Temperature, pulse, and respiration in scurvyFig. 15.—Chart of I. F., aged 7 months, showing a prompt effect on pulse, respiration and temperature of substitution of orange juice (30 c.c.) for autolyzed yeast (30 c.c.) and a further response when the former was replaced by potato (15 g.).
Infantile scurvy may be dormant for a long time. The diagnosis oflatent scurvyis based mainly on thereaction to specific therapy, on the marked improvement when orange juice, tomato, potato or other antiscorbutic food is given. The symptoms themselves are suggestive, and do not enable an absolute diagnosis to be made. In our experience with many cases of this kind the usual course has been as follows: The infant has been generally from 6 to 9 months of age, and fed for a considerable period on pasteurized milk, which may or may not have been prepared with cereal decoction. Nor has it been material whether gruels also had been given. When about 6 months of age the baby ceased to thrive, to gain satisfactorily, to look healthy, and to feed as it should. The most careful investigation or physical examination has failed to solve the difficulty. On the other hand, the history of a diet of heated milk, especially if the quantitywas not large, considered in conjunction with the pallor and poor appetite, the increased knee-jerks, and perhaps a rapid pulse and respiration (the cardiorespiratory syndrome), has awakened suspicion. Orange juice or canned tomato, prescribed in such cases with a view to diagnosis as well as to treatment, frequently brings about a magic result. The following case, the weight chart of which is reproduced (Fig. 14), is fairly typical of this abnormal nutritional state:
H. S., boy, born December 15, 1915, was artificially fed until January 4, 1916, when he weighed 6½ pounds. He was given 28 ounces of Schloss milk a day. (This was prepared from pasteurized milk which was not heated a second time. It contains per litre (quart) 140 c.c. of whole milk, 140 c.c. of 20 per cent. cream, 50 g. of dextrimaltose, 5 g. of plasmon, 0.2 g. of potassium chlorate, and 700 c.c. of water.) By March 1 he weighed 9 pounds, and gained three-quarters of a pound more in the course of this month. During April he gained only 4 ounces. As will be seen from the chart, there was almost a cessation of gain from April 10 to May 3, although yeast was added to the diet. May 2, orange juice was given. The weight advanced at once, the color and the general appearance improved, and an eczematous condition of the face rapidly healed. It will be noted from the chart that the gain occurred, although the food intake remained the same.Epicrisis: A baby 4 months old with latent scurvy, which existed since he was at least 3 months of age.
H. S., boy, born December 15, 1915, was artificially fed until January 4, 1916, when he weighed 6½ pounds. He was given 28 ounces of Schloss milk a day. (This was prepared from pasteurized milk which was not heated a second time. It contains per litre (quart) 140 c.c. of whole milk, 140 c.c. of 20 per cent. cream, 50 g. of dextrimaltose, 5 g. of plasmon, 0.2 g. of potassium chlorate, and 700 c.c. of water.) By March 1 he weighed 9 pounds, and gained three-quarters of a pound more in the course of this month. During April he gained only 4 ounces. As will be seen from the chart, there was almost a cessation of gain from April 10 to May 3, although yeast was added to the diet. May 2, orange juice was given. The weight advanced at once, the color and the general appearance improved, and an eczematous condition of the face rapidly healed. It will be noted from the chart that the gain occurred, although the food intake remained the same.
Epicrisis: A baby 4 months old with latent scurvy, which existed since he was at least 3 months of age.
This condition of latent scurvy is probably the commonest type of the disorder, especially in the larger cities where almost the entire milk supply for infants is pasteurized.It usually passes unrecognized. Most infantsfortunately are given orange juice by the time they are 6 months of age, and may receive a small amount of vegetable or potato before they are much older, so that they are protected from serious harm in this way. But there is no doubt a considerable number, especially those peculiarly susceptible, who quite unbeknown to anyone pass through the state of latent scurvy.
If this large group of cases were included in the incidence of infantile scurvy, we should not look upon it as a disorder which occurs rarely during the first six months of life.
When scurvy goes unrecognized or untreated for a long time, or the antiscorbutic content of the food is exceptionally small, or the patient unusually susceptible, the disorder may progress and resemble the advanced cases described in connection with the adult type of this disease. Happily such instances are rare. One of the most typical and vivid descriptions ofan extreme caseof infantile scurvy is that reported by Vincent:
The infant lay in its bed extremely apathetic and barely conscious. Its face was ashy gray in color, the respirations were extremely frequent, the pulse-rate was 144 per minute, and the temperature 103.2°. When touched it moaned feebly, and made no attempt at movement. The mouth was kept open, the lower jaw hanging away from the face. There was a complete absence of muscular tone, so that the infant appeared to be quite incapable of voluntary movement.The mouth presented a horrible appearance. No sign of the teeth could be discovered, though it was stated that several had appeared. All that could be seen was a purple mass, which was so extensive that on superficial inspection it was difficult to distinguish between the upper andlower jaws, despite their wide separation. Scattered over this purple mass were areas of necrosing tissue, the odor of which was extremely unpleasant.Petechial hemorrhages were distributed over the back and limbs, and a large patch of extravasated blood was found in the region of the left hip.Tenderness was present in all the limbs, as manifested by moaning and by the facial expression. There was a general enlargement over both humeri throughout their length; the ulna and radius did not appear to be thus affected, but the index-finger of the right hand was enlarged, especially at the junction of the metacarpal bone with the first phalanx, the enlargement being at each side of the joint. In the legs the signs were extreme. At both knee-joints the skin was tightly stretched over the swollen epiphyses; the tenderness also was greater than at any other part.Bleeding from the gums and nose had occurred; no history of hæmaturia could be obtained. The motions were semisolid, green, and offensive. During the last twenty-four hours the infant had refused food.The baby was given large amounts of lemon juice and subcutaneous injections of salt solution and the necrosing surfaces of the gums were scraped and swabbed with boracic solution. By the third day the pulse was 100, the temperature 99.8°, the odor from the mouth scarcely noticeable, and the general condition distinctly improved. It continued to improve and to gain in weight and when seen at the end of the sixth week of treatment it was doing well and was quite happy.
The infant lay in its bed extremely apathetic and barely conscious. Its face was ashy gray in color, the respirations were extremely frequent, the pulse-rate was 144 per minute, and the temperature 103.2°. When touched it moaned feebly, and made no attempt at movement. The mouth was kept open, the lower jaw hanging away from the face. There was a complete absence of muscular tone, so that the infant appeared to be quite incapable of voluntary movement.
The mouth presented a horrible appearance. No sign of the teeth could be discovered, though it was stated that several had appeared. All that could be seen was a purple mass, which was so extensive that on superficial inspection it was difficult to distinguish between the upper andlower jaws, despite their wide separation. Scattered over this purple mass were areas of necrosing tissue, the odor of which was extremely unpleasant.
Petechial hemorrhages were distributed over the back and limbs, and a large patch of extravasated blood was found in the region of the left hip.
Tenderness was present in all the limbs, as manifested by moaning and by the facial expression. There was a general enlargement over both humeri throughout their length; the ulna and radius did not appear to be thus affected, but the index-finger of the right hand was enlarged, especially at the junction of the metacarpal bone with the first phalanx, the enlargement being at each side of the joint. In the legs the signs were extreme. At both knee-joints the skin was tightly stretched over the swollen epiphyses; the tenderness also was greater than at any other part.
Bleeding from the gums and nose had occurred; no history of hæmaturia could be obtained. The motions were semisolid, green, and offensive. During the last twenty-four hours the infant had refused food.
The baby was given large amounts of lemon juice and subcutaneous injections of salt solution and the necrosing surfaces of the gums were scraped and swabbed with boracic solution. By the third day the pulse was 100, the temperature 99.8°, the odor from the mouth scarcely noticeable, and the general condition distinctly improved. It continued to improve and to gain in weight and when seen at the end of the sixth week of treatment it was doing well and was quite happy.
It will be well to consider in detail the signs and symptoms which may develop in the course of scurvy.
Hemorrhage.—Hemorrhage of the gumsis one of the characteristic signs of scurvy. For a reason not clearly understood it involves first and foremost the tissues aboutthe upper incisors. If, however, we fix our attention too narrowly to this region we may be led into error; in several instances we have first encountered hemorrhages about the molar or the canine teeth, which had been overlooked because the anterior part of the gums had been found normal. Where teeth are absent or not in the course of eruption hemorrhages do not appear. At the onset the gums may be merely deep red or bluish red, especially if they overlie upper incisors which are close to the surface. Hemorrhage is particularly apt to occur where the edges of the teeth have just broken through the mucous membrane. In this connection the question arises as to whether every hemorrhage of the gums in infants is to be considered a sign of scurvy. This is a matter of some diagnostic importance. We have seen hemorrhages of the gums at the site of erupting molar teeth where, as prolonged observation proved, not even latent scurvy existed. This sign should not, therefore, be regarded as pathognomonic. In two infants entirely free from scurvy we have noted slight hemorrhage of the gums overlying incisor teeth. It should be well understood that such an occurrence is most exceptional; it is to be attributed probably to bacterial invasion or to a constitutional hemorrhagic condition. One of these cases was the following:
The infant was 8½ months old. It had been nursed by the mother up to this time and was well nourished, but when first seen had some fever, probably due to a grippe infection. About ten days later distinct linear hemorrhages of the gums were noted over the two upper incisor teeth. No treatment was instituted for this condition, and it healed within a week. There was no subsequent sign of similar hemorrhage or of other scorbutic manifestation in the months that the baby was under observation.
The infant was 8½ months old. It had been nursed by the mother up to this time and was well nourished, but when first seen had some fever, probably due to a grippe infection. About ten days later distinct linear hemorrhages of the gums were noted over the two upper incisor teeth. No treatment was instituted for this condition, and it healed within a week. There was no subsequent sign of similar hemorrhage or of other scorbutic manifestation in the months that the baby was under observation.
The localization of the hemorrhage in the gums is due largely to trauma, occasioned by the sharp contact of the jaws or of the nursing-bottle. Local infection plays almost no rôle in infants, although in the adult where there is caries of the teeth it frequently incites hemorrhage. Dental caries and gingival infection may lead to local hemorrhage, even where the nutritional conditions are normal.
Subperiosteal hemorrhage is a sign distinctive of infantile scurvy, although it must be borne in mind that it may take place in the scurvy of adults. It involves most frequently the lower end of the femur and the tibia, but occurs in connection with the humerus, the mandible, the scapula and other bones.47The hemorrhage usually manifests itself as a swelling which appears suddenly at the lower end of the femur or femora. It is brought about by trauma, at times in the course of diapering, or by manipulation in testing for local tenderness. The swelling is very tender, and varies in size from an enlargement which is difficult to appreciate, to one which renders the leg fully twice its normal circumference (Fig. 18). It may involve merely a small part of the long bone or extend up or down the shaft for a long distance. As might be supposed from the nature of this lesion, the enlargement persists for weeks, frequently long after the gums and the general symptoms have disappeared. During this period it becomes harder and less tender, and may develop theconsistency of bone; it is in this stage that such swellings have been diagnosed as new growths, and that incision or even amputation of the leg has been resorted to. In subacute cases the swelling—which must be regarded as hemorrhagic rather than scorbutic—may be absorbed gradually in spite of the fact that no antiscorbutic food has been given. This has led to the mistaken conclusion that the scurvy has been cured without dietetic treatment.
Subperiosteal hemorrhage may be clearly seen by means of the fluoroscope or in X-ray photographs (Figs. 16 and 17). The shaft of the bone appears surmounted by an elongated blood-clot, which is more or less distinct according to its age and density. It may become calcified, as clearly seen in figures. More often the periosteum undergoes calcification or ossification, especially near the site of the separation of the epiphysis. This gives rise to a bizarre radiographic picture which may be difficult to interpret—the opaque strip or streamer being almost unrecognizable as periosteum (Fig. 17).
Hess and Unger observed that in several instances where subperiosteal hemorrhage had been diagnosed, X-ray examination disclosed that the swelling of the thigh was due mainly to infiltration of the muscles and subcutaneous tissue. It is surprising how an infiltration of serum gives rise to a swelling which resembles in appearance and consistency the classical subperiosteal tumor.
The skin, mucous membranes and subcutaneous tissues are frequently the sites of hemorrhage. There is a difference of opinion as to how frequently petechial hemorrhages occur in scurvy, particularly as to whether they are encountered early in this disorder. Great variation in this regard may be noted in individuals and in groups of cases occurring at different times. In the cases reportedin 1914 by Hess and Fish, petechial hemorrhages were frequently an early sign, to such an extent that they led to a study of the blood and blood-vessels in this disorder. The hemorrhages in this “scurvy epidemic” were the result of a complication of scurvy with an infectious disease. It is not necessary, however, for infection to exist to bring about a rupture of the small vessels. The idiosyncrasy of the individual has to be considered as well as the fact that infants have a tendency to develop minute skin hemorrhages, especially such as have an exudative diathesis. In the course of scurvy, petechiæ may be found not only in the skin, but in the mucosa of the mouth, especially overlying the hard palate, and also in the palpebral conjunctiva, identical with the minute petechiæ so significant of general sepsis. In addition to these minute hemorrhages larger ones are not infrequently found in various parts of the body, especially in the neighborhood of the joints. They appear as discolorations of various intensities and shades, and are often interpreted as being merely the result of bruises. These have been encountered most often about the knee-joint, on the forehead, or in the concha of the external ear, where they may best be seen by means of transmitted light.
A form of hemorrhage which must be especially mentioned, although it is very infrequent, is that taking place into the orbit, leading to aproptosis of the eyeball, usually the left (Still). This sign should be borne in mind, as it occurs occasionally before other symptoms have rendered the diagnosis clear, and may lead to a diagnosis of tumor.
As mentioned above, hemorrhages into the muscles or between the muscle planes are very common in adults, leading to hard swellings, the typical “scurvy sclerosis.” Such effusions occur much less frequently in infants, dueprobably to their lack of activity. In addition to these hemorrhages there are serous effusions of the muscles similar to those which are found in the pleural and pericardial cavities. These effusions are very striking at necropsy, when one incises the muscles—for example, the muscles of the thigh. During life they are frequently mistaken for subperiosteal hemorrhages.
Less frequently there arehemorrhages into the internal organs. These, however, play a comparatively insignificant rôle in the symptomatology of this disease. At postmortem examination we find numerous hemorrhages of the pleura, pericardium and peritoneum, which rarely produce symptoms during life. Still records a case with marked abdominal pain and swelling, which he believed to have been due to hemorrhage into the wall of the intestine. As previously mentioned, O’Shea met with a case of hemorrhage into the cæcum which was mistakenly operated upon for appendicitis. Hæmothorax and hæemopericardium occur, especially associated with local inflammatory processes of tuberculous nature. The clinical aspect of hemorrhage of the gastro-intestinal and the genito-urinary tracts will be considered elsewhere.
In the scurvy of adults as well as that of infants,the nails and the hairare altered by the nutritional condition. Mention has been made of the hyperkeratosis recently emphasized by Wiltshire as an early sign, occurring especially on the thighs and legs. The skin is frequently dry, the so-called “goose skin” that is seen in some poor nutritional states. The nails are thin, brittle and lined; at times small hemorrhages will be noted beneath them. The hair also becomes thin and dry, and there is a tendency for petechial hemorrhages to develop at the roots.
In a paper on the therapeutic value of yeast and ofwheat embryo the author called attention to the fact thateczemamay occur in connection with infantile scurvy, and be cured by means of orange juice. We have met with eight cases of eczema in infantile scurvy, which, in almost every instance, have yielded promptly to an antiscorbutic, thus proving their scorbutic nature. A case of this kind is the following:
M. L., seven months old, was getting “Molkenadaptierte” milk, and in addition autolyzed yeast. On May 25th it developed nasal diphtheria, but soon afterward did well. On June 9th it was gaining, but its pulse was 160 and respirations 80. A few days later it developed marked eczema about the neck and to a less extent on the back and buttocks. The “capillary resistance test” was negative. Cardiographic tracings showed merely a simple tachycardia. A few days later petechial spots appeared at the site of the eczema. On June 17th orange juice was given. The appetite improved, the cardiorespiratory syndrome disappeared, and the child began to gain. The eczema also cleared up rapidly without any local treatment.
M. L., seven months old, was getting “Molkenadaptierte” milk, and in addition autolyzed yeast. On May 25th it developed nasal diphtheria, but soon afterward did well. On June 9th it was gaining, but its pulse was 160 and respirations 80. A few days later it developed marked eczema about the neck and to a less extent on the back and buttocks. The “capillary resistance test” was negative. Cardiographic tracings showed merely a simple tachycardia. A few days later petechial spots appeared at the site of the eczema. On June 17th orange juice was given. The appetite improved, the cardiorespiratory syndrome disappeared, and the child began to gain. The eczema also cleared up rapidly without any local treatment.
We wish to draw particular attention to this skin condition, as it is generally not mentioned, or has been regarded merely as a chance occurrence. The report of the American Pediatric Society includes two cases of eczema as a complicating condition. This symptom is of special interest in view of the fact that a similar skin lesion constitutes one of the typical signs of pellagra. In a case of infantile scurvy we have seen an eruption at the nape of the neck which was symmetrical and greatly resembled that of pellagra. Andrews refers to the occurrence of eczema in his description of infantile beriberi.
In a paper published a few years ago attention wasdrawn by Hess and Fish to the fact that infantile scurvy frequently is associated with the exudative diathesis of Czerny, a pathological condition which predisposes to the development of exudations of the skin and the mucous membranes. Infants suffering from this condition—intertrigo, eczema, recurrent bronchitis—seem to be particularly susceptible to scurvy and to develop it more quickly than others.
As is well known,edemaconstitutes a not infrequent symptom of adult scurvy. It has not, however, been accorded any place in the symptomatology of infantile scurvy. We do not refer to the edema in connection with subperiosteal hemorrhage or separation of the epiphyses of the long bones, but a mild and peculiar form which is seen early in the disease. It involves most regularly the upper eyelids, and the legs—especially the skin covering the lower part of the tibiæ. In the latter site it differs from edema as usually encountered, in that it does not pit on pressure; it is firm, tense, causing some glossiness of the overlying skin, which is rendered difficult to wrinkle or to pinch between the fingers. Not infrequently the skin is slightly reddened, a sign of interest, in view of a similar, although much more intense, hyperæmia seen in pellegra.
In addition to this very mild edema there may be marked swelling, resulting in what might be called, following the terminology of beriberi, “wet scurvy.” The legs, body and even the face may be swollen. This has been frequently described in adult scurvy, and occasionally in infantile scurvy. The first case of infantile scurvy described in America, that of Northrup, had marked edema of the scrotum. Edema is frequently met with in “ship beriberi,” a disorder considered by some writers to be a combination of beriberi and scurvy.
The symptom leading to the diagnosis of scurvy most often istendernessor swelling of one of the extremities, as the antecedent clinical signs, comprising latent scurvy, are generally overlooked. These manifestations involve usually the distal end of the thigh or thighs. The tenderness is elicited most readily by pressure just above the knee, which causes the baby to wince, and to quickly flex the thigh, a reaction termed by Heubner “the jumping-jack phenomenon.” As a result of pain and tenderness, the leg lies often immobile in a state of pseudo-paralysis (Fig. 18). There may be tenderness elsewhere than in the long bones. Kerley refers to two cases showing tenderness of the spine, and we have seen a similar case. Not infrequently there is tenderness of the chest wall, the earliest symptom noted by nurse or mother being unaccountable crying whenever the baby is lifted by the thorax. This is largely due to the sensitiveness of the ends of the cartilage and bone which are pressed together at their junction.
Infant with marked scurvy. Characteristic positionFig. 18.—Infant with marked scurvy. Characteristic posture and swelling of right thigh.
An early sign of infantile scurvy isbeading of the ribs—the development of a “rosary” similar to that characteristic of rickets (Fig. 19). This has recently been described by Hess and Unger in an article devoted to this subject. That this rosary is truly scorbutic and not rhachitic is proved by the fact that it recedes rapidly when antiscorbutic foodstuff is given, and that it remains uninfluenced by treatment with cod liver oil. A similar scorbutic rosary occurs in guinea-pig scurvy, but has been termed “pseudo-rhachitic.” It is important that this sign should be recognized, as it is probable that much of the confusion regarding the relationship and frequent association of these two diseases is due to considering the beading rhachitic. The interpretation of infantilescurvy as “acute rickets,” the view held previous to the writings of Barlow, was based largely on the development of the rosary. To-day the error is made of regarding early scurvy as chronic rickets; the rickets supposed to be occasioned by a diet of condensed milk is probably more often scurvy. This beading differs generally from the round knobby “rosary” usually encountered. It is more angular, the junction taking on a step-like form, as if the abutting ends of the cartilage and the bone were of unequal size, and not well fitted to each other. In the accompanying radiograph (Fig. 19) it will be noted that the “beads” present an irregular appearance.
Scorbutic beading of ribs. RoentgenogramFig. 19.—Same infant as infigure 17. Scorbutic beading of the ribs (rosary). This developed on a diet which included cod liver oil, and decreased when an antiscorbutic was given. Note peculiar ragged appearance of “beads.”
In Figs.6,16and17will be seen illustrations of aseparation of the epiphysesof the head of the humerus, and of partial and of complete separation of the lower ends of the femora. This is a frequent lesion of fully developed scurvy in infants, children, and even in young adults. It is most frequent at the lower end of the femur, the upper end of the tibia, the head of the humerus, and the costochondral junctions. It is to these epiphyseal separations that the term fracture or infraction usually refers. Union is remarkably perfect even where no splint has been employed, and nature has effected the cure (Fig. 7). Occasionally there is some deformity, as when coxa vara develops. The callus is often remarkably large; an old callus sometimes undergoes destruction in the course of scurvy.
“White line.” RoentgenogramFig. 20.—Radiograph. Infant 14 months of age, showing “white line” at wrist some months after cure of scurvy.
We have referred to use of röntgenograms in connection with separation of the epiphyses, subperiosteal hemorrhage, cardiac enlargement and beading of the ribs. In addition to its application in these connections, the X-ray may be of service to show a peculiar alteration of the ends of the long bones—the white line of Fraenkel.This is portrayed in Fig. 20. It is best seen at the lower ends of the radius and femur, and appears as a white, transverse, somewhat irregular band. Its diagnostic value has been greatly exaggerated, as it is frequently not present when the disease is advanced (observe radiographs illustrating separation of the epiphyses). This sign should therefore not be relied on for establishing the diagnosis. Furthermore, changes may be seen in connection with rickets (cases receiving antiscorbutic diet) which are very difficult to differentiate from the “white line.” It cannot be employed as a criterion of the progress of the case, as it may persist for months after all other signs and symptoms have disappeared.
The joints may be involved in scurvy. In most instances, however, where swelling of the joints is diagnosed, the lesion is periarticular. An effusion of serum or of blood does occur occasionally into the joints and has been found at operation, at necropsy, and by puncture. If these effusions are allowed to go undisturbed, to be absorbed as a result of antiscorbutic treatment, they rarely suppurate. Czerny and Keller report the articular fluid as invariably sterile.
The cardiovascular system has been given but scant attention in connection with scurvy. Adults complain not infrequently of palpitation and pain over the pericardium, or rather of a tightness or oppression in the chest. Little information is given regarding the size of the heart. Darling described enlargement of the heart, especially a right-sided hypertrophy, which he thought was pathognomonic of the Rand type of scurvy. The pulse is described in some cases as slow, and in others as rapid. In descriptions of infantile scurvy the entire subject is generally passed over without mention—for example, inthe excellent report of the American Pediatric Society nothing whatsoever is stated regarding the heart’s action or the pulse. Barlow wrote: “There is nothing to note regarding the heart and lungs.”
Cardiac enlargement. RoentgenogramFig. 21.—Radiograph. Scorbutic infant 14 months of age, showing cardiac enlargement and broadening of shadow at base of heart.
In a paper written a few years ago, it was pointed out by the author that there is frequently enlargement of the heart, and more especially of the right heart. This can be elicited at the bedside and has been substantiated in numerous cases by means of the Röntgen-ray, which demonstrates not only enlargement of the heart, but also a marked broadening at its base, at the site of the large vessels (Fig. 21). These phenomena resemble closely the description of Reinhard in cases of beriberi.
Necropsy protocols usually are incomplete and unsatisfactory in their descriptions of the heart. The excellent monograph of Schoedel and Nauwerk, however, which reports five careful necropsies, contains the following data regarding three:
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 dilated and slightly hypertrophied, the muscles pale and tough.
In addition to this enlargement of the heart, or perhaps associated with it, there is a combination of signs which has been termed “the cardiorespiratory syndrome” (Hess). It will be noted in the above description of a case of subacute scurvy, that the pulse- or heart-beat was frequently over 150, and the respiration 60. These phenomena were noted in several instances before their significance and intimate relationship to scurvy were realized.The heart-beat not infrequently is found to be 200 per minute, and to be characterized by marked lability—increasing to an astonishing degree as the result of slight exertion or excitement. A mild febrile disturbance causing a rise of temperature to little more than 100° F. will send the pulse-rate up 30 beats. It must not be thought that this refers to severe cases; the babies we have in mind are similar to the one cited as an instance of subacute scurvy. Apparently they are not ill, but show merely some tenderness of the thighs, pallor, and the other minor signs described. The cardiographic tracings showed a simple tachycardia with an exceptionally tall T-wave in some tracings, such as is commonly seen in exophthalmic goitre (Fig. 22).
Electrocardiogram showing “cardiorespiratory syndrome”Fig. 22.—Electrocardiogram in case showing cardiorespiratory syndrome. Tachycardia with exceptionally tall T-wave.
The rapidity of respirations is perhaps a more delicate indicator of this disturbance than the pulse and has been found to be markedly affected when the latter was merely slightly increased in rate. For example, in one instance the respirations were 64, 60 and 64 on three successive days, while the pulse was 124, 141 and 136; in other words, there was a 2:1 instead of the normal 4:1 pulse-respiration ratio. The accompanying chart (Fig. 15) illustrates the phenomenon in all its details better than a verbal description. There is one point in connection with it, to which especial attention should be called. This is a reaction evident at a glance at the chart—the sharp drop in the pulse and in the respiratory rate when orange juice was given. It is the essence of the phenomenon; a therapeutic response which proves that the rapidity is scorbutic in nature.
The main involvement of therespiratory systemin scurvy is the polypnœa just described in connection with the cardiorespiratory syndrome. There is no aphonia,a sign so typical of adult and of infantile beriberi, although at times the voice is abnormal and whining. The lungs frequently show some dullness posteriorly, which may be due to engorgement or to the pressure of the enlarged heart. Pneumonia is a frequent complication and edema a terminal event. Hydrothorax associated with hydropericardium is of frequent occurrence, and was noted in the early description of this disease in adults and in the first account of Barlow. These effusions rarely progress to what may be termed the clinical degree and under antiscorbutic treatment are rapidly absorbed.
It is commonly thought that scurvy does not involvethe nervous system; that this is a feature which distinguishes it sharply from beriberi, another “deficiency disease.” This view is incorrect, for the nervous system is probably affected in many cases of scurvy. The rapidity and lability of the pulse, combined with the rapid respirations, would seem to be due to a disturbance of the vagus mechanism. It is true that in beriberi the vagus is involved to a still greater extent, especially its recurrent laryngeal branch which brings about the characteristic aphonia. In scurvy the knee-reflexes are generally increased. Very rarely they are absent in infantile scurvy, as described in adults. It is impossible to judge whether the pain and tenderness in infants are due in part to a sensitiveness of the nerve trunks as well as of the periosteum. Careful studies in adult scurvy should furnish an answer to this question. No methodical examination for areas of anæsthesia or paræsthesia, signs which occur so frequently in connection with beriberi, has been carried out in scurvy. In certain epidemics, however, pains in the limbs have been prominent symptoms.
The optic discs are generally pale in both infants andin adults, with occasional signs ofneuredema. Nyctalopia, so frequently encountered, must be regarded as a circulatory symptom rather than as one of nervous origin.
In a recent paper the author described a focal degeneration of the lumbar cord in a case of infantile scurvy, the lesion involving mainly the anterior horn cells (Figs. 3and4). In view of this report it would be well to watch for corresponding clinical signs of involvement of the spinal cord. Herpes has been described in connection with both adult and infantile scurvy. In one of the early cases in the American literature Fruitnight reported a case with herpes in a girl five years of age. In considering the rôle of the nervous system, mention should be made of cases where sweating constituted an important symptom. Finkelstein lays particular stress on this symptom in infantile scurvy. We have not met with it frequently; possibly it is due in part to complicating rickets.
As would be expected, the nervous system is at times the site of hemorrhage. Such lesions cannot, however, be considered essentially nervous. For instance, hemorrhage into the meninges may occur, as in the case of Sammis, where there was “a general clonic convulsion” before death, and a blood-clot 2½ inches long by ½ inch wide was found at necropsy between the dura and arachnoid. Fife reported a similar case. Finkelstein also has drawn attention to the occurrence of meningeal hemorrhage, and Hess and Fish reported obtaining bloody cerebrospinal fluid from a case with meningeal symptoms. Recently Aschoff and Koch have depicted hemorrhages in the sheath of the sciatic nerve, which undoubtedly must have given rise to symptoms during life.
In view of many of these symptoms, especially thoseinvolving the vagus, scurvy must be looked upon as a disorder which may seriously affect the nervous system. Furthermore, when we note the marked reaction brought about by the antiscorbutic vitamine—for example, the sharp fall in the rate of respirations and of pulse, as shown inFig. 15, after giving orange juice, we must conclude that the antiscorbutic vitamine functions, at least indirectly as an antineuritic vitamine—that it must possess this character to allay the various nervous signs of this disorder.
The urinary system is frequently involved in the course of scurvy. Among 38 cases Still reports that 89 per cent. gave evidence of urinary changes and that 60 per cent. showed hæmaturia. Finkelstein found urinary signs in at least a third of his cases. Our figures, the result of a study of subacute and mildly acute cases, correspond more nearly with those of Finkelstein.
The occurrence of pronounced renal hemorrhage as a first symptom of scurvy is emphasized in many descriptions of this disease, and has impressed itself in the minds of physicians. It is true that this occurs sometimes at the onset, as does hemorrhage into or about the joints, or hemorrhage behind the eyeball. It is well to bear these possibilities in mind, but they must be regarded as very exceptional early signs of this disorder. We have encountered frank hæmaturia but once in the early stage of infantile scurvy. The blood emanates generally from the kidneys, although the submucous hemorrhages of the bladder as well as in the urethra, described both in man and in guinea-pigs, indicate that the blood in the urine may have its origin lower down in the tract. This bleeding should be regarded not as a sign of nephritis, but rather as a hemorrhagic manifestation. It is less frequentin adults than in infants. O’Shea reports some degree of hemorrhage in 15 per cent. of his cases (adults).
A true nephritis, however, may occur in connection with scurvy. There may be albumen and many casts, or a urine loaded with casts and cylindroids. These peculiar casts may appear suddenly, as in the alimentary intoxication of infants, and disappear just as rapidly when antiscorbutic treatment is given. The urine may contain a large number of pus cells as in pyelitis. This condition may be accompanied by irregular fever, but in two instances we have encountered it where the temperature was normal. It is to be regarded, probably, merely as one of the manifestations of secondary infection so commonly associated with scurvy. Some pus cells may continue to be present in the urine for a period of months. This is likewise true of the red cells. We have under observation at present an infant which had subacute scurvy almost three years ago and still has red blood-cells in the urine.
Oliguria is a common symptom of both adult and infantile scurvy. Lind mentioned this symptom, and in this connection remarks on the beneficent effect of antiscorbutic treatment. Charpentier called attention to the fact that in a case of scurvy the urine decreased from 1250 g. to 800 g. The report of the American Pediatric Society mentions scanty urine in 9 cases and suppression of urine in one. This sign, however, was not emphasized until recently, when Gerstenberger, and Hess and Unger drew attention to its frequent occurrence in infants. It has some diagnostic significance and should be borne in mind where a decreased excretion of urine is reported. A counterpart of this symptom is the sudden outpouring of urine frequently noted after antiscorbutic treatmenthas been instituted. This polyuria accounts for the loss of weight or lack of gain which sometimes accompanies unmistakable general improvement, and which is difficult otherwise to understand (Fig. 23). It is interesting to learn that oliguria occurs commonly in both adult and infantile beriberi.
Stationary weight during cure of scurvy. Oliguria followed by polyuriaFig. 23.—Joseph G., aged 9 months. Chart showing stationary weight (due to oliguria followed by diuresis) in spite of marked variation of fluid intake. A=Schloss milk; B=cod liver oil; C=egg yolk; D=1 ounce of orange juice; E=potato (orange juice stopped).
One of the earliest, as well as one of the most constant symptoms of scurvy, is alack of appetite. It is a typical sign of latent scurvy, although occasionally we have met with cases where the appetite remained unimpaired until the hemorrhagic stage was reached. In adults there is sometimes bulimia and a marked capriciousness of the appetite. Anorexia is a true scorbutic symptom, disappearing with remarkable rapidity when antiscorbutic food is given, and not capable of alleviation by tincture ofgentianor other vegetable bitters. Whether it depends upon a lack of secretions in the gastro-intestinal tractis not known, as there has been no thorough study of this aspect of the disorder. The hydrochloric acid generally is deficient in cases of scurvy. Recently McCarrison has laid emphasis on the importance of the impairment of the digestion and assimilative function in scurvy. This subject gains added interest in view of the recent reports of Uhlmann as well as of Voegtlin, showing that water-soluble vitamine acts as a stimulant for the various secretions of the gastro-intestinal tract.
As a result of McCollum’s statement that scurvy is due mainly toconstipation, marked attention has been directed recently to the action of the bowels in this disorder. This question has been discussed in the chapter on etiology, and, therefore, will be referred to in this place merely from the clinical viewpoint. In our experience the activity of the bowel varies greatly in cases of latent or subacute scurvy. In a great many instances it has been normal; more often there has been slight constipation, and exceptionally there has been irregular diarrhœa. In other words, no causative relationship or parallelism could be observed between the emptying of the intestinal tract and the development of scurvy. This in general has been the experience of others. In the report of the American Pediatric Society the bowels are stated as having been regular in 74 cases, irregular in 15, constipated in 126, and diarrhœal in 65. It may be added that we were unable to cure scurvy by means of liquid petrolatum or phenolphthalein, either in infants or in guinea-pigs, and likewise unable to protect guinea-pigs from scurvy by means of various laxatives. On the other hand, opium given in the form of the camphorated tincture did not lead to an intensification of the symptoms,although, in one case, the bowels did not move for over three days.
As complications involving the gastro-intestinal tract may be mentioned the vomiting of blood, which is stated in the above report as occurring in 2 of the 361 cases, as well as bleeding from the bowel, which was noted in 37 cases, in 12 of which there was bloody diarrhœa. However, these are late symptoms, and correspond to the mycotic ulcers which are so frequently found, especially in the large intestine, in cases of scurvy. Mention may again be made of the fact that hemorrhages may occur under the peritoneum and give rise to symptoms simulating appendicitis or general peritonitis.
Jaundice has been described in connection with certain epidemics of scurvy. To our knowledge it has not been reported in infants.
The presence of worms has been frequently reported in the bowel or in the stool of patients suffering from beriberi. There have been no similar investigations in relation to scurvy. It would be interesting to inquire into this question, as it is quite possible that a lack of antiscorbutic foodstuff may favor the presence of parasites in the intestinal canal.
Before closing this consideration of the involvement of the alimentary tract, we would call attention to the relation of stomatitis to scurvy. Among adults this is a common complication. In infants it is uncommon, due to the absence of carious teeth and secondary infection; we have encountered it in but two instances. Stomatitis is of importance in this connection, as it frequently develops on the basis of malnutrition, scurvy being one of the disorders which may constitute the substratum. Such may be the case where stomatitis occurs in epidemic form—for example, among large bodies of troops. It may be remarked that stomatitis at times was a very common disease among the soldiers in the recent war.
TABLE 4
Scurvy is associated with an alteration of boththe blood and the blood-vessels. The characteristic pallor, which is one of the most common as well as earliest symptoms, is due in a large measure to the anemia. This anemia is of the secondary type, but has definite peculiarities, and does not resemble that encountered in the course of tuberculosis, rickets or marasmus. The hemoglobin is greatly diminished, far out of proportion to the decrease in the number of the red cells. Not infrequently we will find a hemoglobin index of 0.5. Table 4, above taken from the article on this subject by Hess and Fish (1914), brings out the details of the blood-picture.It shows that there may be a polycythemica, which may persist after the other signs of the disorder have disappeared. Brandt has recently made similar observations, reporting in one instance over ten million red cells two months after treatment. In soldiers suffering from scurvy Wassermann has encountered cases where, during convalescence, the red-cell count has risen to over six or seven millions and the hemoglobin to 110 or 120 per cent. Under the microscope the red cells show poikilocytosis, anisocytosis and a lack of hemoglobin; they are slightly enlarged, with the occasional occurrence of exceptionally large cells resembling the “dropsical cells” described in connection with chlorosis. Sometimes a few nucleated red cells and myeloblasts are seen; megaloblasts are also reported.48The blood-picture bears a remarkable similarity to that of chlorosis, a point of interest, in view of the fact that both scurvy and chlorosis have been attributed to a disordered function of the endocrine glands. The “dropsical cells” suggest a disturbance of the salt balance in the plasma. In some cases we have found a decreased fragility of the red cells, which also has been described in chlorosis.
The total number of leucocytes is slightly increased. In our cases the mononuclear cells have averaged 66 per cent., which is somewhat high even for infants. This has been the experience of Labor, who, however, also describes an eosinophilia during convalescence, a phenomenon which we have not encountered. Some describe a marked increase in the polynuclear cells, which, probably, is to beregarded as the reaction to secondary infections. There is indeed a marked difference of opinion in regard to the morphology of the blood in scurvy in adults as well as in infants. Some found a large number of one type of cell—for example, nucleated red cells, myelocytes, eosinophiles—whereas others have failed to observe an increase of these cells. The divergent reports probably should be attributed to the fact that the investigators are describing scurvy of various grades of severity, of different stages of development, or complicated by intercurrent disease.
Nobécourt, Tixier, and Maillet have questioned whether there is always complete recovery from this anemia, which is severe from the standpoint of hemoglobin and iron. The older authors reported instances where men have been weakly and ailing for the remainder of their lives after an attack of scurvy. In some infants pallor and anemia may persist for months after apparent cure; however, this is the exception rather than the rule.
In view of the fact that scurvy frequently is classed as a hemorrhagic disease, and that hemorrhages play such an important rôle in its symptomatology, a consideration of the factors concerned in thecoagulability of the bloodis of interest. In an investigation (Hess and Fish) it was found that the oxalated plasma (of blood taken directly from a vein) showed a slightly delayed coagulation time—eight to fourteen minutes. The “bleeding time” carried out according to the simple method of Duke was slightly increased. Holt reports a case where a child bled to death following incision into an epiphyseal swelling at the lower end of the femur. The number of blood platelets is increased, running parallel, as is usually thecase, with the number of red cells (Table 4). This increase in the blood-platelets, recently confirmed by Tobler and by Brandt, is a very exceptional phenomenon, and was not anticipated in connection with a disorder characterized by hemorrhage. The antithrombin content of the plasma is normal.
The investigation was directed to a study of the integrity of the blood-vessels in order to account for the hemorrhages. To this end the “capillary resistance test” was devised.49In the majority of cases this was found to be “positive” (the blood-vessels showing an increased permeability) and to become negative when antiscorbutics were given and the symptoms disappeared. This shows that the cellular structure of the vessels is altered in the course of scurvy, and indicates probably that this is an important cause of the hemorrhages. The edema of the face and ankles, the outflow of serum into the body cavities and into the muscles (Barlow) must be regarded as other evidences of the inadequacy of the vessel walls. The tendency of children with exudative diathesis to develop scurvy is perhaps still another manifestation of vascular weakness. This point of view has been strengthened recently by the pathological studies of Aschoff and Koch, who regard scurvy as a nutritional disorder inwhich there is a lack of some colloidal substance needed for the normal structure of the vessels.
When one makes a subcutaneous puncture in infants suffering from scurvy, a small hemorrhage very often develops at the site of the puncture wound. This is not the case when one makes a hypodermic puncture in a normal person or in a hemophiliac, although it does occur in cases of purpura. This “stick test” is not a constant sign of scurvy, but, like the capillary resistance test, was found in many cases and disappeared with the subsidence of the disorder. It shows that the cells of the skin and subcutaneous tissues are affected, and possibly that their thromboplastic power is diminished.
Nutrition and Growth.—The general nutrition suffers in scurvy as the disease progresses. It is a mistake, however, to picture the scorbutic individual, either adult or infant, as in a state of malnutrition. Not infrequently he appears well nourished, an appearance which is heightened by the slight edema of the face. Infants generally for a period of weeks or months preceding the onset maintain a stationary weight. This may be the only sign of the scorbutic condition. For example:
An infant seen in 1915 gained about one-half a pound during the months of February, March, April and May. At this time it was somewhat over 9 months of age and had never received raw milk or other antiscorbutic food. In June it was given orange-peel juice, and gained 2 pounds within a month. There were no other scorbutic signs or symptoms, and no loss of appetite during the months of February and March, although the baby was suffering from a progressive scurvy.
An infant seen in 1915 gained about one-half a pound during the months of February, March, April and May. At this time it was somewhat over 9 months of age and had never received raw milk or other antiscorbutic food. In June it was given orange-peel juice, and gained 2 pounds within a month. There were no other scorbutic signs or symptoms, and no loss of appetite during the months of February and March, although the baby was suffering from a progressive scurvy.
The growth impulse of the body throughout an attack of scurvy remains unimpaired, being merely in an inactiveor quiescent state.Fig. 14shows this very well, demonstrating that when an antiscorbutic food is added to the dietary the gain may be abnormally great—there may be supergrowth. Generally such marked increases are due to an increase in the consumption of food, following the stimulation of the appetite. However, decided gain in weight may follow the giving of orange juice or other antiscorbutic despite the fact that the intake of food is maintained at the same level.