, 230 salvarsan in, 223 soamin in, 220 transfusion in, 224 Trichuriasis in pellagra, 77 Tuberculosis, 190 Turkey, distribution of pellagra in, 59 history of pellagra in, 59 Typhoid pellagra, 29, 83, 89 T3^pical cases, 18 U Uncinariasis in pellagrins, 75, 77 Unclassified type of psychosis, 174, 178 United States, map showing distribu- tion of pellagra in, 56, 57 United States — cont'd. table showing census by states in, 65 Urine, 197 alkaline, 198 analysis of, 197, 198 decrease in, 197 acidity of, 197 specific gravity of, 197 specific gravity of, 198 Urination, painful, 199 V Variation in pellagra, 88 Varieties of corn, 233 Vertigo, treatment of, 230 W Walk in pellagra, 166 Wassermann reaction,. 190 Weight, 193 loss in, 193 Widow, pellagra in, 21 Woman, married, pellagra in, 25 negro, pellagra in, 27 Women, pellagra in, 33 1 1912