Clinical Phenotypes, Immunosuppressive Exposures, and Outcomes in Pulmonary vs Extrapulmonary Cryptococcosis Among Non-HIV, Non-Transplant Adults: A U.S. Claims Analysis
Abstract
Abstract Introduction Cryptococcosis increasingly affects non-HIV, non-transplant (NHNT) adults, but factors associated with extrapulmonary dissemination remain incompletely defined. We evaluated associations between comorbidities, immunosuppressive therapy, and cryptococcal disease phenotype. Method NHNT adults with cryptococcosis in Merative MarketScan were classified as having pulmonary or extrapulmonary disease. Extrapulmonary disease was further classified as central nervous system (CNS) or non-CNS disseminated disease. Comorbidities and immunosuppressant, systemic glucocorticoid, and antineoplastic exposures during the 6 months before diagnosis were evaluated. Multivariable logistic regression identified factors associated with extrapulmonary disease, with secondary phenotype-specific analyses. Results Among 722 NHNT adults, 52% had extrapulmonary cryptococcosis, including 82% with CNS involvement. Extrapulmonary disease was associated with longer hospitalization, greater ICU utilization, and lower community discharge (all P < .001). Renal disorders (aOR 1.51, 95% CI 1.05–2.18) and immunosuppressant exposure (aOR 2.75, 95% CI 1.61–4.86) were associated with extrapulmonary disease. Immunosuppressant exposure was also associated with both CNS and non-CNS disseminated disease. Among glucocorticoid-exposed patients, longer exposure was associated with extrapulmonary disease (aOR 1.05 per week, 95% CI 1.02–1.08), primarily CNS disease, whereas higher average daily dose was associated with non-CNS disseminated disease only within shorter exposure windows. Conclusions Extrapulmonary cryptococcosis was common among NHNT adults and was associated with substantially greater morbidity than pulmonary disease. Immunosuppressant exposure was consistently associated with both CNS and non-CNS disseminated disease, whereas associations with glucocorticoid duration and average daily dose varied by phenotype and timing. These findings support guideline-recommended systematic evaluation for dissemination and suggest that pre-diagnostic immunosuppressive therapy history may inform assessment of extrapulmonary disease risk.