Open forum infectious diseases · 2026
Clinical Phenotypes, Immunosuppressive Exposures, and Outcomes in Pulmonary vs Extrapulmonary Cryptococcosis Among Non-HIV, Non-Transplant Adults: A U.S. Claims Analysis.
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Jamshad Ameera, Taylor Bayard A, Yang Guozheng, Chen Zhetao, Chen Xianyan, Cluck David B, Henao-Martínez Andrés F, Chastain Daniel B
Аннотация
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.
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.