Development of scurvy in spite of normal gain in weightFig. 24.—Development of scurvy in spite of normal gain in weight in a baby who had been underfed since birth.
Although it may be stated as a principle that the development of scurvy is accompanied by a failure to gain in weight, there are exceptions to this rule. Under certain conditions the weight may follow a perfectly normal course during the entire period. Fig. 24 illustrates this clinical paradox:
A baby was seen in January, when it was 7½ months of age. Toward the end of February, in spite of constant and normal gain in weight, he manifested unmistakable signs of scurvy—peridental hemorrhage over the upper incisor teeth, which were erupting, and tenderness of the lower ends of the femora. The scorbutic nature of these signs were substantiated by their prompt subsidence on the administration of orange juice. We explain the phenomenon as follows: This baby had been starved in a two-fold sense throughout the first months of its life—it had received a diet lacking in caloric value as well as deficient in antiscorbutic vitamine. Its growth impulse had been held in abeyance for months by both of these factors. When sufficient calories were supplied in the dietary, growth was no longer repressed, and a steady gain resulted in spite of the continued inadequacy of the antiscorbutic factor.
A baby was seen in January, when it was 7½ months of age. Toward the end of February, in spite of constant and normal gain in weight, he manifested unmistakable signs of scurvy—peridental hemorrhage over the upper incisor teeth, which were erupting, and tenderness of the lower ends of the femora. The scorbutic nature of these signs were substantiated by their prompt subsidence on the administration of orange juice. We explain the phenomenon as follows: This baby had been starved in a two-fold sense throughout the first months of its life—it had received a diet lacking in caloric value as well as deficient in antiscorbutic vitamine. Its growth impulse had been held in abeyance for months by both of these factors. When sufficient calories were supplied in the dietary, growth was no longer repressed, and a steady gain resulted in spite of the continued inadequacy of the antiscorbutic factor.
It has been shown that during the period of infancy undernourishment must be extreme to occasion stunting of growth in length. In animals Aron demonstrated that lack of nutrition led to a decrease of the fat and of the muscle of the body, but that the skeleton nevertheless continued to grow, and the ash content of the body to increase. In marasmus, or infantile atrophy, the baby usually grows in length, although its weight remains stationary or decreases. In scurvy we have shown that there is frequently a definite retardation of growth in length, an observation which has been recently confirmed by Epstein in babies which developed this disorder in the foundling asylum of Prague during the war. This fact shows how profoundly the metabolism must be disturbed by this disorder. Figure 25 portrays this retardation in growth and the sharp reaction when orange juice was added to the dietary. It also demonstrates that the growthimpulse remains unimpaired and capable of quick response when the essential food factor is furnished.
Retardation of growth in length when no orange juice was given and supergrowth when given once moreFig. 25.—Showing retardation of growth in length during the period when no orange juice was given and supergrowth when it was given once more, O. J.=orange juice. O. P. J.= orange-peel juice. Lower curve represents the normal.
Fever.—Fever frequently accompanies scurvy. It is generally of a low grade, ranging between 100° and 101°, as may be seen inFig. 15. There is a difference of opinion as to whether the rise of temperature should be considered as truly scorbutic in nature, as “scorbutic fever,” or regarded merely as a condition grafted upon the nutritional disturbance. A phenomenon which might seem to argue for its essential scorbutic character is the sharp subsidence on giving antiscorbutic food. On the other hand, this may quite as well be interpreted as due to a secondary reaction, checkingthe absorption of toxins or bacteria. High temperatures—for example, fever of 103° or over—are attributable to a complicating infection and should lead to careful examination for the source of the trouble; pyelitis should particularly be borne in mind. In a recent case fever of uncertain origin disappeared following the transfusion of blood.
We have already considered numerouscomplicationsof scurvy, and shall therefore not go over this ground again. Many of them are due to hemorrhages or to serous effusions in various parts of the body. Another large group in adults as well as in infants are the result of infection. The respiratory tract is particularly susceptible, pneumonia constituting the most common cause of death. In infants we meet with frequent attacks of “grippe,” widespread occurrence ofnasal diphtheria, furunculosis and torpid ulcers of the skin, pyelitis, otitis, adenitis, etc. We have encountered nasal diphtheria—with typical bloody mucous discharge—so frequently in connection with scurvy, that where this local infection occurs among a group of infants they should be carefully examined for latent or mild scurvy. Aschoff and Koch recently have laid emphasis on the frequency with which diphtheria complicated scurvy among adults (soldiers). Dysentery is another complication resulting from an invasion of bacteria. Local infections occur more often in adults than in infants—cervical adenitis following gingival pyorrhœa, “bubo” of the groin following infection of the lower extremity, abscess of the calf of the leg following hemorrhage into this region.
Scurvy sometimes occurs inepidemic form, especially in the army, but also, as in Russia, among the civilian population. This results when a large group of individualshave been maintained on a limited and inadequate ration, and especially where this nutritional condition is complicated by intercurrent infection. It should not be interpreted as evidence of the bacterial origin of scurvy. A few years ago the author reported an epidemic of scurvy in connection with an outbreak of grippe in an infant asylum. Twelve infants in one ward were affected. The signs were atypical—an undue degree of hemorrhage occurring at atypical sites (Table 5). It will be noted from the table that the ages of the infants, the distributionof the hemorrhages, the development of signs (in some instances) in spite of antiscorbutic treatment, the sharply defined epidemic character, distinguish these cases from the scurvy commonly seen. This is an instance where latent scurvy was prematurely changed to acute scurvy by an intercurrent ward infection; an epidemic of grippe precipitated a pseudo-epidemic of scurvy. It is important, especially for army surgeons, to bear in mind that where latent scurvy exists a bacterial invasion will lend the disorder a hemorrhagic character. This has been noted during the recent war in connection with typhus fever on the Eastern front, and was remarked upon during the Crimean War and our War of the Rebellion. Some years ago Wherry made a similar observation in the course of experiments with the plague bacillus—guinea-pigs fed on a cereal diet developed far more hemorrhages subsequent to infection than those which received cabbage in addition.
TABLE 5
A correct and earlydiagnosisof scurvy is the more important in view of the fact that we possess a specific remedy, and that the disorder is not self-limited. Recognition generally presents little difficulties for those who have seen cases, but is a stumbling block where the symptomatology has been gleaned merely from the textbooks. It has been our experience that medical students who were conversant with scurvy from a theoretical standpoint failed to diagnose a case presented to them in the clinic. Where diagnosis is uncertain, the most important aid is an exact knowledge of the previous diet, and observation of the reaction of the patient to antiscorbutic treatment. These diagnostic points should be constantly rememberedin relation to the discussion which follows, and will not be reiterated in the differentiation of scurvy from the various other diseases.
The scurvy of adults and of infants are very similar. The main difference is the subjective symptoms in the adult—pains in various parts of the body—and the fact that the gums are frequently the site of infection and ulceration, as well as of hemorrhage. It might be thought that when scurvy occurs in epidemic form it would be readily recognized, but experience shows that for months it may permeate the ranks of troops or the inmates of almshouses, and pass as rheumatism. This is the cardinal diagnostic error in adult as well as in infantile scurvy—time and again, and in spite of urgent and repeated warnings, patients continue to be treated forrheumatism. Holt writes: “In fully four-fifths of the cases which have come to my own notice this (rheumatism) has been the previous diagnosis.” Such has been our experience. The diagnosis should not be difficult. In sporadic cases, the individual has limited his diet usually on account of indigestion, or diarrhœa, or following some dietetic whim or medical advice given months previously. Where scurvy occursen masseit may follow an inability to obtain fresh food—as during war, on shipboard, in the Tropics or in the Arctic regions—or be the result of a misplaced reliance on some article of food—for example, dehydrated vegetables. More careful investigation will disclose that the “rheumatic” pains and tenderness are not in the joints but in the muscles and tendons. The calf muscles are frequently painful and excessively tender and somewhat swollen or infiltrated; the hamstring tendons or the tendo Achilles may be sore and slightly swollen and the site of slight subcutaneous hemorrhages.In some cases there is bone tenderness, pain on percussion of the shins or of the sternum. These signs may be accompanied by, or even precede, hemorrhages in the gums. The diagnosis of rheumatism in infants indicates a lack of knowledge of pediatrics, as this disease is hardly ever encountered in babies under a year and a half of age.
It is not always easy to differentiate scurvy frompurpura. In either disease the gums may be hemorrhagic and swollen, there may be scattered subcutaneous hemorrhages and pains in the limbs. Occasionally, as in a case seen a few years ago, we may be forced to resort to the dietetic test. A close inquiry into the previous diet, however, a history of previous attacks of purpura, the number, and especially the large size, of the subcutaneous hemorrhages, and above all, the diminished number of blood-platelets, should make diagnosis possible. In scurvy the platelets are almost always over 300,000 per cubic millimetre, whereas in purpura they are reduced to less than 200,000.
In the army it may be difficult to distinguish scurvy fromberiberi, especially if they occur side by side as in the recent English campaign in Mesopotamia. There may be a combination of the two diseases, a picture similar to ship-beriberi, regarded by Nocht as a hybrid of these diseases. The diagnosis is rendered more difficult, as at times scurvy is associated with signs of neuritis. We shall have to depend on the involvement of the gums and the hemorrhages in scurvy, and on the hyperæsthesia, paræsthesia, and anæsthesia in beriberi; marked edema points to the latter disease.
We have thus far had in mind frank and outspoken cases of scurvy. When we come to consider latent or early cases, the diagnosis is more difficult and may haveto be merely tentative. All that need be added, in view of the clinical picture sketched above, is that this condition should not be forgotten in treating adults who have malaise and indefinite “rheumatic” pains and, more particularly, in relation to infants who fail to gain, whose appetite is capricious, whose disposition has become fretful and who have developed the sallow scorbutic complexion. This warning is particularly opportune at present in the United States, where pasteurized milk is fed so extensively to infants, and an antiscorbutic food is not always given.
In addition to the symptoms just enumerated, tenderness of the bones, especially of the distal ends of the femora, should be sought for, the urine should be examined carefully for red blood-cells, and perhaps the ends of the long bones radiographed for “the white line” of Fraenkel.
The experience of Comby with infantile scurvy is illuminating. Among the fifty-five cases which he has seen, the diagnosis was erroneous in forty-five, and among thirteen cases recently met with, the physician failed to recognize the disorder in all but two. The infants had been given sodium salicylate, had been treated with electricity and massage for the supposed acute poliomyelitis, or given mercury for syphilis, or incisions or trephining had been carried out for acute osteomyelitis. Some had been put into plaster casts for coxalgia or for Potts’ disease. This experience requires little comment. It should be added, however, that in the course of an epidemic of poliomyelitis, such mistakes are apt to happen, and, to our knowledge, did occur in the recent epidemic.
In regard to “the pseudo-paralysis” of congenital syphilisdiagnosed as scurvy, it should be rememberedthat this lesion occurs almost always before the fifth month of life. A history of previous papular eruption, the bilateral enlargement of the epitrochlear glands, and the Wassermann test should suffice to establish the correct diagnosis.
Besides the clinical conditions enumerated above, we may add the following, which have been confused with scurvy: Neuritis, hemorrhagic nephritis, calculus of the urinary tract, renal tumor, orbital tumor, appendicitis, peritonitis, pleurisy and pneumonia. Holt writes as follows: “I have known two cases to be operated upon by eminent surgeons, once with a diagnosis of sarcoma and once of ostitis of both tibiæ. Not until the subperiosteal hemorrhages and epiphyseal separations were discovered was the nature of the trouble suspected.” Recently we saw a case of fracture of the distal end of the femur diagnosed as infantile scurvy; the baby had caught its thigh between the bars of the crib and snapped the bone in trying to extricate itself. Finkelstein adds acute endocarditis, hemorrhagic septicæmia with multiple bone swellings, and leukæmia as having been confused with scurvy.
In an interesting account of scurvy in the Russian army during the recent war, Hoerschelman states that tired soldiers at times feign scurvy. They produce a “pseudo-scurvy” by means of scratching the gums with their nails or rubbing them with tobacco, and at the same time bring about hemorrhages of the skin by means of trauma.
Scurvy in the breast-fed infant has been fully considered under etiology. We wish merely to state again that one cannot be too cautious in venturing this diagnosis in a nursing baby. The great majority of reportedcases are not scurvy, but bacterial infections, syphilis, or various forms of intoxication. In establishing a diagnosis the same principles hold as in the case of bottle-fed infants.
The most important consideration in the diagnosis of scurvy is to keep in mind the heterogeneous character of its symptoms, and the manifold diseases with which it may be confused. Surgeons should be alert to this danger when about to perform operations for osteomyelitis or bone tumor. The mistakes occur because cases are infrequently seen and because the signs, being dependent largely upon hemorrhage, occur in such varied locations of the body. Where diagnosis cannot be made from the signs or symptoms, the most important aid is a thorough acquaintance with the previous diet of the individual and observation of his reaction to antiscorbutic treatment.
The outcome of scurvy, as we encounter it in peace time in the Temperate Zone, is generally favorable, so that it plays but an insignificant rôle in our mortality statistics. This results from the fact that we are abundantly provided with a specific remedy, so that if the diagnosis is made early and treatment is prompt and thorough, the patient will rapidly recover and suffer no physical disability. Where antiscorbutic foodstuffs are not procurable, however, this disease constitutes a terrible scourge, causing many deaths and spreading among an army, a ship’s crew, or among the civil population with the rapidity of an epidemic. For example, the ships of the East India Company in their voyages round the Cape often lost nearly one-half of their crews, and in Lord Anson’s famous voyage round the world 380 out of 510 seamen perished from the disease. Moreover, if the antiscorbutic treatment is inadequate or the patient goes untreated for a long period, the cure may be incomplete, a condition of malnutrition and weakness developing, which may persist for years. To appreciate this clinical condition we must refer to the account of physicians who saw thousands of cases of severe and untreated scurvy among the sailors, who were of necessity deprived of aid until they reached land. Lind laid stress on a type of this disease which developed under these circumstances and which he termed “obstinate scurvy.” He writes: “I have met with numerous instances not only among the common seamen, but of officers, with whom it hadtaken such deep root in the constitution as to prove a lasting affliction to them during a great part of their lives. . . . Persons are likewise subject in different periods of their life afterwards to habitual rheumatism, pains and stiffness in their joints; and sometimes eruptions on the skin.” In his treatise on scurvy, published in 1685, Harvey refers to this chronic nutritional disorder as “inveterate scurvy.” He pictures patients who had gone untreated for a long time as “molested with vagrant, ambulative, distending, creeping, vellicating or lancinating pains of several parts of the body. . . . They are often loose and subject to falling into violent fluxes of the belly, diarrhœa and lienteries.”
Infants as well as adults usually recover rapidly and completely from scurvy, the result depending largely upon the early recognition of the disease. We must always bear in mind, however, that from a histologic standpoint the cure is not simultaneous with the magic disappearance of the clinical symptoms, but that months probably elapse before the tissues return to their normal state. It is difficult to give reliable mortality statistics for infantile scurvy, for so many cases are of the rudimentary form that percentages are necessarily misleading. Still writes that in 5 out of 64 cases the disease proved fatal by diarrhœa and exhaustion. The American Pediatric Society reports 29 deaths out of 397 cases, which gives a similar mortality percentage. When infantile scurvy was not so generally recognized by physicians the mortality was much higher, and we find that Barlow encountered 7 deaths in his first series of 31 cases.
Even when the child recovers it may not regain its normal health if it has continued for a prolonged period in a state of chronic scurvy. It may remain pale and fail togain in weight in spite of a liberal and well-balanced diet. Cases of this kind are not infrequent. In this connection it is worthy of note that 4 of the 41 cases of “cœliac disease,” an interesting intestinal condition described by Still, had scurvy just before or during the onset of the disease. This observation conforms to the experience that chronic bowel disorders often follow in the wake of adult scurvy.
In adults the heart may be weakened by scurvy, and death may result from cardiac failure. Cardiac disturbances occur also in infantile scurvy. This involvement might be expected, in view of the tachycardia (cardiorespiratory phenomenon) which is so frequent a symptom of infantile scurvy. The heart may be rapid for months or even for years after the disorder, and tachycardia may develop on the occasion of even a mild infectious disease. For example, a fever of 101°, due to a common coryza, may cause the heart-beat to rise to perhaps 180 a minute. Children so affected succumb readily to infection, especially to pneumonia, which may lead to sudden collapse followed by death.
An important factor in the prognosis of scurvy, as in that of other disorders due to a lack of vitamines, is the marked susceptibility to infection. Even latent or subacute scurvy causes a peculiar susceptibility to diphtheria (especially the nasal type), to coryza, bronchitis, and pneumonia. A perusal of the literature shows that this susceptibility was noted by the older authors in relation to adults.
The local signs usually disappear quickly without leaving any trace. The hemorrhages are absorbed and the eczema heals within a few days. The fractures unite promptly with the formation of an unusually large callus.The urine, which may have contained red blood-cells or have been markedly hemorrhagic, quickly becomes normal and, in our experience, gives no further evidence of renal damage. Still reports, however, the case of a frail child who had a trace of albumen in the urine two years after an attack of scurvy. A rare local injury, which may lead to death, is cerebral hemorrhage. Recently Sammis reported a case of this kind, which was characterized by convulsions during life, and in which subdural hemorrhage was found at necropsy.
If we acknowledge an individual idiosyncrasy to scurvy we should expect a tendency to a recurrence of the disease. Lind was of this opinion, stating that “by observations made on this disease, it appears that those who are once afflicted with it, especially in so high a degree as that squadron was, are more subject to it afterwards than others.” It is difficult at the present day to express a personal opinion on this matter, as clinical experience is meagre and the scurvy of guinea-pigs is so acute that it cannot be used for comparison. Some of the recurrences have been due probably to the fact that the patient had not been completely cured of his first attack. We have met with two cases of recurrences in infants, one of which is of particular interest as it happened in spite of giving lemon juice in the intervening period. The history was as follows:
In September, 1914, one month after the baby was admitted to the institution, it developed scurvy of a moderate grade. It was then six months of age and weighed 10¼ pounds. It was put on a simple mixture containing from 24 to 30 ounces of pasteurized milk and was given in addition ½ ounce of lemon juice a day. It improved, but during the winter had bronchitis, otitis, enteritis, andlater furunculosis. In spite of the fact that it had been receiving an antiscorbutic for almost this entire period, it developed scurvy once more in February, at the age of 11 months, and when it weighed 14½ pounds. It was evident that this baby was peculiarly susceptible to scurvy. It may be added that the second attack was complicated by nasal diphtheria.
In September, 1914, one month after the baby was admitted to the institution, it developed scurvy of a moderate grade. It was then six months of age and weighed 10¼ pounds. It was put on a simple mixture containing from 24 to 30 ounces of pasteurized milk and was given in addition ½ ounce of lemon juice a day. It improved, but during the winter had bronchitis, otitis, enteritis, andlater furunculosis. In spite of the fact that it had been receiving an antiscorbutic for almost this entire period, it developed scurvy once more in February, at the age of 11 months, and when it weighed 14½ pounds. It was evident that this baby was peculiarly susceptible to scurvy. It may be added that the second attack was complicated by nasal diphtheria.
In this connection attention should be drawn to a peculiar and puzzling clinical phenomenon, which we have noted several times. Even if the antiscorbutic treatment is carried out incompletely and only for a short period, recrudescences may not take place. We have seen cases where orange juice was given for merely ten days or two weeks—that is, only until all scorbutic signs had disappeared,—and yet the scurvy did not return, the infants thrived for months thereafter, but were merely somewhat pale and undernourished. In the case of two babies which we have in mind, the diet remained absolutely unchanged, with the exception of the short period of antiscorbutic treatment, but this seemed sufficient to bring about a diminished susceptibility.
“Seek the cure of scurvy neither in the armamentarium of the physician nor in the apothecary shops. The druggist will be of as little aid to you as the art of the surgeon. On the other hand, employ fresh vegetables, the juice of fresh antiscorbutic plants, oranges and lemons or the juice of those fruits preserved with sugar; in this way without other means you will be able to overcome this terrible disease.” This reads like the advice of some modern therapeutist; it is, however, the conclusion of a physician (Kramer) who wrote on scurvy almost two hundred years ago, and shows that the treatment of scurvy has undergone no fundamental change in the intervening years. Our resources, however, have been amplified by an increased knowledge of the relative value of antiscorbutic foodstuffs and by the introduction of some new ones.
Prevention.—In the Temperate Zone, under ordinary conditions, the adult population consumes sufficient antiscorbutic foodstuff to protect it from scurvy. Under exceptional circumstances, however—for example, when the potato crop fails, or, in the case of individuals, when the diet has been unduly restricted, scurvy will be encountered. This disorder is still an important problem, however, in relation to the health of adults in the Tropics, in military expeditions and in Polar explorations. From what has been stated in the preceding chapter, it is evident that, at the present time, no reliance can be placed on dehydrated vegetables as a protective agent. Therecent suggestion of using germinated dried pulses and seeds, under circumstances where fresh food is not available, is practical and probably will be resorted to in the future. To this end the pulses (beans, peas, lentils) are soaked in water for 24 hours, and then kept moist with access of air for about 48 hours at room temperature. During this period they sprout and develop small radicles. They are cooked in the usual way and have been found to possess an antiscorbutic value comparable to that of most vegetables. An individual should receive about four ounces a day of these sprouted seeds. In the treatment of some Serbian soldiers suffering from scurvy, Wiltshire found that this amount of germinated beans brought about a cure. There are, however, two drawbacks to their general use. The prolonged cooking necessary for their preparation reduces their antiscorbutic potency, and they have been found indigestible when consumed in sufficient quantity.
Under similar conditions canned tomatoes can be employed; they have the disadvantage of greater bulk, but are a more potent antiscorbutic, require no preparation whatsoever, and are readily digested. They form part of the present ration of the United States Army, in which they can be given “in lieu of an equal quantity of potatoes not exceeding twenty per cent. of the total issue.”50The necessity of including an antiscorbutic in the army ration has been recognized only in recent years; during our Civil War and for thirty years thereafter there wasno such provision. It was stated at that time that a general scorbutic taint pervaded the troops—a mere euphemism for the widespread existence of subacute or latent scurvy. Even to-day the ration of the French and of the Italian armies makes no definite provision in this regard and the Russians provide merely for a variable quantity of vegetables.
Recently it has been shown that lemon and orange juices (Givens and McClugage) can be dried and still preserve their antiscorbutic value. It is quite possible that concentrated preparations of this kind will be serviceable for army use and in regions where fresh fruit or vegetables cannot be obtained.51
Lind makes numerous ingenious suggestions for preparing antiscorbutic remedies (Lind, pp. 7, 8 and 9) which have a practical as well as historic interest. (Appendix 1.) One of these includes a formula for the preparation of orange and lemon juice which may be preserved for years; another gives a method for the preservation of berries and other fruits which are to be picked when partly ripe and put up in earthen pots; still another gives the recipe for preparing a simple decoction of fir tops, which was found by the Swedes efficacious in preventing the development of scurvy among their soldiers. It is interesting that a similar practice was resorted to in Vienna during the recent war and recommended as a prophylactic for scurvy in children (Tobler).
The prevention of infantile scurvy, especially in its rudimentary form, is of great practical importance, because of its frequent occurrence. There is no question but that breast milk and raw cow’s milk furnish sufficient antiscorbutic vitamine, but there is a difference of opinion as to whether pasteurized milk, or milk that has been brought just to the boiling-point, or even sterilized milk, is adequate in this respect. Much of this divergence of opinion is due to the fact that the various clinicians have not considered or stated the quantity of milk which they have found sufficient to protect, and also because milk itself differs in its antiscorbutic value according to its freshness and probably also according to the fodder of the cows.52Without entering once more into a discussion of this question, it may be stated that unless the cow’s milk is raw, the infant should receive additional antiscorbutic foodstuff. Moreover, this supplement to the dietary should be made as soon as possible, so as not to allow the vitamine deficiency and inadequate diet to exist for even a short period. In our experience there is no contra-indication to the giving of orange juice or of strained canned tomato, the two antiscorbutics with which we have had a large experience, to babies one month of age or even younger. The common practice, however, is to wait until the infant is five or six months of age, whichcertainly must allow a rudimentary scorbutic condition to develop. At the age of a month one teaspoonful of orange juice may be given; it should be diluted with water and sugar added if it is tart. This may be administered notwithstanding the fact that a baby has a tendency to looseness of the bowels, as orange juice, as recently pointed out by Gerstenberger, has practically no laxative action. Occasionally babies regurgitate orange juice, but the reaction usually ceases after a day or two. If it does not, a small amount of an alkali—for example, limewater or sodium bicarbonate—may be added just previous to feeding; in this state the juice will be better tolerated.53The amount of orange juice should be increased so that when the baby is three months of age it receives one tablespoonful.
A few years ago Hess and Fish recommended the use of an infusion of orange peel in infant feeding. The peel was finely grated, soaked overnight in water (1 ounce of the peel to 2 ounces of water), and a small amount of sugar added to this liquid. Animal experiments showed that this preparation possessed decided antiscorbutic value. This decoction may well be used for the sake of economy, and even when the orange juice is employed the infusion of the peel may be added.
An antiscorbutic which vies with orange or with lemon juice in adaptability for infant feeding iscanned tomatoes, as recently suggested by Hess and Unger. Tomatoes are not in good repute among food experts in view of the small amount of calories which they contain—only about100 to the pound—and are regarded with suspicion amounting almost to superstition by mothers and nurses as a food for children. In spite of this fact, it may be stated without hesitation that they are fully as well borne by infants a few weeks or months of age as orange or lemon juice. In considering antiscorbutics, it has been shown that notwithstanding the canning process and subsequent aging, they preserve their potency. The dose is two tablespoonfuls for babies over three months of age. The tomatoes are merely strained through a colander and warmed (not cooked). To illustrate their innocuous character, it may be added that as much as 6 and 8 ounces a day of this juice have been given to a baby under one year of age without producing untoward symptoms. This antiscorbutic should have wide applicability, especially in the United States.54
Another antiscorbutic which can be used in a routine way to prevent infantile scurvy isswede juice, prepared by grating the raw vegetable and squeezing the pulp in muslin. Chick and Rhodes report that this juice has been adopted for use in some of the English infant-welfare centres. It should be given in about the same dosage as the tomatoes, and seems applicable where the swede can be readily obtained.
For babies over six months of age, reliance may be placed on the ordinary household vegetables—potatoes, spinach, carrots, squash, etc. Attention should be paid to the amount which is taken, as one or two teaspoonfuls of a vegetable which is poor in antiscorbutic power, suchas carrots or beets, will be insufficient to protect against scurvy. Especially is this true if the vegetables are old and stale and are cooked for a long period;55some years ago two infants under our care developed scurvy in spite of a small daily ration of vegetables.
Potato in the amounts usually consumed is a valuable antiscorbutic. It is not an exaggeration to state that it is the main antiscorbutic bulwark of man. In giving baked potato to children it is commonly advised to use the floury part just beneath the peel; this should be put through a sieve and mixed thoroughly with boiled milk so as to constitute a cream; for younger babies it can be prepared with water to form a diluent similar to the barley water so commonly employed to dilute cow’s milk (1 tablespoonful of potato to a pint of milk, cooked for 15 minutes). Little reliance should be placed on beef juice in the usual dosage and none on eggs.
Cure.—There is almost nothing in the realm of therapy which is so striking as a scorbutic patient’s prompt reaction to antiscorbutic treatment. It is all the more marvelous as the cure is effected by means of foodstuffs with which we are accustomed to associate no specific virtue. A magic result is seen frequently within 24 or 48 hours. A baby which has had a poor appetite, has been irritable and exquisitely tender, suddenly regains its appetite, is no longer fretful, and can be handled without occasioning crying. Within a week, if the case is mild, all definite symptoms of scurvy may have disappeared, and soon thereafter the infant is thriving and apparently cured. A table is here reproduced (Table 6) from the report ofthe American Pediatric Society showing the duration of treatment before marked improvement was noticed:
TABLE 6
In most instances a gain of weight accompanies improvement. In not a few instances, however, there is a temporary loss or cessation of weight, due in part to an increased excretion of urine. Occasionally there is observed a short exacerbation of the symptoms following the giving of an antiscorbutic—a swelling of the thigh or hemorrhage of the gums. A similar phenomenon has been noted in relation to the treatment of polyneuritis in birds and of beriberi in man.
In the cure of scurvy the same dietetic remedies are employed as in its prevention. Orange juice is the sovereign remedy, and should be given in a dosage of about 2 ounces a day.56Canned tomato is also most efficacious. If these changes in the dietary are carried out, it is not absolutely necessary to alter the food, although it is advisable to do so. Some writers, for example Neumannand Czerny, treat the disorder by giving milk which has been scalded or brought to the boiling-point. Others lay particular stress on changing the source of the milk supply, believing that the sameness of the diet leads to the occurrence of scurvy. Such, however, cannot be the case, as otherwise breast-fed babies would be highly subject to this disease. In the report of the American Pediatric Society one case developed on condensed milk and was cured by sterilized milk, and another developed on pasteurized milk and was cured by sterilized milk and broths. These results are explicable; large amounts of milk were given to effect the cure. It may be said in general that in addition to giving fruit or vegetable juices the milk should be either raw or heated to as low a degree as possible (duration of heating as well as height of temperature). Furthermore, the antiscorbutic treatment should be continued for a period of months, as the clinical improvement far outstrips the restoration of the bones and other tissues. It seems necessary again to call attention to the fact that too great reliance has been placed on the use of beef juice, which has been shown, both in experiment and in the clinic, to possess comparatively weak antiscorbutic properties.
Orange juice may be given intravenously. This method may be resorted to where the patient is in an advanced stage of the disease or where food cannot be tolerated by mouth; for example, in cases such as that mentioned by Cheadle, where death took place owing to the fact that the antiscorbutic could be taken only sparingly, on account of the extreme prostration of the patient. For this purpose the orange juice is obtained in as sterile a manner as possible, boiled for about five minutes and is rendered neutral or slightly alkaline just previous to its injectionby the addition of normal sodium hydroxide. Hess and Unger report three cases where this procedure was carried out without the slightest untoward reaction. In one instance, improvement was noted 16 hours after the injection. In view of the novelty of this treatment it may be of interest to cite a case:
A baby 16 months old had hemorrhage of the gums and tenderness of the legs, which were held in the characteristic flexed and everted position. Eliminative treatment was tried without avail; Dover’s powder and warmth to promote perspiration; caffeine to promote diuresis; and 2 tablespoonfuls of liquid petrolatum three times a day to increase elimination from the bowels. Intravenous injections of salt solution also proved of no value.Four intravenous injections of orange juice were given—6 c.c., 12 c.c., 6 c.c., and 35 c.c. As was stated, improvement was noted 16 hours after the first injection. The infant was less irritable, the gums no longer hemorrhagic, and the “capillary resistance test” (that is to say, the development of petechial spots on the forearm when a tourniquet was applied for 3 minutes to the upper arm) changed from positive to negative.
A baby 16 months old had hemorrhage of the gums and tenderness of the legs, which were held in the characteristic flexed and everted position. Eliminative treatment was tried without avail; Dover’s powder and warmth to promote perspiration; caffeine to promote diuresis; and 2 tablespoonfuls of liquid petrolatum three times a day to increase elimination from the bowels. Intravenous injections of salt solution also proved of no value.
Four intravenous injections of orange juice were given—6 c.c., 12 c.c., 6 c.c., and 35 c.c. As was stated, improvement was noted 16 hours after the first injection. The infant was less irritable, the gums no longer hemorrhagic, and the “capillary resistance test” (that is to say, the development of petechial spots on the forearm when a tourniquet was applied for 3 minutes to the upper arm) changed from positive to negative.
Harden, Zilva and Still have recommended the use of a concentrated lemon juice for the cure of scurvy, constituting a form of “intensive” treatment. In four cases this proved to be of clinical value. Freise has made use of an alcoholic extract of turnips, and Freudenberg of a similar extract of carrots. These preparations did not seem to be markedly potent, and therefore possess no particular therapeutic advantages.
Non-dietetic Therapy.—There is little to be done for the patient in addition to the giving of sufficient antiscorbutic.No one has reported success with any drug. We have tried the use of atropin, adrenalin, thyroid and parathyroid extracts, cod liver oil, autolyzed yeast, lactose, sodium chloride, calcium chloride, etc., without noting any improvement. Mercurials are stated to be positively harmful, especially when ulcers are present. The patient should be kept in bed, and exertion not allowed on account of the involvement of the heart, which has led to sudden collapse and death. The gums may be treated with nitrate of silver stick or tincture of myrrh. If there is fracture of the long bones with displacement, splints should be applied. Under no circumstances should hemorrhagic effusions in or about the joints be incised. The patient should be placed in a room which is well aired and lighted, and should be handled and dressed as infrequently as possible, so as to avoid discomfort and pain. It is particularly important that intercurrent infections should be avoided by shielding patients from contact with those who have infectious diseases, especially respiratory infections.
Studies of the chemical exchanges in scurvy have been surprisingly few. It is a field that should repay investigation, promising to afford a clearer insight into the intermediary metabolism in this disorder. One of the first to touch upon this question was Garrod, who in 1848 reported that there was a diminution of potassium salts in the urine and in the blood of scurvy patients. In 1877 Ralfe confirmed the potassium deficiency in the urine, but denied its importance from an etiologic standpoint, as he was unable to benefit scurvy patients by administering potassium nitrate. He reported an increase of uric acid in the urine, a diminution of the total acidity, and a reduction of the alkaline phosphates. Litten found the analyses of the urine very contradictory in respect to potassium, but stated that beyond a doubt its uric acid content is increased at the height of the disease, although this diminishes rapidly with convalescence. These few and scattered articles comprise the sum of metabolic studies up to the last decade, and even during the succeeding period they have been very few—so few, indeed, that they furnish insufficient data from which to draw conclusions.
The first careful study of the mineral metabolism in a case of scurvy is that of Baumann and Howard, published in 1912. Its conclusions are not very definite. They may be summed up by their statement that “chlorin and sodium were retained during the fruit-juice period, but excreted in excess of the intake during the preliminary period,” and that “more potassium, calcium andmagnesium were retained during the fruit-juice period.”
This same year Lust and Klocman published the first metabolism study of a case of infantile scurvy. The baby was 18 months old and the metabolic changes were investigated during the active, convalescent, and “the healing stage” of the disorder. This study seems to have been carefully carried out. The fact, however, that the infant received 800 c.c. daily of slightly-boiled milk during the active stage, and was improving at this time, may also have had a beneficial effect on the metabolism in respect to scurvy. The results of these writers are surprising—quite different from what they expected or what we should have expected. They write: “The balance of the mineral metabolism, including the total ash, the calcium, phosphorus and chlorin during the florid stage of the disease must be regarded not only as not damaged, compared to that of the healthy child, but indeed as somewhat increased.” “All the more striking, on the contrary, are the results found during the stage of convalescence. Here the balances were all markedly negative, and only after a lapse of weeks was the tendency manifested to a return to normal conditions.” The authors regard these results as indicating a sort of washing out of “dead material” during convalescence—of material which had gathered during the florid stage of the disease. According to their interpretation the disease is due, not to a primary or secondary salt deficiency, but to a disturbance in salt elimination, and in the first place, of a calcium excretion. This is shown by the fact that even in the “stage of healing,” when the total ash and the phosphorus balance once more had become positive, the calcium balance nevertheless remained somewhat negative. The metabolism of infantile scurvy, they believe, far from showing a resemblanceto rickets, manifests quite the contrary tendency. The study of this case of infantile scurvy and that of Baumann and Howard of a case of adult scurvy, comprise the total investigation of the metabolism in human scurvy.
In the course of a recent discussion on rickets before the Medical Society of Vienna, Moll states briefly that in a case of infantile scurvy, at the height of the disease, he found a positive calcium balance, which became poor and later negative on giving fruit juice; in other words, a partial confirmation of the work which has just been cited.
In 1913 Bahrdt and Edelstein reported the analyses of the organs of an infant almost nine months old who died of scurvy; an examination of the tissues, especially of the bones, should be most valuable in checking up determinations of the metabolism during life. This investigation runs absolutely contrary to that of Lust and Klocman. The bones showed a decrease of ash, especially of calcium and of phosphorus, and also a lack of calcium in the muscles, but normal amounts in the liver and in the kidneys. These conditions resemble the deficiency of ash and of lime commonly associated with rickets, and it seems quite possible that this infant had rickets as well as scurvy, and that in this way the discrepancy between the two reports is to be explained. The fact that the water content of the bones was two to three times the normal, also lends emphasis to this interpretation.In any metabolism study of infantile scurvy, great care will have to be exercised that the disorder is not complicated by rickets, and the issue thereby confused. It will be very difficult to avoid this pitfall, for there is no test by which early rickets can be diagnosed. The danger of this complication may be realized when we bear in mind that the majorityof infants have rickets to some degree. An investigation of the chemistry of adult scurvy has an advantage from this point of view.
Chemical examination of the blood has yielded such valuable information regarding metabolic diseases, that it might be expected to shed light on the disturbances of scurvy. The only investigation from this standpoint is that of Hess and Killian, who have reported estimations of the urea, creatinine, sugar, CO2combining power, diastase, cholesterol, chlorine and calcium.57The urea content was normal, varying between 12 and 14 mg. per 100 c.c. of blood; this is the average of twenty-one tests on ten cases of infantile scurvy. (In severe cases of beriberi Yano and Nemoti have recently reported that the blood contains an increase of urea, and that its excretion is frequently disturbed.) The creatinine was estimated in two cases and was found to be 2.0 mg. and 1.7 mg. per cent., respectively,—also normal figures. The blood sugar varied from 0.12 to 0.14 per cent. and was examined in almost all the cases in which urea was estimated; these figures are at the upper level of normality (no attention was paid to the interval elapsing between the feeding and the withdrawal of the blood). The diastatic activity was likewise normal. The CO2combining power showed figures under 40 to 45, according to the Van Slyke method, and indicated therefore a mild degree of acidosis. In six cases the chlorides were estimated, the figures being remarkably constant at about 0.42 or 0.43. Cholesterol was a little below normal in the four cases examined. Contradictory results were obtained in regard to calcium. Earlier tests showed a definite deficiency of this salt, but thosecarried out more recently have generally yielded normal results. Further studies of the blood calcium are highly desirable to ascertain whether it varies in amount in the circulation, and especially in different stages of the disease. This aspect is worthy of particular attention in view of the positive calcium balance noted by Lust and Klocman during the active stage of scurvy, and the negative balance during the period of convalescence.
It is evident from the limited data concerning the blood chemistry of scurvy that it is a field which has been inadequately explored and will repay more intensive study. Investigations of this kind have recently been made possible by the introduction of accurate methods requiring only small quantities of blood.
Studies of the metabolism of animals suffering from scurvy are almost as few as those on man. The work of Morgan and Beger, which is frequently quoted in this connection, is not applicable, as it concerns rabbits, which do not develop scurvy. They found that rabbits fed solely on oats and water suffered in their nutrition (loss of appetite, emaciation, paralysis of hind legs), and could be cured by the addition of sodium bicarbonate to the dietary. In 1916 Lewis and Karr published a paper on the constituents of the blood and the tissues of guinea-pigs fed on an exclusive oat diet. They found the urea content several times greater than normal, but that it fell to normal once more if cabbage or orange juice was given. From the standpoint of scurvy, this investigation is open to the criticism that the diet was too incomplete, and also, as the authors suggest, that the animals suffered from partial starvation and a lack of water.
In the following year Karr and Lewis published a paper on a different phase of this subject, and came to thefollowing conclusions: “No changes in urinary elimination of phenols, nor in the degree of conjugation of the phenols, were observed, provided the factor of partial starvation was ruled out. This is believed to indicate that no increased bacterial action occurs in the intestine of scorbutic guinea-pigs despite the difficulty of evacuation of the fæces.” These results are in harmony with the bacteriological study of Torrey and Hess, who found that there was no increase in the proteolytic flora of the intestine in infants or in guinea-pigs suffering from scurvy.
In 1917Baumannand Howard published the only metabolism study which has been carried out on guinea-pigs suffering from scurvy, and they are of the opinion that this disorder has a profound effect on the mineral metabolism of this animal. The calcium was excreted in notably large amount; potassium was also lost, and to a greater extent than sodium; the only element which was consistently retained during the active stage as well as during the period of recovery, was magnesium. This study was followed shortly by one from the same laboratory, by Howard and Ingvaldsen, carried out on a monkey suffering from scurvy. It was inconclusive, not conforming to the experiments on the guinea-pigs; the authors state that the “changes in the mineral excretion of the monkey during the scorbutic period were not sufficiently significant to admit of easy interpretation.” “The marked loss of the various mineral substances encountered in experiments with man and guinea-pig was not observed in the present series.” It should be remembered, however, that the diets of the guinea-pigs and the monkeys were quite different, the former consisting mainly of oats, and the latter of condensed milk. It isquite possible that the basic diet may play a rôle in the metabolism of this disease, although, as stated elsewhere, its effect cannot be noted clinically. Special attention should be paid to this factor in metabolic studies, in view of the widely-held opinion that the carbohydrates exert a potent influence in the development of beriberi.
The investigations of the nitrogen metabolism in man and in animals have been most unsatisfactory. The two on human beings—an infant and an adult—were negative; that on guinea-pig scurvy cannot be utilized on account of the restricted diet of oats, which contained insufficient nitrogen, whereas the one on the monkey showed some loss of nitrogen, which led the authors to suggest an increased nitrogenous catabolism in scurvy. This comprises the total data on this subject.
Summarizing the results of these few metabolic studies, it may be stated that they harmonize on one point only—the positive balance of calcium during the active stage of the disease. The investigation ofBaumannand Howard on adult scurvy, of Lust and Klocman and of Moll on infantile scurvy, and of Howard and Ingvaldsen on the monkey, are all in agreement in this important conclusion.
In the foregoing there has been frequent reference to the close relationship between scurvy and the incidence of the infectious diseases—to the fact that a scorbutic condition increases the susceptibility to infection. This is indeed one of the most characteristic, as well as one of the most important phenomena associated with scurvy and other disorders resulting from vitamine deficiency. Mention has been made of the special susceptibility to the diphtheria bacillus, and to the organisms leading to coryza and the respiratory diseases, but no doubt this applies also to invasion by other bacteria. We wish, however, to confine ourselves to the nutritional disorders, first in their relationship one to the other, and second, as a group of deficiency diseases, due to a lack of vitamines of various kinds. As is well known, in addition to scurvy, this group generally includes beriberi, a disease attributed to a lack of the water-soluble vitamine, and xerophthalmia, an eye condition which recently has been brought about in rats by placing them on a diet free from fat-soluble vitamine. These, however, form only the nucleus of the disorders which commonly are included in this category. Schaumann, the first to formulate this classification, illustrated his conception of the interrelationship by depicting the various members as spokes of a wheel surrounding a central hub. He included scurvy, rickets, osteomalacia, typical beriberi, ship-beriberi, pellagra and mehlnaerschaden. Funk made a similar classification of disorders which he termed the “avitaminosen.” There isa tendency to enlarge rather than to decrease the membership of this class, and recently war or hunger edema, infantile atrophy and diarrhœa, sprue, cœliac disease, leprosy and others have been proposed as suitable candidates. At the present time it is impossible to determine which and how many of this motley company should be associated with scurvy. Some, possibly, are the result of a lack of vitamine, but for the present it will be well to bear in mind that three vitamines only have stood the test of experiment, and only these three therefore can be definitely connected in a causal relationship with pathologic conditions. In addition to this consideration of the interrelationship of the “deficiency diseases,” the kinship of allied disorders—more particularly of rickets—must be discussed.
Although at first thoughtberiberiand scurvy would seem far apart from a clinical point of view, they have some important features in common. In both there is a tendency to a rapidity of the heart’s action and a marked lability of the pulse, to an enlargement of the cardiac ventricles, to an involvement of the vagus, and to an exaggeration of the deep reflexes. It is unnecessary to describe these signs and symptoms in detail, as they have been fully considered under symptomatology. It has been recorded from time to time that under certain circumstances scurvy has developed in man where one should have expected beriberi, andvice versa. Darling, who has had a large experience in this field, writes: “A deficient dietary in a tropical African negro mine laborer causes severe scurvy, in a Cape Colony African mine laborer, mild scurvy, and in some African negroes a diet that causes scurvy in one set of men causes neuritis in others.” Possibly some minor differences in the dietary can explainthis difference in reaction—for we do not know all the sources of the water-soluble vitamine, but such an experience deserves to be cited as it is not an isolated instance. It is all the more worthy of attention because it harmonizes to a certain extent with the everyday experience of animal investigation. As has been stated elsewhere, a diet of decorticated grain will lead to scurvy in the guinea-pig, to polyneuritis in the pigeon, and to a combination of these diseases in the hog! Results of this kind show that there must be a relationship between the etiologic factors of scurvy and of beriberi. It is unwise at present to attempt to define the relationship more precisely. The remarkable observation, first made by Fuerst, and since confirmed by numerous investigators, that seeds and legumes are devoid of antiscorbutic potency but acquire this power on sprouting, constitutes another link in the evidence of their kinship. Funk has suggested that the antiscorbutic vitamine can be formed from the “antineuritic” vitamine, a theory which is very attractive but needs confirmation and experimental proof. It is quite evident that this change does not usually occur in animals, in view of the specificity of the vitamines for their respective diseases—of the antiscorbutic for scurvy and the water-soluble for beriberi.
It will be noted that “ship-beriberi” is included in this group of diseases. Very little is known about this condition, except what is contained in the investigation of Nocht (1903) and that of Holst and Froelich. It is a very rare condition but of interest because it is characterized by spongy, hemorrhagic gums and other signs encountered in scurvy. The feature which differentiates it sharply from scurvy, however, is an anæsthesia of the extremities. Ship-beriberi is generally regarded as acombination of beriberi and scurvy. Where these two disorders occur concomitantly, the beriberi manifests itself some months before the scurvy, as the latter takes much longer to develop.
In considering the vitamines in connection with diseases of the nervous system, mention may be made of “central neuritis” and the “peripheral neuritis” which has been reported from the West Indies. This bears only a partial resemblance to beriberi, as there is no edema, nor dyspnœa, and its course is more chronic. Judging from the report of Edwards from Jamaica, the cases more closely resemble pellagra, terminating after many years. A degeneration of the cells of the spinal cord was found and “in some isolated patches of the cerebellum and in the roots of the optic and auditory nerves.” The disease occurs among the poor classes whose diet is inadequate chiefly in nitrogen.
Eijkman was the first to draw an analogy between beriberi andpellagra, and thus to suggest that the latter might be a disease due to an unidentified factor; he compared the pernicious effect of a diet of polished rice with that of decorticated corn. Of recent years, largely as the result of the investigations of Goldberger and his co-workers, pellagra has come to be regarded as a dietetic disorder primarily due to a lack of adequate protein, rather than to a lack of a specific vitamine. Its relationship to scurvy cannot, therefore, at the present time, be discussed from an etiologic viewpoint. Apart, however, from the question of etiology, the two diseases have certain clinical symptoms in common. Weston states that “distinguished physicians, who were really astute observers, have mistaken pellagra for scurvy, eczema, various kinds of intestinal troubles, syphilis, and manyother diseases.” In the chapter on symptomatology, attention has been directed to the fact that an eczema which yields to antiscorbutic treatment may occur in scurvy; at times it presents the symmetrical arrangement so typical of pellagra. In other cases a fleeting erythema may be observed, another sign noted frequently in pellagrins. In some instances congestion of the gums has been recorded. In describing a little girl of three who had pellagra, Weston writes: “The gums are also red and swollen, suggesting scurvy.” This child had eaten large amounts of turnips, so that there could have been no question of complicating scurvy. Lombroso and some of the earlier authors drew attention to the fact that fragility of the bones, of the ribs and of the long bones, was often associated with pellagra. These various clinical similarities should not be construed as evidence in favor of the “avitamine” nature of pellagra. They indicate, rather, that in nutritional disorders, whatever may be their underlying cause, the vessels, the bones, and other tissues may suffer and lead to similar—but not identical—clinical pictures.58
The relation between scurvy and rickets is a subject which was discussed by Glisson. With the renewed interest in infantile scurvy which followed Barlow’s work toward the end of the last century, children’s specialists ranged themselves into opposing camps on the question of the interrelationship and interdependency of these twodiseases. Some accepted Barlow’s dictum that infantile scurvy is an absolutely distinct and separate entity; others, for example, Hirschsprung, declared that the so-called scurvy was merely a form of rickets; whereas a third group considered it a combination of rickets and scurvy. This last viewpoint was actively maintained by Cheadle on the clinical side, and later by Schoedel and Nauwerk on the pathologic side—the latter declaring that rickets is “an inseparable component of infantile scurvy,” and that the entire disease should be regarded merely as “an episode in the course of rickets.” Even Barlow, in a paper published in 1894, wrote: “Rhachitic changes already present may act as a physiological determinant of the sites in which scurvy becomes manifest” and “rickets as a basis plus inadequate food gives the simplest explanation of the typical case” (of scurvy).
We had an exceptional opportunity to test this thesis in 1914, in an institution where scurvy broke out among infants who were on a diet of pasteurized milk. All these infants were receiving cod liver oil daily, as prophylactic treatment against rickets. Many infants have been seen since that time, who in spite of receiving cod liver oil developed scurvy, and others in whom large doses of this oil failed to mitigate the scurvy, although it prevented rickets. The same failure has been encountered in the treatment of scurvy in guinea-pigs. This experience has been without exception, both from a prophylactic and a curative standpoint.
Confusion between the two diseases has resulted from the fact that the majority of infants in the Temperate Zone have some degree of rickets. Thus the two diseases have been found very frequently associated in pathologic examination of the bones, leading some to infer that they are in some way interdependent. They have been alsoconfused clinically, as mentioned in another connection, owing to the fact that beading of the ribs—the rhachitic rosary—has been mistakenly regarded as a pathognomonic sign of rickets, whereas it is also a sign common to scurvy. It is important to bear in mind that from the pathologic viewpoint scurvy and rickets present strikingly dissimilar pictures—the former is characterized by an almost complete cessation of activity of bone-forming elements, whereas the latter is distinguished by a hyperplastic condition leading to a marked overgrowth of cartilage and of abnormal bone. Viewed from the pathologic, etiologic and clinical standpoint, we believe that there is no basis for assuming an interrelationship between the two disorders, and that scurvy will develop as readily and as rapidly where rickets is absent as where it is present.59
It is premature to discuss the relationship of these two disorders from the vitamine standpoint. In 1910 Schaumann suggested that rickets was due to a lack of a specific food factor, and somewhat later Funk included it among the “avitaminosen.” Recently Mellanby, as the result of experiments on dogs, has affirmed that the fault lies in a lack of the fat-soluble or a closely-related vitamine. Investigations of the near future will probably decide the merits of this contention; our experience is that rickets develops in infants even where the diet contains adequate fat-soluble vitamine. If rickets is proved to be a disorder depending on a vitamine, it belongs, naturally,in the same group as scurvy. This would indicate relationship, but not interrelationship. Just as the mere fact that a lack of vitamines leads to scurvy and to beriberi does not signify, in theory or in practice, the existence of pathogenetic interrelationship. However, as stated, this is a subject which does not as yet rest on a secure foundation.
Osteogenesis imperfecta and osteomalaciaare disorders of dietetic or metabolic origin characterized by fragility of the bones. The latter has developed new significance and importance due to its increased occurrence in almost epidemic form in the Central Empires at the close of the World War. The etiology of both disorders is most obscure. In the future in considering their pathogenesis it will be well to draw a sharp distinction between them. Osteogenesis imperfecta is a disease in which an injury occurs to the fœtus without any manifest illness in the mother, which seems to indicate a primary lesion of the fœtus (perhaps metabolic); osteomalacia, on the other hand, attacks the mother who gives birth to an apparently healthy fœtus. The latter gains added interest because it is a disease of the bones which is attributed to dysfunction of the endocrine glands, to a disturbance especially of the parathyroid. If this observation is confirmed, it furnishes another anatomical basis for associating the glands of internal secretion with pathologic conditions of the bones.