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Background Cryptococcal meningitis is an uncommon but serious infection with a 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 ≤50 years. Three cases were due to Cryptococcus neoformans with one experiencing a post-infectious 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 two 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 IRIS observed in HIV/AIDS) with prolonged recovery should be of concern. Determining risks factors for cryptococcosis in these patients remains elusive.
Background Cryptococcal meningitis is an uncommon but serious infection with a 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 ≤50 years. Three cases were due to Cryptococcus neoformans with one experiencing a post-infectious 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 two 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 IRIS observed in HIV/AIDS) with prolonged recovery should be of concern. Determining risks factors for cryptococcosis in these patients remains elusive.
AIM: To report 4 cases of Cryptococcus gattii (C. gattii) species complex infection with diverse ophthalmic manifestations, and to review the literature to examine pathobiology of disease, classical ophthalmic presentations and outcomes, and treatment modalities for this emerging pathogen. METHODS: Cases of C. gattii meningoencephalitis with ophthalmic manifestations were identified via chart review at two institutions in Australia and one institution in the mid-west region of the United States and are reported as a case series. Additionally, a MEDLINE literature review was conducted to identify all reported cases of C. gattii with ophthalmic manifestations from 1990-2020. Cases were reviewed and tabulated, together with our series of patients, in this report. RESULTS: Four cases of C. gattii with ophthalmic manifestations are presented; three from Australia and one from the USA. A literature review identified a total of 331 cases of C. gattii with visual sequelae. The majority of cases occurred in immunocompetent individuals. Blurred vision and diplopia were the most common presenting symptoms, with papilloedema the most common sign, reported in 10%-50% of cases. Visual loss was reported in 10%-53% of cases, as compared to rates of visual loss of 1%-9% in C. neoformans infection. Elevated intracranial pressure, cerebrospinal fluid (CSF) fungal burden, and abnormal neurological exam at presentation correlated with poor visual outcomes. The mainstays of treatment are anti-fungal agents and aggressive management of intracranial hypertension with serial lumbar punctures. CSF diversion procedures should be considered for refractory cases. Acetazolamide and mannitol are associated with high complication rates, and adjuvant corticosteroids have demonstrated higher mortality rates; these treatments should be avoided. CONCLUSION: Permanent visual loss represents a devastating yet potentially preventable sequelae of C. gattii infection. Intracranial hypertension needs to be recognised early and aggressively managed. Referral to an ophthalmologist/neuro-ophthalmologist in all cases of cryptococcal infection independent of visual symptoms at time of diagnosis is recommended.
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