Scurvy Past and Present Part 12

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. 3 and 4). 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 role of the nervous system, mention should be made of cases where sweating const.i.tuted 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 2 inches long by 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 b.l.o.o.d.y 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 those involving 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 antis...o...b..tic vitamine--for example, the sharp fall in the rate of respirations and of pulse, as shown in Fig. 15, after giving orange juice, we must conclude that the antis...o...b..tic 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 haematuria. 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 p.r.o.nounced 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 haematuria 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 frequent in 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 alb.u.men 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 antis...o...b..tic 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 a.s.sociated 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 antis...o...b..tic 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 antis...o...b..tic treatment has been inst.i.tuted. 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.

[Ill.u.s.tration: FIG. 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 a _lack of appet.i.te_. It is a typical sign of latent scurvy, although occasionally we have met with cases where the appet.i.te remained unimpaired until the hemorrhagic stage was reached. In adults there is sometimes bulimia and a marked capriciousness of the appet.i.te. Anorexia is a true s...o...b..tic symptom, disappearing with remarkable rapidity when antis...o...b..tic food is given, and not capable of alleviation by tincture of gentian or other vegetable bitters. Whether it depends upon a lack of secretions in the gastro-intestinal tract is 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 a.s.similative 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 to _constipation_, 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 diarrhoea. 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 diarrhoeal 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 b.l.o.o.d.y diarrhoea. 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 antis...o...b..tic foodstuff may favor the presence of parasites in the intestinal ca.n.a.l.

Before closing this consideration of the involvement of the alimentary tract, we would call attention to the relation of stomat.i.tis 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. Stomat.i.tis is of importance in this connection, as it frequently develops on the basis of malnutrition, scurvy being one of the disorders which may const.i.tute the substratum.

Such may be the case where stomat.i.tis occurs in epidemic form--for example, among large bodies of troops. It may be remarked that stomat.i.tis at times was a very common disease among the soldiers in the recent war.

TABLE 4 THE PLATELETS AND OTHER BLOOD-CELLS IN SCURVY ====================================================================== Name Date Platelets Leuko- Erythro- Hmgl. % Remarks cytes cytes (Sahli) -----+------+-----------+--------+-----------+---------+-------------- M. H. 5/ 3 280,000 ...... ......... .. 5/ 4 248,000 10,000 ......... .. 5/ 5 ....... ...... ......... .. Boiled orange juice given.

5/ 8 ....... ...... 4,300,000 35 5/16 ....... 15,900 ......... .. 7/ 2 ....... 6,800 5,456,000 40 Well but pale.

A. L. 5/ 3 300,000 ...... ......... .. 5/ 5 ....... 21,000 ......... .. 5/ 9 ....... ...... 5,480,000 .. 5/11 382,000 ...... ......... .. 5/13 ....... ...... ......... 65 5/16 ....... 11,500 ......... .. H. C. 5/ 8 320,000 20,000 ......... .. 5/ 9 ....... ...... 5,340,000 .. 5/13 ....... ...... ......... 70 5/16 362,000 ...... ......... .. B. B. 5/ 4 496,000 21,000 ......... .. A severe case.

5/13 585,000 14,000 3,200,000 70 5/18 ....... 17,600 ......... .. 7/13 ....... 40,000 =7,672,000= 82 Has gained well lately.

7/15 ....... ...... =7,640,000= 88 H. Y. 5/15 560,000 ...... ......... .. 5/16 424,000 ...... ......... .. 7/ 9 ....... ...... 5,750,000 45 -----------------------------------------------------------------------

Scurvy is a.s.sociated with an alteration of both _the 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 Wa.s.sermann 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.[48] The 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.

[48] Senator regarded the marrow in scurvy as being aplastic. n.o.becourt, Tixier and Maillet report postmortem examinations where the marrow showed an increased number of myelocytes and nucleated red cells of various kinds. They consider the typical blood change an intense myeloid reaction of the blood.

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 be regarded 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.

n.o.becourt, 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 cla.s.sed as a hemorrhagic disease, and that hemorrhages play such an important role in its symptomatology, a consideration of the factors concerned in the _coagulability of the blood_ is 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 the case, 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 antic.i.p.ated in connection with a disorder characterized by hemorrhage.

The ant.i.thrombin 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.[49] In the majority of cases this was found to be "positive" (the blood-vessels showing an increased permeability) and to become negative when antis...o...b..tics 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 in which there is a lack of some colloidal substance needed for the normal structure of the vessels.

[49] A blood-pressure band, or tourniquet, is placed about the arm, and the pressure increased until the forearm becomes cyanosed and the radial pulse is almost obliterated. The pressure is then maintained at this level for 3 minutes. The principle of this test consists in subjecting the capillaries and venules to increased intra-vascular pressure to observe whether this strain results in the escape of blood. In infants the pressure was usually raised to 90 mm.; in some cases it had to be raised higher in order to entirely obstruct the return flow of the blood.

The test is considered to be "positive" when the forearm shows many petechial spots. In normal infants petechiae were almost always absent, or there were few to be seen. This is not a specific test for scurvy, but demonstrates a weakness of the vessel walls, whatsoever may be the cause. It is found to be positive in the majority of cases of scurvy.

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 s...o...b..tic 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 s...o...b..tic 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 antis...o...b..tic food. In June it was given orange-peel juice, and gained 2 pounds within a month. There were no other s...o...b..tic signs or symptoms, and no loss of appet.i.te 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 inactive or quiescent state. Fig. 14 shows this very well, demonstrating that when an antis...o...b..tic 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 appet.i.te.

However, decided gain in weight may follow the giving of orange juice or other antis...o...b..tic despite the fact that the intake of food is maintained at the same level.

[Ill.u.s.tration: FIG. 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 ill.u.s.trates this clinical paradox:

A baby was seen in January, when it was 7 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 s...o...b..tic 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 antis...o...b..tic 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 antis...o...b..tic 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 r.e.t.a.r.dation 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 r.e.t.a.r.dation in growth and the sharp reaction when orange juice was added to the dietary. It also demonstrates that the growth impulse remains unimpaired and capable of quick response when the essential food factor is furnished.

[Ill.u.s.tration: FIG. 25.--Showing r.e.t.a.r.dation 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 in Fig. 15. There is a difference of opinion as to whether the rise of temperature should be considered as truly s...o...b..tic in nature, as "s...o...b..tic fever," or regarded merely as a condition grafted upon the nutritional disturbance.

A phenomenon which might seem to argue for its essential s...o...b..tic character is the sharp subsidence on giving antis...o...b..tic food. On the other hand, this may quite as well be interpreted as due to a secondary reaction, checking the 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 numerous _complications_ of 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 const.i.tuting the most common cause of death. In infants we meet with frequent attacks of "grippe," widespread occurrence of _nasal diphtheria_, furunculosis and torpid ulcers of the skin, pyelitis, ot.i.tis, adenitis, etc. We have encountered nasal diphtheria--with typical b.l.o.o.d.y 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 pyorrhoea, "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 in _epidemic form_, especially in the army, but also, as in Russia, among the civilian population. This results when a large group of individuals have 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 distribution of the hemorrhages, the development of signs (in some instances) in spite of antis...o...b..tic 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 DATA OF EPIDEMIC OF SCURVY ==================================================================== Age Weight Site of Case , _lbs._ Hemor- Date Diet Remarks Mos _oz._ rhages -----+---+------+----------+-------+--------------+----------------- 1. 6 9 6 Humerus, Apr. 19 Breast milk Grippe since end J. H. tibia, (1 week); of February; face. pasteurized nephritis; 10 4 Upper May 9 milk v. Pirquet eyelid previously. negative.

2. 5 12 14 External May 4 Pasteurized Twitchings and L. S. ear, milk formula; convulsions; parietal orange juice signs of intoxi- bones, 1 oz. daily cation; red vertebral since April cells in urine column, 22. blood fever to abdominal 101 F.; v. Pir- wall quet negative.

3. 10 12 8 Femur Apr. 19 Pasteurized Grippe end of A. R. milk formula; January; again vegetables in April; fever Femur June 4 for a month; until April 17; again orange juice v. Pirquet swollen longer; get- positive; and ting orange gums negative.

tender. juice and vegetables. 4. 5 7 Both ears; Apr. 29 Breast milk Grippe through- D. E. parietal since April out March; in- bones. 19; May 30, toxication; changed to nephritis; no pasteurized relapse although milk. no orange juice given.

5. 10 15 13 Ear and Apr. 27 Pasteurized Two teeth; T. K. face milk, cereal, gums negative; vegetable, v. Pirquet soup; orange negative.

juice since April 15. 6. 4 8 4 Tibia May 8 Pasteurized Grippe end of P. G. milk February and formula. first half of March gained 20 oz. during last month; v. Pir- quet negative.

7. 2 6 4 Abdomen Mar. 7 Breast milk Grippe; probable I. P. for past source of week; past- epidemic.

eurized milk previously. --------------------------------------------------------------------

DIAGNOSIS

A correct and early _diagnosis_ of 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 antis...o...b..tic treatment. These diagnostic points should be constantly remembered in 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 pa.s.s as rheumatism.