Identification of titanium in human tissues: probable role in pathologic processes.

Six cases of titanium dioxide exposure involving lung, skin, and synovium are described, with a review of the literature. The patients, four men and two women, were between the ages of 22 and 65 years. The pulmonary changes were characterized by fibrosis and numerous macrophages with abundant deposition of a black pigment. Adjacent areas of bronchopneumonia were also observed. In the skin a severe necrotizing lesion involving the subcutaneous tissue with extension to the muscle was observed in one case and a nonspecific inflammatory response was observed in another; both cases showed abundant black pigment deposition. Electron microscopy and energy dispersive x-ray analysis demonstrated the presence of large quantities of titanium in the pigment granules. There may be a combination of black pigment deposition and fibrosis, necrosis, or a xanthomatous or granulomatous reaction, that, together with negative results on special staining and culture studies for organisms, should raise the suspicion of titanium-associated injury and prompt the study of the affected tissues by x-ray analysis for positive identification.