Chronic beryllium disease: Long-term follow-up of sixty cases and selective review of the literature

Abstract

The diagnosis of beryllium disease invariably raises questions of “proof” or “validation.” Is this case really beryllium disease or is it, in fact, something else? Behind this query is doubt that diagnosis of the disease should be made without obtaining an autopsy or lung biopsy specimen for histologic and metal analysis in every patient. Therapeutic concern did not permit lung biopsy on every patient. Tissues for examination were available from either lung biopsies, postmortem examinations or both in twenty (33 per cent) of sixty patients. Each had a granulomatous pneumonitis. In pathologic studies of the lung in these and other cases Freiman [77] distinguished two general histologic patterns. The most frequent pattern (80 per cent) was a widely disseminated cellular infiltration with little tendency to formation of granulomas; in the less common pattern (20 per cent) cellular infiltration was generally focal and mild and there were prominent well formed granulomas, a histologic appearance quite indistinguishable from that of sarcoidosis. Patients with the latter findings had a longer and more benign course. Beryllium analyses on the lung specimens in this series ranged from 0.03 to 21.0 μg. per 100 gm. tissue. When the validity of the diagnosis is doubted in cases in which neither biopsy nor autopsy examination has been performed, a further explanation of the clinical definition of the disease is needed. The diagnosis is based on two sets of criteria, one epidemiologic, the other clinical. The epidemiologic criterion is a significant beryllium exposure, namely, an exposure to beryllium or its toxic compounds, also one which has produced similar illness in others. The clinical criteria include (1) diffuse densities on roentgenograms, with or without symptoms; (2) patterns of respiratory insufficiency initially characterized by a reduction in lung volumes and/or “diffusion capacity” with later obstructive defect depending on the degree of fibrosis; (3) interstitial pneumonitis, usually granulomatous, determined by examination of lung biopsy or autopsy specimens; (4) systemic toxicity demonstrated by functional or pathologic abnormalities in tissues other than lungs; and (5) beryllium in tissues. A diagnosis consists of significant exposure and the presence of at least the first two clinical criteria. In this series the diagnosis of each patient was based on these findings. Can those cases in which neither autopsy nor lung biopsy was performed really be “proved” and “valid” beryllium disease? The answer is yes. As with many disorders in medicine, the diagnosis is based on clinical criteria, in this instance clinical-epidemiologic criteria, and the proof is based on clinical and epidemiologic facts. Although determination of beryllium in tissue provides additional evidence of exposure to the etiologic agent it is not an essential diagnostic criterion.