Leflunomide-associated fatal cryptococcal meningoencephalitis presenting as rapidly progressive dementia: a case report

BACKGROUND: Cryptococcal meningoencephalitis is a serious opportunistic infection, classically associated with advanced immunosuppression. The increasing use of immunomodulatory drugs, such as leflunomide, has broadened the at-risk population.

CASE REPORT:  A 66-year-old woman with rheumatoid arthritis, on long-term leflunomide therapy, presented with progressive cognitive decline, behavioral changes, and myoclonus over a six-week period. The initial presentation mimicked rapidly progressive dementia. Cerebrospinal fluid analysis showed elevated opening pressure, hypoglycorrhachia, and hyperproteinorrhachia. India ink staining and culture confirmed Cryptococcus spp., which polymerase chain reaction (PCR) identified as Cryptococcus gattii. Despite antifungal treatment with liposomal amphotericin B and fluconazole, her condition deteriorated, leading to persistent intracranial hypertension, secondary infections, and multiorgan failure, resulting in death.

CONCLUSIONS: This case highlights the diagnostic challenges of cryptococcal meningoencephalitis with atypical neurological presentation and its potential association with leflunomide-induced immunosuppression. Early clinical suspicion and a multimodal diagnostic approach are essential for improving prognosis.

Graphical Abstract