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Chronic beryllium disease (CBD) is an exposure-related granulomatous disease mimicking sarcoidosis. Beryllium exposure-associated disease occurs mainly via inhalation, but skin may also be a source of sensitization. A 65-year-old male with a history of war-related shrapnel wounds was initially diagnosed with pulmonary sarcoidosis. Twenty years later, the possibility of a metal-related etiology for the lung disease was raised. A beryllium lymphocyte proliferation test, elemental analysis of removed shrapnel, and genetic studies were consistent with a diagnosis of CBD. This case demonstrates that retained beryllium-containing foreign bodies can be linked to a pathophysiologic response in the lung consistent with CBD.

Background and Aim: Sarcoidosis (SA) is a chronic systemic disorder characterized by infiltration of inflammatory cells in affected organs, resulting in the formation of granulomas. Granulomas are observed in numerous infectious diseases and hypersensitivity reactions (e.g., beryllium). Chronic beryllium disease (CBD) is a multisystem entity caused by dust, fumes or mists of beryllium metal or its salts. Although beryllium has been used for years by several industries in Israel, no case of CBD had ever been reported until recently when we described a 21-year-old female dental technician with CBD who was originally diagnosed as having SA. We launched the current investigation to test the hypothesis that other cases of CBD in Israel were not previously reported because these patients were misdiagnosed as having SA., Methods: Forty-seven patients with confirmed-SA from our outpatient clinic were recalled in order to reevaluate their occupational exposure history. We performed the beryllium lymphocyte transformation test (BeLTT) on each patient with a potentially positive environmental exposure anamnesis to beryllium (14/47)., Results: Two of the 14 patients with evidence of granulomas in lung tissue (pulmonary involvement) and 1/14 with extrapulmonary involvement who all had a positive occupational exposure to beryllium and a positive BeLTT test had been erroneously diagnosed as having SA instead of CBD., Conclusion: Our findings emphasize the vital importance of taking a comprehensive occupational history in the clinical evaluation of patients suspected of having SA.

The link between metal-induced apoptosis and granulomatous inflammation in human disease pathogenesis is not established. The presence of TUNEL positive nuclei in chronic beryllium disease (CBD) pulmonary granulomas suggested the possibility that beryllium (Be) could induce apoptosis in adherent macrophages from CBD bronchoalveolar (BAL) cells. Apoptosis was measured in un-stimulated and Be-stimulated BAL adherent macrophages from CBD (n = 21) and Be-sensitized (BeS, n = 16) subjects. Be-stimulated CBD and BeS macrophages underwent caspase-dependent nuclear fragmentation, cytoplasmic membrane blebbing and CD14 loss. Be-stimulated adherent macrophage apoptosis was not due to TNF-alpha production. Apoptosis, CD14 loss and TNF-alpha production were not observed in unstimulated BAL macrophages. Thus, Be-stimulated BAL adherent macrophage apoptosis occurred whether cells were derived from patients with granulomatous inflammation or not, was caspase-mediated and occurred independent of TNF-alpha levels. We conclude that Be-induced human lung adherent macrophage apoptosis could contribute to the host's continued re-exposure to Be resulting in chronic granulomatous inflammation.