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Chapter VII

Contents

CHAPTER VII

Sarcoidosis

Max Michael, Jr., M.D.

Sarcoidosis was uncommon among U.S. military personnel during World War II; only some 300 cases were diagnosed. However, this disease, though infrequent, resulted in a good deal of lost time because of the inherent difficulties of diagnosis and decision concerning ultimate disposition. The multiple systemic involvement with many bizarre and seemingly unrelated symptoms, the extreme variations in its clinical course, and the utter confusion of opinion as to its management made it a stimulating challenge to the many medical officers who invariably studied each patient. Much was learned about sarcoidosis from this experience, and this information was augmented by further study of many of these patients after discharge from the service.1

CLINICAL PICTURE

A comprehensive review of sarcoidosis, with a description of the clinical features and the diagnostic difficulties encountered in 28 patients, was made by McCort and his associates.2 Individual case reports called attention to unusual manifestations, such as sarcoidosis of the stomach.3 This patient had a filling defect on the greater curvature of the stomach, and the lesion, when resected, had all the histological features of sarcoidosis. There were no other clinical evidences of sarcoidosis at that time or in subsequent followup examinations. Klinefelter and Salley described one patient with renal insufficiency resulting from sarcoidosis.4 The extreme hypercalcemia rather than the postulated sarcoid renal infiltrates was most likely responsible for the uremia.

Since military personnel are often apt to seek medical attention quite early in the course of their illness, it is not surprising that the

1The clinical records of all personnel have been made available for a study undertaken with the support of the Veterans' Administration through their Committee on Veterans Medical Problems of the National Research Council. Only those cases that had the histological picture and clinical features compatible with sarcoidosis were studied. The pathological sections were all reviewed by the Army Institute of Pathology, Washington, D.C.
2McCort, J. J., Wood, R. H., Hamilton, J. B., and Ehrlich, D. E.: Sarcoidosis; Clinical and Roentgenologic Study of 28 Proved Cases. Arch. Int. Med. 80: 293-321, September 1947.
3Gore, L., and McCarthy, A. M.: Boeck's Sarcoid: Case Involving Stomach. Surgery 16: 865-873, December 1944.
4Klinefelter, H. F., Jr., and Salley, S. M.: Sarcoidosis Simulating Glomerulonephritis. Bull. Johns Hopkins Hosp. 79: 333-341, November 1946.


166

complaints occasioning admission to the hospital differed somewhat from those encountered in civilian practice. The incidence of signs and symptoms in a group of 297 patients analyzed by the author is recorded in the tabulation which is to follow. Of this group of patients, 21 percent had no complaints.

Complaints referable to-

Percent

    

Chest

31

    

Peripheral nodes

17

    

Eyes

11

    

Skin

3

    

Other systems

17


Complaints referable to the chest consisted of cough, dyspnea, pain, and wheezing. The surprisingly large percentage who sought medical attention because of lymphadenopathy probably reflects a not unusual concern with the body and the bodily functions while under the stress of military duty. Other less frequent presenting complaints were of considerable medical interest. Two patients developed symptoms related to the hypercalcemia of sarcoidosis, six had joint pains not unlike those of rheumatoid arthritis, and another patient had a severe generalized itching in the absence of demonstrable skin lesions.

The patients with no complaints (21 percent) are particularly interesting. Sarcoidosis was discovered in most of these men when roentgenograms of the chest made at separation from the service showed pulmonary infiltrations or hilar adenopathy or both. The men were completely asymptomatic at that time.5 Diagnosis of the disease in a few of the patients in this group was made while the men were hospitalized for other medical causes, such as trauma. It is safe to say that in many patients sarcoidosis would have caused no symptoms and would never have been recognized if roentgenograms had not been made at the time of separation from the service. The frequency of incidence of sarcoidosis is not generally recognized, no doubt because of the number of cases with minimal or no symptomatology in whom the lesions clear completely. These lesions go undetected unless roentgenograms of the chest are made routinely.

Sarcoidosis is usually, but not invariably, a disease with a benign outlook. Twenty-two patients diagnosed as having sarcoidosis died during the period of Army hospitalization. However, when Ricker and Clark6 analyzed these records, they showed that these 22 deaths did not reflect the true mortality of the disease. It was the cause or contributing cause of death in only six of these patients, including two with disseminated

5In early followup studies in the Veterans' Administration, most of these patients had vague subjective complaints, the assessment of which was extremely difficult since many of the men were receiving compensations for their disease.
6Ricker, W., and Clark, M.: Sarcoidosis; Clinico-Pathologic Review of 300 Cases, Including 22 Autopsies. Am. J. Clin. Path. 19: 725-749, August 1949.


167

tuberculosis and sarcoidosis. Two other patients were later shown to have histoplasmosis with a sarcoid tissue reaction.7 In eight cases of sudden violent death and in six patients dying of other diseases, sarcoidosis was an incidental finding at necropsy.

DIAGNOSIS

Many of these patients were seen in several hospitals in the chain of evacuation before a definitive diagnosis was made, but a high index of suspicion and a diligent search for lymph nodes usually facilitated diagnosis. Actually, a major cause of delay in diagnosis was the conflicting reports of the pathologists with their differences of interpretation of the histological changes found in tissues.

Considerable confusion existed about the relation, if any, between sarcoidosis and tuberculosis. Sarcoidosis has often been considered a manifestation of tuberculosis, but recent evidence does not confirm such a relation. This confusion was evident in the handling of many military patients. Not infrequently, the roentgenograms of the chest were interpreted as revealing tuberculosis, and the biopsies of lymph nodes were regarded as characteristic of this disease. Indeed, several patients were transferred to special hospitals for management of tuberculosis.

Occasionally other diagnostic difficulties were encountered, based on the fact that the sarcoid tubercle with all of its histological features can be produced by various viral, mycotic, parasitic, bacterial, and metallic agents as well as by neoplastic tissue. One patient diagnosed as having sarcoidosis (with a typical clinical and histological picture) had worked for a number of years before induction in a fluorescent lamp factory. The exposure to beryllium fumes was quite heavy, and the incidence of delayed chemical pneumonitis was high in workers in the plant.8 Without a specific test for sarcoidosis, it is difficult to say which disease the patient had, although epidemiological features would indicate berylliosis rather than sarcoidosis.

It is probable that there are other patients among the military cases, as well as in all series of cases of sarcoidosis, who actually have responded with the sarcoid picture to a variety of other agents.9

7Pinkerton, H., and Iverson, L.: Histoplasmosis; 3 Fatal Cases With Disseminated Sarcoid-Like Lesions, A.M.A. Arch. Int. Med. 90: 456-467, October 1952.
8Hardy, H.: Personal communication.
9A recent report of the findings of Histoplasma capsulatum in sections of two patients who had all the clinical and histological features of sarcoidosis and who were so diagnosed is of interest (see footnote 7).
A review of the sections demonstrated H. capsulatum in various "sarcoid lesions." Both patients had caseous adrenals which caused confusion whether this was tuberculosis, though no acid-fast organisms were demonstrable. These patients were carried as sarcoidosis in the Army files and are included in studies of this series. They further underline the need for clean-cut criteria for the diagnosis of the Boeck's sarcoidosis.


168 

TREATMENT AND DISPOSITION

The therapeutic problem was often frustrating, and during World War II it was the general practice to recommend prolonged bed rest which was usually carried out. Other modes of therapy included radiation with ultraviolet and roentgen rays. It is fair to state that no beneficial effect was accomplished by any therapeutic regimen.

Any disease occurring during military duty poses the problem of loss of time and its effect on military forces. Although sarcoidosis occurred infrequently among military personnel, it accounted for a considerable loss of time. The duration of hospitalization was in terms of months rather than weeks; much time was consumed in transportation through the chain of evacuation and in diagnostic workups, often rather slowly accomplished. With the exception of very few men, all were given certificates of disability for discharge when the diagnosis was established, and many were transferred directly to Veterans' Administration hospitals for further care.

FOLLOWUP STUDIES

Followup studies of certain medical problems encountered among military personnel during World War II by the CVMP (Committee on Veterans Medical Problems) of the National Research Council under the sponsorship of the Veterans' Administration have been a farsighted and fruitful endeavor. Sarcoidosis was one of the diseases chosen for such study. Dr. John Ransmeier, who at that time was secretary of the CVMP, felt that some unique epidemiological features of the military cases warranted further study. Accordingly, more thorough epidemiological and clinical analysis of the cases was undertaken, the results of which have appeared elsewhere.10 While such a retrospective study cannot be said to have contributed to an understanding of the illness during World War II, nevertheless it has certain far-reaching implications that seem to warrant a brief résumé in this report.

Some doubt has been cast on the validity of the findings, summarized in the paragraphs which follow, with the implication that the preinduction medical screening in one part of the country was not as adequate as it was in other parts. This seems improbable, since physicians at the various induction stations came from all over the country, not merely from the region where induction occurred.

1. The disease was more prevalent in inductees from the Southeastern United States, more particularly among those from the Gulf and the At-

10(1) Michael, M., Jr., Cole, R. M., Beeson, P. B., and Olson, B. J.: Sarcoidosis; Preliminary Report on Study of 350 Cases With Special Reference to Epidemiology. Am. Rev. Tuberc. 62: 403-407, October 1950. (2) Gentry, J. T., Nitowsky, H. M., and Michael, M., Jr.: Studies on the Epidemiology of Sarcoidosis in the United States: The Relationship to Soil Areas and to Urban-Rural Residence. J. Clin. Invest. 34: 1839, 1955.


169

lantic Coastal Plain areas. The attack rates per 100,000 inductees are indicated in table 23.

2. Sarcoidosis occurred with a greater frequency in Negroes than in whites.

3. A majority of the inductees were born in rural rather than in urban areas.

TABLE 23.-Attack rates for sarcoidosis for World War II servicemen, by race, and region of induction (residence)

[Attack rate expressed as number of cases per 100,000 inductees]

Region of induction1 (residence)

White

Negro

Total

Ratio (Negro: white)

Number of cases

Attack rate

Number of cases

Attack rate

Number of cases

Attack rate

I

29

1.3

156

23.5

185

6.3

18:1

II

25

.6

38

13.3

63

1.5

22:1

III

31

.5

18

8.3

49

.7

17.1

Total

85

0.7

212

18.2

297

2.1

 


1Roman numerals indicate region of greatest incidence (I), region of next greatest incidence (II), and region of lowest incidence (III).
NOTE .-Ratio of rates for regions:
    I: III-Total, 9 : 1; white, 3 : 1; Negro, 3 : 1.
    I: II-Total, 4 : 1; white, 2 : 1; Negro, 2 : 1.

4. The birthplaces appeared to be concentrated within certain soil areas. Speculation on the significance of this epidemiological pattern is warranted. This is not the epidemiology of tuberculosis, an argument against sarcoidosis being caused by the tubercle bacillus. The heavy concentration of cases in the Southeast is explained in part, but by no means in toto, by the heavy Negro population. Various ecologic factors that have been explored have not yet proved fruitful. One would suggest that either (1) there is a concentration of the etiological agent (or agents) in this area or (2) its propagation is favored by climatic, geologic, or environmental conditions in this area; or (3) that people in this region react differently because of environmental factors to the agent or agents.

It is of interest to compare the birthplace of the patients with sarcoidosis with those in the military service during the same time who had Hodgkin's disease. As shown in table 24, the rates for Hodgkin's disease are quite constant, region by region, in contrast to the heavy concentration of sarcoidosis in one region.

Whether servicemen from parts of the country removed from the "endemic area" would acquire sarcoidosis when exposed to these regions is a matter of interesting speculation. Hundreds of thousands of such


170

TABLE 24.-Comparison of attack rates of sarcoidosis with those of Hodgkin's disease

Region of induction2

Sarcoidosis

Hodgkin's disease


Number of total cases

Attack rate

Number of total cases

Attack rate

I

223

7.4

61

2.0

II

36

.85

122

2.8

III

31

.44

190

2.7

Total

290

2.0

373

2.6


1Calculations are based on birthplace rather than on residence in region of induction.
2Roman numerals indicate region of greatest sarcoidosis incidence (I), region of next greatest incidence (II), and region of lowest incidence (III).

servicemen were so exposed in the many large military installations, such as Fort Bragg, N.C., Fort Benning, Ga., and Fort Jackson, S.C., located in the endemic area. A recent study11 seems to indicate that after 10 years no striking general increase of sarcoidosis has occurred in men under these conditions. Since the incubation of sarcoidosis is unknown but is assumed to be many years, perhaps no definite answer to this problem can be given for another decade. Even though hundreds of thousands of men were exposed to the endemic area, it is entirely possible that their contact with the "agent or agents" was too brief or too remote to result in sarcoidosis. Certainly, no major outbreak of sarcoidosis attributable to military service has yet been uncovered.

11Cummings, M. M., Dunner, E., Schmidt, R. H., Jr., and Barnwell, J. B.: Concepts of Epidemiology of Sarcoidosis; Preliminary Report of 1,194 Cases Reviewed With Special Reference to Geographic Ecology. Postgrad. Med. 19: 437-446, May 1956.

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