Cryptococcal Meningitis in Young, Immunocompetent Patients: A Single-Center Retrospective Case Series and Review of the Literature

Background Cryptococcal meningitis is an uncommon but serious infection with high mortality and morbidity. Classically described in immunocompromised patients, including those with solid organ transplants or HIV/AIDS, cryptococcosis has also been reported in young and otherwise healthy patients, albeit rarely. Methods We retrospectively searched for all cases of cryptococcal meningitis in young (≤50 years) and previously healthy patients with no known immunocompromising conditions from January 2015 to January 2022 at Indiana University Health (IU Health). Additionally, a PubMed literature review was performed with the keywords “cryptococcal meningitis” and “immunocompetent” from January 1988 to January 2022. Clinical courses, including outcomes and treatment regimens, were evaluated. Results We identified 4 local cases of cryptococcal meningitis in otherwise healthy patients age ≤50 years. Three cases were due to Cryptococcus neoformans, with 1 experiencing a postinfectious inflammatory response syndrome (PIIRS). The PubMed search identified 51 additional cases, with 32 (63%) being caused by Cryptococcus neoformans and 8 (17%) by Cryptococcus gattii. Of the 51 cases, only 2 resulted in death directly due to cryptococcosis. Fifteen (29%) had PIIRS, with steroid treatment documented in 11 of 15. Antifungal induction regimens and duration were varied but predominately consisted of amphotericin and flucytosine, with a mean induction duration of 5.0 weeks. Conclusions Cryptococcal meningitis in young, previously healthy patients is likely under-recognized. PIIRS (akin to immune reconstitution inflammatory syndrome observed in HIV/AIDS) with prolonged recovery should be of concern. Determining risk factors for cryptococcosis in these patients remains elusive.