Cryptococcus neoformans empyema in a patient receiving ibrutinib for diffuse large B-cell lymphoma and a review of the literature.

We report a case of Cryptococcus neoformans pulmonary infection complicated by empyema in a 79-year-old man with diffuse large B-cell lymphoma treated with R-CHOP and ibrutinib. A literature review identified 25 cases of cryptococcal pleural disease published since 1980. Most cases were caused by the C. neoformans species in immunocompromised hosts with an exudative pleural effusion and lymphocyte-predominant infiltrate. The cryptococcal antigen test was often positive when pleural fluid and serum were tested. The outcome was favourable in most cases with antifungal therapy and either thoracocentesis or surgical resection. We also identified 40 cases of opportunistic infections, most commonly aspergillosis, cryptococcosis and Pneumocystis jirovecii pneumonia, in patients treated with ibrutinib. In vitro studies indicate Bruton tyrosine kinase inhibition impairs phagocyte function and offer a mechanism for the apparent association between ibrutinib and invasive fungal infections.