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Cryptococcus neoformans empyema in a patient receiving ibrutinib for diffuse large B-cell lymphoma and a review of the literature
  1. Christopher David Swan1,
  2. Thomas Gottlieb1,2
  1. 1 Infectious Diseases and Microbiology, Concord Repatriation General Hospital, Concord, New South Wales, Australia
  2. 2 Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia
  1. Correspondence to Dr Christopher David Swan, christopher.swan{at}


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.

  • cryptococcosis
  • cryptococcus
  • empyema
  • pleural infection
  • tyrosine kinase inhibitor

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  • Contributors CDS: consultation of patient, literature reviews of cryptococcosis and empyema and pleural effusions and ibrutinib and opportunistic infections, composition of article draft and final version. TG: consultation of patient, literature review of ibrutinib and opportunistic infections, editing of article draft, care of patient during outpatient clinic appointment. Ilona Cunningham and Haematology team: care of patient during admission and outpatient clinic appointments. Laboratory staff: culture, identification and antifungal susceptibility testing of the Cryptococcus neoformans isolate.

  • Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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