CHAPTER VII
Sarcoidosis
Max Michael, Jr., M.D.
Sarcoidosis was uncommon among U.S. military personnel duringWorld War II; only some 300 cases were diagnosed. However, this disease, thoughinfrequent, resulted in a good deal of lost time because of the inherentdifficulties of diagnosis and decision concerning ultimate disposition. Themultiple systemic involvement with many bizarre and seemingly unrelatedsymptoms, the extreme variations in its clinical course, and the utter confusionof opinion as to its management made it a stimulating challenge to the manymedical officers who invariably studied each patient. Much was learned aboutsarcoidosis from this experience, and this information was augmented by furtherstudy of many of these patients after discharge from the service.1
CLINICAL PICTURE
A comprehensive review of sarcoidosis, with a description ofthe clinical features and the diagnostic difficulties encountered in 28patients, was made by McCort and his associates.2 Individual case reports calledattention to unusual manifestations, such as sarcoidosis of the stomach.3This patient had a filling defect on the greater curvature of the stomach, andthe lesion, when resected, had all the histological features of sarcoidosis.There were no other clinical evidences of sarcoidosis at that time or insubsequent followup examinations. Klinefelter and Salley described one patientwith renal insufficiency resulting from sarcoidosis.4 The extremehypercalcemia rather than the postulated sarcoid renal infiltrates was mostlikely responsible for the uremia.
Since military personnel are often apt to seek medicalattention quite early in the course of their illness, it is not surprising thatthe
1The clinical records of all personnel have been madeavailable for a study undertakenwith the support of the Veterans' Administration through their Committee onVeterans Medical Problems of the National Research Council. Only those casesthat had the histological picture and clinical features compatible withsarcoidosis were studied. The pathological sections were all reviewed bythe Army Institute of Pathology, Washington, D.C.
2McCort, J. J., Wood, R. H.,Hamilton, J. B., and Ehrlich, D. E.: Sarcoidosis; Clinical and RoentgenologicStudy of 28 Proved Cases. Arch. Int. Med. 80: 293-321, September1947.
3Gore, L., and McCarthy, A. M.: Boeck's Sarcoid: CaseInvolving Stomach. Surgery 16: 865-873, December 1944.
4Klinefelter, H. F., Jr., and Salley, S. M.: SarcoidosisSimulating Glomerulonephritis. Bull. Johns Hopkins Hosp. 79: 333-341, November1946.
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complaints occasioning admission to the hospital differedsomewhat from those encountered in civilian practice. The incidence of signs andsymptoms in a group of 297 patients analyzed by the author is recorded in thetabulation which is to follow. Of this group of patients, 21 percent had nocomplaints.
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 particularlyinteresting. Sarcoidosis was discovered in most of these men when roentgenogramsof the chest made at separation from the service showed pulmonary infiltrationsor hilar adenopathy or both. The men were completely asymptomatic at that time.5Diagnosis of the disease in a few of the patients in this group was made whilethe men were hospitalized for other medical causes, such as trauma. It is safeto say that in many patients sarcoidosis would have caused no symptoms and wouldnever have been recognized if roentgenograms had not been made at the time ofseparation from the service. The frequency of incidence of sarcoidosis is notgenerally recognized, no doubt because of the number of cases with minimal or nosymptomatology in whom the lesions clear completely. These lesions go undetectedunless roentgenograms of the chest are made routinely.
Sarcoidosis is usually, but not invariably, a disease with abenign outlook. Twenty-two patients diagnosed as having sarcoidosis died duringthe period of Army hospitalization. However, when Ricker and Clark6analyzed these records, they showed that these 22 deaths didnot reflect the true mortality of the disease. It was the cause or contributingcause 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 fortheir disease.
6Ricker, W., and Clark, M.: Sarcoidosis; Clinico-PathologicReview of 300 Cases, Including 22 Autopsies. Am. J. Clin. Path. 19: 725-749, August 1949.
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tuberculosis and sarcoidosis. Two other patients were latershown to have histoplasmosis with a sarcoid tissue reaction.7 Ineight cases of sudden violent death and in six patients dying of otherdiseases, sarcoidosis was an incidental finding at necropsy.
DIAGNOSIS
Many of these patients were seen in several hospitals in thechain of evacuation before a definitive diagnosis was made, but a high index ofsuspicion and a diligent search for lymph nodes usually facilitated diagnosis.Actually, a major cause of delay in diagnosis was the conflicting reports of thepathologists with their differences of interpretation of the histologicalchanges found in tissues.
Considerable confusion existed about the relation, if any,between sarcoidosis and tuberculosis. Sarcoidosis has often been considered amanifestation of tuberculosis, but recent evidence does not confirm such arelation. This confusion was evident in the handling of many military patients.Not infrequently, the roentgenograms of the chest were interpreted as revealingtuberculosis, and the biopsies of lymph nodes were regarded as characteristic ofthis disease. Indeed, several patients were transferred to special hospitals formanagement of tuberculosis.
Occasionally other diagnostic difficulties were encountered,based on the fact that the sarcoid tubercle with all of its histologicalfeatures can be produced by various viral, mycotic, parasitic, bacterial, andmetallic agents as well as by neoplastic tissue. One patient diagnosed as havingsarcoidosis (with a typical clinical and histological picture) had worked for anumber of years before induction in a fluorescent lamp factory. The exposure toberyllium fumes was quite heavy, and the incidence of delayed chemicalpneumonitis was high in workers in the plant.8 Without a specifictest for sarcoidosis, it is difficult to say which disease the patient had,although epidemiological features would indicate berylliosis rather thansarcoidosis.
It is probable that there are other patients among themilitary cases, as well as in all series of cases of sarcoidosis, who actuallyhave 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 findingsof Histoplasma capsulatum in sections oftwo 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 invarious "sarcoid lesions." Both patients had caseous adrenals whichcaused confusion whether this was tuberculosis, though no acid-fast organismswere demonstrable. These patients were carried as sarcoidosis in the Army filesand are included in studies of this series. They further underline the need forclean-cut criteria for the diagnosis of the Boeck's sarcoidosis.
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TREATMENT AND DISPOSITION
The therapeutic problem was often frustrating, and duringWorld War II it was the general practice to recommend prolonged bed rest whichwas usually carried out. Other modes of therapy included radiation withultraviolet and roentgen rays. It is fair to state that no beneficial effect wasaccomplished by any therapeutic regimen.
Any disease occurring during military duty poses the problemof loss of time and its effect on military forces. Although sarcoidosis occurredinfrequently among military personnel, it accounted for a considerable loss oftime. The duration of hospitalization was in terms of months rather than weeks;much time was consumed in transportation through the chain of evacuation and indiagnostic workups, often rather slowly accomplished. With the exception of veryfew men, all were given certificates of disability for discharge when thediagnosis was established, and many were transferred directly to Veterans'Administration hospitals for further care.
FOLLOWUP STUDIES
Followup studies of certain medical problems encounteredamong military personnel during World War II by the CVMP (Committee on VeteransMedical Problems) of the National Research Council under the sponsorship of theVeterans' 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 uniqueepidemiological features of the military cases warranted further study.Accordingly, more thorough epidemiological and clinical analysis of the caseswas undertaken, the results of which have appeared elsewhere.10While such a retrospective study cannot be said to have contributed to anunderstanding of the illness during World War II, nevertheless it has certainfar-reaching implications that seem to warrant a brief r?sum? in this report.
Some doubt has been cast on the validity of the findings,summarized in the paragraphs which follow, with the implication that thepreinduction medical screening in one part of the country was not as adequate asit was in other parts. This seems improbable, since physicians at the variousinduction stations came from all over the country, not merely from the regionwhere induction occurred.
1. The disease was more prevalent in inductees from theSoutheastern United States, more particularly among those from the Gulf and theAt-
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 toUrban-Rural Residence. J. Clin. Invest. 34: 1839, 1955.
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lantic Coastal Plain areas. The attack rates per 100,000 inductees areindicated 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.
[Attack rate expressed as number of cases per 100,000inductees]
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 ofgreatest incidence (I), region of next greatest incidence (II), and region oflowest 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 certainsoil areas. Speculation on the significance of this epidemiological pattern iswarranted. This is not the epidemiology of tuberculosis, an argument againstsarcoidosis being caused by the tubercle bacillus. The heavy concentration ofcases in the Southeast is explained in part, but by no means in toto, by theheavy Negro population. Various ecologic factors that have been explored havenot yet proved fruitful. One would suggest that either (1) there is aconcentration of the etiological agent (or agents) in this area or (2) itspropagation is favored by climatic, geologic, or environmental conditions inthis area; or (3) that people in this region react differently because ofenvironmental factors to the agent or agents.
It is of interest to compare the birthplace of the patientswith sarcoidosis with those in the military service during the same time who hadHodgkin's disease. As shown in table 24, the rates for Hodgkin's disease arequite constant, region by region, in contrast to the heavy concentration ofsarcoidosis in one region.
Whether servicemen from parts of the country removed from the"endemic area" would acquire sarcoidosis when exposed to these regionsis a matter of interesting speculation. Hundreds of thousands of such
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TABLE 24.-Comparison of attack rates of sarcoidosis with those of Hodgkin's disease
Region of induction2 | Sarcoidosis | Hodgkin's disease | ||
| 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 residencein region of induction.
2Roman numerals indicateregion 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 militaryinstallations, 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 after10 years no striking general increase of sarcoidosis has occurred in men underthese conditions. Since the incubation of sarcoidosis is unknown but is assumedto be many years, perhaps no definite answer to this problem can be given foranother decade. Even though hundreds of thousands of men were exposed to theendemic area, it is entirely possible that their contact with the "agent oragents" was too brief or too remote to result in sarcoidosis. Certainly,no major outbreak of sarcoidosis attributable to military service has yet beenuncovered.
11Cummings, M. M., Dunner, E., Schmidt, R. H., Jr., and Barnwell, J. B.: Concepts of Epidemiology of Sarcoidosis; Preliminary Report of1,194 Cases Reviewed With Special Reference to Geographic Ecology. Postgrad.Med. 19: 437-446, May 1956.
