1410. Serious Cryptococcal Infections with Ruxolitinib Use: A Case of Meningitis and a Review of the Literature

Abstract

BackgroundRuxolitinib is an inhibitor of Janus kinase (JAK) 1 and 2 and is approved for the treatment of myelofibrosis and polycythemia vera. Infectious complications associated with its use include reactivation of herpes simplex, zoster, hepatitis B, and tuberculosis, mucormycosis, and progressive multifocal leukoencephalopathy.MethodsSeven cases of ruxolitinib-associated cryptococcal infections have been reported: three cases of meningitis, two cases of pulmonary disease, and two cases of disseminated disease (Table 1).ResultsWe present a 72-year-old male with a history of JAK-2-positive polycythemia vera with secondary myelofibrosis, and concurrent multiple myeloma who presented with 3 weeks of chronic cough and 3 days of fever with severe bifrontal headache after remodeling a large birdcage in his backyard. The patient was on ruxolitinib, ixazomib, and weekly dexamethasone. Cerebrospinal fluid (CSF) analysis showed an elevated opening pressure of 29 cm of CSF, 173 leucocytes with a predominance of lymphocytes, protein of 87 mg/dL and a normal glucose level. BioFire FilmArray® Meningitis/Encephalitis panel detected targets for Cryptococcus in the CSF, and CSF cryptococcal antigen was positive at 1:4. CSF fungal cultures were subsequently positive for Cryptococcus neoformans, susceptible to liposomal amphotericin B (LAMB) and fluconazole. Ruxolitinib was discontinued, treatment with LAMB and flucytosine (5-FC) was associated with significant improvement of headache over the next week. Repeat CSF analysis in 2 weeks was culture negative with a negative cryptococcal antigen test. The patient completed 3 weeks of LAMB and 5-FC and then transitioned to oral fluconazole for a year.ConclusionRuloxitinib and other JAK inhibitors suppress host immunity through impaired T-cell activation and downregulation of cytokines. The JAK-Signal Transducer and Activator of Transcription pathway is one of the most active pathways in host defense against cryptococcus, and use of JAK inhibitors like ruxolitinib may predispose to severe cryptococcal infections. Bird exposure is a risk factor, making environmental contact counseling for patients on ruxolitinib important. Fluconazole prophylaxis needs to be considered in select cases. Disclosures All authors: No reported disclosures.