Case Presentation: We present a case-series of 3 immunocompetent patients who presented with cryptococcal meningitis.Case 1: A 49-year-old HIV-negative male, with a history of treated tuberculosis and Hepatitis B, presented with dizziness. CT chest revealed a cavitary lung lesion, and subsequent bronchoscopy and endobronchial ultrasound (EBUS) with lavage and biopsy demonstrated cultures positive for C. neoformans. Cryptococcal antigen was 1:1280 in serum and 1:320 in cerebrospinal fluid (CSF) (< 1:8). MRI brain revealed nodular enhancement suggesting cryptococcal meningitis. Patient improved with treatment and was discharged with Infectious Disease and Immunology follow-up. Case 2: A 35-year-old HIV-negative male from El Salvador presented with altered mental status, headache, and blurry vision. He had been diagnosed with a dural venous sinus thrombosis 5 days prior and was started on apixaban. He had no other significant medical history. CT chest revealed micronodules with reticulonodular pattern and tree-in-bud opacities, with upper lobe predominance. CT abdomen revealed hypodensities throughout the liver and spleen. CSF cultures grew yeast, and blood cultures revealed C. neoformans. Cryptococcal antigen was 1:1280 in serum and CSF (< 1:8). MRI brain revealed bilateral cerebral hemisphere edema and leptomeningeal enhancement of the occipital lobe. Prior sinus thrombosis was unchanged. Work-up included a negative hepatitis panel and normal free light chain analysis. Patient improved with treatment. Case 3: A 33-year-old HIV-negative male presented with headache and blurry vision. Patient was treated for cryptococcal meningitis 2 months prior at an outside hospital. He had no other significant medical history. Cryptococcal antigen was 1:320 in serum and 1:2560 in CSF (< 1:8), with MR orbits showing bilateral perineural enhancement of the optic nerve sheaths. Patient was treated and discharged, but course was complicated by episodes of recurrent cryptococcal meningitis. Patient ultimately underwent multiple rounds of treatment as well as craniectomy and temporal lobectomy.

Discussion: We describe a case series of three HIV-negative patients with C. neoformans meningitis, which has been rarely reported in the literature. (1-4) Prior case reports in immunocompetent individuals note travel to Mexico and Puerto Rico (5), pest control work (2), or exposure to horses, pigeons, or bats. (6, 7) A few report no risk factors including HIV, hematologic malignancy, organ transplant, or liver disease, chronic steroid use, travel, or animal exposure. (4) In our series, three patients presented with new-onset cryptococcal meningitis with no identifiable immunocompromising condition or medication. It remains uncertain what risk factors predisposed our patients to cryptococcal infection.

Conclusions: We present a case series of three presumed immunocompetent patients with new-onset or recurrent cryptococcal meningitis. No risk factors were identified during admission, with all 3 patients negative for HIV and no prior history of opportunistic infections. It is important to be aware of this phenomenon and consider testing for invasive fungal infections in immunocompetent patients presenting with neurologic signs concerning for infectious etiology.