Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study

<b>Background:</b> Blastomycosis can cause severe disease with progressive respiratory failure and dissemination even in immunocompetent individuals. We sought to evaluate risk factors for severe disease and mortality using clinical and laboratory data within a large health system in an...

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Main Authors: Timothy R. O’Dowd, Jack W. Mc Hugh, Elitza S. Theel, Nancy L. Wengenack, John C. O’Horo, Mark J. Enzler, Paschalis Vergidis
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/7/11/888
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author Timothy R. O’Dowd
Jack W. Mc Hugh
Elitza S. Theel
Nancy L. Wengenack
John C. O’Horo
Mark J. Enzler
Paschalis Vergidis
author_facet Timothy R. O’Dowd
Jack W. Mc Hugh
Elitza S. Theel
Nancy L. Wengenack
John C. O’Horo
Mark J. Enzler
Paschalis Vergidis
author_sort Timothy R. O’Dowd
collection DOAJ
description <b>Background:</b> Blastomycosis can cause severe disease with progressive respiratory failure and dissemination even in immunocompetent individuals. We sought to evaluate risk factors for severe disease and mortality using clinical and laboratory data within a large health system in an endemic area. <b>Methods:</b> We performed a retrospective cohort study of patients diagnosed with blastomycosis at all Mayo Clinic sites from 1 January 2004 through 31 March 2020. Diagnosis was established by culture, histopathology/cytopathology, serology, antigen testing, or PCR. Disease was categorized as mild for patients treated in the outpatient setting, moderate for hospitalized patients who did not require intensive care, and severe for patients admitted to the intensive care unit. Logistic regression was used to evaluate risk factors for severe disease. A Cox proportional hazards model was constructed to evaluate mortality. <b>Findings:</b> We identified 210 patients diagnosed with blastomycosis. Mean age was 51 years (range, 6–84). Most subjects were male (71.0%). Extrapulmonary disease was confirmed in 24.8%. In this cohort, 40.5% of patients had mild disease, 37.6% had moderate disease, and 21.9% had severe disease. Independent risk factors for severe disease were neutrophilia (odds ratio (OR) 3.35 (95% CI 1.53–7.35), <i>p</i> = 0.002) and lymphopenia (OR 3.34 (95% CI 1.59–7.03), <i>p</i> = 0.001). Mortality at 90 days was 11.9%. Median time from diagnosis to death was 23 days (interquartile range 8–31 days). Independent risk factors for mortality were age (OR 1.04 (95% CI 1.01–1.08), <i>p</i> = 0.009), neutrophilia (OR 2.84 (95% CI 1.04–7.76), <i>p</i> = 0.041), and lymphopenia (OR 4.50 (95% CI 1.67–12.11), <i>p</i> = 0.003). <i>Blastomyces</i> immunodiffusion had an overall sensitivity of 39.6% (95% CI 30.1–49.8). Sensitivity was higher among those who were tested 4 weeks or longer after the onset of symptoms. Urine <i>Blastomyces</i> antigen had a significantly higher sensitivity of 80.8% (95% CI 68.1–89.2) compared to serology. There was a trend towards higher antigen concentration in patients with severe disease. The sensitivity of PCR from respiratory specimens was 67.6% (95% CI 50.1–85.5). <b>Conclusion:</b> In this cohort, we did not find an association between pharmacologic immunosuppression and disease severity. Lymphopenia at diagnosis was an independent risk factor for mortality. This simple marker may aid clinicians in determining disease prognosis.
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spelling doaj.art-d359e917077b4e5dafe475132e954b8b2023-11-22T23:54:58ZengMDPI AGJournal of Fungi2309-608X2021-10-0171188810.3390/jof7110888Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort StudyTimothy R. O’Dowd0Jack W. Mc Hugh1Elitza S. Theel2Nancy L. Wengenack3John C. O’Horo4Mark J. Enzler5Paschalis Vergidis6Department of Medicine, Mayo Clinic, Rochester, MN 55905, USADepartment of Medicine, Mayo Clinic, Rochester, MN 55905, USADepartment of Laboratory Medicine and Pathology, Division of Clinical Microbiology, Mayo Clinic, Rochester, MN 55905, USADepartment of Laboratory Medicine and Pathology, Division of Clinical Microbiology, Mayo Clinic, Rochester, MN 55905, USADepartment of Medicine, Division of Infectious Diseases, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USADepartment of Medicine, Division of Infectious Diseases, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USADepartment of Medicine, Division of Infectious Diseases, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA<b>Background:</b> Blastomycosis can cause severe disease with progressive respiratory failure and dissemination even in immunocompetent individuals. We sought to evaluate risk factors for severe disease and mortality using clinical and laboratory data within a large health system in an endemic area. <b>Methods:</b> We performed a retrospective cohort study of patients diagnosed with blastomycosis at all Mayo Clinic sites from 1 January 2004 through 31 March 2020. Diagnosis was established by culture, histopathology/cytopathology, serology, antigen testing, or PCR. Disease was categorized as mild for patients treated in the outpatient setting, moderate for hospitalized patients who did not require intensive care, and severe for patients admitted to the intensive care unit. Logistic regression was used to evaluate risk factors for severe disease. A Cox proportional hazards model was constructed to evaluate mortality. <b>Findings:</b> We identified 210 patients diagnosed with blastomycosis. Mean age was 51 years (range, 6–84). Most subjects were male (71.0%). Extrapulmonary disease was confirmed in 24.8%. In this cohort, 40.5% of patients had mild disease, 37.6% had moderate disease, and 21.9% had severe disease. Independent risk factors for severe disease were neutrophilia (odds ratio (OR) 3.35 (95% CI 1.53–7.35), <i>p</i> = 0.002) and lymphopenia (OR 3.34 (95% CI 1.59–7.03), <i>p</i> = 0.001). Mortality at 90 days was 11.9%. Median time from diagnosis to death was 23 days (interquartile range 8–31 days). Independent risk factors for mortality were age (OR 1.04 (95% CI 1.01–1.08), <i>p</i> = 0.009), neutrophilia (OR 2.84 (95% CI 1.04–7.76), <i>p</i> = 0.041), and lymphopenia (OR 4.50 (95% CI 1.67–12.11), <i>p</i> = 0.003). <i>Blastomyces</i> immunodiffusion had an overall sensitivity of 39.6% (95% CI 30.1–49.8). Sensitivity was higher among those who were tested 4 weeks or longer after the onset of symptoms. Urine <i>Blastomyces</i> antigen had a significantly higher sensitivity of 80.8% (95% CI 68.1–89.2) compared to serology. There was a trend towards higher antigen concentration in patients with severe disease. The sensitivity of PCR from respiratory specimens was 67.6% (95% CI 50.1–85.5). <b>Conclusion:</b> In this cohort, we did not find an association between pharmacologic immunosuppression and disease severity. Lymphopenia at diagnosis was an independent risk factor for mortality. This simple marker may aid clinicians in determining disease prognosis.https://www.mdpi.com/2309-608X/7/11/888blastomycosisserologyimmunodiffusioncomplement fixationurine antigenPCR
spellingShingle Timothy R. O’Dowd
Jack W. Mc Hugh
Elitza S. Theel
Nancy L. Wengenack
John C. O’Horo
Mark J. Enzler
Paschalis Vergidis
Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study
Journal of Fungi
blastomycosis
serology
immunodiffusion
complement fixation
urine antigen
PCR
title Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study
title_full Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study
title_fullStr Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study
title_full_unstemmed Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study
title_short Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study
title_sort diagnostic methods and risk factors for severe disease and mortality in blastomycosis a retrospective cohort study
topic blastomycosis
serology
immunodiffusion
complement fixation
urine antigen
PCR
url https://www.mdpi.com/2309-608X/7/11/888
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