Introduction: Cryptococcal meningitis is a life-threatening infection typically diagnosed by detection of cryptococcal antigen (CrAg) in the cerebrospinal fluid (CSF) or serum. CSF CrAg has high sensitivity and specificity, but false-positive results are rare. Autoimmune disorders may contribute to occasional diagnostic interference, and inflammatory myopathies have not been widely explored as a potential confounder. We present a case of statin-induced necrotizing autoimmune myopathy (IMNM) with a false-positive CSF CrAg, leading to a diagnostic dilemma. Description: A 65-year-old man with diabetes presented with progressive bilateral lower extremity weakness and altered mental status. MRI showed diffuse myositis. Lumbar puncture revealed an elevated opening pressure (>35 cm H2O), elevated protein, and positive CSF cryptococcal antigen. Serum CrAg and HIV testing were negative. ID was consulted for possible cryptococcal meningitis, but the patient was afebrile, immunocompetent, and lacked meningeal signs. A repeat CSF antigen test and microbiology review confirmed a false-positive CSF CrAg. Subsequent muscle biopsy and antibody testing revealed anti-HMGCR positive necrotizing autoimmune myopathy, likely triggered by prior statin use. Antifungal therapy was withheld, and the patient improved with IVIG and immunosuppression. Discussion: This case underscores the importance of clinical context when interpreting diagnostic tests. While CSF CrAg is typically reliable, false positives may occur due to cross-reactivity or sample interference—particularly in autoimmune or inflammatory states. Though a direct link between IMNM and CrAg cross-reactivity is not established, this case raises the possibility of nonspecific immune complex activity or protein interference mimicking fungal antigen detection in the CSF. The elevated opening pressure further complicated the diagnostic picture.
Noreen et al. (Sun,) studied this question.