A fatal case of chronic Cryptococcus neoformans meningitis progressing over a 4-year period following cladribine therapy.

Background: Globally, cryptococcal meningitis (CM) remains most common in human immunodeficiency virus (HIV)-infected individuals. However, Cryptococcus neoformans increasingly causes CM in patients with non-HIV immunosuppression due to glucocorticoid treatment, organ transplantation, and hematological cancer, among others. The clinical presentations of cryptococcal disease are highly host dependent, resulting in varying disease presentations in immunocompromised patients. Case Summary: Here, we report a fatal case of CM in a patient previously treated with cladribine due to hairy cell leukemia. The patient had an atypical presentation, and the disease progressed slowly over a 4-year period, hampering timely diagnostics and treatment. Retrospective analyses of the cerebrospinal fluid and blood revealed that the cryptococcal antigen (CrAg) test was already positive when the patient initially presented with pleocytosis 3 years prior to the CM diagnosis. Conclusion: This case adds valuable knowledge to our current understanding of CM due to the unusual time course and furthermore demonstrates important pitfalls associated with cryptococcosis in HIV-negative patients, including the atypical disease presentation and diagnostic challenges which resulted in a diagnostic delay of 3 years. Morbidity and mortality remain high, and with a growing population of non-HIV immunocompromised patients, increased awareness of CM and low threshold to screen these patients for CrAg are warranted.