Pulmonary Cryptococcosis With Suspected Central Nervous System Involvement in a Patient With Sarcoidosis and CD4 Lymphopenia: A Case Report

Sarcoidosis is a multisystem granulomatous disorder associated with immune dysregulation and impaired cell-mediated immunity, which may increase susceptibility to opportunistic infections, including cryptococcosis. The clinical and radiological overlap between sarcoidosis progression, neurosarcoidosis, and cryptococcal infection can create a significant diagnostic challenge, particularly when neurological symptoms are present. We present a 50-year-old male with a 15-year history of pulmonary sarcoidosis and CD4 lymphopenia who developed pulmonary cryptococcosis with subsequent symptoms concerning for central nervous system (CNS) involvement after self-discontinuation of antifungal therapy. His clinical course was notable for neck stiffness, photophobia, headaches, cognitive slowing, positive serum cryptococcal antigen testing, bronchoscopy confirming Cryptococcus species, and recurrent herpes zoster, suggesting impaired cell-mediated immunity. Cerebrospinal fluid culture showed no growth after antifungal therapy had already been initiated, and CNS involvement was considered clinically suspected rather than microbiologically confirmed. Treatment was complicated by acute kidney injury attributed in part to amphotericin B-associated nephrotoxicity, requiring transition to fluconazole consolidation therapy. This case underscores the importance of maintaining a high index of suspicion for opportunistic infections in patients with sarcoidosis who develop atypical, progressive, or neurological manifestations. Early cerebrospinal fluid evaluation, including cryptococcal antigen testing when clinically indicated, and careful infectious disease assessment before escalation of immunosuppressive therapy are essential to avoid diagnostic delay and guide appropriate treatment.