A 36-year-old male IV drug user presented with complaints of headache, blurry vision, photophobia, and neck stiffness in the setting of chronic suppressive therapy with fluconazole for previous cryptococcal meningitis infection. On admission, he was afebrile, hemodynamically normal, and physical exam revealed no focal neurological deficits. Cerebrospinal fluid was positive for cryptococcal antigen 1:5, serum was positive for cryptococcal antigen 1:20, and cultures yielded Cryptococcus spp. HIV test was negative and CD4 count was normal. Workup revealed the speciation of Cryptococcus to be C. gattii and he was found to have anti-GM-CSF. He was treated with liposomal amphotericin B and flucytosine for 14 days. Symptoms resolved by day 5, and he was discharged in stable condition.

We highlight the clinical importance of GM-CSF by presenting an immunocompetent patient with recurrent Cryptococcal meningitis despite suppressive therapy. While initial suspicion of immunosuppression due to his drug use, he was HIV negative prompting Cryptococcus speciation and subsequent identification of anti-GM-CSF.

Anti-GM-CSF increases the risk of recurrence, results in more severe manifestations of cryptococcal infection, and poses potential risk for developing PAP. This case highlights the need for prospective studies on the role of chemoprophylaxis for cryptococcal meningitis in patients with anti-GM-CSF and necessitates physician-patient discussion of risk for recurrence and future disease.