Cryptococcal meningitis in a patient with VEXAS syndrome: a case report

Vacuoles, E1 enzyme, X-linked, autoinflammatory somatic (VEXAS) syndrome is a recently described multisystem disease. Opportunistic infections in VEXAS syndrome are increasingly being recognized and attributed to multiple factors, including immune dysregulation due to an aberrant ubiquitination pathway, secondary effects from chronic immunosuppressive treatments and underlying patient comorbidities. Given the limited consensus on antimicrobial prophylaxis, clinical practice is heterogeneous, with varying treatment outcomes.

Herein, we report a rare case of cryptococcal meningitis in a patient with treatment-refractory VEXAS syndrome, on chronic moderate-dose corticosteroids (an average of 20 mg prednisolone equivalent per day) and ruxolitinib. The patient initially presented with acute confusion and fevers, with elevated inflammatory markers and worsening cytopenia. The differential diagnoses included an acute flare of VEXAS syndrome and intercurrent infection. Further testing revealed the presence of Cryptococcus neoformans in the cerebrospinal fluid. Treatment with prolonged antifungal therapy was successful.

The case raises important considerations, firstly regarding antimicrobial - particularly antifungal - prophylaxis given limited evidence in the literature, secondly a prompt diagnosis and treatment of cryptococcal infections, and finally regular interval screening for opportunistic infections in this vulnerable patient cohort. A multidisciplinary approach to care is required to improve morbidity and mortality from atypical infections in VEXAS syndrome.