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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Autores principales:	Timothy R. O’Dowd, Jack W. Mc Hugh, Elitza S. Theel, Nancy L. Wengenack, John C. O’Horo, Mark J. Enzler, Paschalis Vergidis
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	blastomycosis serology immunodiffusion complement fixation urine antigen PCR Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d359e917077b4e5dafe475132e954b8b
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spelling	oai:doaj.org-article:d359e917077b4e5dafe475132e954b8b2021-11-25T18:05:28ZDiagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study10.3390/jof71108882309-608Xhttps://doaj.org/article/d359e917077b4e5dafe475132e954b8b2021-10-01T00:00:00Zhttps://www.mdpi.com/2309-608X/7/11/888https://doaj.org/toc/2309-608X<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.Timothy R. O’DowdJack W. Mc HughElitza S. TheelNancy L. WengenackJohn C. O’HoroMark J. EnzlerPaschalis VergidisMDPI AGarticleblastomycosisserologyimmunodiffusioncomplement fixationurine antigenPCRBiology (General)QH301-705.5ENJournal of Fungi, Vol 7, Iss 888, p 888 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	blastomycosis serology immunodiffusion complement fixation urine antigen PCR Biology (General) QH301-705.5
spellingShingle	blastomycosis serology immunodiffusion complement fixation urine antigen PCR Biology (General) QH301-705.5 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
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.
format	article
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
title	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_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_sort	diagnostic methods and risk factors for severe disease and mortality in blastomycosis: a retrospective cohort study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d359e917077b4e5dafe475132e954b8b
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Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study

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