Unusual Neuropsychiatric Presentation of Cryptococcus neoformans Meningoencephalitis in an Immunosuppressed Patient with Rheumatoid Arthritis: A Case Report

Central nervous system (CNS) cryptococcosis caused by <i>Cryptococcus neoformans</i> is a severe opportunistic infection that primarily affects individuals with impaired cellular immunity. Although the classic presentation includes headache, fever, and meningeal signs, chronically immunosuppressed patients may develop atypical neuropsychiatric manifestations, leading to diagnostic delays. We report the case of a 53-year-old man with rheumatoid arthritis (RA) receiving long-term prednisolone and etanercept therapy, who presented with a 7-day history of depressive mood, anhedonia, social withdrawal, irritability, and progressive confusion. Neurological examination revealed disorientation without focal deficits. Brain imaging showed only mild cortical atrophy, and cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis, low glucose, and elevated protein levels. Multiplex PCR (FilmArray^®) of CSF identified <i>Cryptococcus neoformans</i>, CSF positive to <i>C. neoformans</i>. The patient was treated with liposomal amphotericin B followed by fluconazole, resulting in gradual improvement of both neurological and psychiatric symptoms. This case highlights an unusual presentation of CNS cryptococcosis in a non-HIV immunosuppressed patient with RA, emphasizing that acute psychiatric or cognitive changes can be the predominant manifestation. Clinicians should consider fungal infections in the differential diagnosis of acute neuropsychiatric symptoms in patients receiving chronic corticosteroid and biologic therapy. Early recognition and molecular diagnosis can facilitate timely antifungal treatment, potentially improving prognosis and reducing morbidity associated with delayed therapy. This report underscores the importance of awareness of atypical presentations of opportunistic infections in immunosuppressed populations.