Transcriber’s notes:
In this HTML version, page numbers are listed in the right margin, hyperlinks are indicated by a dotted underline, and transcriber comments are marked by a red dashed underline; scrolling the mouse over such words will reveal the original text. Footnote markers in the text are hyperlinked to the footnotes located at the end of the book.
The book contains numerous spelling inconsistencies. No change has been made to those representing archaic spellings (e.g. somethimes, urin, feavers, joynts) and those occurring in quotations. Spelling variants occurring with similar frequency have been left in their original form (e.g. Röntgen/Roentgen, rachitic/rhachitic, albumen/albumin – the correct spellings is used for egg albumen but both are used randomly for serum/urine albumin). Most other spelling inconsistencies have been changed to the more-frequent or more-accurate form (e.g. twofold→two-fold, guinea pig→guinea-pig, oedema→edema, neuroedema→neuredema, gm.→g., Luborsch→Lubarsch, Bauman→Baumann, McCluggage→McClugage, Eijkmann→Eijkman). Although the spelling of 'fæces' and its adjective 'fecal' is not consistent, the two spellings are used consistently throughout the book and therefore have not been altered. Similarly 'hemorrhage' and 'hemoglobin' are consistently spelt thus, while other words pertaining to blood consistently use the æ ligature, e.g. 'hæmatemesis', 'hæmatoma', 'hæmaturia', 'leukæmia', 'hyperæmia'.
Wrong or missing French accents and typos have been corrected where necessary. German expressions in the bibliography contain various apparent inconsistencies that have not been changed because of my unfamiliarity with the language and what was perhaps legitimate at the time of writing (e.g. Moeller-Barlow'sche Krankheit, Moeller-Barlow'scher Krankheit, Moeller-Barlowscher Krankheit and Barlow'schen Krankheit; Muench. med. Woch., Muenchn. med. Woch. and Muenschner med. Woch.; Beiträge z., Beitraege zur, Beitrag zur). The term Gernest-mark on p. 108 should probably be geruestmark (or perhaps gerüstmark) as used elsewhere in the book (pp. 96, 107, 108 and 128).
The book also contains numerous hyphenation inconsistencies. Some of these have been altered to conform with the most common usage in the text, but most have not been changed because hyphenation is notoriously variable and subject to fashion.
Subheading use is somewhat inconsistent; for example, under the subheading Alimentary Tract in chapter IV, there appear various non-alimentary items, and in the same chapter Microscopic Pathology appears as a stand-alone subheading whilst its equivalent Gross Pathology is relegated to an in-line paragraph introduction.
The bibliography contains two very similar references attributed to Gee. The second appears to be a duplicate of the first, but it is probable that the title is incorrect because the publication details (1889, XXV, 85) relate to a different paper by Gee entitled ‘Bloody Urine the Only Sign of Infantile Scurvy’, and although there are several comments in the book about scurvy and haematuria (blood in the urine), e.g. p. 204, none cite Gee's paper.
The second entry for Morse, J. L. in the bibliography should be numbered as (2) and the source should be Boston Med. and Surg. Journal, 1914, CLXX, 504. (not Jour. Am. Med. Assn.)
Inconsistent punctuation in the bibliography list has been corrected (e.g. semicolon→colon).

SCURVY
PAST AND PRESENT

BY
ALFRED F. HESS, M.D.

CLINICAL PROFESSOR OF PEDIATRICS, UNIVERSITY AND BELLEVUE HOSPITAL
MEDICAL COLLEGE, NEW YORK CITY

ILLUSTRATED

PHILADELPHIA AND LONDON
J. B. LIPPINCOTT COMPANY

COPYRIGHT, 1920, BY J. B. LIPPINCOTT COMPANY

PRINTED BY J. B. LIPPINCOTT COMPANY
AT THE WASHINGTON SQUARE PRESS
PHILADELPHIA, U. S. A.

PREFACE

Interest in scurvy has been stimulated in the last few years as the result of a new and broader conception of nutrition. It has come to be realized that in addition to the substances heretofore recognized as of essential importance in the dietary—the proteins, fats, carbohydrates and the salts—there is still another group, termed “vitamines,” “accessory food factors” or “food hormones,” which must be included in order to render the diet complete and adequate. It has become increasingly evident that the attention of physiologists and of clinicians has been focussed too sharply and too narrowly on the caloric value of foodstuffs. At the same time we have begun to appreciate the existence of a group of nutritional disorders which depend largely on a deficiency of these illusive vitamines or food factors, and which evidently are of vital importance to the welfare of the individual and of mankind. Scurvy is one of this newly-constituted group, and due to this association has acquired a fresh and broader significance. It is in this light that the intensive research work must be interpreted, which has been applied within the past few years, both in this country and abroad, to problems relating to this disorder. It is clear that the subject is in its infancy, and is destined to participate in a consideration of many of the nutritional and infectious diseases of the adult and the child.

The World War has tended also to demand a renewed consideration of scurvy. This disorder has played a rôle in all wars—in the campaigns of the Cæsars, the pilgrim ages of the Crusaders, and the numerous wars of the last century. In the recent war it existed among the various armies, particularly those in the East, to an extent greater than at first was realized. In Mesopotamia it is stated to have been one of the decisive factors in forcing the surrender of the British at Kut. Its incidence, however, was not limited to the military forces. Reports from England and the continental countries clearly indicate that scurvy prevailed among the civilian population during the past few years to a degree unknown in peace times. This was especially true of infants and children.

For the past seven years I have been engaged in an investigation of scurvy both in the laboratory and in the clinic, and have treated various aspects of the subject in a large number of articles published in various medical journals. In the course of these studies there has been ample opportunity for a comprehensive review of the widely-scattered literature. No treatise on scurvy has been published in English since the classical work of Lind in 1772. The time, therefore, seemed opportune to gather into one volume the recent advances in this field and to offer to the clinician, to the hygienist, and to the biological chemist a presentation of the existing status of this important nutritional disease.

It is with pleasure that I acknowledge my obligation to Dr. Lester J. Unger, who has assisted in carrying out much of the work described in this volume. Thanks are due also to Dr. Charles Gottlieb for the radiographs which are here reproduced, and to Dr. Gertrude McCann for seeing the work through the press. To my associates in the clinic who shared in the observations, and to friends who read various chapters in the course of their preparation, I wish to express my appreciation.

Alfred F. Hess.

New York,
August, 1920.

CONTENTS

ILLUSTRATIONS

SCURVY
PAST AND PRESENT
CHAPTER I
HISTORY OF SCURVY[1]

Outbreaks on Land.—Like many other diseases, the life history of scurvy shows several distinct phases. We hear of it first as a plague, infesting armies and besieged towns; then as a dread disease, decimating the sailors of the navy and of the mercantile marine, and, since the end of the last century, more often as a nutritional disturbance, endangering the health of infants. Very recently it has acquired an entirely new interest, as the representative of a class of disorders which has revealed the essential importance to man of unknown dietary factors.

It is difficult, as may be imagined, to define with precision the earliest description of scurvy, as the older references are so vague as to be open to individual interpretation. The reference of Hippocrates to a large number of men in the army who suffered from pains in the legs and gangrene of the gums, which was accompanied by loss of teeth, seems sufficiently definite to be identified as this disease. The Greek, Roman and Arabian writers do not seem to have been acquainted with scurvy. This is as we should expect, for fruits and vegetables grew in such plenty in these southern countries that scurvy must have been a disorder of rare occurrence.

An interesting early description of scurvy, and one which is quite convincing, is that of de Joinville, who accompanied the Crusaders in their invasion of Egypt under St. Lewis, about the middle of the thirteenth century. He refers to the lividity and spongy condition of the gums, and describes how “the barber surgeons were forced to cut away the dead flesh from the gums to enable the people to masticate their food” he describes their debility, their tendency to faint, and the black spots on their legs. The disease broke out in Lent, during which time the soldiers partook of no meat, but consumed a species of eel which they believed “ate the dead people” and therefore led to this loathsome disease.

It is probable that scurvy existed in the northern parts of Europe and Asia ever since they were settled by man. We should hardly expect to have records of this condition, in view of the low educational status of the people, their greatly restricted literature, and their lack of intercourse with the people in the southern countries. In the sixteenth century, with the development and spread of education, we begin to hear of scurvy from various sources. Claus Magnus, in his “History of the Northern Nations,” published in 1555, described the disease which he tells us flourished among the soldiers in the camps and in the prisons. About this time Ronsseus, Echtius and Wierus wrote special treatises on this disease, and recommended many dietary measures which we recognize to-day as most efficacious. The number of monographs on this subject multiplied with great rapidity in the course of the next twenty-five or fifty years; none of them, however, added anything essential to our knowledge. In 1645 the Faculty of Medicine at Copenhagen published a “consilium” for the benefit of the poor, treating of the causes, prevention and cure of this disease, which was prevalent among the Danes and other northern nations.

The colonists of the northern part of America were sorely afflicted with scurvy. It is said that the French met with such high mortality during the severe winters in Canada, that they frequently debated the wisdom of abandoning this settlement. This was true also in regard to the English and their settlement in Newfoundland. Indeed, it was scurvy which forced the early settlers in Hudson Bay to discontinue their intentions of colonizing that region.

In an essay published in the eighteenth century (1734), Bachstrom described an epidemic of scurvy which occurred in 1703 during the siege of Thorn, in Prussia, by the Swedes, which caused the death of 5000 of the garrison, in addition to a large number of the inhabitants. It is interesting to note that this epidemic took place in the middle of the summer, and not in the cold season. From this time on we meet with many descriptions of scurvy in connection with the wars at various periods. For instance, in the Russian armies, in the war between the Austrians and the Turks in 1720; in the English troops who had taken Quebec from the French in 1759; among the French soldiers in the army of the Alps in the spring of 1795. It is unnecessary to review these accounts in detail. This period is distinguished rather by the appearance of a great classic on Scurvy, the work of the English naval hygienist, Lind (1752). This book has intrinsic value to-day, and, at the time it appeared, served to crystallize the conception of scurvy, which had been stretched out of all proportions to include an ever-increasing conglomeration of clinical conditions. Scurvy had become the Alpha and Omega of professional routine, the catchword of the day, the asylum ignorantiæ of the practical man. Into this chaos, as Hirsch expresses it, “the first beams of light fell when Lind’s classical work appeared.”

It will be of little value to consider the great number of epidemics of scurvy which occurred from this time to the present day. They may be found in tabular form in the excellent survey of scurvy by Hirsch. The literature of this long period may likewise be found in a work of encyclopædic character, that of Krebel, which gives the titles, with a summary of the various articles on this subject, appearing to the year 1859. If we look over the chronological table compiled by Hirsch, we note a remarkable similarity regarding the incidence of the recurring epidemics. In almost all cases they broke out among troops, whether in Russia, in India, in Africa, or in our United States. The epidemics which are not attributable to military life or campaigns are found to have taken place generally in prisons, insane asylums, poorhouses or houses of refuge and correction. It would seem that no war is omitted from this list of sickness and death. There are in all 143 land epidemics between 1556 and 1877, two occurring in the sixteenth century, four in the seventeenth, 33 in the eighteenth, and 104 in the nineteenth century. The marked increase in the nineteenth century occurred in institutions, in asylums and prisons, rather than in the armies. This fact may be ascribed to altered social conditions which led to a great multiplication of eleemosynary institutions.

Coming down to more recent times, we learn that scurvy occurred extensively during the Crimean War, and that it was prevalent also among the troops in our own Civil War. In the “Medical and Surgical History of the War of the Rebellion,” we find the following statements:

“A scorbutic tendency was developed at most of our military posts during the winter season, after the troops had been confined to the use of the ordinary ration with the desiccated vegetables. The latter in the quantities failed to repress the disease. At posts which could be readily supplied with potatoes only the taint was manifested, on account of a want of liberality in the issues.” And again: “Among the white troops during the five and one-sixth years covered by the statistics, 30,714 cases of scurvy were reported; and 383 deaths were attributed directly to that disease.”

Munson writes: “It (scurvy) prevailed among our troops during the Civil War and its recognition was a surprise and shock to professional ideas preconceived from practice in civil life.”

As is well known, the besieged in Paris during the Franco-Prussian War in the winter of 1870–71 suffered severely from scurvy. The accounts of their pitiable condition have been portrayed for us by numerous French writers (Delpech, Hayem, Lasèque and Legroux). The people lived mainly on rice and bread, with an occasional addition of potatoes or horse meat. The winter was exceptionally severe, which was supposed to have intensified the scorbutic condition. Not only were the inmates of the prisons on the Seine attacked, numbering about one thousand, but even the patients in the military hospitals developed the disease. It is of interest to remember that the siege lasted but little over four months, from September 17th to January 27th, the date of the armistice.

In the Russo-Japanese War, after the siege of Port Arthur, it was found that one-half of the garrison of 17,000 men had scurvy.

Although there are certain parts of the world where scurvy is of frequent occurrence, no country has been entirely free from it. As might be expected, it has been particularly prevalent in the North, where vegetation is scanty—in Greenland, Alaska, Russia and the Baltic States. It has likewise prevailed in the tropics when the crops have failed. India has been conspicuous for its large number of epidemics; some years ago scurvy occurred in Arabia among the English troops stationed at Aden, both among the British and the native troops. A recent communication from Aruba, a small island of Dutch Guiana, lying north of Venezuela, illustrates how devastating scurvy still is in some parts of the world. This account tells of 3000 cases of this disease which occurred in 1915 among a population of less than 10,000, owing to the fact that the crops had failed almost entirely during the years 1912, 1913 and 1914.

Fig. 1.—A comparison between the requisitioned quantity (in thousand pound units) of potatoes and other vegetables, and the quantity received per month by an institution in which more than 200 cases of scurvy occurred at the beginning of April, 1916. The total height of column represents the amount needed and requisitioned; the solid black portion the amount received. The number of inmates in the institution remained approximately the same.
The chart illustrates our great dependence on the potato during the winter months. This is due not only to its intrinsic antiscorbutic potency, but, probably quite as much, to the fact that fully twice as many pounds of potatoes are consumed during the winter as of all other vegetables combined. Therefore, if this crop fails or is dehydrated, scurvy will develop in the spring.

It is important for us to realize that we are still dependent on the annual crops for our protection from scurvy; in other words, the world is leading a hand-to-mouth existence in regard to its quota of antiscorbutic food. The truth of this condition has been realized for Ireland, sadly illustrated by numerous epidemics, notably the great epidemic of 1847 reported by Curran. It was demonstrated by the outbreaks of scurvy in Norway in 1904 and 1912, and was brought to the attention of many in the United States in the spring of 1916. In this year our potato crop fell far below the normal, with the result that scurvy appeared in various parts of the United States, especially in institutions (Fig. 1).

The fact that scurvy may occur in any land and climate, even in the garden spots of the world, is strikingly shown by the epidemics reported from Algiers, and the ravages of this disease among the gold seekers in California in 1849. Nothing could be more incongruous than the occurrence of a deficiency disease in this land of plenty.

Outbreaks at Sea.—It is doubtful, however, whether attention would have been focussed so early and so sharply on scurvy, had it not been for the voyages of exploration undertaken in the sixteenth century. These long trips on sailing vessels, where for many months little or no fresh vegetable or animal food was obtainable, were almost as if designed to make a test of the dietetic origin of scurvy. The result was inevitable—five to six months after the ships were out of touch with land, the majority of the crew frequently were incapacitated by this disease, thereby wrecking many an expedition.[2]

The earliest account of the outbreak of scurvy at sea is that of Vasco de Gama, who in 1497 discovered a passage to the East Indies by way of the Cape of Good Hope. The narratives of subsequent explorers, especially those of Cartier and of Drake, are replete with descriptions of the ravages of scurvy. The expedition of Lord Anson in 1740 is always cited as a memorable example of an undertaking which foundered as the result of scurvy. After a cruise of four years, this expedition had lost from this disease more than four out of five of the original number of its crews. In striking contrast to this picture, and to that furnished by the voyages of earlier navigators, is that of Captain Cook, who in 1772 undertook a voyage lasting over three years, sailing from 52° north to 71° south, with a loss of but one of his crew from disease, and that not from scurvy. This remarkable feat, more than any other, centered attention on the feasibility of preventing scurvy, and resulted in measures tending to eradicate it from the navy. Captain Cook attributed the absence of scurvy among his crew to “sweetwort,” an infusion of barley, which he prepared fresh and served liberally. He also prized the antiscorbutic value of sauerkraut.

We find accordingly in 1795, at the instance of Sir Gilbert Blaine, that improvements were introduced in the victualling of the fleet. As the result of a regular ration of lemon juice, the incidence of scurvy fell precipitously. It is due largely to this provision that between the years 1779 and 1813, according to the statistics of Sir Jay Barrow, the morbidity and the mortality in the British Navy was decreased by 75 per cent.

It has been shown that it took a generation after the efficacy of antiscorbutics had been demonstrated in various expeditions, for an antiscorbutic to be included in the ration of the navy. The merchant marine of England was far more conservative, and for many years after scurvy had been eradicated from the navy we still read of its occurrence on the vessels making voyages to India, China and Ceylon. Gradually, however, its incidence became less and less. Its toll of death, before preventive measures were employed, may be appreciated from the fact that it has been estimated that scurvy destroyed more sailors than all other causes incidental to sea life, including the great slaughter of naval warfare. Sir R. Hawkins stated in the latter part of the sixteenth century that he could give an account of 10,000 mariners who had been destroyed by scurvy during the twenty years that he had been at sea.

As is well known, scurvy has played an important rôle in Arctic and Antarctic explorations, and has been the cause of the failure of many of these expeditions. It is now realized that the development of scurvy is quite preventable, that if a sufficient quantity of meat (especially raw meat) is consumed, explorers can be entirely independent of a supply of fresh vegetables. This fact was brought out by the Arctic Survey Committee (British), who “were appointed to enquire into the causes of the outbreak of scurvy in the recent Arctic expedition” (1877), and who reported that it may result from an absence of fresh meat. That this conclusion was sound has been proved by the experiences of Nansen and of Johansen, who wintered safely in Franz-Josefsland on a diet of meat and bacon. More recently Stefánsson has carried out successful Arctic explorations, depending entirely on fresh meat as antiscorbutic foodstuff and making no provision whatsoever for vegetable food.

Infantile Scurvy.—Glisson, to whom we owe the first description of rickets, likewise was the first to recognize scurvy in infants. In his classic treatise on rickets, written in 1668, he writes as follows:

“The scurvy is sometimes conjoyned with the affect. It is either hereditary, or perhaps in so tender a constitution contracted by infection, or lastly, it is produced from the indiscreet and erroneous Regiment of the infant, and chiefly from the inclemency of the air and climate where the child is educated.”

“The scurvy complicated with this affect hath these signs: 1. They that labor under this affect do impatiently indure purgations; but they who are only affected with the Rachites do easily tolerate the same. 2. They are much offended with violent exercises, neither can they at all endure them. But although in this affect alone, there be a kind of slothfulness and aversation from exercise, yet exercise doth not so manifestly, at least not altogether so manifestly hurt them, as when the scurvy is conjoyned with the Rachites. 3. Upon any concitated and vehement motion they draw not breath without much difficulty, they are vexed with diverse pains running through their joynts, and these they give warning of by theyr crying, the motion of the Pulse is frequent and unequal, and somethimes they are troubled with a Palpitation of the Heart, or threatened with a Lypothymie, which Affects are for the most part soon mitigated, or altogether appeased by laying them down to rest. 4. Tumours do very commonly appear in the Gums. 5. The urin upon the absence of the accustomed feavers is much more intense and increased.”

Glisson’s description of scurvy was entirely lost sight of, overshadowed by his description of rickets, so that for over two hundred years no word of infantile scurvy is to be found either in the English or other literature. There is no doubt that from time to time cases must have occurred, but they were looked upon probably as rickets or as a manifestation of one of the hemorrhagic diseases.

In 1859 Moeller described some cases which evidently were scurvy, but which he termed “acute rickets.” He realized that they presented a novel clinical picture but failed to recognize that they represented a disorder quite distinct from rickets.[3] This article was followed within the next few years by reports of other German writers (Bohn, Steiner, Foerster) who, accepting Moeller’s point of view, considered these cases merely as an acute form of rickets. They were led to this erroneous conclusion chiefly on account of the lack of marked involvement of the gums, which they considered an essential sign, influenced by their conception of adult scurvy. This viewpoint has pervaded the German literature even to the present day, when it is still considered necessary to bring further evidence that infantile scurvy in its pathogenesis and pathology is identical with adult scurvy.

In 1871 Ingerslev, an assistant of Hirschsprung in Copenhagen, wrote a paper on “A Case of Scurvy in a Child,” which is quite convincing. Two years later Jalland, an English physician, reported a similar case of “Scurvy in a Ten-Months-Old Infant.” In 1878 Cheadle reported three cases of infantile scurvy with typical tumefaction of the gums, and obscure tenderness of the legs, and followed this paper by two others, which appeared in 1879 and 1882. Cheadle clearly recognized the disease as scurvy. However, as the title of his first paper—“Three Cases of Scurvy Supervening on Rickets in Young Children”—indicates, he considered it a condition engrafted upon rickets. About this time (1881) Gee presented a brief but accurate account of five cases of scurvy which he termed “osteal or periosteal cachexia.”

In 1883, Barlow published his classical paper on this subject, the first to furnish anatomical proof that this disorder of infants presented the pathological changes characteristic of adult scurvy. Previous to this publication there had been but one autopsy report, that by Moeller, which had been incorrectly interpreted. The work of Barlow was accepted remarkably quickly in England and in America, but less promptly on the Continent. This was probably due to the fact that infantile scurvy was occurring far more frequently in these two countries, and that the subject was open therefore to more prompt investigation. This increased prevalence of infantile scurvy in the two great English-speaking nations has continued to the present time, and no doubt is due to the extensive employment of artificial feeding and of proprietary foods. In 1894 not less than 106 cases were reported to the Academy of Medicine of New York City by various physicians, and in 1898 the comprehensive investigation of the American Pediatric Society appeared, which was based on 379 cases.

It was soon evident that infantile scurvy occurred to a greater or less degree throughout the civilized world. In France, Monfalcon had reported a case in 1820 which is sometimes referred to as the earliest case of infantile scurvy mentioned in the literature. It relates, however, to an older child and was published as a case of scorbutic rickets. Netter was one of the first in France to recognize the true nature of the disorder, and published several papers in 1898 describing typical cases. Infantile scurvy was, however, almost unknown in that country until what is termed “lait maternisé” and “lait fixé” came into vogue. This is apparent from a table prepared by Lecornu, which gives a list of all cases in the French literature between 1894 and 1904, and of the diets on which they came about. The former of these milk preparations is subjected to various manipulations and then heated to a temperature above the boiling point; the latter is shaken violently in a machine to render the fat globules smaller, and is then sterilized by one of the usual methods.

Switzerland has undergone an experience similar to that of France. Previous to 1903 only five cases of infantile scurvy had been published from that country. In this year Stoos published an additional five. In 1907 Bernheim-Karrer reported nine cases, all of which had developed on homogenized milk, a process very similar to that employed by the French to break up the fat globules. The increase of infantile scurvy in Switzerland may be judged by the fact that a commission was formed in the following year to investigate its occurrence.

In Germany there was for many years continued discussion as to the true nature of scurvy. Some believed it to be a form of rickets, others a form of scurvy; still others a combination of scurvy and rickets. Some thought it merely hereditary syphilis, and not many years ago Naegeli looked upon it as an entity distinct from scurvy on rickets. The subject attained additional importance through an epidemic of infantile scurvy, which broke out in Berlin in 1898, among infants who received milk from one of the largest dairies. The episode led to prolonged discussion in the Berlin Medical Society, and to several excellent papers, among which that by Neumann deserves particular mention.

The disorder has been reported in Holland by DeBruin, who recorded numerous cases; in Denmark, by Hirschsprung, who refused to recognize its scorbutic nature; in Italy, by Concetti, and by others. It was not long before there were reports of cases from almost every part of the world, including Australia (Money) and East India (Nichols).

In view of the fact that scurvy is endemic among adults in Russia, we should also expect to find infantile scurvy widespread in that country. In point of fact, quite the contrary seems to be the case. In connection with the great scurvy epidemic in Russia (1898–99), Tschudakoff personally examined over 10,000 persons and found 11.11 per cent. of the people sick with this disease. He states that in the course of this large experience he did not meet with a single case under the age of five years. Fuerst writes that Filatow, the great Russian children’s specialist, declared that he knew of no case of Barlow’s disease described in the Russian literature. This is not literally correct, as Doepp described an epidemic of scurvy in the St. Petersburg Foundling Asylum occurring in 1831. It serves to emphasize, however, the paucity of cases among infants in this great land of endemic adult scurvy. Lyabmow, in referring to the scurvy in Kazan, tells us that among 28,000 cases only a few infants were affected, and Rauchfuss made the statement at the International Congress at Copenhagen, in 1884, that although he had seen a great many cases of scurvy, he had never seen it in children one to two years of age. We shall not, in this place, comment on this interesting and apparently paradoxical situation, but shall have occasion to refer to it in considering the pathogenesis. It may be added that in Norway and Sweden, where scurvy is to some extent also endemic among the adult population, there is a similar lack of scurvy among infants.

Scurvy in the World War.—The greatest advance in medicine during the past generation has been in the fields of hygiene and preventive medicine. One might therefore have expected that the World War would have differed from previous wars in a notable absence of scurvy among the troops and the civilian population. This is true to a limited degree only. Reports which have been published in the course of the war, and especially since hostilities have ceased, show that the troops who were incapacitated by scurvy must have numbered many thousands. As was to be expected, scurvy occurred most often in Russia, where it is endemic. The largest number of cases was reported by Boerich, who as director of a Red Cross Central Station in Russia saw 1343 cases. Other German physicians who had charge of caring for the Russian prisoners give accounts of the occurrence of some hundreds of cases of scurvy. An article by Much and Baumbach gains added interest from the novel suggestion that scurvy is transmitted by means of vermin. That scurvy must have reached large proportions is shown by the fact that in July, 1916, a medical commission was sent by the Germans to investigate the scurvy in a Russian army corps, and that it was necessary to establish for this disease in every division a sanatorium comprising 100 beds. Hoerschelman, who wrote an account of this investigation, blames the bad hygienic surroundings, the lack of sleep, the overexertion, as well as the deficiency of food, for the occurrence of the epidemic. As usual, very few cases occurred among officers. He describes a number of instances where scurvy was feigned by rubbing the gums and making them bleed, or by irritating them with the juice of tobacco. These reports on scurvy in Russia bring us little new from a purely medical standpoint. They emphasize the occurrence of night-blindness as an early and frequent symptom. It is difficult to judge whether this manifestation was due entirely to the scurvy, or was in part the result of other deficiencies in the diet. For instance, Hift states that the night-blindness was cured by cod liver oil, or by the water in which beef liver had been cooked. This would point rather to a deficiency of the fat-soluble vitamine, as these substances could have little effect in curing scurvy. The cases reported by Wassermann, where neuritic pains in the legs played a considerable rôle, evidently are also not simple scurvy, but may well be the result of more than one food deficiency or a complicating ostitis. In the same way some reports show clearly that “hunger edema” complicated scurvy.

Scurvy occurred next in frequency among the nations neighboring Russia. Speyer tells us that a German sanitary commission was sent to Bulgaria largely with the object of investigating scurvy in that country. The excellent monograph on the pathology of scurvy just written by Aschoff and Koch was founded on an experience in Roumania among Turkish, German and Austrian soldiers. Added to its other woes the Servian army was visited by scurvy. Wiltshire gives us a description of this disease based on an observation of 3000 cases in the first half of the year 1917. In regard to scurvy in this part of the world, Morawitz writes that when he reached Roumania he was surprised to find scurvy the most prevalent disease in the army, and that since the spring of 1917 it was widely disseminated among the German troops. Lobmeyer writes of scurvy among the Turkish troops, and Disqué reports 500 cases among prisoners captured in Turkestan.

Along the Western front very few cases are described. There is an account by Korbsch of 51 cases in this area in 1915. Schreiber describes 30 cases among the German prisoners of war captured in the beginning of 1917, which were diagnosed as purpuric rheumatism. Arneth recounts that sporadic cases of scurvy occurred among the German troops, especially among the older soldiers, and that in many cases this was combined with the hunger edema. He attributes the scurvy to a dependence on dehydrated vegetables in the ration.

From all these accounts it is evident that scurvy played an important rôle in the general nutrition of the troops on the Eastern front. Probably it was of the latent variety, which is exceedingly difficult to diagnose, but which increases the susceptibility to infection, and intensifies the severity of all medical or surgical diseases. Von Niedner takes this point of view, stating that although scurvy had been largely prevented in this war, the obscure rudimentary type had not been eradicated. He remarks upon a fact, noted in our Civil War and other wars, that under these conditions eruptions assume a hemorrhagic character in typhoid fever, cerebrospinal fever, rheumatism and other infections. Pick made a similar observation at a medical meeting in Vienna in reference to scurvy in the Austrian army, drawing attention to the hemorrhagic diathesis existing among the troops and expressing the opinion that scurvy was occurring in this war as in previous wars.

Very little scurvy seems to have broken out among the British troops in Europe. Thirty-two cases were reported as occurring in the middle of 1915 at a divisional rest station in France. It made marked inroads, however, on the health of the Colonial troops in Mesopotamia. In the report of the Mesopotamia Commission we read that 7500 men were lost to the force in 19 weeks as a result of scurvy, and that this happened in the summer of 1916 although additions had been made to the ration in the previous spring. A conception of the extent of the scurvy may be formed from the accompanying table, published by Willcox:

It will be noted that thousands of cases occurred among the Indian troops. This was due to the fact that the British ate more potatoes and fresh meat. In his official report of the outbreak of scurvy among Indian troops, Colonel Hehir writes: “The only vegetable now allowed is 2 ounces of potatoes and the only fresh meat 28 ounces a week. It is very doubtful whether this authorized ration, if not supplemented by other vegetables and more meat, is sufficient to prevent scurvy.” In the account which this officer gives of the medical conditions during the siege of Kut-el-Amara, it is stated that there were 1050 admissions for scurvy, fully developed, incipient and latent. It is remarked that those Indians who ate horseflesh were decidedly less affected. From the fact that special hospitals for scurvy were established in June, 1916, at Bagdad, Amora and Basrah, it is evident that a large number of cases must have been encountered. Most significant in this connection, however, are the preventive measures which were instituted by the British government. A body of 256 men, designated as the Madras Gardener’s Corps, were dispatched to Mesopotamia to plant gardens all over the country and to supply packets of seeds to various units. At Bagdad alone their output of vegetables was over 400,000 pounds. This certainly constitutes a remarkable innovation in the hygiene of armies.

The French army was not entirely spared from scurvy. In 1917 Harvier, an army surgeon, was surprised to discover that 95 per cent. of the 800 troops of which he had charge suffered from scurvy; he tells us that other epidemic centres were recognized later outside this sector. Elsewhere we read of the occurrence of scurvy in France, involving 40 per cent. of the 1700 men of the South African Labor Corps, and that this disorder was still more serious in another company owing to the fact that it was not recognized (Dyke).[4] Benoit reported 63 cases which he discovered in 1917 among 300 laborers. According to his account, all these laborers received the same food, and those with scurvy recovered quite independently of any change in the dietary.

There are many accounts of scurvy among the Italian troops. Vannutelli gives a description of an epidemic of some 200 cases of infectious purpura with manifestations of hemorrhagic scurvy. Another writer informs us that in June, 1916, scurvy broke out among some Italian troops stationed at an altitude of 1500 to 2000 metres (Gingui). Vallardi gives an account of 180 cases among Italian troops in Macedonia, accompanied by slight jaundice and enlargement of the glands.

The American soldiers seem to have been practically spared from scurvy. This was due probably to their ample ration and to the fact that they were in the field for a comparatively short period. The Surgeon-General’s report to date, which has been kindly furnished me, showed but 5 cases in 1917 occurring in Europe and the United States, and but 15 cases reported during the year 1918.

The civilian population of the various warring countries was by no means spared. There are no reports from Russia to indicate the extent of scurvy, but from what is known of the food conditions prevailing there toward the end of the war, one can be certain that the number must have been large. The greatest amount of scurvy has been reported from Austria, more particularly from Vienna. Previous to the war scurvy was a rare disease in this city, both among adults and infants. During the war, however, as the result of a lack of fresh food and the dependence on dehydrated vegetables, a large number of cases developed. Tobler reports over 200 cases in children between the ages of two and fifteen years, which occurred in 1917 in child-caring institutions where the milk supply was markedly deficient, where fresh vegetables were lacking, and the supply of potatoes gave out about Christmas, 1916. A conception of the deficiency of the milk supply may be gained from the statement that there were but sixteen quarts a day for about 1500 people. Some of these children were undergoing fresh-air treatment and were out of doors in the “sun stations” day and night. For the cure of these children a simple decoction of fir-tops was used, a therapeutic procedure stated by Lind to have been of value in the Russo-Swedish War of 1708.

That scurvy must have occurred extensively among the infants in Vienna may be gathered from the report of Erdheim, who records 31 autopsies on infants under the interesting title of the “Barlow Heart.” In Berlin scurvy occurred also in the foundling asylums, as reported by Eric Mueller and by Brandt. This was caused by a diet of pasteurized milk and dehydrated vegetables. In an article bearing the suggestive title of “On a Marked Increase in Barlow’s Disease in the Years of the War 1917–1918,” Epstein states that in Prague there had been an endemic increase of infantile scurvy since August, 1917. The only information regarding scurvy among the adult civilian population of Germany is that furnished by Morawitz, who states that this disorder occurred sporadically. Here again it is probable that there were many latent or rudimentary cases which were not recognized.

In Great Britain there are reports which show that scurvy manifested itself in institutions caring for the poor. In Glasgow we learn of 50 cases developing in the Poor Law Hospital in the course of fifteen months, and in Newcastle of 16 cases appearing in the Poor Law Infirmary in the course of three months.

It is probable that when more detailed reports are available, it will be found that there was far more scurvy than was appreciated during the course of the war. It will be impossible, however, to gain even an approximate knowledge of the extent to which this disorder prevailed, as in many instances it was inextricably interwoven with other nutritional diseases. The situation which Enright describes in Cairo among the Turkish prisoners suffering from war edema, where there was “evidently a scorbutic factor involved,” probably held true for many other parts of the world. War and scurvy must still be regarded as associated evils, for war is closely linked with famine and food deprivation—the dominant factor in the production of scurvy.

CHAPTER II
PATHOGENESIS AND ETIOLOGY

At the outset it may be stated that there is no longer any reason to doubt that adult scurvy and infantile scurvy are one and the same disease, having an identical pathogenesis. For many years, far longer than the facts warranted, there was discussion whether Barlow’s disease was true scurvy or merely a form or a complication of rickets, or perhaps a distinct hemorrhagic disease. This question may be relegated to the past, so that we may proceed to consider the pathogenesis of scurvy in the infant and in the adult under a common heading.

There is no need of studying all the theories which have been advanced to account for scurvy. They have been manifold and most of them have died a natural death. For many years the potassium deficiency theory, suggested by Garrod, gained wide acceptance. That scurvy should be attributed to a lack of this salt is readily comprehensible in view of the abundance of potassium in the antiscorbutic foodstuffs, the fruits and the vegetables. It was not long before it was evident that this was not the correct solution, as the salts of potassium served neither to prevent nor to cure scurvy. This theory was accordingly modified to include only organic potassium. Experiment, however, failed to support the validity of this hypothesis, and it was gradually abandoned.

Another theory which had a short but popular career was the citric acid theory, which was maintained vigorously by Netter. This explanation seemed logical in view of the marked potency of the citrous fruits, and particularly when it was shown that human milk contains a greater percentage of the salts of citric acid than cow’s milk, and that some of these salts are lost in the course of heating. This hypothesis withstood neither the practical test nor chemical investigation. It was found that the various salts of citric acid, either singly or in combination, are unable to cure scurvy. This treatment has been employed repeatedly on man and on animals with little or no success; we also have resorted to it in vain. It was shown, furthermore, that it rested on an insecure chemical basis, as boiled milk contains but 0.1 g. per litre less citric acid than raw milk—an amount which is negligible from a therapeutic point of view.

Before considering what may be termed the prevailing theories, a few lines must be devoted to the acidosis theory championed by Sir Almroth Wright. According to this writer scurvy is due primarily to an excess of acid compared with alkaline food.[5] A theory of this nature was open to verification, and soon collapsed when put to the test. It was found, in the first place, that an addition of alkali was unable to cure experimental scurvy. It may be added that we have found it of no value in infantile scurvy. Holst and Froelich pointed out that potatoes and peas, two excellent antiscorbutic vegetables, have an alkaline and not an acid ash; that adding hydrochloric acid to dandelion juice improves rather than diminishes its potency; that 1 g. of cabbage, which suffices to protect a guinea-pig from scurvy, does not contain sufficient alkali to neutralize an acid state; and, finally, that scurvy is not encountered in the well-established acidosis of diabetes.

Let us turn to some of the current theories of the etiology of scurvy. For years many have held to the toxic theory, believing that poisons either were consumed in the food or formed in the intestine by means of bacterial action. At present this view is held by the minority. The situation in this respect may be compared to that of beriberi, about which there is also no consensus of opinion, a minority attributing it to the action of an unknown toxin.

A consideration of the clinical course of scurvy sheds but little light on this aspect, and can be interpreted as well for as against the action of a toxin. The nervous system, which is well known to be particularly vulnerable to toxins, is but slightly affected—the cardiorespiratory phenomena (indicating an involvement of the pneumogastric nerves), the occasional changes in the optic disks, and the abnormality of the tendon reflexes constitute the aggregate. In a general way it may be stated that the symptoms resemble those brought about by poisons of various kinds—the cottonseed poisoning in swine, the toxic products of the wheat embryo, or even mercurial poisoning in man.[6] The nervous symptoms, especially the irritability of the heart, remind one of the enterogenous intoxication or enterotoxic polyneuritis described by Von Noorden. Such analogies are interesting and suggestive, but can be accorded little weight in deciding the question at issue.

If a toxin is to be regarded as the proximate cause of infantile scurvy, the question naturally arises as to the nature of the toxin. Is it exogenous or endogenous? There is sound basis for believing that the hypothetical poison is not introduced preformed in the food. In the first place, infantile scurvy frequently develops in babies who receive milk of the very best grade indeed, in contradistinction to rickets, this is not preëminently a disease of the poor. Furthermore, there is no relation between the concentration of the food mixture and its liability to induce scurvy. For example, if among a large number of infants receiving pasteurized milk from a common source, some are given the milk diluted by one-half, others given it diluted by one-third, and still others whole milk, the last group will show the least tendency to scurvy, which we should not expect were the poison contained in the food. Nor is it at all uncommon to encounter scurvy in an infant which has been fed with a very dilute milk mixture. Another side of this question should, however, be mentioned—stale pasteurized milk is more apt to produce scurvy than the freshly pasteurized, but here again the injury is in inverse ratio rather than in direct ratio to the amount consumed. There are reports of adult scurvy having been occasioned by decomposed food, such as Torup’s investigation of Nansen’s polar expedition, but the diet had not been faultless in other respects. The experiments of Jackson and Harley, who produced scurvy in monkeys by feeding tainted tinned meat, cannot be unreservedly accepted, as they are substantiated by no pathological examination of the bones, and the diarrhœa and the blood and mucus in the stools do not suggest simple scurvy.

Of those who held to the toxic origin of scurvy the majority had in mind an endogenous toxin, although the conception of the nature of this poison varied greatly. The minority report of the American Pediatric Society states that “scurvy appears to be a chronic ptomaine poisoning due to the absorption of toxins.” Neumann considered scurvy a chronic poisoning, formed probably from the albumin of the milk, and considered the fact that the infant refused to take the harmful food as weighty evidence of its toxic nature. Kohlbrugge included scurvy in his group of “fermentive diseases,” due to the overgrowth of harmful bacteria in the intestine, which are normally restrained by the acid reaction of the chyme. McCollum and Pitz, on the basis of a study of experimental scurvy, suggested that as the result of a break in the metabolism it might be due to the retention of fæces and consequent absorption of toxins. Still more recently Gerstenberger suggested that as the result of the break in the metabolism of carbohydrates, a defunctioning substance, possibly oxalic acid, is produced, which has a strong affinity for calcium.

It is of no avail to discuss these various hypotheses—the formation of intestinal toxins—except where they are based on observations which can be tested and controlled. This is true solely of the relation of constipation to scurvy, and we shall confine ourselves therefore to a consideration of this aspect of the question.

There can be no question whether retention of fæces of itself can bring about scurvy; this is excluded by the marked instances of constipation frequently encountered among thriving babies. The majority of bottle-fed babies and a large number of the breast-fed suffer from a greater or less degree of constipation. On looking over our records of infantile scurvy from this point of view, and comparing them with non-scorbutic infants, we have not been able to note a characteristic distinction. Some of the infants had normal stools, others suffered from constipation, while the records of a great number showed occasional loose stools. Furthermore, in cases of latent or subacute infantile scurvy, it was of no moment whether a laxative was given or whether constipation was induced by means of opium. The report of the American Pediatric Society shows that the majority have had a similar experience; the bowels were regular in seventy-four instances, irregular in fifteen, constipated in one hundred and twenty-six, and diarrhœal in seventy-seven. In this connection, it may be pointed out that the preparation termed “malt soup,” the diet which in our experience has been most frequently associated with scurvy, is essentially laxative, and, on the other hand, that one of the most potent antiscorbutics is potato, which has no definite laxative property. It may be added, as noted elsewhere, that scurvy developed in infants in spite of their receiving cod liver oil or olive oil for long periods. It is evident, therefore, that the retention of fæces is not the essential factor in the etiology of scurvy. Its secondary rôle, especially after scurvy has developed, will be considered later in this chapter.

TABLE 1

In order to elucidate this question Torrey and Hess made a study of the relation of the intestinal flora to the scurvy of guinea-pigs and of infants. In guinea-pigs they found in the intestinal tract merely such bacteria as are encountered on the oats and hay fed these animals. The bacteria were few in number and hardly any were actively proteolytic. Furthermore, there was no change in the flora on adding antiscorbutic food, although the scorbutic symptoms disappeared. Recently Givens and Hoffman, as the result of a similar study, have come to the same conclusion. The investigation of infants led to similar results, and is illustrated in Table 1. It will be seen that the infants were all on a high carbohydrate diet, and that in two instances the flora was compared, not only during the active scorbutic process, but after orange juice had been given for a week or more. The bacteria were such as one should expect on a diet rich in carbohydrates; putrefactive organisms were present only in small numbers; and in the case in which they were most numerous (S), they had disappeared upon the subsequent examination, although the scurvy had become more marked. It is evident, therefore, that in the scurvy of infants as well as of guinea-pigs there is no overgrowth of putrefactive bacteria in the intestinal tract, and therefore no basis for the hypothesis of ptomaine or similar intoxication. Other poisons may, however, be absorbed from the intestine as the result of a prolonged deprivation of an essential vitamine.

There are those who believe that scurvy is of bacterial origin, some going so far as to regard it as a communicable disease. This viewpoint was maintained by the famous Boerhaave and supported with all the weight of his authority by Villemin in the seventeenth century. It is a view held by many, if not by the majority, of physicians in Russia to-day, and recently has been advanced by European army surgeons. This question illustrates in an interesting manner how the trend of the day influences medical thought—it has been suggested lately by Much and Baumbach that the scurvy microörganism may be carried by means of lice. But clinical experience points absolutely against the infectious nature of scurvy. Indeed, the only episode which lends any support to this opinion is its widespread and seemingly epidemic character; the fallacy of such deductions has been well illustrated in regard to beriberi, which for many years was regarded as an infectious and communicable disease. The fact that whenever scurvy occurs among a body of troops the officers are spared, constitutes convincing evidence against its communicability. This peculiarity of incidence was noted by Hoerschelman and others in the recent World War, and is referred to in the Report of the War of the Rebellion. Many of the earlier writers, in discussing the occurrence of ship scurvy, drew attention to the paucity of cases among the officers.

When we turn to bacteriological studies we find that some years ago Ausset claimed to have isolated “a pasteurella type of organism” from a case of infantile scurvy, and suggested it as the causative agent of this disorder. On the other hand, Hart, Rehn, Hirschsprung, von Starck, Schmorl, and recently Boerich, have failed to find bacteria in the blood, although the total number of cultures must be admitted to have been small. Czerny and Keller report negative bacterial growth from fluid aspirated from affected joints.

The only articles considering this important question from the experimental side are those of Jackson and Moody, and of Moore, who conclude tentatively that scurvy may be a bacterial infection. Jackson and Moody cultivated a diplococcus from the tissues of scorbutic animals after death, reproduced hemorrhages by inoculating cultures of these microörganisms into the circulation, and recovered the bacteria from the tissues some weeks later. Their results are open to the criticism that bacteria were found only after death, and that all blood cultures during life proved negative. An article by Moore, however, which has just appeared from this same laboratory, states that “an organism of the streptococcus viridans type was isolated from the blood” in a case of adult scurvy. In one instance we recovered an organism of this type from the blood of an infant suffering from scurvy. It is highly important that more blood cultures should be carried out in the course of human or animal scurvy, and that particular note should be made of the stage of the disorder when they are taken.

There is no doubt that invasion of the blood-stream does occur readily in the course of scurvy, but this takes place generally after the disease has developed and must be regarded as a secondary phenomenon and therefore unessential from an etiologic standpoint. Indeed one of the striking and important symptoms of scurvy is the marked susceptibility to infection (furunculosis, nasal diphtheria, “grippe,” etc.), which comes about as the result of the nutritional disturbance. An excellent example of this interrelationship is the “epidemic” of hemorrhagic scurvy described in the chapter on symptomatology. Hemorrhages coming about in this way should be regarded as focal complications rather than as truly scorbutic. It should be realized that, at the present time, it is not possible to distinguish between local symptoms which are truly nutritional or scorbutic in nature, and those which are bacterial and of secondary origin.

The newest theory, and the one at present most widely accepted, is the vitamine (accessory factor) theory. It was evident to Lind in the seventeenth century that scurvy could be prevented and cured by means of fruits or vegetables, a fact which became increasingly clear to succeeding generations. Until the latter part of the nineteenth century, however, this miraculous virtue of plants stimulated little inquiry and no research. As far back as 1841 Budd realized that “the explanation depended on the study of organic chemistry, and the experiments of physiologists,” but until recently it was not perceived that the solution of the problem involved the introduction of a new chemical factor. This view suddenly took shape after Eijkman in 1897 showed the nature of polyneuritis in fowl, and Hopkins in 1906, going a step farther, demonstrated the necessity of one or more unidentified food factors for the normal nutrition of the rat. The work which established this novel theory on a scientific basis in relation to scurvy was the classic investigation of Holst and Froelich, referred to so frequently in connection with experimental scurvy. These investigators showed that the mere drying of vegetables was sufficient to deprive them of their antiscorbutic power, although from a chemical standpoint they seemed unaltered; that high degrees of heat had generally the same effect; that under certain conditions these foods withstood prolonged heating, demonstrating that the antiscorbutic factor was not a ferment; that acids and alkalies played no essential rôle in the etiology; that fats, proteins and carbohydrates were not significant factors; that as little as 1.0 g. of cabbage suffices to afford protection to a guinea-pig. In other words, by a process of exclusion they showed that it is a disorder due to the lack of an unidentified food factor.

Subsequent studies, carried out within the past few years, have served only to strengthen this viewpoint. For example, an “artificial orange juice” composed of the various salts, citric acid, and sucrose in the proportions in which they are found in the natural juice, failed, in the experience of Hess and Unger, to protect or to cure guinea-pigs—demonstrating that this preparation did not contain the essential factor. In the same way, Harden and Zilva were able to protect animals from scurvy with a preparation of lemon juice which had been almost entirely deprived of its salts. It is needless to multiply these examples. It is sufficient to state that there has been no investigation during the last years of intensive study of scurvy, which has tended to weaken the vitamine hypothesis. It may be stated, therefore, that experiments have demonstrated that scurvy is due essentially to the lack of a specific vitamine. It is unwise to proceed farther and place it in the group of so-called “deficiency diseases,” including beriberi, pellagra, etc., unless the reservation is made that these several diseases may present marked differences. It is quite possible that one may be what might be termed a simple deficiency disease, whereas another may have important additional etiologic factors. At any rate, unless it is realized that there has been no proof that all are due to similar deficiencies, we may, by stamping them all alike and by grouping them together, be misled into taking their close relationship for granted. In regard to scurvy, there may well be other etiologic factors, but they are of a secondary character. Bacterial invasion has been referred to in this connection, and it is possible that toxins are absorbed from the intestine after nutrition has been disturbed. Diarrhœa and digestive disturbances may play a rôle. Whether the total intake of food or the correlation of its constituents—protein, carbohydrate, fat and salts—affects the action of the vitamine, is one which has not been well studied clinically or experimentally. In regard to beriberi, it is claimed that there is a direct ratio between the quantity of carbohydrate ingested and the amount of vitamine required. No such interrelationship exists in regard to scurvy. This was evident a few years ago (1917) when some infants receiving pasteurized milk, prepared with the addition of 3 per cent. flour, did not tend to develop scurvy more readily than others receiving simple pasteurized milk. A consideration of the antiscorbutic vitamine will be postponed for a subsequent chapter.

Etiology.—In considering infantile scurvy we are concerned almost entirely with the artificially-fed baby. It is true that in the literature we meet with scattered reports of scurvy in breast-fed babies and that these cases seem to constitute a noteworthy group; in point of fact, they are comparatively few. The collective investigation of the American Pediatric Society includes ten infants who had been given breast milk exclusively, and Concetti adds another ten in his compilation of 682 cases.[7] In spite of their paucity these cases require separate consideration because they represent an important aspect from an etiologic standpoint. How are we to explain the fact that human milk may lead to rather than protect against this disorder? On investigating more closely it is found that these cases differ in several important respects from the group which has been artificially fed. They are of a different age; instead of being in the second half year of life they are generally but a few months old. Furthermore, the signs are not the same. The hemorrhages involve the upper extremities fully as frequently as the lower extremities, and often appear at unusual sites—for example, on the scalp or as large subcutaneous effusions at various parts of the body. In many instances it has been noted that the nursing mothers were suffering from some debilitating disease such as tuberculosis or syphilis, or had an insufficient supply of milk, or that there had been some other unusual factor, as Freund has shown in an article devoted to this particular aspect. It is not necessary, however, to fall back on these attendant circumstances to exclude from consideration many of the cases. For example, Crandall’s case of “scurvy in an infant of six weeks” should be invalidated, not because, as Freund suggests, the mother had rheumatism and insufficient milk, but because of the age of the infant, and the course of the disease; first one arm was involved, then the other, then hemorrhages appeared on the skin, and finally it was cured by giving a teaspoonful of fresh cream before each nursing. Had the baby really suffered from scurvy it could not have been cured by this means. Southgate’s case must also be rejected, not because the mother was tuberculous but in view of the symptoms—the arms and legs were pseudoparetic, “the legs, feet and hands were double their normal size,” and moderately large hemorrhages were present on the back and chest. It seems hardly necessary to discuss in detail the score of cases which comprise this group, as, in general, the same criticism applies to all. Some evidently were congenital syphilis, still more must be regarded as sepsis, and others as unknown toxic conditions. Apart from these cases the question must be considered whether scurvy can occur in a breast-fed infant. Personally, we have never met with a case of this kind, and, as Finkelstein aptly remarks, there has been “no necropsy of a breast-fed case or conclusive X-ray picture.” It seems possible only if an infant, for a period of months, has obtained a scanty supply of milk, or when the milk has been exceedingly deficient in the antiscorbutic vitamine. Even under such conditions it does not seem possible for scurvy to become manifest in six weeks (Crandall’s case), or in four weeks, as in a case reported by the American Pediatric Society, unless we believe that the infant suffered also from a certain degree of intrapartum or congenital scurvy. In view of the fact that an infant requires about one pint of milk to furnish it with an adequate daily quota of the antiscorbutic factor, it is theoretically possible, under extreme conditions, for it to become scorbutic, in spite of being nursed at the breast. Such an occurrence must be regarded as exceedingly rare, far more so than the current statistics illustrate, for considerably less than a pint of milk a day will prevent the appearance of manifest scurvy for a period of several months. Some of the reported cases may have been latent scurvy, rendered acute by a complicating bacterial infection.

It might be expected that by ascertaining the occurrence of infantile scurvy in countries where it is endemic, we could learn under what conditions and how frequently breast-fed babies develop this disorder. Approaching the question from this angle, it is found that the available data is meagre and not entirely convincing. Peculiarly enough infantile scurvy has rarely been reported from Russia, where scurvy is, in many sections, endemic. For example, although Tschudakoff, who personally examined over 10,000 persons, in connection with the great scurvy epidemic in Russia (1898–99) found 11.11 per cent. of the people suffering from this disease, he did not meet with a single case under the age of five years. Fuerst writes that Filatow, the celebrated Russian children’s specialist, declared that he knew of no instance of Barlow’s disease described in the Russian literature.[8] Shortly after the recent war scurvy broke out among the wet-nurses in an infant asylum in Vienna. A very few of the infants nursed by these women developed the disorder, far fewer than might have been expected (personal communication). Hopkins recently wrote a communication to the effect that in the island of Aruba, in the Dutch West Indies, they had been unable to grow any crops in 1912, 1913, 1914, that 3000 cases of scurvy had developed there during the year 1915, and that in 1917 it was again being noted. In answer to a personal inquiry regarding the occurrence of scurvy among the infants of Aruba, he wrote that “infantile scurvy is very rare,” although “most all of the babies are breast-fed for about a year.”[9]

On the other hand, descriptions of the coincidence of scurvy in mother and nursling are even more fragmentary; in fact, we have been able to find but two reports of this kind. The one most frequently cited is that of Cheadle, which consists merely of the following bald statement: “With the exception of one or two doubtful cases, of which the details of breast-feeding and diet are imperfectly given, the only instances of scurvy arising in sucklings are those when the nursing mother has been suffering from scurvy at the time.” The other report has been gleaned from a recent editorial in the British Medical Journal, which refers to the above mentioned outbreak of scurvy in Vienna, affecting in some cases both mothers and breast-fed infants.

It is difficult to pass judgment on this question in view of the paucity of data. In the near future, probably, when we learn in detail about the epidemics of scurvy which occurred during and immediately following the war, we shall be in a better position to weigh its pros and cons. In view of the above data it does not seem that nursing infants readily develop scurvy, even though their mothers do not obtain a full quota of antiscorbutic vitamine in their food. This appears to be the clinical result, whatever its interpretation may be. It cannot be explained on the assumption that human milk contains a particularly large quota of this factor. In a test carried out to elucidate this question it was found that eight ounces a day of breast milk was insufficient to alleviate the symptoms in a case of scurvy, and that twelve ounces barely sufficed. This milk was from a woman who was on a liberal diet containing an adequate supply of vegetables. It had been previously demonstrated that sixteen ounces of cow’s milk is sufficient to cure infantile scurvy, so that it is evident that human and cow’s milk do not differ essentially in this respect. There are, however, other factors to be considered—for example, the incomparable freshness of the milk suckled from the breast, which may endow it with additional potency, or the possibility that the lack of vitamine may be compensated for by the large quantity of milk consumed. It also may not be entirely immaterial whether the vitamine is supplied in one dose, as, for example a daily feeding of orange or tomato juice, or whether this factor is furnished to the infant in frequent small quantities in the mother’s milk throughout the day. In this connection we cannot help contrasting the relation of beriberi to breast feeding. As is well known, infants which develop beriberi are almost always nursed and not bottle-fed, and show signs of this disorder, although the mothers are in apparent health, and give no clinical evidence of disease.

Turning to a consideration of the artificially-fed infant, there exists a somewhat similar situation in regard to the occurrence of scurvy on a diet of raw cow’s milk. In almost all reports of this kind the quantitative viewpoint is entirely disregarded, and little or nothing is stated to indicate how much milk the infant consumed. And yet this factor is of essential importance in interpreting the cause of the nutritional failure. It is clear, for example, that if a baby receives but eight ounces daily of raw milk—one-half the requisite amount—it may well develop scurvy, notwithstanding the fact that the milk has not been heated. In addition to the quantity, there are other factors which play a greater or less rôle in the relation of raw milk to the etiology of scurvy. It is no doubt of consequence whether the fodder of the cows was rich or very poor in the antiscorbutic factor, and, accordingly, whether the baby received what may be termed an “antiscorbutic-rich” or an “antiscorbutic-poor” milk. Furthermore, the age of the milk must be borne in mind, for we have found that even raw milk loses some of its potency on becoming stale.[10]

One of the mooted questions relative to the etiology of scurvy is the rôle of heated milk, and more particularly of pasteurized milk. In view of the vogue which pasteurization has acquired in the large municipalities, especially in the United States, this aspect has assumed increasing importance, and deserves detailed investigation. Pasteurization has achieved so much in limiting the infectious diseases, especially the diarrhœal disorders of infancy, that it has come to be looked upon as heresy to deprecate its virtues in any regard.

It has become increasingly evident that in the course of pasteurization milk loses an important measure of antiscorbutic vitamine. The term pasteurization, when employed in this connection, is not meant to be synonymous merely with the heating of milk to 140° to 165° F., but embraces the entire commercial process—the heating, handling, subsequent cooling, aging and all other factors involved. There can be no doubt that milk which has undergone this elaborate treatment has suffered in its antiscorbutic property. In 1914 Hess and Fish reported mild cases of scurvy occurring among infants who had received milk heated to a temperature of 165° F. for thirty minutes. This degree of heat is claimed by many physicians and hygienists, including the National Commission on Milk Standards, not to destroy its chemical constituents. Nevertheless typical cases of scurvy supervened after this diet had been followed for a period of six to nine months. Subsequent experience, published by Hess in 1917, with milk heated to only 145° F., served to confirm the previous observations. That these cases were true scurvy was proved by the fact that a cure resulted when raw milk was substituted. A similar experience in Berlin reported by Neumann and others was convincing, but was not heeded in this country. In 1901 one of the largest dairies in that city established a pasteurizing plant where all milk was raised to a temperature of about 60° C. After an interval of some months infantile scurvy began to be reported from various sources throughout the city. Neumann depicts the situation as follows: “Whereas, Heubner, Cassel and myself had seen only thirty-two cases of scurvy from 1896 to 1900, the number of cases suddenly rose from the year 1901, so that the same observers—not to mention a great many others—treated eighty-three cases in 1901 and 1902.” At a spirited meeting held by the Berlin Medical Society in 1903 to discuss this subject, Heubner was able to report 65 cases. An investigation was made, and the pasteurization discontinued. The result was almost immediate, the cases decreasing just as suddenly as they had increased. These reports and others demonstrate that unless additional antiscorbutic food is given, a diet of pasteurized milk will lead to the development of scurvy. As the antiscorbutic vitamine is not entirely destroyed by pasteurization, the severity of the disorder will be in inverse ratio to the amount of milk which is consumed.

It has been our experience that milk pasteurized in the home or institution did not lead to scurvy to the same extent as that which was commercially pasteurized. Babies fed on home-pasteurized milk did not develop manifest scurvy. The difference in the two processes consists mainly in the amount of handling during the process of heating and the subsequent aging which the milk undergoes. An interval of forty-eight hours usually elapses between commercial pasteurization and the delivery of the milk to the consumer. In New York city most of the better-grade milk is pasteurized at the farm, so that it is subjected to a longer period of aging than the poorer grade, which is not pasteurized until it reaches the city. Although our results indicated the effect of freshness or staleness on milk which had been heated, they showed also that other factors must be involved, for home-pasteurized milk which is forty-eight hours old is superior to the commercial product of the same age. This difference we believe is due to the handling which the milk undergoes, to the mechanical processes involved in commercial pasteurization.

In considering this aspect of the development of infantile scurvy on a diet of heated milk, it is of interest to refer to the experience of Switzerland and of France. In 1907 Bernheim-Karrer reported nine cases of scurvy which occurred on “homogenized” milk. This milk is forced between rapidly-rotating surfaces at a temperature of 55° to 65° C. at a pressure of 150 atmospheres. This process had been introduced the year previous by a large dairy which was well known for its excellent grade of milk. Before this innovation, milk usually had been boiled for a long while before being fed to infants. In France a similar epidemic of scurvy followed the introduction of the use of homogenized milk (lait fixé). Lecornu gives an interesting account of this episode, remarking on the large number of cases of scurvy occurring on this milk compared with sterilized milk, which was employed so much more extensively. These experiences furnish excellent examples of the harmful effect of industrial methods on milk, especially on its antiscorbutic vitamine. Lecornu also emphasized the scorbutic influence of “lait maternisé,” which is similar to the German Gaertner milk, and is subjected to dilution, centrifugation, and sterilization.[11] He states that before this preparation was introduced scurvy was practically unknown in France. Lecornu attributes the deleterious effect of the “lait maternisé” and the “lait fixé” to bacterial contamination, as does Bernheim-Karrer. We believe, rather, that its loss of potency is due to the mechanical processes to which it has been subjected.

Boiled and, more particularly, sterilized milk, is regarded as a common cause of infantile scurvy and figures prominently among the foods held accountable for this disorder. It has been pointed out, however, that thousands of infants, especially in Europe, receive milk of this kind, and do not develop scurvy. Statistics such as those of Variot, who has distributed in his out-patient department, during a period of twelve years, 400,000 quarts of sterilized milk (heated in half-litre bottles and hermetically sealed at the farm) without observing a case of scurvy, must be accorded weight in this connection.[12] Escherich, some years previously, stated that he did not meet with scurvy in Graz, although he was accustomed to feed babies on sterilized milk. Budin, the celebrated French children’s specialist, writes: “As for the so-called infantile scurvy which is alleged to follow the use of sterilized milk, I have heard a very great deal about it during the last few years, but I am still looking for my first case.” Evidence from such sources cannot be summarily cast aside, but must be given due consideration. It is evident that the mere heating or sterilization of milk, although it reduces the antiscorbutic vitamine, does not do so to a degree sufficient to lead to the production of clinical scurvy. Our experience accords with that of the above observers. Some years ago we fed infants with milk which had been boiled for five minutes, and, at another time, made use of home-made evaporated milk which had been heated for a period of seventeen hours, until it had been reduced to one-eighth its volume. This evaporated milk was well borne for months, although slightly caramelized in the course of heating, and did not lead to any signs of scurvy. Clearly there are other factors involved in this question besides the mere subjection to heat. We believe that every step in the process is important—the freshness of the milk, whether or not it is agitated and exposed to the air, whether it is sealed carefully and used soon after sterilization,[13] and, finally, whether the baby receives a sufficient quantity. If this milk, which has certainly lost some of its vitamine content, is given in small amount, it will not supply an adequate amount of the antiscorbutic factor.

Neumann, Czerny, and others state that they have even cured infantile scurvy by giving boiled milk obtained from a different source. In the Berlin epidemic, Neumann laid particular emphasis on the fact that the milk which induced scurvy had been doubly heated, having been pasteurized commercially and later boiled in the home before it was fed to the baby. Plantenga has also laid stress on the influence of two-fold heating, citing an interesting experience with scurvy in his clinic. When the milk was pasteurized one day and boiled for five minutes on the subsequent morning, 23 cases of infantile scurvy developed among the 200 infants attending his dispensary. The following year when the procedure was altered so that the milk was merely pasteurized, no case of this disorder developed. There can be no doubt that milk which has been heated twice must have lost more of its antiscorbutic properties than milk which has been heated but once, and that aging also must contribute to this loss. Whether there is what may be termed a peculiar sensitization of milk following pasteurization, has not been definitely shown.

Up to the present time dried milk has played an insignificant rôle in the etiology of infantile scurvy. One of the factors which has hindered the general acceptance of dried milk by physicians and laymen has been the fear that its use might lead to the development of Barlow’s disease. It is therefore important to consider this aspect of the subject, especially as dried milk seems destined to be used to an increasing extent. A recent report to the Local Government Board by Coutts states that “Millard and Naisch in England confirmed the testimony of Miele in Belgium, and Gautier and Genevoix in France, that scurvy is not to be feared” from this foodstuff. This coincides with our experience, namely, that dried milk not only does not lead to scurvy, but may contain sufficient antiscorbutic vitamine to cure this disorder. Recently a scorbutic baby was fed with milk which had been dried by the so-called Just-Hatmaker process—whereby it is subjected on a drum for a few seconds to about 230° F.—with the result that the hemorrhages of the gums began to be absorbed in about three days, and all symptoms to disappear shortly thereafter. This infant received dried milk to the equivalent of 24 ounces of fresh milk, and this preparation had been dried and canned somewhat over three months before it was used. Recently two infants, suffering from marked scurvy, were treated with milk which had been dried six months previously. The one received only sixteen ounces a day and the other a quart; both recovered within a few days after this food had been substituted for malt soup. Not long ago, as reported elsewhere in a paper by Unger and myself, after curing a baby of scurvy by means of this milk, it was maintained in health for a subsequent period of three months on a diet which contained no additional source of antiscorbutic vitamine. These results are emphasized as illustrating the peculiar relationship of drying and of the application of heat to the antiscorbutic vitamine, and because recently several reports have appeared, for example, that of Barnes and Hume in England, and of Hart, Steenbock and Smith in this country, to the effect that dried milk is devoid of antiscorbutic value. The difference of opinion is due to the assumption that dried milk is a uniform product and has identical antiscorbutic properties. For milk to retain its antiscorbutic value, notwithstanding drying, it must have been rich in vitamine before desiccation, it must have been dried quickly, and packed within the shortest possible interval in air-tight, preferably hermetically sealed, containers. As in relation to the heating of milk, so in regard to its drying, it is not the degree of heat to which it is subjected which is all important, but rather the associated conditions. The merits of each process will have to be tested individually and perhaps even each particular brand of milk.[14]

In the foregoing, the dictum has been accepted without comment that fresh milk may be either rich or poor in antiscorbutic vitamine. This point of view has recently gained general acceptance, on the assumption that the milk of the stall-fed cow is markedly deficient in this factor. Recent work by Hart, Steenbock and Ellis gives evidence that “summer pasture milk is much richer in this nutritive factor than dry feed milk or winter produced milk, involving the use in the ration of corn silage or sugar mangels.” In some experiments (unpublished) we have found that dried milk shows similar variations, being a much more potent antiscorbutic when obtained from cows fed on fresh fodder than a similar milk from the same cows on fodder containing a minimum amount of antiscorbutic vitamine. The supposition of a direct quantitative ratio between the antiscorbutic intake in the food and output in the milk needs confirmation, especially as it does not quite coincide with the experience among human beings in countries where adult scurvy is endemic. In such countries—for example, Russia—nursing infants do not develop scurvy to the extent that would be expected, and it is possible that this exemption is due in part to a selective secretion of antiscorbutic vitamine into the milk.

As is well known, a diet of condensed milk leads to scurvy. This is not surprising, considering the prolonged heating to which this milk has been subjected. It is probable that many cases of mild scurvy developing on this food and characterized by beading of the ribs (rosary) and other indefinite manifestations, have been erroneously diagnosed as rickets.

It is hardly necessary to discuss separately the various kinds of milk which have led to scurvy in the course of infant feeding.[15] The principles laid down in the preceding discussion hold good for milk of all kinds. Heat will destroy a certain amount of vitamine, and, if the heating is followed by aging, still more will be lost. If an interval elapses and a second heating ensues, there will be further loss of vitamine. It should never be forgotten in considering foods in their relation to the causation of scurvy, that the amount of food given must not be overlooked. For example, a pint of ordinary pasteurized milk will lead to scurvy, whereas a quart in most cases will be sufficient to tide the baby over until the period of mixed feeding. No general rule can be laid down, however, as may be judged from the fact that dried milk which has been subjected to almost all the influences which are deleterious to the antiscorbutic vitamine—heating, drying, aging, all carried out in a neutral medium—nevertheless retains its specific potency.

Infantile scurvy has always been far more prevalent in England and in America than in Europe, notwithstanding the fact that on the continent practically all milk for babies is boiled or sterilized. This has been ascribed, and probably rightly so, to the widespread usage of proprietary foods in the English-speaking countries. Among the cases reported by the American Pediatric Society about 60 per cent. had been given foods of this description. How is this relationship to be explained? These preparations in general may be stated to consist of cereals, sugar, with occasionally a small amount of dried milk; they are mixed with varying proportions of water and milk and then cooked. It is evident that two important causative factors of scurvy are thus furnished, namely, a small and inadequate quota of milk and the application of heat. In most instances not more than sixteen to twenty ounces of milk are used to make up the day’s feeding, and frequently this has been previously pasteurized. But there is an additional factor which comes into play in this connection, one to which we have recently drawn attention in treating of “The Deleterious Effect of the Alkalization of Infants’ Food.” It has been shown that the antiscorbutic vitamine is peculiarly sensitive to the faintest alkaline reaction, in which medium it rapidly undergoes deterioration, and even total destruction if heat is applied. Proprietary foods, with but few exceptions, are alkaline, having been rendered so by the addition of potassium carbonate or bicarbonate, in order to prevent acid fermentation of the fat and to counterbalance the relative poverty of potassium in cow’s milk. Little or no regard has been paid to this reaction; the textbooks on children’s diseases give this point no consideration whatsoever, expressing the salt content merely in terms of total ash. By this means ideal conditions are furnished for the destruction of a large part of the vitamine, and if this factor is not present in excess, scurvy will readily develop. It is to these various circumstances—the deficiency of milk, the alkalinity and the heating—that the scorbutic quality of proprietary foods is to be ascribed.

The most flagrant example of an infant’s food leading to scurvy is “malt soup”—an alkaline preparation of malt, which is prepared with flour and a small amount of milk.[16] This food brings about scurvy almost invariably unless an antiscorbutic is added to the dietary. That this effect is due to the alkaline potassium carbonate was shown by a recent test which is illustrated in chart. (Fig. 2). Here we see that in a case of scurvy, when the food was altered and prepared with the same amount of milk and alkali, the disorder did not abate (although the carbohydrate had been discontinued), but when the potassium carbonate was omitted a gain in weight ensued, and, we may add, the symptoms disappeared.

Fig. 2.—Human scurvy: weight curve of a baby that developed scurvy on a diet of malt soup (period 1). During period 2 the flour and malt soup were omitted from the diet, the same amount of milk and potassium carbonate being continued. The disorder did not abate. The only change in period 3 was a discontinuation of the potassium carbonate. This brought about a gain in weight and cure, showing the destructive effect of the alkali on the vitamine.

A test of this kind once more raises the question whether carbohydrates lead to the development of scurvy. As previously stated, there are many who believe that the carbohydrates, especially starch, have this harmful effect by requiring a large amount of the various vitamines for their metabolism. This relationship was first brought forward by Bradden and Cooper in regard to beriberi. It is a suggestion which cannot be disregarded in view of the great amount of scurvy which comes about on diets rich in carbohydrates, especially those containing malt sugar. We do not believe, however, that the harmful effect which this foodstuff exerts can be explained on the above hypothesis, as experience has shown that infants may receive for many months equally large amounts of carbohydrates—cane sugar, flour, or a combination of both—and nevertheless not manifest a similar tendency to develop scurvy.

Age Incidence.—Scurvy may occur at any age if the diet does not furnish sufficient antiscorbutic factors. As a matter of fact, it is encountered most often among infants and adults, not because these two age-groups are particularly susceptible, but because there are peculiar attendant circumstances. In the case of the infant, it is due to the fact that for almost the entire first year of its life it is dependent entirely upon milk, a foodstuff poor in antiscorbutic vitamine, and containing, under favorable conditions, barely enough to meet its requirement. If, therefore, the potency of the milk is weakened, or if an insufficient quantity is fed, and more particularly when both of these factors are involved, a scorbutic condition will ensue. The reason why older children, those over one and a half or two years of age, do not develop scurvy is largely due to their varied and liberal diet, which is amply provided by the mother or guardian, so that even in times of want they receive more than their due share of the available food supply.[17]

From a clinical standpoint scurvy may be said to occur in infants during the second half year of their lives. There is general agreement on this point; it is borne out by the investigation of the American Pediatric Society and by the statistics of various individuals. On the basis of a large experience, Still states that nearly eighty per cent. of the cases appear between the ages of six and ten months, and that in no case did the disorder occur before the age of five months. It is of importance from both the etiologic and the therapeutic standpoint to distinguish clearly between the age when infantile scurvy is commonly diagnosed, and the earlier stage when it appears as a general nutritional disorder. We must remember that scurvy generally takes from six to nine months to become manifest, this developmental period varying mainly in proportion to the degree of the dietary deficiency. It is evident, therefore, that there must be a prolonged period of nutritional failure which precedes the diagnosis. This stage consists of two early phases, the first months where the faulty diet causes no apparent change and seems to have no deleterious effect on the infant, and the second, of latent and subacute scurvy. The “latent” condition is one merely of unsatisfactory nutrition and retarded growth, which it is not possible to interpret; “subacute scurvy,” which develops subsequently, is distinguished by characteristic signs and symptoms. We shall not review their symptomatology, as it is given in the chapter devoted to this topic. The subject is brought forward in this connection to emphasize the fact that the scorbutic condition occurs far earlier than is generally realized, and furthermore, that if the earlier and more subtle symptoms of scurvy were comprehended, the age incidence would fall earlier than the current figures indicate. The earliest instance of this disorder which we have seen occurred in a baby four and a half months of age.

Age does not seem to play a definite rôle in regard to the incidence among adults. Scurvy frequently has been encountered among old men, and is of common occurrence among the most vigorous of the nation, the young soldiers and sailors. Some have stated that it takes place less often among soldiers in the twenties than among those in the thirties, but this has not been demonstrated. The fewest cases have been reported among children over two years of age. It was due to the apparent immunity of this age-group that, until very recently, German writers doubted the identity of infantile and adult scurvy. The exclusion of children of this age is merely fortuitous and, moreover, is by no means absolute. One of the earliest cases of scurvy in children, reported by Montfalcon, occurred in a child six years old. Bateman in America described a case in a child of about this age. Barlow, in one of his first articles, reported scurvy in a small group of older children. The case so frequently quoted by German authors in this connection is that of Fraenkel, who described both clinically and pathologically a case of scurvy in a boy eight years of age. These cases by no means exhaust the number which are reported. Recently, Tobler has given us an account of scurvy, occurring during the war, in a Viennese foundling asylum which harbored children between the ages of two and fourteen.

Season and Climate.—Many of the older writers laid great stress on the influence of season on the occurrence of scurvy, which they believed broke out particularly in the cold and damp months of the fall, winter and early spring. It is true that most of the epidemics have occurred at these seasons of the year. This is merely what should be expected, considering that the disease depends mainly upon the supply of fresh fruits and vegetables. Where conditions are abnormal, as in war, there have been notable exceptions to this seasonal incidence. In the “Report of the War of the Rebellion” there is an instructive graph illustrating the occurrence of scurvy in our Civil War and in the Crimean War, which shows that this disease prevailed to the greatest extent during the winter months in the former, whereas in Crimea, the season of greatest frequency was the summer time. One of the severest outbreaks of scurvy on record is that which occurred at the siege of Thorn in Germany in the year 1703. During the months of July and August, when the weather was excessively hot, scurvy ravaged the besieged army. There are, furthermore, many reports of scurvy in the tropics during the dry season. In the island of Aruba, in the Dutch West Indies, which has been visited by scurvy year after year, and which is referred to elsewhere, the disease is endemic during the dry, hot season. Formerly it broke out on the men-of-war and vessels of the mercantile marine while they were in southern waters. As regards infantile scurvy, it has always seemed to us that season played a slight rôle; that cases which occurred in the summer tended to be less severe and to be characterized by periods of intermission rarely observed in the winter time.

The effect of climate has been accorded a variable place in the etiology of scurvy. Lind believed that a damp, cold climate, such as that of the Low Countries, was conducive to scurvy. On the other hand, since it is realized that diet is the essential element, all other factors have been regarded as of no moment whatsoever. It is difficult to pass judgment on this question, since scurvy is now endemic in such a limited area of the world. It seems quite possible that a damp, cold climate, which depresses the various functions of the body, may exert an influence where the quota of antiscorbutic foodstuff is not quite adequate. Exposure to infection is also greater under such climatic conditions.

Economic status has to be considered in connection with infantile scurvy. Numerous writers have drawn attention to the fact that scurvy is seen relatively more frequently among the infants of the well-to-do and the rich than among those of the poor. This curious and paradoxical situation is due to the zealous care which the former receive—the extreme precautions in sterilizing the milk, the addition to the formulas of expensive proprietary foods, the watchfulness to avoid the child’s obtaining a chance bit of fruit or vegetable. Since the popularization of commercially-pasteurized milk in the larger municipalities, and the advertising propaganda for the sale of “baby foods” which has extended their use among the masses, this distinction in the social status has been largely obliterated.

Sex seems to play no part in the etiology of scurvy. Several writers have claimed, however, that there is a certain degree of racial immunity. For example, Sheppard reports that the Zhob Kakai seldom develops scurvy, although he naturally excludes vegetables from his diet, and Boerich noted among the prisoners of war that the Slavs, especially the White Russians, were more susceptible.[18] Of course a lack of susceptibility of this nature can be merely relative. Such a racial distinction may seem far-fetched, but if we admit that disposition and habits of life can play a rôle, it is quite possible for races to vary in their predisposition to this disorder. Moreover, we shall see that individuals differ markedly in this respect. Lind and others repeatedly emphasize the fact that the indolent and slothful sailor was stricken with scurvy far oftener than the one who was active, and claimed that physical exercise even tended to bring about a cure.[19] Those who have had a large experience with scurvy in adults are almost unanimous in believing that a psychic element enters into its etiology. In this way, in a measure, they account for the frequency of scurvy among defeated troops, in besieged armies, and among men depressed by homesickness, fatigue, and discouragement. This point of view cannot be lightly disregarded, bearing in mind that depressed mental states alter the functions of the organs and markedly affect secretion. The many cases and epidemics in institutions for the insane cannot, however, be attributed to this cause, but are probably almost entirely due to a want of supervision of the dietary. Among infants, the question of the influence of race and of the mental state needs but little consideration.[20] For some time we have carefully observed the course of scurvy among happy and contented infants compared with those of an unhappy and fretful disposition; in some instances the former, although the diet was similar, seemed to develop scurvy less readily than the latter.

There can be no doubt that there is predisposition to scurvy, as there is, probably, to every nutritional disorder. Among soldiers and sailors a certain number develop scurvy on the same ration which does not harm others. Some years ago when scurvy developed among a group of infants fed on pasteurized milk, this idiosyncrasy was noted. The distinction, however, is rarely sharply defined. Careful clinical investigation will generally show that the infants which seem to be spared are not thriving quite normally; they are somewhat pale, and do not gain in weight as they should, and their appetite is poor. The most interesting experience of this kind is the following which is frequently cited: In a family where the first child developed scurvy, Finkelstein took the precaution, in the case of the second child, to have the milk boiled for as short a time as possible, and to begin mixed feeding early. In spite of these precautions this boy also developed scurvy. Finkelstein states that once before he had met with a similar mishap. An experience which he relates, regarding a foster-mother, an excellent nurse, who had three infants in succession develop scurvy in spite of preventive measures, is also of interest in this connection. The latter occurrence evidently cannot be attributed to hereditary or family predisposition, and serves to emphasize the inherent difficulties of the subject. v. Starck’s report of an instance where twins were fed on similar milk mixtures and one developed scurvy, whereas the other thrived satisfactorily, is a striking illustration of the rôle of idiosyncrasy. This case, as well as many others, fails to be absolutely convincing in view of the fact that the daily intake of milk is not recorded.

A predisposition to scurvy cannot be ascribed to a condition of general malnutrition. For example, among infants it has never seemed that those suffering from marasmus or atrophy were particularly prone to develop scurvy. Whether syphilis, tuberculosis or malaria tends to precipitate the onset of this disorder cannot be stated.[21] In view of the fact that prematurity is such an important factor in the pathogenesis of rickets, it would be of interest to know whether a similar relationship exists between infantile scurvy and prematurity. The only clinical condition which we have found predisposing to scurvy is the “exudative diathesis” of Czerny, a term which implies a tendency to develop exudations of the skin or of the mucous membranes. Probably it is not without significance that in this diathesis the blood-vessels may evince a decided weakness, an increased permeability, as demonstrated by the “capillary resistance test.” (See [Symptomatology].)

Nothing whatsoever is known regarding the possible influence of the fat, protein, carbohydrate and salt content of the diet on the development of scurvy. Is it entirely immaterial whether one or another food element largely predominates, or is the antiscorbutic factor to some extent modified by other components of the food? Influences of this kind, which at most are secondary, cannot be ascertained by the biologic test which at present has to be relied on to measure the development of scurvy and the potency of antiscorbutics. It is quite possible that the course of scurvy may be affected by the character of gastric and intestinal digestion, by the activity of the glands which pour their secretions into these organs, by the destruction or elimination of the antiscorbutic factor in the food. The frequent association of dysentery and scurvy noted during the recent war and referred to by many previous writers, shows the effect of intestinal disorders. These hypotheses are tentatively advanced because it is evident that some factor exists, apart from the mere antiscorbutic value of the diet, which at times exerts a potent influence on the development of scurvy. Cases developing in spite of a moderate amount of antiscorbutic food, and others not responding to the addition of vegetables or fruit to the diet—although not numerous—have occurred too frequently and have been reported by too experienced observers to be brusquely disregarded. For example, Neumann, one of the keenest clinical students of scurvy, stated that he had met with four instances of this nature. Hess and Fish reported two similar experiences.

The secondary etiologic factors are mainly predisposing; a few words, however, must be added concerning what may be termed exciting factors. Infection is the most important condition which may suddenly and precipitously induce scurvy. This fact was brought to our attention in 1912 in connection with the outbreak of scurvy among infants receiving pasteurized milk. Its explanation was not clear at the time, but was elucidated by subsequent experience, and was described in 1917 as follows: “Latent scurvy was prematurely changed to florid scurvy by the presence of a ward infection; an epidemic of ‘grippe’ precipitated an epidemic of scurvy exceptional in its hemorrhagic tendency.” The association of scurvy and infection has been recently emphasized by McCarrison and others, and seems to hold good for the other so-called deficiency diseases. In this connection one other exciting cause of scurvy may be mentioned, namely, trauma. The older writers noticed that following a fall or an accident, a sailor frequently developed scurvy, and Barlow in 1894 remarked on the influence of trauma in connection with infantile scurvy. As might be inferred, its effect is mainly to induce premature rupture of the weakened blood-vessels; in infants we have seen this occasioned by pressure exerted on the lower end of the thigh to ascertain the presence of tenderness. Viewing the situation broadly, it must be acknowledged that except for the realization that scurvy is due to a new food factor—a vitamine—our fundamental understanding of its pathogenesis has advanced but little, in spite of the employment of experimental methods and the availability of modern technic.

It is doubtful whether mere clinical studies will contribute in a large measure to the solution of the pathogenesis of scurvy. Much may, however, be learned by investigations of the metabolism in human scurvy—an aspect of the problem which, as will be brought out in a subsequent chapter, hardly has been explored. By this means may be acquired a clearer understanding of the effect of an antiscorbutic deficiency on the tissues and on cellular activity. Much may be expected from physiologic and pharmacologic studies of the specific vitamine, although it is not yet available in a pure state. Finally, it is probable that the solution of similar questions relating to the pathogenesis of cognate disorders—a study which is engaging the best efforts of so many workers throughout the world—will shed light on this particular disease.

CHAPTER III
THE ANTISCORBUTIC VITAMINE[22]

We shall not discuss the subject of vitamines in general, but confine ourselves to the more limited field of the antiscorbutic vitamine. The recognition of the “accessory” dietary factors is of such recent date, however, that it will be well to consider briefly how attention came to be directed to them and how their existence was ascertained. As in the case of so many scientific discoveries, it is difficult to point to the exact time when the advance was made. On looking back we find that Lunin, in 1881, noting that mice were unable to live on a diet consisting of protein, fats, carbohydrates, salts and water, came to the conclusion “that other substances indispensable to nutrition must be present in milk besides caseinogen, fat, lactose and salts.” This work did not stimulate similar investigations, nor did Lunin, as might have been expected, allude to scurvy. The work which focussed attention on this novel aspect of dietetics was the report of Eijkman, in 1897, to the effect that when fowl are fed decorticated rice, they develop a disease resembling beriberi, and that the paralytic symptoms disappear on feeding them rice polishings or its alcoholic extract. Here, for the first time, was a positive rather than a negative experiment, and one capable of simple verification. The subject was placed on a scientific basis by the classic investigation of Hopkins, who experimented with purified food substances, and demonstrated how diets which were deficient could be rendered adequate. As early as 1906 he wrote “the animal body is adjusted to live either upon plant tissues or other animals, and these contain countless substances other than the proteins, carbohydrates and fats.” “In diseases such as rickets, and particularly in scurvy, we have had for long years knowledge of a dietetic factor, but though we know how to benefit these conditions empirically, the real errors in the diet are to this day quite obscure.” The work of Osborne and Mendel, and McCollum and Davis in this country, of Schaumann, Funk, Stepp and others, all led to the conclusion that purified diets are unable to satisfy the nutritive requirements of rats or mice, and that extracts of the natural foods suffice to render the diet adequate.

The same rule holds for man, who, when deprived of these vitamines, develops the so-called deficiency diseases—typically modern disorders. Regarded as a group, they are a consequence of our altered mode of life and peculiar civilization. They follow naturally upon the development of immense cities housing millions of people, who necessarily must receive perishable foodstuffs produced at a great distance. To even a greater extent they are the product of countless ingenious methods devised mainly to render foods stable—drying, heating, the addition of preservatives—most of which accomplish their object, but incidentally rob the food of its essential vitamine.

None of the vitamines has been isolated in a pure state. The nearest approach to this desired end has been the work of Funk, who obtained the water-soluble vitamine in a state of such concentration that about 3 mg. sufficed to cure a pigeon of polyneuritis. In considering the attributes of the antiscorbutic vitamine, it must be borne in mind that this factor is referred to as it exists in various foods; for example, in orange juice or in cabbage, and furthermore, that the method of ascertaining its presence or concentration is limited to the crude biological test of animal feeding.

The antiscorbutic factor is distinguished by being the most sensitive of the three vitamines, the most unstable, the least resistant to physical or chemical processes. It may be regarded as one of the most delicate indicators of the biological integrity of foodstuffs; however, as Falk and his co-workers have shown, the enzyme property of living matter is still more readily destroyed. The antiscorbutic vitamine is soluble in water, and therefore is termed by some the “water-soluble C” factor. It is also soluble in alcohol, as shown by the experiments of Hess and Unger and of Harden and Zilva, and the therapeutic tests on infants of Freise and of Freudenberg.[23] It possesses, therefore, the solubility of the water-soluble vitamine. Some have suggested that it may be derived from this vitamine, others that instead of one there may be a series of antiscorbutic factors—suggestions based on pure hypothesis. Holst and Froelich showed that this vitamine passes, without appreciable loss, through dialyzing parchment, and Harden and Zilva (2) that it can pass through a porcelain filter. The latter, using the method of Seidell, demonstrated that this vitamine is not adsorbed by fine precipitates such as fuller’s earth, differing in this respect from the water-soluble vitamine; and that in a mixture of equal volumes of autolyzed yeast and orange juice, the antiscorbutic vitamine remained unaffected, whereas the water-soluble A was entirely removed.

One of the most distinctive characteristics of the antiscorbutic factor is its sensitiveness to even moderately high degrees of heat. In this respect it differs markedly from the water-soluble or so-called “antineuritic vitamine” which withstands exposure to high temperature. The reaction of the antiscorbutic vitamine in this regard is not a simple one, and cannot be expressed by a mere statement of the degree of heat and the length of exposure. Numerous other factors, especially the reaction of the medium, but also the physical environment, must be taken into consideration—for example, cabbage is more resistant to the action of heat than its juice. An understanding of the relation of antiscorbutics to heat may perhaps best be obtained by considering the subject in connection with some definite foodstuffs. The most exhaustive study from a quantitative standpoint is that of Delf. She showed that when cabbage is subjected for an hour to a temperature of 80° to 100° C., 90 per cent. of its antiscorbutic vitamine is lost, and that 80 per cent. is lost when a temperature of 90° to 100° is maintained for twenty minutes, or a temperature of 60° for a period of sixty minutes. This experiment shows that the destructive influence of heat is enhanced to a comparatively slight degree by a rise of temperature, only about threefold when it is raised from 60° C. to the boiling point. This result points to a temperature coefficient of about 1.5 to 10° C. of temperature. It is suggested by Delf that this low coefficient of destruction is opposed to the enzyme or protein-like theory of the nature of the vitamine, and suggests a simpler constitution. On the other hand, we must bear in mind that the proteins which have been used in experiments and found to possess a high coefficient of heat, have been tested in the pure state, whereas the vitamine of the cabbage is bound up in the cell.

Experiments with this vitamine as found in milk accord with the above investigation, demonstrating that intensity of heat is not as destructive as prolonged heating. This agrees with the clinical experience that milk which has been boiled for a few minutes does not induce scurvy as readily as pasteurized milk which has been heated for 45 minutes to 140° or 165° F. (Hess and Fish).

As demonstrated by tests with orange and with lemon juice, the antiscorbutic vitamine is greatly protected from the destructive effect of heat when it is associated with an acid. This was shown first by Holst and Froelich and has been confirmed by numerous observers. An excellent example of marked thermostability conferred on a food by its acid reaction is furnished by the tomato, which is strongly antiscorbutic even after it has been subjected to the canning process. Conversely, Harden and Zilva have shown that the vitamine is destroyed by alkali even when dilute (one-fiftieth normal sodium hydrate) and kept in contact at room temperature; this alteration does not take place at once, but in the course of several hours.

It is true that the antiscorbutic factor is peculiarly sensitive to drying, but there are exceptions to this rule, so that it is incorrect to state, as does the British Report of the Medical Research Committee, that “it may be regarded as an axiom that dry or dried foodstuffs will not prevent scurvy.” We have shown that fresh milk dried by the Just-Hatmaker process may retain by far the greater moiety of its virtue. In this regard rapidity of desiccation and subsequent protection from oxidative processes are important factors. The general rule holds true, however, that this vitamine, in contradistinction to the “water-soluble” vitamine, is readily damaged and destroyed by drying.

This vitamine is peculiarly sensitive to aging, especially when it is present in an alkaline or neutral medium; but even in an acid medium its potency soon diminishes. Harden and Zilva found this to be the case with lemon juice stored for a fortnight in the cold room, and our experience has been similar in regard to orange juice kept in the refrigerator under a layer of liquid petrolatum. In milk the antiscorbutic factor diminishes with age, especially following pasteurization, in the course of which most of the acid-forming bacteria have been destroyed. Aging has the least effect when the food with which the vitamine is associated has been dried. This is true not only of lemon and of orange juice as demonstrated experimentally and clinically, but even of milk, which even after it has been dried and stored for months, may still possess marked curative value.[24]

Experiments by Harden and Zilva showed that exposure of lemon juice to ultra-violet rays for eight hours does not influence its antiscorbutic activity, that exposure of autolyzed yeast for the same length of time likewise does not impair its “antineuritic” potency, but that under identical conditions the fat-soluble factor in butter becomes inactivated. Similar tests carried out by the author with orange juice led to the same result. It thus appears that one of the vitamines—not the most unstable—manifests a peculiar sensitiveness to a certain form of physical or chemical action.

In view of the fact that shaking partly destroys pepsin and rennin, as shown by Shaklee and Meltzer, it would be of interest to ascertain whether this process brings about any impairment of the antiscorbutic vitamine. Particular interest is attached to this question because it is generally recognized that milk loses some of its potency in the course of handling—whatever may be comprised by this term. In experiments on the fat-soluble vitamine Steenbock and his co-workers found that “somewhere in the course of the manipulation to which the butter fat had been subjected, factors had been introduced which were responsible for a vitamine destruction.”

Before discussing the question of the manner in which the antiscorbutic vitamine functionates, it may be well to state briefly the type of the disturbance which its deficiency occasions. The chief manifestation is damage to the integrity of the endothelium of the vessels, resulting in hemorrhage—whether from diapedesis or from rhexis or both of these conditions, the microscope does not inform us. Nor can it be stated positively that the endothelium has not been injured by a secondary toxic or bacterial factor. However this may be, the end result of the deficiency is endothelial damage, a pathologic condition which may be demonstrated clinically in scurvy by the “capillary resistance test” ([chapter VII]). The other marked functional alteration in scurvy is increased susceptibility to infection; but how a vitamine deficiency induces this vulnerability cannot be explained. Clinical tests show that the blood contains sufficient antitoxin (diphtheria) to afford protection. Harden and Zilva found that “guinea-pigs fed on an unrestricted mixed diet, on a quantitatively restricted mixed diet, and a scorbutic diet showed no differentiation in amboceptor and agglutinin titres, and in the complement activity of the blood.” If this is to be interpreted as indicating that the protective substances of the body undergo but little alteration, we must consider whether susceptibility to infection, as well as tendency to hemorrhage, is not due largely to alteration in the cement substance of the endothelial and epithelial membranes.

The Mode of Action of the Vitamine.—One of the most interesting as well as puzzling questions in regard to the antiscorbutic vitamine concerns the manner in which it prevents or cures scurvy. It is a subject which at present is in a state of flux, hardly having emerged from the realm of hypothesis, so that detailed consideration will profit little. At first the modus operandi was explained and accepted as enzyme action, but it was soon evident, in view of the thermostability of the vitamine, that it could not be classed as a ferment or enzyme in the generally-accepted sense of this term. In general, it may be stated that there are two main views: one that the vitamine acts directly, and the other that it acts indirectly through the function of the endocrine glands. Direct action, furthermore, may be accomplished in at least one of three ways. The vitamine may (1) serve as a source of nutriment for the tissues, (2) exert an antitoxic effect on toxic products, or (3) function as a catalyzer. The first interpretation is evidently the simplest and conforms to the long-established knowledge of caloric food factors. That such small amounts as 2 c.c. of orange juice daily should suffice to protect an animal from nutritional disaster runs counter, however, to former conceptions of food nutrition. Further than this there is little against this viewpoint. In its favor is the fact that, up to a certain point, antiscorbutics act in direct ratio to the amount given; for example, 2 c.c. of canned tomato juice is insufficient to prevent scurvy in guinea-pigs, 3 c.c. will protect some but not all of a series, whereas when the amount is increased to 4 c.c. daily all animals will be saved. As we are considering new food factors it is manifestly unwise to judge them by old standards, and to decide offhand that they cannot possess such a high degree of nutritive power. This question must be regarded as still open.

The antitoxic theory suffers from the fact that the toxic origin of scurvy cannot be established. Before this is possible, it is clear that it will be difficult to bring forward convincing evidence of a neutralizing substance. Against this theory is the fact that elimination therapy is of no avail in the treatment of infantile scurvy. Hess and Unger (1919) failed to alleviate the symptoms by means of catharsis, diuresis, sweating and repeated intravenous injections of normal salt solution. In its favor it may be advanced, in a general way, that the vitamine, in many characteristics, resembles an antitoxin—in its extreme lability, its destruction by heat, aging and alkalies. On the other hand, antitoxins also are readily destroyed by acid which, as has been shown, exerts a protective influence on the antiscorbutic factor. The rapidity of action of the vitamines, one of the most impressive phenomena, calls to mind the neutralizing action of an antitoxin, and probably has given rise to the analogy. Williams suggests that the vitamines have “a general, non-specific, antitoxic or eliminative action” on toxic substances resulting from the metabolic decomposition of food.

The theory has been advanced that the action of the vitamines is catalytic. Although this viewpoint has been taken regarding the water-soluble rather than the antiscorbutic vitamine, it will be well to review briefly the work on which it is based. Among the first to suggest this hypothesis were Vedder and Clark, who noted a relationship between the amount of vitamine required by fowls and their carbohydrate intake. Funk in 1913 made a similar observation in regard to beriberi, and in the following year, with von Schoenborn, showed that a vitamine-free diet led to hyperglycæmia, with diminished amount of hepatic glycogen, and that the addition of water-soluble vitamine diminished the hyperglycæmia and increased the liver glycogen. The work of Burge and his co-workers on the catalase content of tissue led to a similar conclusion. Their results may be summarized by the statement that the oxidative processes are hampered and fail to balance the autolytic changes, and, furthermore, that a relationship exists between the catalase activity, acidosis and normal oxidative processes. This theory would presuppose that scurvy is due to the formation of toxins which are normally in process of continual destruction in the body. According to some, these catalyzed toxic substances are metabolic in character, originating from incompletely oxidized food; according to another interpretation, they are the product of autolyzed tissue cells (tissue toxins). The difficulty with this explanation is that scurvy cannot be prevented or cured by a diet containing food of high catalytic power. For example, wheat embryos which, according to recent investigations of Crocker and Harrington, have a high catalytic activity, were found of no therapeutic value in relation to infantile scurvy (Hess, 3).

This problem has been approached from quite a different angle. As is well known, certain bacteria require serum, blood, milk, etc., in order to grow satisfactorily on artificial culture media. It has been established recently, primarily by the work of Lloyd, that this peculiarity in the cultivation of microörganisms is due largely to their requirement of vitamine. She found a relationship of the inverse order between the amount of amino acid present in the culture medium and the amount of vitamine required to stimulate the growth of strains of meningococcus. Reasoning from this experience, she suggests that the action of the accessory growth factors is to increase the reaction velocity of the proteolytic metabolism. Here we find the vitamines once more regarded as catalyzers. This author, however, associates their activity with proteolytic rather than with carbohydrate metabolism. Interesting and suggestive work of similar nature has been carried out in relation to the growth of protozoa and of yeasts (Eddy). Investigations of this kind, dealing with unicellular organisms propagated on a simple food, have the advantage of greatly simplifying the problem.

The recent work of Dutcher falls under this caption, differing merely in the fact that he attributes to the vitamines an indirect action. He has demonstrated that the tissues of polyneuritic birds show a decrease in catalase activity to a point 56 per cent. below normal, and that this activity is largely restored when the birds are cured with vitamine. According to this writer the vitamine functions as a metabolic stimulant, and its lack results in a depression of the body oxidations with an accompanying formation of toxic metabolic products, injurious to the nervous system. The action is regarded as coming about in an indirect manner, being accomplished through the hormone action of the vitamines on one or more glands of internal secretion.

The endocrine hypothesis, suggested by Funk in his monograph, is not without some corroborative evidence. In testing the pharmacologic action of the water-soluble vitamine, Uhlmann found that it stimulated the various glands of the digestive tract, in this respect acting like pilocarpine. Some years ago Albert expressed the opinion that the action of this vitamine was “vagotropic” like atropine, and recently Dutcher has reported definite relief and cessation of polyneuritic symptoms by means of pilocarpine (0.5 mg. subcutaneously). He claims equally good results from thyroxin, the hormone of the thyroid gland, from desiccated thyroid and from tethelin (pituitary). Voegtlin and Myers conclude, as the result of experiments with brewers’ yeast, that the chemical and physical properties of secretin and vitamine are identical.

The early work of Funk and Douglas, which showed that various glands of internal secretion diminish in size and undergo degenerative changes when the diet is vitamine-free, the newer work of McCarrison and of Dutcher to the same effect, clearly point to an intimate relationship between some of the endocrine glands and the vitamines. As regards scurvy, the only work is that of Rondoni, McCarrison and of LaMer and Campbell on the adrenal glands, which were found by all to be enlarged in guinea-pigs suffering from this disorder. These investigations must be regarded as tentative rather than conclusive until confirmed by similar necropsy reports in man. In this connection it should be noted that thyroid, parathyroid or suprarenal extract is of no avail in the treatment of scurvy. This failure may, however, be explained by the fact that the normal balance of glandular activity was not established. We must bear in mind, however, that although the vitamines may influence the secretion of the glands of internal secretion, this explanation does not satisfactorily account for the symptoms of the “deficiency diseases.” These disorders do not in the slightest respect resemble the clinical pictures which we are accustomed to associate with a lack of activity of the glands of internal secretion. If the polyneuritis of beriberi and the hemorrhages of scurvy are attributable to a diminished secretion of the endocrine glands, then it will be necessary to revise present conceptions of their physiologic functions.

The Fate of the Vitamine in the Body.—One of the most important questions in relation to the antiscorbutic vitamine, quite apart from its chemical nature, physiologic function, and its source, is its fate in the human body after it has reached the alimentary canal or been carried to the tissues. It can be readily appreciated that our knowledge of this aspect is very meagre. We shall endeavor, however, to detail what little is known of this subject, conscious of the fact that investigations of the next few years may contradict our present viewpoints.

Most of the constituents necessary for the construction of tissue or for carrying on its functions can be synthesized by the animal body from the basal foodstuffs. It has been ascertained within the past decade that certain constituents—for example, some amino-acids of the protein molecule—are building-stones which cannot be primarily elaborated by the cells, but must be supplied by the food. At present the vitamines—including the antiscorbutic vitamine—are included in this new and essential group of substances which the human organism cannot manufacture. Animal experiments seem to bear out this conception of the vitamine whether we regard them as dynamic or as indispensable tissue elements in the structural sense.

A closely-related but less fundamental question is that of the ability of man to store vitamines—whether the tissues can hoard an excess of these factors, or whether, in this respect, we are carrying on a precarious hand-to-mouth existence in regard to cellular nutrition. It is of course clear that at all times the various organs and tissues must contain a certain amount of the vitamines. This has been shown for the water-soluble or “antineuritic vitamine” by the fact that even the organs of birds which have died of polyneuritis contain an appreciable quantity of the specific vitamine, although an insufficiency of this very factor has led to their death. That such is the case is demonstrated for the antiscorbutic vitamine by the fact that muscle tissue contains sufficient antiscorbutic to protect individuals subsisting largely on a diet of which raw meat constitutes the sole antiscorbutic agent (Stefánsson). It is very probable that some organs contain more of the vitamines than others; this has been proved for the “antineuritic” factor, and seems to hold good for the antiscorbutic—the liver being particularly rich. No quantitative study has been carried out from this point of view regarding the antiscorbutic vitamine, and it would be well worth our while to ascertain the relative antiscorbutic potency of the various organs of the body. Some time ago we undertook experiments to determine whether the guinea-pig is capable of storing this vitamine. One series of guinea-pigs was fed daily 6 c.c. of orange juice for a period of two weeks, whereas another series, of about the same weight, was given, in addition to the basal ration, only 3 c.c. per capita (the minimal protective dose). After this preliminary period both series were placed on a diet containing practically no antiscorbutic. Both groups came down with scurvy after about the same interval, leading to the conclusion that there could have been little if any storing of the excess vitamine by those which received twice the “minimal protective dose.” The experiments of Harden and Zilva, who fed a concentrated lemon juice, showed that this potent agent also was unable to provide against a subsequent period of antiscorbutic deficiency. It should be realized that the results of these tests on guinea-pigs cannot be applied to man without tests on other species.

It might be thought that the blood—the purveyor of the vitamines to the tissues—would be particularly rich in these essential factors. Such, however, was not our experience in respect to the antiscorbutic vitamine. The blood possibly varies greatly in this respect according to the diet of the individual, or even according to the interval elapsing after the ingestion of antiscorbutic food. Our opinion is based on the surprisingly poor therapeutic effect of blood transfusion in the treatment of scurvy. To illustrate: An infant weighing about fifteen pounds received six intravenous injections of citrated blood—one of 200 c.c., given by the direct method, and a month later five smaller transfusions with citrated blood, which aggregated 205 c.c.[25] In spite of this addition of blood, the hemorrhage and congestion of the gums did not disappear, nor the general condition improve, as would have happened had 50 or 75 c.c. of orange juice been given by mouth. It seems probable that small quantities of vitamine are being transmitted at all times by the blood and supplied to the cells, but that its normal content of this factor is not great. The antiscorbutic potency of blood may perhaps be compared to that of milk. Animal investigation may show that various vessels—for example, those supplying or draining certain glandular organs—differ in the antiscorbutic quality of the blood which they carry. It is evident, therefore, that many transitory factors may influence the vitamine content of the blood, and that—as in the case of milk and fruits and vegetables—we are not dealing with a constant and unvarying agent.

Nothing whatsoever is known concerning the excretion of the antiscorbutic vitamine. No attempts have been made to recover it from the urine, or to ascertain if, when large amounts are ingested, the excess is thrown off by the body. This suggests the question—a corollary of that raised in connection with the vitamine content of the blood—whether it is immaterial if the vitamine is taken frequently in small amounts, or is provided only occasionally and at longer intervals in larger amounts. Is it of no moment whether the infant receive its quota of antiscorbutic every few hours through the medium of the breast milk, or only once a day in the form of orange juice or tomato? If we turn to studies on the other vitamines for enlightenment as to the possibility of excretion, we find that Muckenfuss recovered the water-soluble factor from ox bile and from human urine.[26] In this article he proposes the interesting question of a possible variation in the vitamine output under pathological conditions, which may be responsible for the development of functional disturbances in children.

It would be of interest to know the fate of the antiscorbutic vitamine in the gastro-intestinal tract. How is it affected by a lack of the acid gastric juice, or by the alkaline intestinal secretions, or by the bacteria in the lumen of the gut? From which part of the intestine is it largely absorbed? May an appreciable amount undergo destruction before this is accomplished? None of these questions can be answered satisfactorily in the present state of our knowledge, but they suggest that the mere fact that an adequate quota of antiscorbutic vitamine is provided in the food does not necessarily insure an adequate supply for the tissues. If in addition to the question of intake we must take into account that the vitamines may suffer various vicissitudes, it may come to pass that pathological conditions at times destroy or render them partially inactive. In this way we may account for irregularities in the clinical course of disorders associated with vitamine deficiency.

Of prime importance, however, is the effect of the vitamines on the glands of the alimentary tract and on the digestive processes. A diminution of gastric juice, or in some instances a total absence, has been observed in adult scurvy, and noted by us in two cases of infantile scurvy. As mentioned elsewhere, some consider the function of the water-soluble vitamine analogous to that of secretin. In applying this hypothesis to scurvy it must be borne in mind that the sequence may be reversed, that the lack of vitamine may not lead to the gastric achylia, but that the achylia may come about secondarily as the result of the malnutrition.

We have referred to “irregularities” in the course of the “deficiency diseases.” A careful perusal of the literature leaves one with the impression that the most experienced observers are not entirely satisfied with the exclusively etiologic relationship of the vitamine to its respective nutritional disorder. In regard to scurvy, more particularly, there are numerous scattered reports where the disorder did not yield to antiscorbutic foods as might have been expected, or where, on the other hand, it suddenly and inexplicably retrogressed, although there had been no alteration in the dietary.[27] These instances are not common, but they occur from time to time, and their occurrence must be accounted for. In relation to beriberi and avian polyneuritis improvement of this kind has frequently been explained on the theory of a sudden mobilization of vitamines from the tissues. There is, however, no data on which to base such explanations, and it may be that a lack of parallelism between vitamine intake and the clinical course may be due at times to processes taking place in the alimentary tract.

The fat-soluble vitamine has been termed by some the growth vitamine. All the vitamines, however, are closely associated with the function of growth, which their deficiency tends to inhibit. In the chapter on symptomatology, it will be pointed out that infants suffering from scurvy fail to grow normally both in length and in weight. To a certain extent this may be due to a loss of appetite, which is one of the characteristic phenomena accompanying the scorbutic condition. On the other hand, this anorexia may be secondary and not primary to the impairment of the growth impulse, which may lead to a dysfunction of various body processes.

It is of little value to look ahead and try to foresee what the next decade will bring forth in regard to the nature of the vitamines. Investigation has broadened remarkably during the past few years and now embraces the chemical field—chemical and adsorption methods, the large realm of biology, including studies in physiology and pharmacology; and recently pathology has once more been called upon to aid in the solution of the problem. Probably additional vitamines will be discovered. From time to time it has been suggested that a specific growth vitamine exists quite distinct from the three which are recognized, and recently Mellanby has suggested still another food factor—a specific “rachitic vitamine.” When we reflect that the characteristic functions of the various organs—the kidneys, liver, etc.—must depend on essential differences in chemical structure, the complexity of the entire problem of unidentified factors becomes evident.[28]

CHAPTER IV
PATHOLOGY

Physicians have had a general knowledge of the pathology of scurvy for a great many years. Lind, in his “Treatise on the Scurvy,” published in 1772, included a chapter on “dissections” and a postscript on “Appearances on Dissections of Scorbutic Bodies,” based on a large, although indefinite, number of postmortem examinations. In the century which followed, there are to be found many reports of scurvy, especially in connection with the frequent wars, but it is surprising how little detailed pathologic information they furnish. Barlow’s publication in 1883, establishing the identity of the scurvy of adults and of infants, must be regarded as the modern milestone in the study of the pathology of this disorder. This work did not contribute richly to the data of the subject, or suggest novel interpretations, but directed attention to a new source of material—the increasing number of cases of infantile scurvy—at a critical moment when the opportunity for the study of scurvy in the adult was rapidly becoming less. At the time of Barlow’s exposition of the true nature of “acute rickets,” scientific medicine was concentrating its interest on pathology. Tissues were being carefully studied by means of the microscope, and scurvy was subjected to this new method of investigation. As a result of intensive application of this technic, a lesion of the bones was identified and established as characteristic of scurvy. Study was focussed so exclusively on the bones, that for many years, indeed until very recently, the other organs of the body were neglected. This is true of the gross as well as of the microscopic anatomy. Protocol after protocol gives a hasty account of the appearance of the various organs, merely as a routine introduction to a careful and often minute study of the bones (Table 2). As the result of this myopic vision, enlargement of the heart, for example, which should have been noted many years ago, was, until recently, unobserved—indeed, the heart is but occasionally mentioned in the protocols.

TABLE 2

A new era in the pathology of scurvy was inaugurated by the availability of experimental scurvy and also by the stimulation occasioned by the recent conception of vitamines and the so-called deficiency diseases. In endeavoring to elucidate this fascinating problem, it has gradually been realized that pathology may be of service—for example, in relation to the involvement of the endocrine glands. Accordingly, studies of the minute pathology of the various organs have been undertaken in many laboratories throughout the world (Italy, India, England, Germany and the United States). An additional stimulus to investigation in pathology has been furnished by the recent war, which, as shown elsewhere, led to a great increase in scurvy among both the military and civilian population. The excellent report of Aschoff and Koch from Roumania was made possible by this catastrophe, and will no doubt soon be followed by others of similar character.

Gross Pathology.—General Appearance.—The skin usually is pale, livid, and dotted with numerous petechiæ. These vary in size from the tiniest pin-points, barely recognizable to the naked eye, to ecchymoses of moderately large size. The most frequent site is the lower extremities. The trunk is always less affected, hemorrhages tending to occur along the mid-line and especially around the umbilicus. There may be also larger superficial hemorrhages, showing great differences in color, from the redder tone of the more recent, to the blues, browns and greens of the older lesions. Bleeding from the nose and mouth is not uncommon in fatal scurvy, and occasionally exophthalmos is present, usually unilateral, and due to subperiosteal hemorrhage of the orbital plate of the frontal bone. Rigor mortis is generally slight, and, according to Lind and to von Opitz, decomposition takes place rapidly.

There may be great emaciation, especially where secondary infection has supervened. General wasting occurs, however, in uncomplicated scurvy due to starvation—the result of lack of appetite or a deficiency of the general food supply. Children, especially infants, are undersized, as illustrated in treating of the symptomatology, and their bones may be decidedly smaller than normal. Generally there is some edema about the ankles, and in children a somewhat characteristic puffiness about the eyes. General anasarca also occurs, in some cases associated with renal involvement. Peculiar boggy, “tumor-like” masses of localized edema may be present, which were considered by the earlier writers (Lind) to be one of the typical lesions of this condition.

Hemorrhages.—Hemorrhage is such a striking manifestation that it is not surprising to find it was regarded by the older writers as the pathognomonic sign of scurvy. The bleeding may take place into almost any organ, and vary from small petechiæ to very extensive extravasations. The hair follicles and sweat glands are particularly susceptible, as Lasèque and Legroux noticed in cases occurring in the French prisons. Aschoff and Koch, during the recent war, noted the same peculiarity of involvement, calling attention also to the fact that previous skin diseases such as keratosis or seborrhea seemed to predispose to this localization.

Trauma plays a very important rôle in determining the location of the deeper as well as of the superficial hemorrhages. In adults, especially in soldiers, in whom the greater number of cases have been recorded, the lower extremity is the commonest site, between the knee and ankle, the area most exposed to blows as well as acted upon by static congestion. In infants, the inner aspect of the thighs is a frequent site due to the trauma of the diaper.

The most characteristic hemorrhage, the subperiosteal, will be fully discussed when considering the bone lesions. The deeper hemorrhages may be very extensive. They tend to follow the connective-tissue strata, and in the muscles are usually limited by the muscle sheaths. The blood surrounds the muscle fibres, which appear quite intact. The neighboring blood-vessels are congested and may contain thrombi, both venous and arterial. Such thrombi are found also in areas where extravasation has not taken place, and conversely, hemorrhages occur where no thrombi are demonstrable, so that a mutual causal relationship cannot be proved. Further evidence in regard to the mechanism of these extravasations is presented in the discussion of the minute anatomy. Brownish pigment, undoubtedly derived from the blood, is frequently found in the neighborhood of the hemorrhagic areas. New connective tissue also grows in these areas, so that in healing cases a marked formation of scar tissue will be found. Bizarre forms of hemorrhage at times have given rise to confusion in diagnosis; hemorrhage involving the right lower abdominal quadrant may simulate appendicitis; when occurring in the region of the transverse colon it has been mistaken for an epigastric new-growth.

Certain parts of the body seem less predisposed to hemorrhage. The central nervous system is often spared, notwithstanding extensive bleeding elsewhere, the meninges being somewhat more frequently involved. Hemorrhage of the lungs is also less common than might be expected, and it is probably true as Lasèque and Legroux suggested, that previous pulmonary disease, particularly tuberculosis, is an important predisposing factor.

Anasarca.—This comprises the second characteristic lesion found in scurvy at necropsy and was referred to in the earliest records of the disease. In the account of his dissections Lind writes: “The breast, belly and several other parts of the body were filled with this water or serum,” mentioning also the pericardium and ventricles of the brain. He also noted that all the tissues seemed to contain an excessive amount of fluid, a condition which may be so striking that the muscles appear bathed in serum. In one of his first cases with postmortem verification, Barlow described this appearance as follows: “The muscular walls of the thorax were pale yellow and watery, as though they had been bathed in serum.” In many cases this edema is most marked in the neighborhood of the hemorrhages, for example, in the muscles of the thigh when subperiosteal hemorrhage has taken place; less frequently it is produced by venous thrombosis.

Any or all of the serous cavities may be involved in this hydrops, the order of frequency being pericardium, pleuræ, peritoneum, and joint surfaces, especially the knee. The fluid is clear and straw-colored, or, in the event of secondary infection, becomes cloudy and fibrino-purulent. Later the exudate may become organized so that the entire cavity is filled with a solid mass, which binds the organs together and obliterates the cavity. The exudate may be blood-stained or apparently consist entirely of clotted blood.

Heart.—In the protocols of most necropsies, the heart is passed over with scant mention. For example, Lind’s only statement in this regard is that “all those who died suddenly, without any visible cause of their death, had the auricles of their heart as big as one’s fist, and full of coagulated blood.” Barlow accords it no attention, nor do most of the writers who immediately followed him. The first careful description of the heart is to be found in the excellent work of Schoedel and Nauwerk, which contains the following record in regard to three of the five necropsies on infantile scurvy: (1) Pericardial fluid somewhat increased, both ventricles moderately dilated, the right somewhat hypertrophic. (2) The heart showed a hypertrophy of the right and left ventricles, as well as dilatation of the right ventricle. (3) The right ventricle is dilated and slightly hypertrophied, the muscles pale and tough. There is no word of comment relative to these cardiac changes, which evidently were considered fortuitous. The same observation holds true in regard to a necropsy on an eight-year-old child reported by Ingier, which showed a moderate hypertrophy of the left ventricle. We look in vain, likewise, for information on the subject in the work on guinea-pig scurvy by Holst and Froelich, and that on scurvy in the monkey by Hart and Lessing. The first linking of cardiac enlargement with scurvy is found in a paper by Darling, who described “right-sided hypertrophy and degenerative changes in the vagus and all its branches.” Hess described and demonstrated by means of roentgenograms the enlarged heart in infantile scurvy. Recently Erdheim, in an article entitled “Das Barlowherz,” reported the occurrence of enlargement of the heart, especially of the right ventricle, in 21 out of 31 necropsies of infantile scurvy, and concluded that a direct ratio exists between the degree of enlargement and the intensity of the disorder. These reports gain added interest in view of the enlargement of the right heart so frequently encountered in beriberi, and described by Andrews in infants dying of this condition. In addition to the definite statement of Darling regarding adults, mention may be made of the observation of Aschoff and Koch, that in two cases of uncomplicated scurvy there were fatty degeneration and dilatation of the heart. Fatty degeneration of the muscle is frequent, brown atrophy exceptional. Sato and Nambu also found hyperæmia and atrophy with increase of connective tissue between the muscle fibres.

The pericardial cavity contains almost invariably an increased quantity of fluid, which may be so great as to impede the heart’s action. Adhesive pericarditis has been described. The cardiac valves are normal, unless previously damaged.

Lungs.—The lungs are almost always congested, but apart from this are remarkably free from abnormality. Smaller or larger hemorrhages are described occasionally, which are usually considered truly scorbutic; Andrews, however, found similar lesions in beriberi. In the necropsy of Stephen Mackenzie’s case, described by Barlow, these small hemorrhages are stated to have resembled small red tubercles scattered throughout the lung. There may be pulmonary infarcts. Edema of the lungs is not uncommon, as we should expect, especially as a terminal condition. Pneumonia, lobular or lobar, is one of the most frequent complications and causes of death. Active tuberculosis is a not uncommon secondary manifestation.

Subserous hemorrhages are almost the rule; if infection supervenes, the pleuræ become thickened and covered with an exudate of pus and fibrin.

Alimentary Tract.—The lesions of the gums so well recognized clinically are fully discussed under symptomatology. The remarkable fact that these hemorrhages do not appear in edentulous gums has been the centre of the controversy as to the identity of adult scurvy and Barlow’s disease. This same lack of involvement is noted in adults whose teeth have been extracted. Where teeth are present, the gums are swollen and edematous, often of a livid, reddish color; less frequently, pale and pouting. Hemorrhage is seen at the edge of the gum adjacent to the teeth. In advanced cases the gums are enormously swollen, fungous, ulcerated and covered with a foul, greenish, necrotic mass, which may extend widely over the buccal mucous membrane. The teeth become loosened and fall out. Secondary infection undoubtedly plays the chief rôle in producing this condition, for the most severe forms are found only where caries and pyorrhœa preëxisted. This seat of infection may serve as the source of dissemination throughout the body, giving rise to many of the lesions found at postmortem, especially in the lower part of the intestinal tract.

The stomach shows no characteristic changes. Congestion of the mucosa is frequent, at times associated with small superficial erosions; the latter gain added interest in view of their occurrence in guinea-pig scurvy. Hemorrhages occur here also and may involve any of the mural coats.

The duodenum shows often intense congestion. This occurs with sufficient frequency to demand attention, especially as a similar condition has been described in other disorders grouped with scurvy. Willcox and others found congestion of the duodenum and of the lower intestine in beriberi, and Andrews described not only congestion but even minute hemorrhages. Small duodenal ulcers are by no means infrequent both in human and in guinea-pig scurvy (Holst and Froelich). The presence of such marked congestion surrounding the papilla of Vater would lead us to expect the occurrence of catarrhal jaundice associated with scurvy. But, on the contrary, icterus has rarely been noted in scurvy. Urizio has described jaundice in this connection, but it is difficult to decide whether his cases were true scurvy, as they occurred in an epidemic of jaundice and no histologic examination of the bones was carried out.

The intestine may present a variety of lesions.[29] The mucosa is frequently congested and swollen, and the solitary follicles and Peyer’s patches enlarged. These changes may progress to necrosis and extensive ulceration. In an outbreak of scurvy occurring in this country in 1917, in a large institution for epileptics, ulceration was a frequent lesion at necropsy.[30] Dysentery, a frequent complication of scurvy in some epidemics, may add to this ulceration and lead to even complete sloughing of the inner lining of the intestine. Hemorrhages are found in the mucous, serous or muscular layers. Here, as elsewhere, the hemorrhages vary in size from petechiæ to large infiltrations of blood. A very striking picture is sometimes presented by the pale, edematous intestinal wall dotted or streaked with vivid red.

Liver.—The liver is frequently congested, as would be expected in view of the involvement of the right heart. Erdheim found congestion, however, in only nine among thirty-one necropsies, although enlargement of the heart was present twenty-one times. There may be hemorrhages in the glandular tissue or under the peritoneum. “Cloudy” and fatty degenerations occur occasionally, and in some cases an early cirrhosis. Lind found abscess of the liver, and wrote that in a few instances “the matter or corruption was hardened, as it were, into a stone.”

Spleen.—This organ is usually somewhat enlarged and congested. Charpentier, in the Paris epidemic of 1871, found it often three to four times the normal size and very soft, and Lind tells us that “the spleen was three times bigger than natural, and fell to pieces, as if composed of congealed blood.” It must be remembered that the pathologic as well as the clinical picture of the scurvy of Lind and his time was generally complicated by infection. The enlargement is usually by no means so great, and no doubt is due in part to intercurrent infections. On section, it is found frequently to contain much reddish-brown pigment. Hemorrhage may also occur. In beriberi, Andrews observed frequent congestion of the spleen and also a loss of normal markings.

Pancreas.—There is but one reference to a lesion of the pancreas in scurvy, that of Sato and Nambu, who encountered hemorrhage of this organ in one case among the necropsies performed in the course of the Russo-Japanese War.

Kidneys.—Here again, congestion and hemorrhage are the two lesions most commonly found. The kidneys also may show any of the forms of nephropathy ordinarily recognized, but these must be regarded as complicating conditions and not a part of the true scurvy.

Small hemorrhages may be found in the uterus, bladder or urethra. They are especially common in the bladder, both in man and in the guinea-pig, and in some instances may be the cause of the hæmaturia noted during life.

Lymph-nodes.—General enlargement of the lymph-nodes has been described, but occurs probably only in advanced cases where a general infection has been superadded. As a rule the enlargement is confined to nodes draining areas where hemorrhage has occurred. On section these nodes are reddish or brownish as the result of the pigment which they contain, the “black and red spots of different sizes” mentioned by Lind. Following infection they may become purulent, resulting in the inguinal buboes so frequently mentioned by the older authors,[31] or in the purulent mesenteric nodes associated with intestinal ulceration.

Organs of Internal Secretion.—Until recently these organs have received but little attention. It is probable, however, that in the near future they will be the object of close study and that new information will be acquired as to their condition in this disorder. Hemorrhages are commonly seen in the adrenals, enlarging them greatly and giving them a deep red color; the hemorrhage generally involves mainly the medullary portion.[32] It is probable that careful scrutiny will disclose hemorrhages in the other glands of internal secretion. The question of the involvement of these glands will be again considered under the microscopic anatomy, and has been taken up from a functional standpoint in treating of the possible indirect action of the vitamines.

The brain and the spinal cord likewise have been but little studied. It is hardly to be expected that much will be learned from an investigation of the gross pathology of these organs, but the microscopic anatomy offers a promising field of research. Hemorrhage may occur into the brain substance, into the cord or the membranes surrounding them. Pachymeningitis hemorrhagica interna has been described frequently (Meyer, Hayem, Sutherland, Sato and Nambu) and may give rise to the symptoms of meningitis. Sutherland reports an instance where thrombosis of the basal artery was found postmortem. In one case, that of Feigenbaum, hemorrhage of the cord was diagnosed during life and confirmed at necropsy.

The peripheral nerves may be the seat of hemorrhages, the blood lying between the nerve trunk and its sheath. This is particularly well illustrated in the recent work of Aschoff and Koch.

Bones.—Palpation of the body will often reveal distinct lesion of the bones, such as fractures, either ununited or healed with the formation of large calluses; subperiosteal hemorrhages, especially of the distal end of the femur or of the tibia, may be evident to the eye as well as to the touch. Crepitation of the bones may serve to further establish the break in continuity of the bones. This lesion was well known to the older writers. Lind writes that “in some, when moved, we heard a small grating of the bones. Upon operating those bodies the epiphyses were found entirely separated from the bones; which, by rubbing against each other, occasioned this noise.” “All the young persons under 18 had in some degree their epiphyses separated from the body of the bone, this water having penetrated into the very substance of it.” Poupart was also struck by this phenomenon in young adults.

Another bony alteration which is readily palpable is “beading” of the ribs, the counterpart of the rhachitic rosary. This has not been considered a sign of scurvy, and when noted clinically or at postmortem has been passed over without comment, just as has been the case with cardiac hypertrophy. In infants the beading has been attributed to rickets, and this error has been largely responsible for the general opinion that almost all infants suffering from scurvy suffer also from rickets. If we scan the literature with this question in mind, we find numerous casual references to beading of the ribs in scurvy. Fraenkel’s frequently cited case of a child of seven who died of acute scurvy, showed beading of the ribs during life as well as after death. The true scorbutic character of these enlargements was substantiated by microscopic examination. In their pathologic studies on scurvy among soldiers, Aschoff and Koch frequently describe beading of the ribs, which they attribute to an infraction of the costochondral junctions.[33] There may be fracture at this junction, or a separation of the cartilages from the sternum, as described by Lind.

This beading of the ribs, which involves mainly the middle tier, was described by Holst and Froelich in their classic report of guinea-pig scurvy, and has been noted by all subsequent investigators in this field. It has usually been called “rhachitic” or “pseudo-rhachitic” in spite of the fact that this junction is the site of typical scorbutic microscopic lesions. Hart and Lessing refer to the “rhachitic rosary” in monkeys, likewise not realizing that it is the product of scurvy.

The subperiosteal hemorrhage has long been recognized as a lesion characteristic of scurvy.[34] It occurs exceptionally in the upper extremities, and most commonly at the lower end of the femur; it may, however, involve almost any of the bones, and has been described in connection with the scapula, cranial vault, orbital plate of the frontal bone, ribs, etc. It varies greatly in its size, being confined to a small area or extending a long distance on the shaft of the bone. It rarely is as large as one would expect from external appearance, as much of the swelling is due to edema and hemorrhage into the soft parts. The periosteum rarely becomes separated at the line of junction of the epiphysis and diaphysis. The underlying blood coagulates rapidly, and the periosteum begins to calcify within a few weeks, as shown by the X-ray.

The most frequent site of fracture, or separation of the epiphysis, is the lower end of the femur. This may be accompanied by local swelling, or be discovered at necropsy, or during life by means of the X-ray in cases in which it has not been suspected. An interesting fracture reported by the author, and also mentioned by Kaufmann and by Schoedel, is that of the head of the femur leading to the development of coxa vara. In the author’s case, the condition was found in a scorbutic infant who had never stood on its feet. Schoedel suggests that scurvy may at times be the etiologic factor in coxa vara as well as in some cases diagnosed as congenital dislocation of the hip.

On sectioning the bones longitudinally the cortex is noted to be exceedingly thin, a mere shell and very brittle. The trabeculæ are so thin and reduced in number that the bone has become a very fragile structure. The marrow is no longer deep red at the ends of the long bones, but yellowish, frequently presenting a patchy appearance. It has a gelatinous consistency. This “Geruestmark” is one of the characteristic anatomical changes of scurvy, and will be fully described in considering the microscopic picture. Hemorrhages can be clearly distinguished in the marrow, and are of varying shades denoting their irregular occurrence. These hemorrhages were considered by Looser to be the cause of the connective-tissue formation in the marrow, but do not occur with sufficient constancy to warrant this interpretation. Moreover, this “frame-work marrow” is found where there is no evidence of previous hemorrhage.

MICROSCOPIC PATHOLOGY

Skin.—As pointed out by Aschoff and Koch, examination of skin which to gross appearance was the seat of typical small hemorrhages, showed various lesions. In some, perhaps the most typical forms, there had been a fresh extravasation of red blood-cells. This condition is found usually in the subepidermal layers, especially in the papillary stratum. These small hemorrhages occur very frequently about the hair follicles and sweat glands, especially when they have been diseased. Where the bleeding has been of long standing, dark brownish pigment deposits are found and all blood-cells may have disappeared. Phagocytic cells are almost always present and may be of the “wandering” or of the more fixed connective-tissue type. Many round cells may be seen in these areas lying between the connective-tissue strands or around the blood-vessels. Rheindorf, as quoted by Tuechler, has called attention to this round-celled reaction, which in many instances gives a picture analogous to the granulomas, and which leads him to infer an infectious origin for these lesions. Other areas which appeared to be the seat of hemorrhage are shown by the microscope to be small abscesses or new connective tissue often loaded with pigment and detritus, apparently representing the final stage of these lesions. Aschoff and Koch have found that suitably-stained preparations frequently show a loss of elastic fibres, which Rheindorf states constitutes one of the earliest changes of this disorder. The blood-vessels in the vicinity of the hemorrhages are congested, especially the capillaries and small venules.

The muscles also present a similar diverse picture of old and recent hemorrhages, pigment deposit and round-celled infiltration. Increase of connective tissue is usually found between the fibre bundles and in some cases where the hemorrhages are apparently of long standing, as evidenced by loss of contour of the red cells and pigmentation of the surrounding areas, this scar tissue formation is very marked. Changes in the muscle fibres themselves have not been encountered by all observers. Hayem describes widespread fatty degeneration and a deposit of pigment within the fibres, Leven a loss of sarcolemma, while Lasèque and Legroux found fatty changes which were equally marked in muscles showing no hemorrhage. On the other hand, Aschoff and Koch, in their careful studies, did not find noteworthy fatty change of the fibres, but observed often that the fibres within the hemorrhagic areas seemed shrunken and were stained abnormally deep with eosin.

In monkeys dying of experimental scurvy, Hart and Lessing describe granules in the muscles, which, judged by their staining affinities, evidently contained calcium and were similar to those found in the adrenal glands.

Blood-vessels.—A similar difference of opinion obtains in regard to the changes in the walls of the blood-vessels, especially of those in hemorrhagic areas. This question is of particular interest because of its bearing on the problem of the mechanism involved in the escape of the blood. Since it has been demonstrated that neither the clotting time nor the viscosity of the blood is markedly changed in scurvy but that weakness of the vessel walls exists, as demonstrated by “the capillary resistance test,” it is natural that we should seek an explanation in the microscopic pathology of the vessels. So far no change has been found. The application of some of the newer stains, such as those for mitochondria and other cell granules, has not been resorted to for this study, and might furnish valuable information.

Hayem found fatty infiltration of the walls of the small veins and capillaries, and believed this to play an important rôle in the etiology of these bleedings. Lasèque and Legroux also found occasional fatty changes. Other authors have failed to demonstrate similar lesions, or have considered them due to postmortem change. Koch searched in vain for “rents” in the vessel walls to account for the escape of blood. Hyaline degeneration has also been described, but is believed to result from secondary infections and not to be an intrinsic lesion of scurvy (Sato and Nambu, Aschoff and Koch).

Thrombosis of vessels is found both in the neighborhood of hemorrhage and elsewhere, the thrombi at times completely occluding the vessels and giving rise to typical wedge-shaped infarcts. The lung often shows areas of this kind.

Lungs.—Hemorrhages of various size occur in the tissue of the lung or in the air spaces. Hemorrhagic infarcts also have been described, and Sato and Nambu report hyaline degeneration of the blood-vessel walls. Secondary pneumonias, usually broncho-pneumonic in type, are of common occurrence, and in many epidemics constitute the prevailing cause of death. Tuberculous lesions are also frequently present, and are stated to assume fresh activity as the result of the nutritional disorder. Edema occurs frequently, the fluid in the acini often containing red blood-cells. Subpleural hemorrhages, thickening of the pleura, purulent or fibrinous pleurisy are common lesions.

Heart.—Although hypertrophy and dilatation of the heart have been noted by several observers, microscopic changes have rarely been recorded. Meyer, and also Leven, report fatty degeneration of the muscle fibres, which, however, was found by Aschoff and Koch in only one case. Sato and Nambu described an increase of connective tissue, and others anemia and pigmentation. Thickening of the pericardium and subserous hemorrhages also occur.

ALIMENTARY TRACT

Gums.—Where it has been possible to examine the gums of early cases, where swelling, redness or bluish discoloration are the chief symptoms and before secondary infection has set in, the microscopic picture is very similar to that of the skin. Small hemorrhages, round-celled infiltration, increase of connective tissue, clumps of pigment containing cells, or a diffuse deposit of brownish granules complete the picture. Congestion and edema are usually evident. The changes are most pronounced in the deeper layers of the submucosa and about the muscles, leaving the superficial layers strikingly intact, beneath an apparently normal epithelium. In the later stages, erosion of the mucosa occurs, and the upper layers of submucosa become involved. Polynuclear cells appear in great numbers, abscesses and ulcers are formed, which with proper staining can be shown to harbor the various types of mouth bacteria, cocci, spirillæ, etc. The pigmentation becomes intense, and a marked increase of the newly-formed connective tissue takes place.

The lesions of the stomach are neither characteristic nor, as a rule, very striking. Hemorrhages occur, the larger ones generally in the subperitoneal layers, the smaller ones in any of the coats. Thickening of the wall follows or accompanies these hemorrhages. Superficial erosions of the mucosa or even ulcers may be seen.

The striking congestion of the duodenum has been fully discussed in considering the gross pathology. At any level in the intestinal tract hemorrhage may take place, with the resulting pigmentation and scar tissue formation. The lymphoid structures—solitary follicles and Peyer’s patches—are usually intensely congested and often the seat of hemorrhage. They constitute the sites of predilection for ulcerative processes of the gut. Bacteria can be demonstrated at times in the submucous layers; however, no type has been found to predominate, the flora being composed of the usual intestinal forms. Aschoff and Koch have demonstrated in these ulcers the spirilla and fusiform bacilli so commonly found in the mouth. These follicular ulcers may be found in any part of the intestine, and may be shallow erosions, or extend through the follicle into the deeper tissues. Hemorrhages are commonly located about the follicles. The epithelial layer is edematous, often showing an increased number of cells.

The lymph-nodes may be congested, or edematous and hemorrhagic. Pigment is usually present and in some cases the peripheral sinus is distended with pigment-loaded cells. Where secondary infection has occurred, extensive necrosis of the glands is seen. This is found frequently in mesenteric nodes where severe intestinal lesions are present. The nodes lying in the drainage paths of hemorrhagic areas, especially the inguinal nodes, show active resorption of blood and blood pigments, and, as noted above, may be the seat of infection.

Liver.—In this organ, likewise, no change is found with sufficient regularity to warrant its acceptance as a distinctive lesion of scurvy. Fatty infiltration is, however, very common in the centre as well as in the periphery of the lobules. It is frequently associated with congestion, which may be so great as to lead to atrophy. In one case of Aschoff and Koch the picture resembled that of primary liver atrophy. The organ frequently contains extravasated blood or depositions of old blood pigment. It should be noted that Boerich described early cirrhosis in several of his cases, and that Aschoff and Koch record that one of their severe, acute cases showed “a recent cellular cirrhosis.” An exceptional lesion is reported by Reinert—a “leucocytic” infiltration of the liver and spleen occurring in a three-year-old child, and resembling that seen in pseudoleukæmia. Finally, it should be remembered in this connection that Hart and Lessing found calcium deposits not only in the muscles and adrenal glands of their monkeys, but also in the liver.

The spleen shares the general congestion of the internal organs. Sato and Nambu invariably found large numbers of pigment granules in this organ. Hirschsprung noted many Malpighian corpuscles, Reinert describes a true hyperplasia of the splenic pulp, and others mention infarcts and subcapsular hemorrhages.

The kidneys are often normal. On the other hand, various forms of nephritis are found, with cloudy swelling or interstitial change—a not infrequent complication of scurvy. More typical of the primary disease are congestion and hemorrhages, the bleedings occurring either under the capsule, into the interstitial tissues, or into the lumina of the tubules. Hayem found fatty infiltration of this organ and Aschoff and Koch a slight change of this kind in one case.

Adrenals.—A new interest in the study of the adrenals in diseases of the “deficiency” group has been created by the recent work of McCarrison. This author found the adrenals increased in size and weight in guinea-pigs dying of scurvy, whereas the adrenalin content of these glands was markedly decreased. On section there was hemorrhagic infiltration, “usually circumscribed in extent and situated around the periphery of the adrenal cortex.” This was seen even in early cases before hemorrhage had occurred elsewhere in the body. He describes also “degenerative changes in the cellular elements of cortex and medulla” consisting of vacuolation and disintegration of the cells with disappearance or loss of staining reactions of their nuclei. Rondoni, some years previously, had called attention to this increase in size and hyperæmia of the adrenals in guinea-pigs fed exclusively cereal diets. He, as well as McCarrison, noted an increase, though much less marked, as the result of starvation. LaMer and Campbell recently have confirmed McCarrison’s report of an augmentation in the weight of the adrenal glands in guinea-pigs fed on diets deficient in the antiscorbutic factor.

Comparable lesions have as yet not been found in human scurvy. These glands have been found normal by Jacobsthal, Schoedel and Nauwerk, Ingier and Epstein. In the cases of Aschoff and Koch no abnormality was noted except an almost constant increase in lipoid content. In those of Boerich the glands were normal in all but one case; in this instance the medulla was somewhat increased in size. In passing, we may repeat that Hart and Lessing found calcium deposits in the adrenals of four of their five monkeys, a lesion which has never been recorded in man.

It is valuable in this connection to compare the adrenal in scurvy with that of beriberi. In this disorder, Albert found the adrenal normal in one case, and Andrews describes only congestion in his eighteen necropsies. Ono found an increased adrenalin content in nine fatal cases, and states that the medulla appeared “fatter” than normal. More data will have to be obtained before it can be determined whether characteristic changes occur in scurvy, and how to interpret the hypertrophy described by several authors as common to guinea-pig scurvy.

Pancreas.—Sato and Nambu appear to be the only investigators who have described lesions in the pancreas. They found hemorrhages in one case among thirteen.

Thymus.—This organ has rarely been examined. Aschoff and Koch found no abnormalities in adults, nor did Jacobsthal in a case of infantile scurvy. Boerich noted enlargement in one instance.

Other Organs of Internal Secretion.—Very little attention has been paid to these organs. Aschoff and Koch state that the thyroids and hypophyses were normal in their cases.

Generative Organs.—No abnormalities have been described.

Central Nervous System.—The most frequent abnormality of the central nervous system is, as would be expected, hemorrhage; this has been discussed in the section dealing with gross pathology. No specific changes have been found in nerve-cells or fibres of the brain.

In a case of fatal scurvy in an infant a “focal degeneration of the lumbar cord” has been described, extending for a distance of about a quarter of an inch (Hess). The lesion differed from that of poliomyelitis in the absence of round-celled infiltration and of the characteristic changes in the anterior horn cells (Figs. 3 and 4). The outstanding feature was a loss of cells in the lateral groups of the left anterior horn; there were also fewer nerve fibres in this region, but this diminution was less striking. No definite interpretation of this case can be made as the data are insufficient to permit a conclusion as to whether the lesion was truly scorbutic or the result of an associated process. Schoedel and Nauwerk found no change in the spinal cord stained by Marchi’s method.

Peripheral Nerves.—The sheaths of the large nerves as well as those of the vessels are very often invaded by hemorrhage. The extravasated blood is found to lie around but rarely among the nerve fibres, which do not show any pathological alteration. Ingier is one of the very few to describe a degeneration of the nerve fibres. In one guinea-pig in which scurvy was induced she found “many marked degenerated fibrillar bundles of both sciatic and peroneal nerves, slight degeneration of the phrenic nerves and one vagus and its cardiac branch.” Another animal is referred to as having shown “very marked and well-developed degeneration of the nerves of the lower extremities.” It is open to question whether starvation played a rôle in the causation of these lesions. Schoedel and Nauwerk, and Aschoff and Koch examined these nerves but failed to find any lesions; the latter directed their attention especially to the vagus of twenty-two cases.

Retinal hemorrhages were found by Jacobsthal, and by Kitamura, who records “decided edema of the retina, marked bleeding and circumscribed hypertrophy of the nerve fibres” such as is found in albuminuric retinitis. These changes are considered again under the symptomatology of scurvy.

Bones.—Our knowledge of the minute pathology of the bones is far more complete and detailed than that of any other structure. This was to be expected in view of the fact that this is the only tissue in which the lesions are diagnostic. In considering the microscopic pathology it must be remembered that all the bones are rarely affected by scurvy, and that those that are involved show the scorbutic changes to a varying degree. One of the peculiarities of the lesion is that it involves the end of the diaphysis or rather the junction of the diaphysis and the cartilage. The bones most apt to show typical changes are the ribs; we shall therefore describe a section made through a costochondral junction.

The costochondral junction is generally swollen, somewhat beaded, and when cut longitudinally shows on gross examination a transverse yellowish bar, corresponding to the area of disorganization which will be described below. Under the microscope the line of juncture is not sharp and straight as is normally the case, but presents a wavy or irregular contour, the cartilage jutting into the bony end of the rib, instead of abutting in neat apposition to it. The bone is hollowed out and irregularly concave, whereas the cartilage presents a convex appearance. At the site of the junction is the Truemmerfeld area, where the normal tissue is splintered and fragmented. Everything in a state of disorder—trabeculæ of bone of various shapes and sizes lie scattered about, the cells irregularly arranged and much distorted, signs of recent hemorrhage, unrecognizable detritus. The picture is that of weakened bone having been crushed by the pressure of the more compact cartilage. Higher magnification shows that there are few osteoblasts (generally associated with the deeper fragments of bone), a varying number of intact red cells, according to the occurrence of hemorrhage, and occasional spindle- and star-shaped connective-tissue cells. Covering this mass of detritus there is frequently, as Aschoff and Koch have emphasized, more or less protective fibrin which has undergone some hyaline or connective-tissue organization.

The cartilage is also not normal. Its cells do not present an orderly arrangement, the proliferating columns having disappeared in the central convex portion, and being present to a varying extent near the periosteal borders. If we judge from sections of early scurvy in guinea-pigs, this disturbance of the columnar formation of the proliferating cartilage is one of the early signs of scurvy, and is associated with an unevenness and irregularity in shape and size of the bone trabeculæ. In young individuals, where cartilage activity is great, these changes are most marked and the entire zone of active cells may be somewhat widened.

Fig. 5.—Infantile scurvy. Epiphyseal junction of lower end of femur: (a) calcified cartilage at “Truemmerfeld” (b) hemorrhage in the fibrous marrow (Gernest-mark). Bone cortex and trabeculae abnormally thin. McCallums’ Text Book of Pathology. W. B. Saunders Co.

Below the Truemmerfeld is the Geruestmark or framework marrow, another distinguishing feature of scurvy. This extends for about 5 to 10 mm. toward the lymphoid marrow, where it ends more or less abruptly. It is composed of a loosely-constructed fibrillar tissue on a gelatinous-appearing groundwork, of sparsely scattered cells, and bony trabeculæ which are markedly thin and weak. Here and there are hemorrhages and blood pigment, especially adjacent to the “Truemmerfeld.” Another feature which strikes one at first glance is that the entire marrow area is incompletely filled by the thin and greatly-depleted trabeculæ of the spongiosa. The question has been raised whether this rarification is to be considered entirely of scorbutic origin. It is due evidently to a lack of function of the osteoblasts, which are diminished in number, and are represented by a layer of shrivelled spindle cells along the walls of the atrophied bony columns. They may fail almost entirely, as may its osteoid border, which is significant of active bone tissue. The lack of bony structure and rarification clearly is not due to an increase in the number or the function of the osteoclasts, for these do not appear in excess. It is mainly the result of normal bone resorption with a lack of normal bone regeneration. Aschoff and Koch suggest that the framework marrow may be able to manufacture bone, but cannot accomplish this because there is a lack of material from which to make osteoid tissue. This, they believe, constitutes the primary deficiency—a lack or faulty development of cement substance, which in turn may depend on an alteration of colloid material. Regarded in this light, the lesions of the bones resulting in fracture and those of the blood-vessels resulting in rupture and hemorrhage are dependent on a deficiency of the same basic material.

Hemorrhage occurs in the bone as elsewhere; it is almost never lacking. It appears either as large hemorrhages in the spongiosa, especially where the normal marrow joins either the Geruestmark or the Truemmerfeld, or merely as scattered cells, possibly the result of diapedesis. The blood-vessels in these areas are narrow and extremely thin-walled. The most typical site of hemorrhage is beneath the periosteum, a lesion widely known on account of its clinical significance ([Fig. 16]). Here the blood may extend for a considerable distance along the shaft, but rarely beyond the epiphyseal line. The clot forms readily, demonstrating that the nature of the hemorrhage is not a defect in coagulation, and in its midst may be seen fibrin, pigment, granulation tissue, and more or less firm connective tissue—constituting the callus. The inner surface of the periosteum is frequently lined with newly-formed bone and with a more or less dense deposition of lime salts, which becomes heavier in the course of the healing process, and is readily observed in radiographs. This periostitis ossificans may result in the clot being surrounded by a perfect shell of bone, with bony columns penetrating the deeper layers.

As the result of the lack of bone formation and the consequent weakening of the corticalis and the spongiosa, frequently a separation of the diaphysis from the epiphysis results. This lesion should not be regarded as a true separation, for, as Barlow pointed out, the line of cleavage is not at the junction, but below it, involving the uppermost region of the diaphysis. It is therefore correct to speak of a fracture or infraction. This lesion is generally accompanied by a deformity of the surface contour of the junction, due to a displacement of the cartilage, as a result of which “angular beading” of the rib is brought about. In some instances the cartilage is “telescoped” into the crushed end of the bone. To a varying extent fibrin covers the end of the fractured bone; the angles adjacent to the periosteum contain blood which becomes organized into dense connective tissue, thus serving as a splint for the fractured parts. In the course of healing a large number of foreign body giant-cells appear, blood-vessels sprout from the periosteum as well as the bony surface, and the necrosed tissue gives place to an active formation of callus, which generally leads to complete regeneration and restitution. It is remarkable how quickly and perfectly an epiphysis may become reunited to its shaft (Figs. 6 and 7). Sometimes, however, this takes place with resulting deformity, as in the development of coxa vara of the femur.

As Czerny and Keller have stated, it is difficult to define sharply the relation of bone fragility to scurvy. Histologically there is great similarity between the “osteotabes infantum” described by Ziegler and conditions sometimes found in infantile scurvy. The main distinction is that in the latter disorder the lesion is less generally distributed throughout the skeleton, and is particularly marked in a limited area of the bones (epiphyses). In considering this question it should be borne in mind that, experimentally, osteoporosis and scurvy can be brought about by diets which are absolutely dissimilar. For example, Bartenstein showed that young guinea-pigs develop osteoporosis and multiple fractures on a diet of raw milk containing an adequate quota of antiscorbutic vitamine.

Rickets and infantile scurvy are commonly found associated, although they bear no causal relationship to each other. The distinctive characteristic of rickets is the broad area of osteoid tissue which is formed at the epiphyseal junction, a broad band of incompletely calcified cartilage not found in scurvy. In the latter disease osteoblastic bone growth is greatly inhibited, but what growth does take place occurs in a normal and orderly manner. The osteophytes, for example, which so commonly develop at right angles to the axis of the bone in the subperiosteal hemorrhages, are composed of apparently normal bone. Another marked distinction between the two conditions is the paucity of blood-vessels in the cartilaginous area and in the marrow in scurvy, compared with the increased vascularity so generally encountered in rickets. It is evident, therefore, that although these two nutritional disorders bear a superficial resemblance to each other pathologically, they are radically different and almost antithetical.

CHAPTER V
EXPERIMENTAL SCURVY

There is no mention whatsoever of scurvy in animals previous to 1895, when Theobald Smith wrote: “When guinea-pigs are fed with cereal (it has been observed for some years in this laboratory), with bran and oats mixed, without any grass, clover, or succulent vegetable, such as cabbage, a peculiar disease, chiefly recognizable by subcutaneous extravasations of blood, carries them off in from four to eight weeks.” Smith did not pursue the subject further.

Coincident with the appreciation of the value of experimental methods, one would have expected attempts to produce scurvy in animals. The disorder had been recognized for a great many years, the fact that it was occasioned by a dietary deficient in fresh food was widely known, so that it would seem natural for clinicians or laboratory workers to have tried to induce the disease in animals by a similar restricted diet. There is, however, no suggestion of such an experiment in the voluminous literature on scurvy. The explanation of the neglect of an experimental study of scurvy appears to be that this was considered a disorder which required little investigation—its etiology, its prevention and its cure seemed thoroughly understood. It is strange that the mere fact that such a severe disturbance responded, as if by magic, to the administration of simple foodstuffs should not have awakened curiosity as well as wonder, and stimulated inquiry into the nature and significance of the curative agent.

In 1903 Bolle published the results of experiments on guinea-pigs which had been fed for various periods on raw or sterilized milk. He reported that the animals developed a marked fragility of the bones, varying in intensity in proportion to the degree of heat to which the milk had been subjected. These changes Bolle interpreted as typical scurvy, but it is difficult to decide whether the disorder was actually true scurvy, in view of the indefinite description of the bone lesions.

Bartenstein repeated Bolle’s work and described in detail the changes in the bones. From his work we learned that it was of little moment whether the animals were fed raw or sterilized milk—their nutrition failed within about the same length of time, and they died within a month. The chief pathologic change was a marked fragility of the bones, leading to spontaneous fractures, or to breaking of the bones in the course of ordinary manipulation. Bartenstein described the disorder as “beginning with the degeneration of the marrow, and secondarily leading to an atrophy of the bone due to increased absorption and deficient new formation of bone, especially at the endochondral lines of ossification. As the result of the osteoporosis, spontaneous fractures occur without noticeable hemorrhagic diathesis.” He found a deficiency of calcium in the bones of animals suffering from even a mild degree of this disorder. Hart and Lessing are of the opinion that we cannot accept Bartenstein’s diagnosis of scurvy. They compare this disorder to that described by Ziegler as “osteotabes infantum,” in which there is a more or less pronounced “jelly marrow” which has replaced the lymphoid cells in scattered areas. They sum up their analysis of the question with the statement that “the primary marrow changes in the diaphysis, the marked lacunar absorption by osteoclasts, the absence of subperiosteal hemorrhages, do not indicate typical scurvy.” Schmorl produced comparable lesions in dogs and came to the conclusion that the disorder was one “very similar” to scurvy but not identical with it, the essential difference being that in all animals there was a most marked absorption of bone by osteoclasts.

Similar results were obtained by others. In 1904 Peiper and Eichloff attempted to produce scurvy in dogs by means of a diet composed exclusively of raw or of sterilized milk. The following year we find a report by Esser of feeding goats on sterilized milk. None of these studies hits the mark; a condition of fragilitas ossium was produced rather than typical scurvy.

In 1907 the first systematic and convincing experimental study of scurvy appeared. In this year Holst and Froelich published a preliminary account of their classic work, undertaken in an endeavor to fathom the nature of “ship beriberi,” a disorder which disabled so many of the sailors in the Norwegian navy. We must remember that until recently attention has been focussed on the infectious diseases, and little thought given to the investigation of nutritional disorders. Although experimental investigation in this field may be stated to have been initiated by this work, it in turn had been stimulated by a conception of dietary diseases which had just begun to be realized. This new viewpoint was the result of the work of Eijkman. As has been mentioned in considering the pathogenesis of human scurvy, Eijkman demonstrated that hens developed polyneuritis, a disease resembling beriberi, when fed on polished rice, and that the simple change to a diet of unpolished rice, or the addition of rice polishings to the dietary, sufficed to protect or to cure. This work had been repeated and substantiated. It was evident to those who considered the question that the old lines of thought in regard to food and dietetics inadequately explained remarkable phenomena of this kind. It was also clear that nutritional disorders were subject to experimental investigation in a way similar to the infectious diseases, which were absorbing the interest of the various laboratories. It is unnecessary to review the rapid rise of investigative work in this field. It may be stated, in general, that during the past few years the investigations of scurvy have become so numerous that an established research technic may be said to have developed in connection with its study.

Attempts have been made to produce scurvy in various animals, but it has been brought about regularly only in the guinea-pig and in the monkey. Experiments on the dog are as yet too few to justify our regarding this animal as definitely available for this study. The nutrition of rats, mice, rabbits, hogs, pigeons, fowl, receiving a diet identical with that which regularly occasions scurvy in guinea-pigs, either progresses normally or a state of malnutrition develops which cannot be identified with scurvy. Recently Hart, Steenbock and Smith have reported that cattle can be reared to maturity on a diet which will produce scurvy in the guinea-pig in four to five weeks. We are therefore confronted with the remarkable and inexplicable phenomenon, a fact concurred in by almost all investigators, that a diet induces either normal nutrition or malnutrition, according to the experimental animal employed. A diet of polished rice, or other decorticated grain, will lead to the development of scurvy in the guinea-pig, to polyneuritis in the pigeon or fowl, or, according to Holst and Froelich, to a combination of these disorders in the hog.[35] The basis of these divergent results cannot be surmised, and is worthy of the most thorough investigation. It may well be that the elucidation of this problem—for example, why we are able to bring about scurvy in the guinea-pig but not in the rabbit, will shed light on the pathogenesis of this disorder. Are we to conclude that some of these animals have the power to synthesize the vitamine whereas others must depend upon the food for it, or are we to presuppose an ability to maintain normal life and function without any or with a minimal amount of this vitamine? The difference between these two groups, the susceptible and non-susceptible animals, probably is not as absolute as we have been wont to regard it. Recently Harden and Zilva have shown that although rats are able to thrive on a diet free from antiscorbutic vitamine, they show an appreciable gain in weight when this factor is added to the dietary. If such be proved to be the case, we must regard the non-susceptibility of the rat, the rabbit, etc., as relative rather than absolute.

From time to time a doubt has been raised as to whether we should accept guinea-pig scurvy as the counterpart of human scurvy. This question can be answered only by comparing the disorder in the one species with that in the other—as to mode of production, pathology, symptomatology, means of cure and all other phenomena. Viewed from these standpoints it is found that in almost every respect the disorder is identical in man and in the guinea-pig. The outstanding distinction is the difference in the length of time elapsing before the development of symptoms. In the child or in the adult it takes about six months of the deficient diet before clinical symptoms are manifest and a diagnosis can be established; in the guinea-pig the disorder can be recognized two weeks after restricting the diet. In the one instance we seem to be dealing with a nutritional disorder which is chronic or at least subacute, and in the other with a markedly acute condition. This distinction is open, however, to certain qualifications. In the first place, we must consider the duration of life of the two species, the comparatively short span of the guinea-pig compared with that of man. It must be borne in mind, furthermore, that the guinea-pig is placed on a diet absolutely devoid of all antiscorbutic vitamine, whereas this rarely obtains in human beings. For example, the diet which is most markedly scorbutic for infants is the “malt soup” previously mentioned, but even this food contains an amount of the antiscorbutic factor which is not negligible. But after taking these differences into consideration, it is nevertheless evident that the guinea-pig is far more sensitive to scurvy than man. This does not indicate that the guinea-pig is an unsuitable experimental animal, any more than the fact that the pigeon is more susceptible to polyneuritis than man indicates that it is unsuited to investigations of beriberi. It merely prevents our carrying out delicate quantitative experiments, and cautions against drawing too finely-spun deductions. In all nutritional investigations it should never be forgotten that conclusions drawn from experiments on animals are merely provisional, and must await substantiation on man, and, furthermore, that where differences in reaction are noted, the clinical data should be accorded full consideration.

Pathogenesis of Guinea-pig Scurvy.—From a pathogenetic point of view guinea-pig scurvy and human scurvy show remarkable points in common. Any diet that leads to the development of scurvy in man likewise brings it about in the guinea-pig, and contrariwise, any food which cures the disorder has the same beneficent effect on both species. This similarity extends so far that, as will be shown in the chapter on antiscorbutics, the relative potency of the various foods is approximately the same for man and for the guinea-pig. The parallelism generally is striking. The dietary which has been commonly employed in experimental scurvy has been that first suggested by Holst and Froelich, namely, oats, hay and water. Recently, however, this dietary has been enlarged in order to make it more complete, so as to include adequate protein, water-soluble and fat-soluble vitamine, and inorganic salts. To this end the group of workers at the Lister Institute (Chick and co-workers, Harden and Zilva) place their animals on a basal diet of one part of crushed oats and two of wheaten bran, and a daily ration of 50 to 60 c.c. of milk autoclaved for one hour at 120° C. This milk still retains a small amount of antiscorbutic vitamine. Cohen and Mendel have employed, apparently with good result, a “soy bean cracker,” containing soy bean flour which has been heated for 30 minutes at 15 pounds’ pressure (120° C.), 3 per cent. of sodium chloride, the same percentage of calcium lactate and of dried brewers’ yeast, and raw milk sufficient to supply 5 per cent. of butter-fat.

The use of raw milk was introduced by Jackson and Moore, and adopted by McCollum and Pitz and again by Pitz in a series of interesting experiments. The milk was given ad libitum. The results of these investigations were puzzling at first, until it was shown by Chick, Hume and Skelton that the dietary on which they were based contained a fundamental error which accounted for their lack of consistence. Although milk is not rich in the antiscorbutic factor, it possesses it in moderate degree, so that the outcome will be quite different according to whether a guinea-pig takes, for example, 50 c.c. or 100 c.c. daily. It is quite evident, therefore, that a food of this kind cannot be offered ad libitum, and that if this rule is not observed, most disconcerting results will follow.[36] This basic error in framing the dietary has made it impossible to accept the deductions of these authors. The conclusions of McCollum and Pitz are so striking and have led to such wide discussion, that they require consideration, in spite of the fact that the error in the dietary is now recognized. These authors found that the cæcum of their animals was greatly distended with putrefying fæces. As the cæcum is extraordinarily large and delicate in this species, they drew the deduction that the development of scurvy in the guinea-pig was due principally to the retention of fæces. “An impacted cæcum, the seat of putrefaction, may cause injury to the cæcal wall, sufficient to permit the invasion of the tissues by bacteria, or the animals may perhaps be injured primarily by the absorption of toxic products of bacterial origin.” Accessory dietary factors or vitamines, according to this theory, are supposed to play no part in the disorder, and antiscorbutics, such as orange juice, are considered to owe their efficacy mainly to their laxative properties, and to be replaceable by other laxatives such as phenolphthalein or oleum petrolatum. The efficacy of orange juice is supposed to be due to its content of citrates, and to be replaceable by what was termed “artificial orange juice,” a mixture composed of the various salts, citric acid and sucrose, in the proportions in which they are found in the natural juice.

These reports stimulated renewed interest in experimental scurvy, suggesting new aspects, and therefore directing attention to points requiring investigation. There were no data at hand on the consistency of the contents of the bowel in guinea-pigs, so that it was necessary to make appropriate observations in normal and in scorbutic animals. It was soon reported by various workers, Rappleye, Cohen and Mendel, Hess and Unger, and others, that there was no definite relationship between the occurrence of scurvy and impaction of the cæcum. In [Fig. 8] we see portrayed the stool output of a guinea-pig during the period in which it was developing scurvy, and during a subsequent period when it was being cured by means of orange juice. It is clear that there was no significant variation in the output during these divergent periods. A similar conclusion was arrived at by those who examined the cæcums of animals postmortem. Cohen and Mendel write: “Summarizing our experience with nearly one hundred scorbutic animals, we conclude that actual impaction of the fæces in the cæcum occurred in about one-quarter of the cases, and visible damage to wall, i.e., congestion or hemorrhage, or impaction, or both, was found in perhaps half of the cases. It should be noted that this statement covers all the diets we have tried.” We concur in this conclusion. Not infrequently we found the cæcums of markedly scorbutic pigs to contain semi-fluid fæces, the consistency of its contents depending on the character of the diet, quite apart from its adequacy and lack of the antiscorbutic factor. For example, a diet rich in milk, containing 100 c.c. or more, led to the formation of rather solid fæces; if oats were added to the milk diet the fæces in the cæcum were found to be still more solid, and this portion of the gut more often impacted. This condition could be detected by palpation even during life. Just as we encountered scorbutic animals on an oat, hay and water diet, who had semi-fluid fæces in the cæcums, so we met with others which were on a milk diet, and showed no signs of scurvy, although their cæcums were impacted with fæces of a putty-like consistence. Guinea-pigs do not seem to be able to tolerate a diet containing a large quantity of the fat of cow’s milk. Such a diet leads to impaction of the large intestine resulting in death, but does not induce scurvy. Jackson and Moore produced a condition of this kind by feeding pigs with cream containing 26 to 28 per cent. fat. “In every case,” they write, “the large intestine was distended with light mustard-colored semi-solid fæces.” This pathological condition is not understood, but is quite distinct from scurvy, and remarkable in view of the fact that the milk of the guinea-pig contains as high as 25 per cent. of fat. It is an interesting illustration of the marked biological difference in the butter-fat of various species.

Fig. 8.—Shows a period with the development of scurvy, and one where it was cured by giving orange juice. It will be noted that there was no marked constipation while the animal had scurvy. During a period of a few days the amount of stool was scanty, corresponding to the decreased intake of oats and hay on the days preceding. Broken line represents clinical course of scurvy.

Nor was it found, as McCollum and Pitz claimed, that antiscorbutics were replaceable by laxatives in the diet. Without entering into the details of this aspect of the subject, which will be considered in the chapter on symptomatology, it may be stated that attempts to prevent the occurrence of scurvy or to cure it by means of laxatives invariably failed. Chick, Hume and Skelton, as well as Hess and Unger, gave oleum petrolatum to a series of pigs without the slightest favorable effect. Hart, Steenbock and Smith recently reported that they had administered 1 c.c. of this oil on alternate days to one series of pigs, and 2 mg. of phenolphthalein on alternate days to another series, without relieving the scurvy. Cohen and Mendel, in order to test the adequacy of their diet as to roughage, supplemented it with additions of considerable filter paper and sawdust, “without averting the appearance of scurvy.” It is evident, therefore, that constipation does not play an essential rôle in the pathogenesis of scurvy in the guinea-pig, and that antiscorbutics are by no means synonymous or interchangeable with laxatives. These results accord with observations on infantile scurvy.

The Pathology.—The pathology of guinea-pig scurvy is essentially that of human scurvy. Hemorrhages and separations of the epiphyses or fractures of the long bones dominate the macroscopic picture. The hemorrhages are found rarely in the gums, but are common about the joints, in the muscles of the jaw or in those of the hind legs. They may be subcutaneous and appear as bluish discolorations at various parts of the body, especially if the disorder has resulted in death or if infection has been superadded. On stripping the skin we often note hemorrhages in the intercostal muscles, and beading of the ribs at the site of the costochondral junctions, least marked in the upper and in the floating ribs. This has been frequently described in connection with guinea-pig scurvy; its similarity to the rosary of human rickets has been drawn attention to recently by Jackson and Moore. It should not be regarded as “pseudo-rhachitic,” but as typically scorbutic, from a microscopic as well as a macroscopic viewpoint. On closer examination a yellowish-white transverse line may be seen at the epiphyseal junction of the ribs, and frequently some subperiosteal hemorrhage. Beading of this character has been reported by Ingier also in the “snuffles” of hogs and as the result of trauma. A similar enlargement of the chondral junctions of the sternum may be found on examining its posterior surface.

The joints of the body always show some changes. The epiphyses are enlarged to a variable degree, resembling the epiphyses typical of human rickets. As in infants, this change is met with most commonly at the wrist joint, involving the ulna and the radius. The knee-joint is likewise often involved, especially the ends of the tibia; the elbow, ankle, and the shoulder may also show an articular swelling of the bones. About these joints hemorrhages in the subcutaneous tissues may be seen, or edema extending along the extremities. Not infrequently a fracture of one of the long bones is found, which may or may not have been diagnosed during life. The common site of fracture is the lower part of the tibia or fibula. Much more frequent than fractures are separations of the epiphyses, which long since have been recognized as typical of infantile scurvy. Even gentle handling in the course of performing the necropsy may occasion a lesion of this kind—of the tibia at the knee, of the radius or ulna at the wrist, or indeed at any of the epiphyseal junctions. The infracted ends occasionally may be seen held insecurely by a delicate band of periosteum. The shafts of the bones are brittle, rarefied, and easily broken.

On opening the chest, slight hemorrhages may be noted in the pericardium and in the visceral and costal pleuræ. The heart is frequently enlarged, and the pericardial sac contains an excess of serum; the right ventricle, however, is not found disproportionately hypertrophied. Pneumonia is met with very frequently and constitutes a common terminal infection.

On opening the abdomen we may note subperitoneal hemorrhages of the muscular wall or of the coils of intestine. The liver and spleen are generally normal, as is the pancreas. The kidney frequently shows minute hemorrhages beneath the capsule and on section.

The adrenals not infrequently are large. This fact was first brought out by Rondoni and Montagnani, and is of added interest in view of its confirmation by McCarrison as well as by LaMer and Campbell. Its significance is discussed at length in the consideration of the adrenal gland in human scurvy. In view of the fact that fasting leads to a similar hypertrophy, and that guinea-pig scurvy frequently is complicated by fasting, these observations should be extended. In all investigations of this kind, bacterial cultures should be taken of the adrenals, or other organs, to be certain that there is no complicating infection.

There have been no reports as to the effect of scurvy on the size of the testicles, ovary, thymus, thyroid or parathyroid glands in the guinea-pig, such as have been made by McCarrison in relation to avian polyneuritis.

The alimentary tract occasionally shows macroscopic changes similar to the lesions found in man. The entire canal is frequently very empty, especially the stomach and the small intestine, due to the lack of appetite for some days previous to death. In the stomach we may find areas of congestion or numerous small superficial ulcers surrounded by congestion and covered with mucus; occasionally these ulcers are somewhat larger and deeper. The larger ulcers are more frequently situated in the first part of the duodenum, often proximal to the papilla of Vater. Holst and Froelich described this lesion in one of their early communications. More common than ulceration of the duodenum is a diffuse congestion of its upper part. This lesion is of note because it has been described frequently in the protocols of human necropsies, and is found in beriberi, in avian polyneuritis, and in pellagra in man. Its significance is unknown, and has indeed never been discussed.

Lower down in the bowel there are occasionally areas of congestion and ulceration, but no section seems particularly predisposed to these lesions. The contents of the bowel, especially of the cæcum, as mentioned above, depend more on the character of the food than on the existence of scurvy. If the diet has consisted of milk and oats, the cæcum will be found full and perhaps impacted, whereas if hay and oats have been fed, the cæcum will be less full and its contents semisolid.

In view of the fact that many of the animals have taken very little food for some days previous to their death, it will be well to describe briefly the macroscopic picture of simple starvation in guinea-pigs. When guinea-pigs are given only water they live about one week; if orange juice is added to this water diet they succumb a little later to starvation. Under all these conditions the striking pathologic change—absent in scurvy—is edema. It is true that the limbs may show slight edema in scurvy, and that the pericardial and the pleural sacs, and even the peritoneal cavity, occasionally contain a small quantity of serum, but it is comparatively an insignificant amount. Moreover it is difficult to decide to what extent this edema is due to scurvy, and to what extent to starvation. In typical starvation, on the other hand, such as occurs on the limited diets enumerated above, we find marked subcutaneous edema, sometimes a true anasarca, and frequently also ascites. We are reminded of the “war edema” and its frequent association with starvation. Another distinction between the two conditions is the fact that the marrow in starvation is yellow and not red as in scurvy. In passing, it may be mentioned that the ascites was greater when orange juice had been given than where the animal received only water.

In perusing the literature but one study has been noted on the effect of a scorbutic diet on the fœtus. This investigation was carried out on a large series of guinea-pigs by Ingier (1915). The following comprise her conclusions:

“1. Pronounced cases of Barlow’s disease may be produced in the fœtus as early as ten to fifteen days after the commencement of dieting pregnant guinea-pigs with oats and water. There are wide individual variations. The scorbutic changes in the skeleton are greatest in the earlier embryonic stages. The fœtuses of that period, with practically no exceptions, die and show marked traces of impeded growth.

“2. Fœtuses from the later period of pregnancy are born alive, and apparently fully developed, with comparatively slight changes in the osseous system.

“3. Even a short extension of the period of extra-uterine dieting on milk from scorbutic mothers, and later on oats and water, is sufficient to change the latent scurvy into a highly-pronounced case.

“4. The fœtus cannot be kept alive longer than the adult animal, about twenty-eight days, either by intra-uterine dieting alone or by combined intra- and extra-uterine dieting.

“5. The mothers show signs of the disease at an early period and are more severely attacked than non-pregnant animals. Death also occurs comparatively often in the first period of gestation.”

In these experiments intra-uterine fractures, premature births and still-born litters are frequently mentioned. This suggests naturally an inquiry as to whether similar occurrences have been observed in human scurvy. In considering the pathogenesis of human scurvy, we have remarked on the meagreness of the data on this most interesting aspect of this disorder. In view of the similarity between human and guinea-pig scurvy, we should expect not only miscarriages and still-births to result, but cases of congenital scurvy, especially of the latent or rudimentary type.

Scurvy Has Been Induced Also in the Monkey.—The most extensive investigation of this kind is that of Hart and Lessing, who brought about scurvy in several young Macaci Rhesi which had been fed for some months on boiled condensed milk with the addition of cooked rice and pig-nuts. Typical scurvy resulted in all but one instance, and in this case an old animal was used and a different pathological picture developed. These experiments require brief reviewing, as the clinical signs and gross pathology in monkeys differ somewhat from those encountered in guinea-pigs, and particularly as these distinctions render scurvy in monkeys and in infants practically identical.

Apart from general listlessness and lack of activity, the first sign is hemorrhage of the gums, the characteristic sign of infantile scurvy. This is stated to be constant; in the guinea-pig it is most exceptional. Another sign characteristic of infantile scurvy is the subperiosteal hemorrhage, which in the guinea-pig may be found as a small effusion near one of the larger joints or the costochondral junctions, but in the monkey consists of large effusions, similar to those described by Barlow. Subperiosteal hemorrhages of the cranial bones were constantly seen, and not infrequently involvement of the scapula and of the maxilla. Hemorrhage into the orbit leading to exophthalmos and to hemorrhagic discoloration of the upper lid—a lesion not infrequent in human scurvy—is also described; in guinea-pigs we have met with exophthalmos only in two instances. In all other respects scurvy in the monkey resembles that in the guinea-pig, even to the extent of the scorbutic rosary of the lower true ribs. Hart and Lessing describe the presence of the “white line” of Fraenkel, which is referred to at length in treating of the symptomatology of human scurvy. This is a shadow, seen by means of the X-ray, traversing the long bones near their epiphyses—a definite “shadow band” associated with a narrow light zone lying just beneath it. This “white line” has been noted likewise by Talbot, Dodd and Peterson in the scurvy of monkeys.

Microscopic Pathology.—Turning to the microscopic pathology, we find that the changes are similar to those described elsewhere in connection with human scurvy. It will be unnecessary, therefore, to give more than a general survey of the typical alterations. Little has been added to the description of lesions so carefully depicted in the first report of Holst and Froelich (1907). The bone marrow at the ends of the diaphyses in proximity to the epiphyseal junction loses its normal lymphoid character and is replaced by a reticular or fibrillated substance, the so-called “framework” marrow (Geruestmark of Schoedel and Nauwerk) containing a homogeneous mucoid tissue and only a few osteoblasts and marrow cells. The number of blood-vessels is considerably reduced and fresh hemorrhage or blood pigment is frequently seen. The osseous tissue itself shows marked changes, corresponding to the rarification and brittleness noted on gross examination. The osseous trabeculæ are fewer in number and those which remain are slender and irregular, and frequently appear as isolated islets. The cortical substance also becomes very thin. There are marked alterations in the intermediate cartilages, especially of the ribs.[37] Instead of the cells being arranged in orderly rows, they are irregularly placed, and frequently greatly reduced in size and number. The bone trabeculæ on which they abut are not well formed or of equal length, and do not present an even and transverse plane, but are misshapen, small, so that the line of junction with the cartilage is zigzag. In cases of marked scurvy the junction may be entirely disorganized and deformed, showing fractures of the rarefied bone and hemorrhages in the neighborhood. This leads frequently to a macroscopic deformity of bone, a bulging of the surface at the costochondral junction—the scorbutic “beading” or “rosary” of the ribs. Recently Delf and Tozer have described these changes, classifying them as those occurring in “incipient,” “definite,” “acute,” “chronic definite,” and “chronic acute” scurvy. [Fig. 9] shows these types in diagrammatic form. In this figure we see how varied may be the manifestations of this nutritional disorder, according to whether it has existed for a shorter or a longer time; in some instances the picture is very puzzling. The “incipient scurvy” corresponds to what we have termed clinically “latent scurvy” in infants, a condition which cannot be diagnosed and is manifested merely by a faulty nutrition which responds promptly to the addition of an antiscorbutic to the diet. There have been no histologic examinations in man at this incipient stage, but we may infer that they are similar to the bony changes found in the guinea-pig. When the scurvy has become chronic in an animal which has lived for months on a quota of antiscorbutic food sufficient to preserve life but insufficient to prevent the development of scurvy, we find a microscopic picture at the costochondral junction differing widely from that seen in the acute stage. Not only are the columns of cartilage cells represented merely by misshapen vestiges, but an ossified band (Fig. 9⁵) is seen at the junction. It is probable that this is frequently the cause of the marked cessation of growth which has been described in connection with this type of scurvy in infants. Delf and Tozer interpret this ossified band at the junction as “an attempt to strengthen the junction in an abnormal manner, the normal process having broken down.” If the animal is again deprived of antiscorbutic food the ossified band breaks down, the junction becomes deformed and disorganized, and a condition of “chronic scurvy (acute)” is stated to have developed.

1. Diagram of normal rib-junction.

2. Diagram of rib-junction to illustrate “Incipient Scurvy.” This rib-junction is very nearly normal, but shows what may be regarded as the first recognizable signs of the onset of the disease; these are: (a) An appearance of general abnormality (when compared with the normal). (b) Unevenness of the junction and slight disorganization of the rows of cartilage cells. (c) Shortening of the length of the rows of cartilage cells. (d) Shortening, and decrease in number of the trabeculæ. (e) Increased amount of blood in the marrow cavity.

3. Diagram of rib-junction to illustrate “Definite Scurvy.” Histological signs vary considerably in these cases (according to the severity of the disease), and may approach in appearance those characteristic of the “Acute” condition. The rows of cartilage cells may be almost normal, but are more often noticeably shortened and usually somewhat disorganized or arranged in circular groups. The trabeculæ are usually about half the normal length and have a truncated appearance. The junction as a whole may present an uneven, slightly disorganized appearance and there is sometimes a certain amount of macroscopic deformity.

4. Diagram of rib-junction to illustrate “Acute Scurvy.” In these cases the junction and rows of cartilage cells are often completely disorganized, causing a marked macroscopic deformity of the bone. The bone of the shaft is frequently fractured. The marrow is no longer in contact with the edge of the junction and the space is filled with a mass of connective tissue; this is very characteristic in cases of fracture. A condition in which the trabeculæ have almost disappeared and the rows are much shortened is also found in “Acute Scurvy,” in those ribs in which no fracture of the shaft has occurred; usually, however, there is little or no ossification across the junction. There is frequently hemorrhage into the marrow cavity.

Diagrams 5 and 6 illustrate types of “Chronic Scurvy.”

5. May be described as “Chronic Definite Scurvy.” The rows are much shortened but not disorganized and an ossified band extends across the junction.

6. May be described as “Acute Chronic Scurvy.” The junction is deformed, and the rows are very disorganized; the trabeculæ have disappeared and an ossified band extends across the junction. There is no connective tissue to be seen and no existing, or recent, fracture.

It has been noted by many investigators that changes in the teeth take place in the course of scurvy. They become somewhat yellow and lose their glistening appearance, and occasionally break off. The molars commonly become loosened, so that they can readily be removed from their alveolar sockets; less frequently this is true of the incisors. Until recently, however, this subject has not been studied in detail, and no significant histologic changes in the teeth have been described. Jackson and Moore showed that with marked changes in the teeth there was often “great dilatation of the veins in the pulp attended by more or less hemorrhage into the pulp,” and that “in guinea-pigs fed on oats and hay there was almost complete necrosis of the pulp of the incisor teeth, also more or less necrosis in the pulp of the molars.”

Recently an intensive study of this subject has been made by Zilva and Wells, which is of special interest because it describes the first beginnings of these lesions, and particularly because we have no knowledge whatsoever of the dental changes which occur in human scurvy. These investigators found a fibroid degeneration of the pulp of the teeth, a pulpar fibrosis. “It is clear at once,” they write, “and it is an important fact that no trace of cellular organization, no trace of cell nuclei, no trace of interstitial cement substances can be found anywhere. Nerves, cells, blood-vessels, and odontoblasts have all shared the process of fibrication and are no longer recognizable.” These radical changes in the teeth, brought about by a deficiency of antiscorbutic vitamine, were demonstrated not only in guinea-pigs but also in monkeys. In some instances they were found where a histologic examination of the costochondral junctions showed nothing abnormal. “Profound changes were recorded where the scorbutic changes during life were so slight as to be almost unrecognizable,” and, they continue, “the mildest degree of scurvy which could just be discovered at the postmortem examination produced well-defined changes in the structure of the teeth.” If this work is confirmed, we must consider the teeth as one of the first tissues of the body to be affected by scurvy. The authors quite rightly raise the question whether the teeth of young children may not likewise be injured by a deficiency of antiscorbutic vitamine, whether this may not play a rôle in the dental caries so prevalent among civilized communities. It is evident, they state, that such transient conditions of infantile scurvy as have been described by Hess as “subacute” or “latent” scurvy, may occur more often than is usually suspected, and may reasonably be expected to influence dentition. It seems quite possible that the caries of the permanent teeth is due not only to infantile rickets but also to infantile scurvy.

Besides the typical histologic changes in the bones there are alterations in other organs which require mention. All investigators have found a degeneration of the muscles, showing a loss of their striations, swelling of the fibres, and the presence of irregularly-distributed vacuoles and granules. The interstitial tissue frequently is permeated with edema, as we should expect from gross appearances. Holst and Froelich have reported a fatty degeneration of the heart muscle, as well as of the epithelium of the mucous membrane of the glands of the stomach and of the intestine. Hart and Lessing, in their protocols of necropsies on monkeys, describe an interesting lesion associated with the degenerated muscle fibres—a collection of granules staining deep blue with hæmatoxylin and dissolving on the addition of acid. These granules, interpreted as being composed of calcium, were found in the muscles of the limbs, of the tongue, and in the heart. It is reasonable to attribute their formation to an absorption of bone throughout the body. Similar calcium deposits were seen frequently in the adrenal glands, in their cortex, or at the border of the cortex and medulla. This lesion gains special interest in view of the calcium deposits described so frequently in connection with mercurial poisoning, more particularly as the symptoms of scurvy and of this toxic condition have marked clinical resemblances.

There has been but little histologic investigation of the nerves in experimental scurvy. In fact, the only systematic study of the kind is that of Holst and Froelich, whose attention was drawn to this field in an attempt to solve the relationship between scurvy and ship beriberi. These writers found a true Wallerian polyneuritis in only two pigs, one of which had been fed on wheat bread made with yeast, and the other on decorticated barley. In many instances, however, there was extensive degeneration of the axis cylinders without degeneration of the sheaths. They do not, however, attribute great importance to these changes, as the same lesions were found in the nerves of animals fed on cabbage and fresh potatoes. In view of the confusing reports on the nerves of birds in experiments on polyneuritis, one cannot be too careful in drawing conclusions from histologic studies of this kind.

In the study by Jackson and Moore on experimental scurvy in guinea-pigs, the histology of the blood-vessels is carefully considered. “Marked thinning of the wall” was found and depicted; “the wall as a whole had partially melted away, leaving few traces.” These parts of the wall contained many small round bodies resembling cocci, which were stained a deep blue by the Wright and the Giemsa methods. These bodies were present also in the lumen of the vessel and in the inner layers of the more normal portions of the wall. In addition to such changes in the veins, “lesions having the shape, location, and characteristics of infarcts, were found in the ends of the diaphyses of the long bones.” As a result of this pathologic picture the authors are of the opinion that they may have been dealing with a mild infection. This is quite possible, as scurvy tends to render the tissues less resistant to the entrance of bacteria. We believe, however, that even if such were the case, the phenomenon must be regarded merely as secondary in its relation to the pathogenesis of scurvy.

Following the study on the pathology of experimental scurvy, Jackson and Moore undertook to determine primarily whether the small stained bodies seen in the sections of the scurvy lesions were bacteria. This investigation has been cited frequently as presenting cogent evidence in favor of the infectious nature of scurvy, so that it will be necessary to consider it fully; the general question of whether scurvy is a bacterial infection is discussed under the consideration of etiology.

As is well known, Morpurgo, a generation ago, claimed to have produced rhachitic lesions in young rats by means of artificial infection with a gram-positive diplococcus. Pappenheimer brought about similar lesions in rats by the injection of a suspension of bone marrow from a rhachitic animal. Koch injected a streptococcus longus intravenously into young dogs, occasioning gross bony changes of the epiphyses and costochondral junctions, and microscopic changes resembling scurvy—an irregular line of ossification and “a framework” marrow, which, however, showed regions of osteoid. Jackson and Moody were able to isolate from the crushed tissue of their guinea-pigs “a diplococcus of low virulence with a tendency to form chains and produce green (color) on blood agar.” Pure strains of these organisms inoculated into the circulation of guinea-pigs and rabbits, living under ordinary conditions (a mixed diet consisting of green vegetables, hay and oats), gave rise in most instances to hemorrhagic and other lesions in the bones, joints, muscles, lymph-glands or gums. Hemorrhages were found beneath the periosteum in the region of the lower incisor teeth and the acetabulum and ribs. These results are far from constituting evidence in favor of the microbic origin of scurvy. They show merely that the tissues of scorbutic animals frequently harbor bacteria, and that injections of these bacteria will bring about hemorrhages which may be subperiosteal in character. They are open to the specific criticism that scurvy was produced readily in the rabbit, an animal which otherwise does not develop scurvy, and, furthermore, they differ from feeding experiments in inciting scurvy notwithstanding the fact that the animals were receiving an antiscorbutic diet (green vegetables). Cultures of the hearts’ blood of the affected animals were sterile in every instance; a result obtained likewise by Holst and Froelich.

Further studies of this kind should be carried out and should include cultures of the blood and tissues of guinea-pigs in the various stages of scurvy, especially the early stage. In addition, a histologic study should be made of the bones of animals injected with bacteria (preferably streptococci), in order to ascertain whether notwithstanding an unrestricted diet, typical lesions can be produced by this means.

For further details of the pathology of scurvy, the reader is referred to the chapter on human pathology.

Symptoms.—Let us consider the symptomatology of guinea-pig scurvy. In the course of an observation of many hundreds of animals we have been struck by the striking uniformity of the signs and symptoms. The animals made use of were almost invariably of moderate size, weighing from 200 to 300 grams. Where heavier pigs were employed the disease progressed less rapidly, but the signs were the same; they were, however, more difficult to elicit, owing to the subcutaneous fat. Most of the animals were on a diet of hay, oats and water ad libitum, but there was no variation in symptoms where fat and fat-soluble vitamine were supplied by an addition of egg yolk or of cod liver oil, or where egg albumen was fed to render the protein adequate, or where the inorganic salts were supplemented by additions of sodium or calcium chloride.