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

Abstract

Background: 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. Methods: 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. Findings: 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), p = 0.002) and lymphopenia (OR 3.34 (95% CI 1.59-7.03), p = 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), p = 0.009), neutrophilia (OR 2.84 (95% CI 1.04-7.76), p = 0.041), and lymphopenia (OR 4.50 (95% CI 1.67-12.11), p = 0.003). Blastomyces 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 Blastomyces 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). Conclusion: 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.

Keywords: PCR; amphotericin B; blastomycosis; complement fixation; immunodiffusion; itraconazole; lymphopenia; serology; urine antigen.

Figure 1

Cumulative 90-day survival grouped by age and presence of lymphopenia at diagnosis. L: lymphocyte count.

Figure 2

Disease severity and Blastomyces urine antigen level. Horizontal lines represent mean values (p = 0.06).