Sarcoidosis in the British Army a ten year survey

Brit. 07. Dis. Chest (i968) 62, Ioo.

Sarcoidosis in the British Army A Ten Year Survey N. K. Corn* Cambridge Military Hospital, Aldershot

WHEN clinical and radiological features are typical the diagnosis of sarcoidosis may be made with confidence. In patients presenting less typical features histological evidence is necessary, but the disorder generally pursues such a benign course that in practice the diagnosis is often made without such evidence, and a retrospective survey of the disease must contain a proportion of subjects in whom the diagnosis cannot be regarded as being more than highly probable. Such surveys are therefore concerned not with proven cases, but with those labelled as having sarcoidosis. With this limitation in mind it seemed of interest to examine the Army's experience of the condition, representing as it does a highly selected population--that is to say a young, fit and overwhelmingly male section of the community.

Subjects During the ten-year period 1954 to 1963 inclusive 69 patients were recordecl as suffering from sarcoidosis. This is after exclusion of those who were subsequently shown to have some other disorder such as pulmonary tuberculosis; it represents a yearly incidence of 2"3 per hundred thousand of the population at risk. Only two of these patients were female, but then women accounted for only 2-1 per cent. of service people during this period. The main findings are summarized in Tables I to IV. TABLE I. AGE OF DETECTION

Age Group 15-19 eo-24 25-29 30-34 35-39 40-44

Number of Gases 8 32 15 9 2 3

Apparent annual incidence per Ioo, ooo at risk 0. 9 2"4 5"6 4 .0 I'4 2"6

* Present address, British Military Hospital, Singapore

(Receivedfor publication, December 1967)

SARCOIDOSIS

IN T H E

BRITISH

ARMY

TABLE II.

-- A T E N MODE

Y~AR

SURVEY

IOI

OF PRESENTATION

Routine radiography Routine radiography but admit respiratory symptoms on questioning Respiratory symptoms Erythema nodosum Erythema nodosum associated with fever and respiratory symptoms Erythema nodosumplus arthralgia Joint symptoms alone Lymph node enlargement observed by patient Erythema nodosum with arthralgia and chest symptoms Ocular manifestations Miscellaneous rarities

Number of cases

% of total

24

34

IO

14

9 7

13 io

3 3 3

4 4 4

3

4

2 2 3

3 3 4

TABLE

I I I . C L I N I C A L FEATURES OCCURRING AT O N S E T OR AT ANY SUBSEQUENT STAGE DURING THE COURSE OF THE DISEASE

No signs or symptoms Erythema nodosum Lymph node enlargement Acute respiratory symptoms with constitutional disturbance Chronic pulmonary symptoms Arthropathy Splenomegaly Ocular manifestations Hepatomegaly Salivary gland enlargement Miscellaneous rarities

TABLE

IV.

RADIOLOGICAL

Hilar adenopathy alone Hilar adenopathy with infiltration Mottling alone Fluffy opacities Fibrotic changes Not recorded or normal

Number of cases

% of total

21 16 14

3° 23 2o

13 II

19 16

9

13

4 4 3 2 6

6 6 4 3 9

FEATURES

Number of cases

% of total

28 23

4° 33

9 3 2 4

13 4 3 6

100

CONI

To turn to the laboratory investigations, the serum calcium was recorded in thirty-two patients; it was greater than ii mg per Ioo ml in six. Liver biopsy was successfully undertaken on eleven occasions, providing a definite diagnosis in six: and lymph node biopsy was diagnostic in 22 out of 25 instances. The Kveim test was performed only four times, with three positive results. The follow-up is unfortunately limited by military circumstances, it being the usual procedure to invalid from the Army conscripts found shortly after entry to have radiological appearances interpreted as sarcoidosis. A n u m b e r of those subsequently developing the disease were also invalided where this was felt to be in the best interests of the patient or of the service. O n account of this, thirty-two of these patients were lost from observation almost at once: in 25 of the remaining 37 the disease had apparently resolved or become quiescent within five years. In six more it did so at a later date, and in only five was the illness noted to pursue a more protracted course. Four cases are considered sufficiently unusual to be worth recording in greater detail. Case I A thirty-seven year old Warrant Officer noticed loss of temperature sensation in his right foot when stepping into his bath, and over the ensuing three weeks found that he had difficulty in running and in balancing, and that he had frequency of micturifion and failure of erection. He was admitted to hospital and found to have impairment of pain, temperature, and light tactile sensation in both legs and the lower trunk with a sensory level at the seventh thoracic dermatome: there was some weakness in the left leg and an extensor plantar response on that side. The cerebrospinal fluid protein was 200 mg per i oo ml and there were 65 white cells per cubic millimetre, mainly lymphocytes. His chest radiograph showed hilar adenopathy and scalene lymph node biopsy showed changes typical of sarcoidosis. Within three months he had greatly improved, two years later there was slight residual alteration in sensation in the lower extremities, and after eight years he was fit enough to be commissioned. Case H A twenty-seven year old medical officer had undergone appendicectomy eight years previously when a chronically inflamed appendix was removed, no evidence of mesenteric adenopathy or other abnormality being noted at operation. The present admission was occasioned by the appearance of a small painless lump in the scar which was explored and found to be composed of granulation tissue, subsequent histology showing the picture of "non-caseating tuberculosis". A chest radiograph revealed the presence of bilateral hilar adenopathy. A year later he remained well and the radiograph had completely cleared. This was clearly a case of infiltration of a scar during the active phase of systemic sarcoidosis rather than a local "sarcoid" reaction.

SARCOIDOSIS IN T H E

BRITISH

ARMY-

A TEN

YEAR

SURVEY

I0 3

Case III*

A twenty-four year old soldier was admitted to hospital with right lower lobar pneumonia with effusion and was found to have enlarged lymph nodes in the neck, axillm, and groins, and a palpable spleen, the chest film also showing bilateral gross enlargement of the hilar glands. An axillary node biopsy revealed non-specific changes only. He became gravely ill, further features including brisk h~emolysis with a positive direct Coomb's test and hmmoglobinuria, and a leukmmoid blood reaction with 4o,ooo white cells per cubic millimetre including numerous immature forms. He was treated with antituberculous drugs and steroids. Over three weeks or so the pneumonia resolved and the fever settled, with regression of the hilar glands; the white cell count became normal and the h~emoglobin rose again. The steroids were discontinued after a two month course. Other investigations whilst he was in hospital included negative Paul Bunnell and LE cell tests; the electrocardiogram was abnormal with ' O ' waves and inverted ' T ' waves in the chest leads. He was well enough to be discharged after four months in hospital but at follow-up appointment a month later he again had generalized lymph node enlargement and a pleuropericardial friction rub. Over the next fcw months the hilar nodes enlarged again and progressive nodulation was noted throughout both lung fields. Biopsies of liver, bone marrow and kidney were unhelpful throughout this period. A year after his original admission he was admitted to the Brompton Hospital, London, where he underwent thoracotomy and lung biopsy; the histology showed classical sarcoid follicles. He made an uneventful recovery, but a curious sequel was that he subsequently developed disseminated lupus erythematosus. As in the case of his sarcoidosis it was possible to satisfy the most rigid diagnostic criteria, so that this seems to be an instance of a patient developing two uncommon and unconnected disorders with certain manifestations in common. Case I V

A young man of seventeen presented at the Westminster Hospital, London with a two week history of bilateral impairment of vision associated with headache, fever and malaise. He was found to have gross bilateral disseminated choroidoretinitis and generalized lymph-node enlargement. The cerebrospinal fluid showed a raised pressure with lymphocytosis and a protein of 13° mg per xoo ml. The Mantoux reaction was negative to one in a hundred but became positive at this dilution with the addition of cortisone, and the chest radiograph showed a bilateral fine miliary infiltration. The possibilities of tuberculosis or toxoplasmosis were considered but were not substantiated by further investigation, and a tentative diagnosis of Sarcoidosis was made. He improved and was discharged from hospital, being called up for National Service the following year when he was admitted to a military hospital on account of his chest film. He was now hypertensive and renal function was impaired: he was subsequently invalided from the service and later the same year was re-admitted to the * Cases I I and I I I have been described previously by Scadding (1967).

IO 4

CONI

Westminster Hospital with headaches and paroxysmal nocturnal dyspncea. The blood pressure was I8O/I3O m m H g and he had gallop rhythm and advanced hypertensive retinopathy superimposed upon the old choroiditis. Papilkedema and increasing cardiac failure developed, culminating in his death. At post mortem, microscopic examination of the hilar lymph nodes lent unequivocal support to the diagnosis of sarcoidosis although the renal lesion was not proven to be of a similar nature. The kidneys showed fibrinoid necrosis of the afferent arterioles and other changes of malignant hypertension, but there was no apparent nephrocalcinosis so this must remain of unexplained cause. Further sarcoid lesions were found in the interventricular septum of the heart, although the electrocardiographic abnormalities had merely been those of hypertensive disease. Discussion The prevalence of a condition such as sarcoidosis is impossible to determine with accuracy, but one method of assessment is the mass radiographic survey which gives an indication of those with the disease at a given point in time. Among civilian populations, Semple and Hughes (1959) reported a rate of nine per IOO,OOO and McGregor (1961) in two such surveys found figures of six and five per IOO,OOO. It might be anticipated that rather higher yields would result from youthful military populations and Schonholzer (1957) found changes interpreted as being due to sarcoidosis in 13 per I oo,ooo examinations in the Swiss Army. However, Douglas (i 964) gives the rather low figures of four, three, five and seven per ioo,ooo for the mass miniature radiography pick-up rate for four consecutive years in the British Army. A more valid, though not comparable, assessment of prevalence is given by the actual yearly attack-rate in a population at risk, and this is the figure quoted here. In the U.S. Army the annual frequency was found by Cooch (1961) to be eleven per IOO,OOOand the difference is probably at least partially explained by the considerable number of American negroes in the army, for the disease has a marked predilection for this particular ethnic group: eighteen negroes with sarcoidosis were found for every one white person (Gentry et al., 1955). The bias towards the twenty-five to thirty-four year old age group is in keeping with a number of other clinical series, including that of Cooch (I 961). Although this may be influenced by the rejection of those noted to have evidence of the disease at roudne pre-enlistment radiography, it conflicts with the experience of Ricker and Clark (1949) in their three hundred U.S. Army cases, and with that of Gundelfinger and Britten (I 96 I) in the U.S. Navy, who reported a rather younger group to be principally afflicted. Concerning the clinical features the present study is in agreement with that of Siltzbach (1967) who found that routine radiography was the commonest cause for attendance and respiratory symptoms the second commonest. In a large proportion with respiratory symptoms, however, it is apparent that these symptoms are often seen on closer scrutiny to be at least possibly irrelevant, consisting often of an acute tracheo-bronchial infection to which the under-

SARCOIDOSIS

IN

THE

BRITISH

ARMY

-- A TEN

YEAR

SURVEY

IO 5

lying sarcoidosis, detected on account of the radiograph which was thereupon ordered, m a y or may not have rendered them more susceptible. The incidence of erythema nodosum (23 per cent.) in the present series is comparable with that (31 per cent.) observed by James (1959) in his account of 2oo patients. The series of U.S. Air Force men studied by Singer, Hensler and Flynn (1959) had a considerably higher incidence of lymph node enlargement (56 per cent. as compared with 20 per cent.), and a prominent feature also recorded by them was significant weight loss (44 per cent. of cases) which was very seldom emphasised among the soldiers studied here. The presence of arthropathy in nine of these patients is perhaps an unexpectedly high proportion as care has been taken only to include those in whom there was some objective evidence of joint involvement rather than a vague reference to arthralgia. Although both upper and lower limbs were from time to time affected, the knees and ankles were the joints most commonly involved, and usually presented with stiffness, tenderness, effusion and soft tissue swelling which invariably cleared up, leaving no residual deformity or disability. Kaplan (1963) in an extensive review of the literature encountered a group with a persistent polyarthritis of rheumatoid type, but otherwise recorded features similar to those described here with a distinct group presenting with erythema nodosum and migratory polyarthritis with or without chest manifestations. It is perhaps worth mentioning the close relation between the incidence of hilar adenopathy found here (4 ° per cent.) with that observed by Siltzbach (43 per cent.). Summary Sarcoidosis in the British Army has been surveyed over the ten-year period 195 4 to 196 3 inclusive, when the condition was diagnosed in 6 9 patients on clinical or radiological grounds. This represents an annual incidence of 2"3 per IOO,OOO of the population at risk. The main clinical and radiological features are presented, b u t a disease so protean in its manifestations is bound sometimes to pursue a rather bizarre course and four such cases are briefly reported. Acknowledgements

The author has great pleasure in expressing his gratitude to ProfessorJ. G. Scadding and Mr. A. It. Gould for their help and advice; to Dr. C. J. Gavey for permission to report Case IV" and to Major-General R. J. G. Morrison for suggesting and encouraging this investigation. References

COOCH,J. W. (1961). Amer. Rev. resp. Dis., Pt 2. 84/5, lO3. DOUGLAS,A. C. (1964). Acta med. scand., Suppl 425, 176. GENTRY,J. T., NITOWSKY,H. M. & MICHAEL,M. (I955). O~.Clin. Invest., 34, 1839GUNDELFINGER,B. F., & BRITTEN, S. A. (1961). Amer. Rev. resp. Dis. 84/5 Pt 2, xo9. JAMES, D. G. (1959). QuartoT. Med., 28, lO9. KAPLAN,S. (1963). Arch. intern. Med., H2, 924MCGREGOR, I. (1961). The Two Tear Mass Radiography Campaign in Scotland z957-195& Edinburgh: H.M.S.O. RICKER, W., & CLARK, M. (1949). Amer. ft. din. Path., I9, 735.

xo6 SCADDXNQ,J. G. (I967). Sarcoidosis, pp. 9 I, 464. London: Eyre & Spottiswoode. SCHONHOLZER, G. (I947). Schweiz. med. Wschr., 77, 585SEMPL~-, A. B., & HUGHES, T. L. (I959). Report on Liverpool's X-ray Campaign. SINGER, E. P., H~-NSLER, N. M., & FLYNN, P. F. (I959). Amer. 07. Med., ~6, 364 . SILTZBACH, L. E. (I967). Med. Clin. JV. Amer., 5x, 483 •

CON~