Cryptococcal Meningitis Revealing Late-Onset Combined Immunodeficiency After Two Decades of Recurrent Infections: A Case Report.

Adult-onset inborn errors of immunity pose a significant diagnostic challenge because of their non-specific clinical presentation and frequent delay in diagnosis. We report a case of a 53-year-old woman with a nearly two-decade history of recurrent infections whose clinical course culminated in cryptococcal meningitis, prompting a comprehensive immunologic evaluation. Following the systematic exclusion of secondary causes of immunodeficiency, immunologic testing revealed hypogammaglobulinemia and profound CD4+ T-cell lymphopenia (188 cells/µL), consistent with combined humoral and cellular immune dysfunction and supporting classification within the late-onset combined immunodeficiency (LOCID) phenotype. Following appropriate antifungal therapy, subsequent immunoglobulin replacement therapy and filgrastim were associated with sustained clinical improvement. This case highlights that cryptococcal meningitis in HIV-negative patients should prompt a systematic evaluation for an underlying primary immunodeficiency and underscores the importance of recognizing the LOCID phenotype as an uncommon but potentially treatable cause of opportunistic infections in adults.