Incidence of Intrathoracic Sarcoidosis Among Young Adults Participating in a Trial of Tuberculosis Vaccines

Abstract

The 54,239 participants in the Medical Research Council trial of tuberculosis vaccines have now been followed from the age of about 14 years (in 1950–2) to an age of about 27, with routine chest radiography, tuberculin tests, postal inquiries, and home visits. Up to the end of 1963, 52 cases of sarcoidosis had been discovered among them. Thirty-five of the cases were detected as a result of routine chest radiography, and all 52 had at least one abnormal chest radiograph. These cases were classified as sarcoidosis by a special assessor, who was kept unaware of the results of tuberculin tests and whether any vaccination had been performed. Biopsy information was not often available, but the diagnoses made by the patient's own physician and the routine trial assessor agreed closely with the classifications of the special assessor. Of the 52 patients, 48 showed bilateral hilar lymph-node enlargement, 20 showed pulmonary abnormalities, and 11 had erythema nodosum ; no eye, bone, or other skin abnormalities were reported. The course of the disease has been benign and relatively short. The incidence of intrathoracic sarcoidosis was similar in those who were vaccinated on entry to the trial (whether with B.C.G. or vole-bacillus vaccine) ; in those, also initially tuberculin-negative, who were left unvaccinated (by random selection) ; and in those who were initially tuberculin-positive (whether the degree of sensitivity was strong or weak). It is concluded that tuberculosis vaccination at the age of 14 years did not protect against sarcoidosis, or promote this disease, and that the incidence of sarcoidosis in this population group over a period of more than 10 years was not influenced by the initial tuberculin status of the participant. The attack rate of sarcoidosis in the whole population group was closely dependent on age, rising steeply to an annual rate of 1.49 per 10,000 at ages 20-22½ years, though this may under-estimate the true incidence. The average annual incidence at 15–25 years was three times as great in females as in males. The sex and age pattern of sarcoidosis differed noticeably from that of tuberculosis in this same population. There were also geographical differences in sarcoidosis incidence (the trial was undertaken in the London, Birmingham, and Manchester areas), which were not in line with the differences in tuberculosis incidence. A detailed comparison was made of the results of routine tuberculin tests in the sarcoidosis patients, both before and after they developed the disease, with corresponding results in those who did not contract sarcoidosis. No differences in sensitivity were apparent before the start of the disease, suggesting that the incidence of sarcoidosis was not related to the level of previous tuberculin sensitivity ; but there was a tendency for tuberculin sensitivity to be depressed in the sarcoidosis patients at and shortly after the start of their disease. We are grateful to Professor J. G. Scadding for acting as the special assessor for this investigation. We are indebted to Dr. T. M. Pollock (formerly co-ordinator of the M.R.C. vaccines trial) and Dr. C. S. Hunter (formerly in charge of one of the vaccines trial teams), who initiated the collection of information on the sarcoidosis patients. We also thank the members of the M.R.C. Tuberculosis Vaccines Clinical Trials Committee and Dr. L. E. Siltzbach for their helpful comments on the draft report. © 1965, British Medical Journal Publishing Group. All rights reserved.