Abstract Introduction Cryptococcus neoformans is an encapsulated yeast that typically affects immunocompromised hosts, particularly those with HIV/AIDS or receiving chronic immunosuppressive therapy. Pulmonary cryptococcosis in immunocompetent individuals, though rare, is increasingly recognized and often poses a diagnostic challenge due to its nonspecific clinical and radiologic features that often mimic bacterial pneumonia. Early identification and timely antifungal therapy are vital to prevent dissemination and improve outcomes. Case Presentation A 58-year-old man with type 2 diabetes mellitus and hypertension, and a lifelong non-smoker, presented with several weeks of drenching night sweats, high grade fevers and unintentional weight loss. He denied exposure to mold, birds, or hot tubs, and had no history of travel, incarceration, or substance use. Initially diagnosed with multifocal pneumonia, he completed courses of doxycycline, Augmentin and prednisone without improvement. On readmission, he was febrile and hypoxic SpO2 88% on room air with a productive cough. Extensive infectious workup-including HIV, tuberculosis, aspergillus, histoplasmosis, blastomycosis, and legionella-was negative. Although the initial serum cryptococcal antigen (sCrAg) test was positive, it was attributed to cross-reactivity from Rothia mucilaginosa in sputum. When the patient failed to improve, a repeat sCrAg by lateral flow assay revealed a markedly elevated titer of 1:2048. Transbronchial biopsy with Gomori methenamine silver (GMS) staining confirmed C. neoformans. Induction therapy with amphotericin B and flucytosine was initiated but was discontinued on day 7 due to amphotericin induced nephrotoxicity. He was transitioned to high dose fluconazole (1200 mg daily for 3 weeks), followed by consolidation (800 mg daily for 8 weeks) & later maintenance therapy (200 mg daily for 12 months). His sCrAg titer declined to 1:512, with radiologic improvement. Discussion This case highlights an unusual presentation of cryptococcal pneumonia in an apparently immunocompetent host, where diabetes mellitus may have contributed to subtle immune vulnerability. Although Cryptococcus gattii is more often implicated in immunocompetent hosts, C. neoformans can also occur due to subtle or unrecognized immune dysfunction. Proposed mechanisms include anti-GM-CSF autoantibodies, mannose-binding lecithin deficiency, & defects in Toll-like receptor, Th1, or Th17 pathways. Additionally, mild or occult immunosuppression from diabetes mellitus, chronic organ disease, malnutrition, or corticosteroid exposure may predispose to infection. Persistent radiologic abnormalities and stable or persistently elevated antigen titers despite therapy may indicate chronic infection, necessitating prolonged maintenance treatment. Early histopathologic confirmation, individualized antifungal management, & maintaining a high index of suspicion are essential for optimal outcomes in atypical presentations of pulmonary cryptococcosis. This abstract is funded by: none
Samreen et al. (2026) studied this question.