# Tropical Diseases/Chapter 27

CHAPTER XXVII
PELLAGRA
Synonyms.— Pellarina, mal de la rosa, mal rosso, flema salada, Alpine scurvy, Asturian leprosy, Asturian rose, disease of the Landes, dermotagra, psilosis pigmentosa.
Definition.— An endemic disease of slow evolution, characterized by a complexity of nervous, alimentary, and cutaneous symptoms, which make their first appearance during the spring months (sometimes the autumn months), and recur year after year at the same season, remitting more or less during the winter months. It is for the most part confined to field-labourers. The more distinctive features are— (a) a remitting dermatitis of the ex- posed parts of the body; (b) marked emaciation; (c) profound depression alternating with mania.
Geographical distribution.— Europe: Pellagra has a wide distribution in Southern Europe. It is found in northern Portugal, in Spain, in Italy, in the south-west of France, in the Austrian Tyrol, in Hungary, Croatia, Dalmatia, Bosnia, Servia, Bulgaria, Turkey, Greece, Corfu, Roumania, Bessarabia, Kherson, and Poland. Sambon has shown that, though hitherto practically unrecognized, it prevails endemically throughout the British Isles.* Africa: ​Algeria, Tunis, Egypt, the Red Sea coast, Rhodesia, Nyasaland, and among the Kaffirs and Zulus. Sand-with found it in 1900 among the coloured lunatics on Robben Island. Asia: Information is scanty, but it has been reported from Asia Minor and North Behar in India (Ray, 1902), Singapore, Philippine Islands. America: The United States, Mexico, Central America, Brazil, the Argentine, Barbados, and probably in other West India Islands. Australasia: Neirte has reported it in New Caledonia.
History.— The history of pellagra is comparatively recent. The disease was recognized and described almost simultaneously in Italy and Spain. In Spain it was first described by Casal in 1762 under the name of mal de la rosa. In Italy the disease, under the name of Alpine scurvy, was described by Odoardi in 1776, but it had been recognized previously by Pujati in 1740. Ramazzini, in 1700, writes of a disease under the name of mal del padrone, which appears to have been pellagra. Frapolli, who described the disease in 1771 under the name of pelagra (sic), says that probably it is the same as pellarella, a disorder mentioned as early as 1578 in the rules of admission to the Ospedale Maggiore in Milan.
The earliest mention of pellagra in France dates from 1829, when Hameau published an account of cases observed since 1818 around Teste-de-Buche and in the plain of Arcachon.
In Roumania the first recognition of the disease is assigned to the year 1836; in Corfu, to 1839.
We know nothing of the history of pellagra in Egypt prior to the publication of Pruner's " Topographie Médicale du Caire," in 1847. Pruner's statements were discredited by Hirsch and others, but recently Sandwith has shown that the disease is very prevalent in Lower Egypt, and also, though to a less extent, in Upper Egypt.
In the United States of America, although there is evidence of its sporadic occurrence there for a considerable time —at least fifty years— before its nature was recognized, pellagra was first diagnosed as such in 1907. It is prevalent especially in the south - eastern States. Dr. H. F. Harris, Health Officer of the Georgia State Board of Health, estimated that there were 50,000 cases of pellagra in his State alone.
Etiology. Sex.— Both sexes are liable, but in different places the disease exhibits a very different predilection for the one or other sex in accordance with the occupations and habits of the people, and
Spanish-derived name of "the rose," still now used in Scotland to indicate pellagra and other easily confounded erythematous conditions of the exposed parts. ​presumably consequent greater or less degree of exposure to the causative agent.
Age.— Hitherto pellagra was considered to be a disease of middle age, the majority of cases occurring between 20 and 50. Sambon has shown that within the endemic centres children are attacked, and that no age is exempt, he having seen the characteristic symptoms in a woman over 100 years old and in infants of barely 3 months.
Occupation.— The disease is most prevalent among field-labourers. The inhabitants of towns, even of those in the very heart of intensely pellagrous districts, enjoy an immunity similar to that of town-inhabitants as regards malaria. Felix points out that pellagra is quite exceptional among the Jews, who, as a race, rarely engage in agriculture. Bouchard says that herdsmen in pellagra regions are exempt. Although pellagra occurs most frequently in rural labourers living from hand to mouth, it does attack people in good circumstances. This has long been recognized in Italy, and the figures given by Gruner for the southern States of the United States— 258 cases had lived in poverty, 59 in comfort, 6 in affluence— show that the same remark applies to America.
Season.— Of all diseases with marked seasonal connection, pellagra is one of the most striking. As in the case of malaria, the pellagra season varies in different localities, but is always the same in the same locality.
In Europe the disease invariably appears in manifest and epidemic form during the spring and autumn quarters of the year, the spring outbreak being by far the most severe, the autumnal recurrence often inconspicuous or lacking. In Egypt, according to Chalmers, there is a spring invasion occurring in the months of April and May, and an autumn recurrence in November. In Nyasaland, according to Dr. Stannus, pellagra seems to prevail chiefly during August, September, and October, which are the spring months in the southern hemisphere, and again, though to a less extent, in January, February, and March (fall recurrence). In the United States of America, owing to the vast extent of territory and great variety of climates, the periodical incidence of the disease is necessarily different in different sections. In the northern States, as in ​Europe, the disease exhibits the usual well-marked double incidence, the spring outbreak occurring in May and June, the autumnal one in September and October. In the far south the disease may appear as early as January, and may be met with at any period of the year. In Barbados the disease seems to prevail more or less from May to October or November. Whilst the wide range of pellagra throughout the world might lead one to believe that climate exerts no special influence, the very definite seasonal periodicity of the disease shows that climatic factors display an important, though indirect, part in its etiology.
Topographical distribution.—This has been carefully studied by Sambon in Europe, in America, and in the West Indies. His observations tend to show that, like malaria, sleeping sickness, and yellow fever, pellagra is a disease of locality, and is contracted solely within certain rural districts where exist the conditions essential to its propagation.
Sambon points out that the presence of pellagrins in a locality is not necessarily evidence of endemicity. In Italy he visited several Alpine villages where numerous cases had been reported, and in every instance he found that the local pellagra consisted entirely of imported cases. The patients were adult mountaineers, who every spring went to labour in the subjacent affected regions; young children and adults who had never left their mountainous district were not affected. All pellagra cases, in whatever part they occur, may be traced to exposure within the endemic centres of the disease; while individuals who there contract the infection, but leave the infective area, are not a source of danger to those with whom they come in touch, however intimate the association. According to Sambon, pellagra is readily contracted at the appropriate season within its endemic stations, and the period of incubation may be very short about a fortnight. He mentions several instances of large families from healthy districts, in which all or most of the respective members contracted the disease soon after taking up residence in a pellagrous area. On several occasions he met families all the elder members of which were pellagrins, whilst 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. Pellagra everywhere presents the same peculiar topographical distribution: its stations or endemic foci are irregularly scattered and always confined to well-defined rural areas either intersected by streams or connected with other water bodies. A striking feature of its distributional peculiarities is the exemption of towns; "pellagra stops at city gates," and when the disease is epidemic the crowded town escapes the scourge. ​Epidemiology.— An important epidemiological feature of pellagra, in addition to those already mentioned, is the marked fluctuation of its prevalence from year to year. At times there may be long periods of quiescence, followed by years of considerable activity during which the disease may be looked upon as a new invasion. Pellagra is in no way contagious. The sound may associate with the sick and remain healthy. Doctors, nurses, and attendants on pellagrins are not known to contract the disease. Pellagrous wet-nurses do not infect their charges, and attempts to transmit the disease by inoculation have failed.
Associated diseases such as ankylostomiasis, bilharziasis, tuberculosis, sprue, dysentery, and syphilis play a very important part in favouring the development of pellagra, in accelerating its course, in modifying and aggravating its symptoms, and in determining its mode of termination.'
The virus.— Pellagra has been ascribed to the most varied causes, such as insolation, poverty, insanitary dwellings, syphilis, irritant oils, bad water, alcohol, garlic, onions, maize. Some have regarded it as a modified or degenerate form of leprosy, others as "sunstroke of the skin," and D'Oleggio, in 1784, proposed that it should be called " vernal insolation." " Sun disease " was an old popular name, and certainly the skin manifestations of pellagra are influenced by the action of the direct rays of the sun. This was proved experimentally, first by Gherardini, who varied the limits of the eruption by systemati- cally displacing parts of the clothing ; and later by Hameau, who obtained differently shaped patches of erythema by means of gloves fenestrated in different ways. In smallpox and also in other exanthemata we notice a decided influence of light, more particularly of the actinic rays, on the production of their skin eruptions. Although light may influence the eruption in pellagra, this is no adequate reason for concluding that insolation is the cause of the disease, any more than that it is the cause of smallpox. In support of the sunlight hypothesis, certain experi​ments on the effect of sunlight on animals fed on a too restricted (unphysiological) diet have been advanced recently; but it is evident from what we now know of the seasonal, epidemiological, and topographical habits of pellagra that such an hypothesis is untenable.
It would be idle to discuss the arguments brought forward to show that pellagra is caused by bad water, insanitary dwellings, poverty, syphilis, leprosy, rancid oil, sour milk, acid wine, bad cheese, rye, millet, buckwheat, common salt, onions, or garlic. The maize theory, on the other hand, demands,because of its popularity, a searching scrutiny.
The general opinion is that pellagra appeared soon after the introduction of maize into Europe, and that it advanced pari passu with the extension of maize cultivation, and with the more general adoption of the new cereal as an article of food. For these and other reasons maize is still held by many to be the causative agent of pellagra, just as a condition of rye is known to be the cause of ergotism; and, as in the latter case, various theories have been advanced to explain the operation of the assumed cause.
The morbific action of maize has been variously attributed to —
    (a) Deficiency in its nutritive principles.
    (b) Specific toxic substance contained normally in the grain.
    (c) Poisons elaborated after it has been ingested.
    (d) Toxic substances elaborated during decomposition of the grain.
    (e) Fungi or bacteria found on maize.
(a) Deficiency in nutritive principles.— Maize stands high as regards alimentary value. Insufficient nourishment may bring about inanition and marasmus, but never causes specific lesions like those of pellagra. Entire populations who live solely on rice or potatoes remain quite free from this disease, although these foods are far inferior to maize in nutritive value.
(b) Specific toxic substances normal to maize.— Those who advanced this theory were obliged to stipulate for a special personal susceptibility, otherwise the immunity of the millions who live on Indian corn could not be accounted for.
(e) Poisons elaborated from maize within the alimentary canal.— Neusser regards pellagra as a peculiar form of auto-intoxica​tion. A similar theory was propounded by De Giaxa in 1903. The latter ascribes the disease to a poison resulting from the action of Bacillus coli on sound maize after ingestion. He claims to have produced the anatomical lesions of pellagra in dogs by feeding them on porridge made with sound maize, and also to have obtained the same symptoms and lesions in animals inoculated with a toxin produced in vitro by the cultivation of Bacillus coli in maize media. These theories are disposed of by the harmlessness of maize in non-pellagrous districts.
(d) Toxic substances elaborated in decomposing maize.— Lombroso, in 1871, claimed that pellagra is due to the ingestion of certain toxic substances elaborated by saprophytes acting on the grain. In conjunction with others, he obtained from fermenting maize a watery extract containing a narcotic principle resembling conin, and" also an alcoholic extract and a red oil, both containing an alkaloid resembling strychnine, " pellagrozein." These two toxins combined, he holds, give rise to pellagra in the same way as sphacelinic acid and cornutin are believed to give rise to ergotism. In fowls inoculated with the toxins, Lombroso observed diarrhoea, loss of feathers, and death; in rats, wasting, choreiform movements, muscular spasm, and death; in men, vomiting, diarrhoea, desquamation of the epidermis, giddiness, dilatation of the pupil, and malnutrition.
These acute symptoms are in no way comparable to pellagra; identical results follow the administration or inoculation of analogous substances prepared by similar methods from wheat and other harmless foods.
Different investigators have extracted from damaged maize very different substances. Hausemann found a narcotic tetanic poison which he called "maizina." Selmi demonstrated the presence of ammoniacal acrolein. Pellogio extracted a bitter substance which produced paralytic symptoms. In 1881 Monselice analysed various specimens of damaged maize collected in pellagra districts, but was unable to find any alkaloid; he pertinently remarks that artificially fermented maize and the ordinary damaged maize are two very different things. In 1894 Pelizzi and Tirelli made experiments on dogs and rabbits, administering per os, or injecting subcutaneously or endovenously, the toxic substances obtained from cultures of the bacteria of maize. They observed spastic paresis of the posterior limbs and other symptoms which they considered characteristic of pellagra. Gosio, having observed that the commonest saprophyte of maize is Penicillium glaucum, prepared pure cultures of this fungus and extracted a substance belonging to the aromatic series. Ferrati made some experiments with a tincture of penicillium-damaged maize, and found that it is exceedingly toxic to rats, the animals dying in a few hours. Di Pietro noticed that only a certain variety of Penicillium glaucum has toxic properties. The poisonous substance is not present in cultures before the third day; it is a glucoside, and is found in the spores only. Experiments on guineapigs, dogs, cats, and rabbits produced symptoms very different from ​those obtained by Lombroso and others, but Di Pietro considered them characteristic of pellagra. Di Pietro also tested the toxic properties of Penicillium glaucum on himself, and suffered from pyrosis, vomiting, giddiness, weakness in the legs, slight tremor of the arms, frequent micturition. Lastly, in 1904, Fossati declared that he induced pellagra by feeding or inoculating guineapigs with maize damaged either by Aspergillus fumigatus or Penicillium glaucum. These results are mutually contradictory.
(e) Micro-organisms found on maize.— Ballardini, in 1845, was the first to attribute pellagra to a living organism, a mould (Sporisorium maydis}, which he found in the greenish stain (verderame) frequently seen in the germ-groove of maize grains. Experiments gave rise to gastritis and diarrhoea in man, loss of feathers and general wasting in fowls. Lombroso pointed out that Sporisorium maydis, on account of its rarity, could not be the cause of pellagra, and that Ballardini had probably confounded the Sporisorium with Penicillium glaucum. A special commission reported against Ballardini's discovery, on the ground that the verderame was common in many non-pellagrous districts of Italy. However, notwithstanding this, Ballardini' s theory was accepted by many in Italy, and by Roussell and Costallat in France.
In 1860 Pari incriminated the maize smut (Ustilago maydis), pointing out that the spores of this fungus are invariably present in the dust of the hovels of the peasants, who store their maize in the rooms in which they sleep . Generali fed two horses on fodder mixed with the maize smut, and claimed that after seven months one of the animals presented a skin eruption on the parts most exposed to the sun. But Prof. Imhof, who made some experiments on himself, proved that the maize smut is harmless to man.
In 1881 Majocchi found in both normal and diseased maize a very motile micro-organism which he named Bacterium maydis. He claimed to have found this organism in the blood, brain, liver, heart, kidneys, lungs, intestinal mucosa, and erythematous skin of pellagra patients, and on these grounds brought it forward as the causative agent of the disease, Cuboni found a similar bacillus in damaged maize and in the stools of pellagra patients. Paltauf, who investigated pellagra in 1889 on behalf of the Austrian Government, examined fifteen patients, but found Cuboni's bacterium in the stools of one only. However, he found it to be a very common saprophyte of damaged maize, and, together with Heider, proved that the maize toxins were partly due to the metabolic action of this organism. At the same time he showed that Bacterium maydis is no other than the well-known potato bacillus (Bacillus solanacearum) and that its toxic effects do not resemble pellagra.
In 1896 Carrarioli also claimed to have found a bacillus in the blood, saliva, and stools of pellagra patients. He stated that he had inoculated the toxic products of this organism ​subcutaneously into various animals, and that he also had invariably obtained symptoms similar to those of pellagra. He went so far as to name the organism Bacillus pellagra.
In 1902 Ceni stated pellagra to be a true mycosis due to two different species of Aspergillus, A. fumiyatus and A.Jlavescens. He declared that the season in which pellagra symptoms appear in man corresponds to " the cycle of annual biological evolution " of these hyphomycetes. Moreover, he stated that he had been able to isolate almost constantly, and usually in pure culture, the two aspergilli from the lungs, pleura, pericardium, and meninges of pellagra cadavers, and, further, that the spores of the fungi pass through the intestinal wall and thus reach the other organs.
In a later work Ceni, together with Besta, ascribes pellagra not to the organisms themselves, but to elaborated toxins. More recently Ceni and Besta describe two special varieties of Penicillium glaucum as' the true cause. According to these authors the toxic properties of one variety are excitative and therefore cause the acute forms of the disease ; those of the other, being narcotic, give rise to a more chronic type. Tiraboschi, who made (1905) a very careful study of the hyphomycetes found on maize grains in pellagra districts, states that he never found A. flavescens, and believes that Ceni anel Besta must have confounded it with Aspergillm variant, which is very common. He also states that A. fumigatus is rare, while Ceni and Besta stated that both A. flavescens and A. fumigatus are very common, and in some seasons even more common than Penicillium glaucum.
The fungus incriminated by the majority of authors as the causative agent of pellagra is, strange to say, the common blue mould, Penicillium crustaceum (P. glaucum), which is found everywhere and on the most heterogeneous media.
In contemplating the fungus theory of pellagra it is interesting to note that of all the diseases known to be caused by fungi, such as thrush, ringworm, pinta, tinea imbricata, mycetoma, actinomycosis, pneumonicosis, not one in any way resembles pellagra.
Of the more recent etiological theories concerning pellagra the following may be mentioned: Dr. Licorish of Barbados believes that the disease is due to an excessive sugar diet; Auld ascribes it to a magnesium infiltration from the ingestion of maize; Dr. Pixley of South Carolina incriminates rancid fats; and Dr. Mizell of Georgia considers cotton-seed oil as an important factor. Kaubitschek thinks the cutaneous lesions due to an elementary poison, probably a lipoid constituent of corn plus the chemical rays of sunlight. Smith and Hedger suggest that Diplodia zeœ may have some connection with pellagra.* Long is inclined to incriminate the intestinal ​amœbæ. Prof. Alessandrini of Berne first (1910) ascribed the disease to a filaria, the eggs of which he stated he had found in the skin of pellagrins, but later (1914), together with Scala, asserted that the primary cause of the disease is a deficiency of alkaline salts in water. Without these, silica, which is normally present in water, cannot be neutralized, and its presence gives rise to pellagra.
In examining the numerous observations that have been made, there is one fact which stands out very prominently, and that is that each investigator claims to have reproduced true pellagra, either in animals or man, sometimes in himself, by inoculating beneath the skin, injecting into the veins, or administering per os the special organism or toxic product which he happens to have isolated. But the peculiar symptoms and anatomical lesions of pellagra, together with its epidemiology, seasonal habit, and geographical distribution, show very clearly that the disease must have one specific cause and cannot be brought about by each, or all, or any of the numerous aforementioned nematodes, protozoa, fungi, bacteria, and chemical products. It would be unwise, therefore, to place much reliance on these experiments. The interpretation of experiments is often as fallacious as the interpretation of ordinary natural facts. The history of the investigation of almost every disease furnishes examples in plenty.
The maize theory of pellagra is based chiefly on the belief that the disease appeared soon after the introduction of maize into Europe, and that it everywhere followed the extension of maize cultivation, and increased with the more general adoption of the new cereal as an article of food. This opinion has been repeated by almost every writer on pellagra. Neither the statement nor the argument is indisputable. Maize was introduced into Europe by the Spaniards from South America soon after the discovery of the western world, and the history of its cultivation in Spain, France, and Italy begins about the middle of the sixteenth century. Italian pellagrologists, eager to establish a relationship of cause and effect between the introduction of the new cereal into Italy and the first appearance of pellagra, which ​they assign to the beginning of the eighteenth century, hold that the incriminated corn was not extensively cultivated until after the middle of the seventeenth century, ignoring all evidence of its cultivation, sale, and consumption between the middle of the sixteenth and the beginning of the seventeenth centuries.
Although not recognized prior to the middle of the eighteenth century, there is every reason to believe that pellagra is as old as any other disease. Owing to the complex, protean, and frequently obscure nature of its syndrome, we lack definite information that might enable us securely to trace the history of pellagra in the medical records of the past; but wherever it occurs— in Italy, Spain, France, Roumania, Hungary, Egypt, the United States of America, the West India Islands those who first discovered it never claimed that it was a new disease, but invariably affirmed that it had long existed in the respective locality although confounded ' with other maladies. The wide range of pellagra throughout Europe at the time of its first recognition is irrefutable evidence of the antiquity of the disease, because pellagra is essentially a place-disease, and has never shown any disposition to spread after the manner of cholera and plague. It has been objected that if pellagra existed long before it was recognized, and if maize was introduced earlier than supposed, the possibility that they appeared together still remains, and the dates would merely be moved back. That is not so, because whilst maize was certainly not imported prior to the discovery of America by Columbus in 1439, there is strong scientific evidence to prove the great antiquity of pellagra, and, in any case, ample historical evidence to prove that the disease was widely distributed throughout both Spain and Italy at a time when maize could not have become a staple in the alimentation of either country.
Against the maize theory stand two decisive facts: (1) The occurrence of pellagra in people who have never eaten maize, as, for instance, in the British ​Isles; (2) the absence of pellagra amongst maize-eating populations living in close proximity to or in the very midst of pellagrous areas, as evidenced by the well-known immunity of towns in Italy. To overcome these embarrassing facts, so telling against the maize theory, the comfortable term " pseudo-pellagra" was invented. The disease is pellagra when it fits in with the orthodox theory and when it can be connected in any way with maize; but when this is not possible, the disease becomes a " pseudopellagra " !
After pointing out (Brit. Med. Journ., 1905) how unsatisfactory are the prevailing theories as to the causation of pellagra, Sambon suggests that it probably belongs to the protozoal group of diseases. The skin lesions, the chronic course, the implication of the nervous system, the beneficial effect of arsenical treatment, he claims, support the protozoal hypothesis. The mononuclear increase in the blood of pellagra patients is an additional argument in favour of the suggestion.
Sambon goes farther than this. He has advanced the hypothesis that the hitherto unrecognized protozoal cause of pellagra is insect-borne, and probably by some blood-sucking midge belonging either to the Chironomidæ or to the Simuliidæ. In favour of this hypothesis he adduces not only the analogy of malaria and trypanosomiasis, but the facts that pellagra is a rural and not an urban disease; that it affects principally field -labourers; that it occurs in the neighbourhood of streams or other water bodies. In his reports he describes many circumstances observed in Italy and elsewhere in support of his views perhaps the most telling is that which refers to the islet of Burano, in the vicinity of Venice. Pellagra is common in Burano and on the neighbouring mainland; but whereas on the mainland the principal sufferers are women, in Burano the disease is confined to men. There are no streams in the town-like islet of Burano, and consequently no Simuliidæ. How account, then, for the local pellagra? And how account for the disease being confined to men? ​According to Sambon, the explanation lies in the circumstance that the men, in their vocation as fishermen, often have occasion to visit the mainland and to pass the night there, and are consequently exposed to the bites of Simuliidæ and other midges; whereas the women, having no occasion to leave the island, escape infection.
Fig. 71.—Simulium larva. (Drawn by W. McDonald.)
Simuliidæ are minute (1-4½ mm.), thick-set, dark-coloured flies, provided with moderately long legs often banded with white, and large, broad, transparent wings. They are known in America as "buffalo gnats." They have a peculiar dancing flight, and the females are vicious biters (the males are inoffensive). The eggs are laid in patches on stones or water-weeds, to which they become attached. The larvæ are unmistakable; they have an elongated, club-shaped body, of a greenish-brown colour, supplied with a large terminal sucker at the larger posterior extremity, by means of which they attach themselves to pebbles, water-weeds, and drift-wood. The larva spins a silken thread which offers a further means of attachment and serves to weave the characteristic pocket or slipper-like cocoon at the time of pupation. The cocoon is open at the larger anterior end, from which protrudes the anterior portion of the pupa with two lateral tufts of long feathery filaments. (Figs. 71, 72, and 73.)
Chironomidæ.—Of this large family only a few genera (Culicoides, Leptoconops, Ceratopogon) come under suspicion. They are exceedingly minute dusky flies, the females seldom more than 1½ or 2 mm. in length. They usually occur in swarms, and are chiefly confined to wooded and shady spots at the mouth of rivers and in the vicinity of the sea. They are among the most irritating and bloodthirsty of insects. The larvæ are worm-like and transparent. They are aquatic, and are found at the surface of stagnant water in ponds, pools, hollow tree-stumps, and epiphytic plants.
Goldberger, who failed to communicate the disease to any one of 16 men by the administration of the discharges, secretions, and tissues of no fewer than 67 pellagrins, rejecting the idea of a germ cause of ​pellagra, quotes experimental evidence to the effect that deficient fresh animal and leguminous food and excess of starchy foods induce pellagra. He recommends a diet in accordance with this view—a view held by many of his compatriots, and supported, though by no means established, by the fact that the attendants of pellagrins in asylums and elsewhere do not contract the disease as they possibly might were it of germ origin.
Fig. 72.—Simulium pupa in cocoon. (Drawn by W. McDonald.)
Since the establishment of the vitamine theory of beriberi and scurvy a similar etiology has been suggested for pellagra.
Symptoms.—Pellagra visually begins with feelings of weakness and a consequent disinclination to work. The patient is pale, has a peculiar staring look, and complains of headache, giddiness, and vague ​but often severe pains in the back and joints. His character changes; he becomes irritable, and at the same time stupid and morose.
At first the tongue is coated; later it loses its epithelium, the denudation extending not infrequently to the palate and gullet, and giving rise to a sore condition, often accompanied by a saltish taste and copious salivation. The gums may be swollen and bleed easily, a condition which gave rise to the name "Alpine scurvy." There may be eructations of gas, nausea, and vomiting. The appetite is variable. The epigastric region, and sometimes the lower part of the abdomen, are tense and painful. Constipation may be present, but in many instances there is diarrhœa of pale fermenting stools resembling those of sprue, and the stools may contain blood.
Fig. 73.—Simulium nigrogilvum, imago. (Drawn by W. McDonald.)
From the commencement an erythema, not unlike a severe sunburn, is observable on those parts of the body which are, as a rule, unclothed and exposed to the sun. The eruption is symmetrical and characteristic. (See Frontispiece.) It appears suddenly, first on the back of the hands and feet, then on the forearms, legs, chest, neck, face, and, it may be, on the perineum, or on the female genitalia. The patches of erythema are irregular in outline and intensity. The affected area is swollen and tense, and the seat of burning or itching sensations which become particularly acute on exposure to the sun. The congestion disappears completely, but temporarily, on pressure. Petechiæ are common on the affected parts, and blebs may form with clear, opaque, or blood-stained contents of feebly ​alkaline reaction. The eruption usually lasts about a fortnight, and is followed by desquamation, which leaves the skin rough, thickened, and permanently stained of a light sepia colour. It is on account of this roughness of the affected skin that the disease is called " pellagra," an Italian word meaning rough skin.
Implication of the nervous system is indicated by tremor of the tongue, exaggerated deep reflexes, and mid-dorsal spinal tenderness. The patient suffers from obstinate sleeplessness, occasionally from uncontrollable sleepiness. He experiences great weakness, especially in the lower extremities, and is subject to peculiar attacks of giddiness, with a tendency to fall forwards or backwards. Another characteristic symptom is a feeling of ourning in the palms of the hands and the soles of the feet. " Chvostek's sign," mechanical irritability of the facial nerve, is said to be present in the majority of cases.
As a rule there is no marked permanent elevation of temperature, but periods of slight fever occur irregularly.
Two or three months after onset the symptoms abate and, although the affected skin areas remain dark-coloured and rough, the disease appears to be arrested. Next spring, however, the whole series of phenomena recurs in a more severe form. The eruption assumes a darker colour. The depression of spirits deepens into melancholia, which may have maniacal interludes, with a peculiar tendency to suicide, especially by drowning. The general feeling of weakness increases, the patient loses weight and is unable to work; his gait becomes uncertain and somewhat of the spastic paraplegic type. The pains in the head and back become very acute, and there may be lightning pains, cramps, twitchings, tremors, and even epileptiform seizures of the cortical variety. Diarrhœa may now be troublesome.
For several years the disease may thus recur in the spring with increasing severity. The patient becomes greatly emaciated, paralytic, and completely demented. Helpless, bedridden, suffering from incontinence of urine and uncontrollable diarrhœa, covered ​with bedsores, and neglected, he dies from exhaustion or from some intercurrent disease.
The duration of pellagra is exceedingly variable. It may last only two or three years; it usually extends to ten, fifteen, or more.
In a proportion of cases, more especially if the patient leaves the endemic area and comes under favourable hygienic influences early in the disease, recovery may take place.
Cases differ considerably. In some the nervous symptoms predominate, in others the gastro-intestinal, in others again the cutaneous. Forms of hyperæs thesia may occur in different regigns of the body. Ocular symptoms, such as ptosis, hemeralopia, diplopia, amblyopia, mydriasis, are not uncommon. The urine is generally alkaline, and may rapidly become ammoniacal. It may also contain tube casts and traces of albumin. The erythrocytes and hæmoglobin are diminished. Sambon and Terni in Italy, Grigorescu and Galasescu in Roumania, have noticed a relative increase of the mononuclear leucocytes, a point differentiating the eruption of pellagra from ordinary erythemas; but it cannot be said that, although usually disturbed, the differential leucocyte count is constant or characteristic.
A very acute form has been described under the name of " pellagra typhus." In this there are intense prostration, high temperature, muttering delirium, pronounced nervous tremor, generalized rigidity and convulsions.
It has been estimated that in Italy from 4 to 10 per cent, of the pellagrins become permanently insane. Similarly, in the United States of America the pellagrins are becoming a notable feature in the lunatic asylums.
Morbid anatomy.— The pathological characteristics essential to pellagra are usually obscured by complicating diseases.
A constant and striking feature is the great emaciation. The viscera show chronic degenerative changes, particularly fatty degeneration and a characteristic deep pigmentation. The intestinal walls ​are greatly attenuated through wasting of their muscular coat, while at the same time the mucous lining is hyperæmic and, not infrequently, ulcerated. The liver and spleen are usually atrophied. The suprarenal capsules may be larger than normal, and the cortex may be black, while the medulla is whitish in colour, but as a rule they are perfectly normal.
There may be actual wasting of the brain, and the ventricles may be distended by an excess of fluid. In the cord the lateral columns and the crossed pyramidal tract are especially implicated, but the direct cerebellar tracts usually escape. The anterior cornual cells are frequently atrophied and deeply pigmented. The posterior columns do not escape, the median portion being often degenerated. The degenerative changes in the lateral columns are chiefly in the middle and lower third of the dorsal region, those of the posterior columns principally in the cervical and upper dorsal region.
Mott (Brit. Med. Journ., July 3rd, 1913) has given a detailed account of the histological changes in the nervous systems of two cases of pellagra one of English, the other of Egyptian origin. He remarks as to the changes in the cerebrum, cerebellum, pons, medulla, and spinal cord, that in none of the sections was there any evidence of meningeal or peri vascular infiltration with lymphocytes, plasma cells, or polymorphonuclear leucocytes. This absence of chronic meningo-encephalitis, a chronic inflammatory condition so characteristic of certain protozoal diseases, contraindicates the protozoal theory of pellagra, although it cannot be said to disprove it, for in malaria the vessels may be crowded with parasites and yet no perivascular or meningeal reaction be detectable. Moreover, although all the changes were like those produced by a chronic toxæmia, the cause of that toxæmia has not been demonstrated. All the posterior spinal ganglia cells showed, in varying degree, a marked chromatolysis, swelling of cells, and disappearance of Nissl's granules, and all the anterior horn cells and their hornologues in the medulla and pons a varying degree of peri​nuclear chromatolysis. There was marked chromatolysis of the cells of Clarke's columns. The Betz cells of the cortex and the cells of Purkinje showed similar changes, but in a less degree.
Diagnosis.— Of course, doubtful cases are occasionally encountered, but a localized erythema associated with nervous symptoms, particularly mental symptoms, great debility and seasonal recurrence, in a person in or coming from a pellagrous district, can hardly be confounded with any other disease.
Treatment.— Arsenic in large doses is now regarded as a drug of value in the treatment of pellagra. Fowler's solution by mouth 5 drops two or three times daily, increased by 1 drop daily until evidences of a toxic nature are induced or hypodermically in combination with carbonate of soda (3 to 5 gr.) two or three times a week, is said to be productive of good results if given early in the disease, and, of course, combined with good hygienic conditions and removal from the endemic area. Atoxyl, soamin, and salvarsan have also been commended. No case should be regarded as cured until the patient has been absolutely free from all symptoms for at least two years.
In its advanced stage the disease is practically incurable. In Italy the Government, basing its action on the maize theory of pellagra, has provided grain drying appliances for bakeries, and other hygienic advantages, including better house accommodation, also special asylums (pellagrosari) for the treatment of the disease in its earlier stages. It is stated that a decrease of the malady has followed these measures. Notwithstanding, pellagra seems to have increased of late years, especially round Perugia and in other districts of northern Italy in which these measures have been most strictly carried out.
As there has been no instance of a nurse or attendant in any of the lunatic asylums of the United States acquiring the disease, it is evident that pellagra is not a directly communicable disease, and that therefore any apprehension on this account is unwarranted.
* ↑ * Until 1912 pellagra was not known to be endemic in the British Islands. It is true that three or four cases had been described and correctly diagnosed between 1863 and 1909, but they had not attracted any attention. Indeed, Sand with, who had had the opportunity of studying pellagra in Egypt, stated that the published accounts did not tally with the disease as he knew it, though the symptoms were somewhat similar to those of pellagra. Since 1912 Sambon has had the opportunity of examining over a hundred cases of indigenous pellagra in England, Scotland, and Wales, and he has established that pellagra is widely distributed throughout the British Isles, having endemic stations as far north as the Shetlands. He also believes that the disease is of long standing in these isles, as evidenced by the
* ↑ * Tizzoni claims to have solated a bacterium, the "Strcpto-bacillus pellagrœ, " from the blood, cerebro-spinal fluid, and tissues of pellagrins, and to have been able to transmit the disease to monkeys by the inoculation of the organism.