A case of ibrutinib-associated cryptococcal meningitis with a steroid-responsive immune reconstitution syndrome

Background

Cryptococcus is an important cause of central nervous system infection in immunocompromised hosts. Although best described in those with advanced HIV infection, it is increasingly being seen in other settings, including in patients on ibrutinib (a Bruton tyrosine kinase inhibitor). In order to manage this opportunistic infection well, clinicians must understand both the pathogen and the host immune system.

Case Report

We present a case of cryptococcal meningitis (CM) in an HIV-negative patient on ibrutinib for chronic lymphocytic leukaemia. At presentation, he was fungaemic with Cryptococcus neoformans and had a lymphocytic cerebrospinal fluid (CSF) with positive cryptococcal antigen. He improved initially with liposomal amphotericin B and flucytosine. Four weeks into treatment, however, he suffered an unexpected clinical and radiological deterioration, with new confusion and hallucinations, accompanied by widespread leptomeningeal enhancement and new occipital micro-abscesses on neuroimaging. CSF cultures remained sterile and his deterioration was attributed to an inflammatory phenomenon due to immune reconstitution, following cessation of ibrutinib and fungal clearance. He was treated with steroids with a good radiological and clinical response.

Discussion

An immune reconstitution inflammatory syndrome is well described in HIV; there is also increasing recognition of a post-infectious inflammatory response syndrome in non-HIV-associated CM. This case highlights the challenge of managing opportunistic infections in novel risk groups of immunocompromised hosts and illustrates the dynamic interplay between pathogen and host immunity. We review here the key immune mechanisms involved in inflammatory syndromes relating to cryptococcal meningitis.