The dimorphic fungus Blastomyces dermatitidis, is one of the most frequent causes of endemic fungal infections in the United States as well as various other parts of the world. Clinical presentations vary widely, ranging from asymptomatic to disseminated systemic infections. Blastomycosis usually has a predilection for the lungs, but extra pulmonary manifestations are present in 25-40% of cases, involving the skin, bone, genitourinary tract, and CNS. A fungal culture of tissue specimens and fluids is confirmatory. The mainstay of treatment are the azole antifungals, i.e., itraconazole, and for disseminated disease, amphotericin B. We present a case of a young male with pulmonary blastomycosis who presented with a long incubation period. The non-resolving nature of his symptoms prompted further lab and imaging studies, ultimately leading to full and successful recovery.

BACKGROUND: Blastomycosis is an endemic fungal disease predominantly observed in the northern regions of North America. It manifests primarily as pulmonary disease but can also involve dissemination to the skin, bones, and genitourinary tract. Detailed Case Description: We describe a case of a patient in Southern California with disseminated blastomycosis following his occupational exposure to decaying wood. The patient was treated with intravenous amphotericin therapy followed by oral itraconazole therapy with full resolution of his symptoms.
CONCLUSIONS: The patient\'s case presentation serves as a reminder regarding Blastomyces infections diagnosed outside of endemic regions and suggests a potential link between blastomycosis and a novel occupational exposure surrounding axe throwing.

A 25 year old male presented with several weeks of fevers and testicular pain. Workup demonstrated scrotal and prostatic abscesses. Fluid from these following surgical drainage revealed Blastomyces dermatitidis. He was treated with 12 months of oral anti-fungal therapy and repeat Blastomyces urine antigen was negative at follow up. While disseminated blastomycosis most commonly presents with pulmonary and cutaneous manifestations, genitourinary symptoms are rarely seen, but important to consider.

Blastomycosis is caused by a thermally dimorphic fungus that thrives in moist acidic soil. Blastomyces dermatitidis is the species responsible for most infections in North America and is especially common in areas around the Great Lakes, the St. Lawrence Seaway, and in several south-central and southeastern United States. Other Blastomyces species have more recently been discovered to cause disease in distinct geographic regions around the world. Infection almost always occurs following inhalation of conidia produced in the mold phase. Acute pulmonary infection ranges from asymptomatic to typical community-acquired pneumonia; more chronic forms of pulmonary infection can present as mass-like lesions or cavitary pneumonia. Infrequently, pulmonary infection can progress to acute respiratory distress syndrome that is associated with a high mortality rate. After initial pulmonary infection, hematogenous dissemination of the yeast form of Blastomyces is common. Most often this is manifested by cutaneous lesions, but osteoarticular, genitourinary, and central nervous system (CNS) involvement also occurs. The diagnosis of blastomycosis can be made by growth of the mold phase of Blastomyces spp. in culture or by histopathological identification of the distinctive features of the yeast form in tissues. Detection of cell wall antigens of Blastomyces in urine or serum provides a rapid method for a probable diagnosis of blastomycosis, but cross-reactivity with other endemic mycoses commonly occurs. Treatment of severe pulmonary or disseminated blastomycosis and CNS blastomycosis initially is with a lipid formulation of amphotericin B. After improvement, therapy can be changed to an oral azole, almost always itraconazole. With mild to moderate pulmonary or disseminated blastomycosis, oral itraconazole treatment is recommended.

Blastomycosis is a systemic mycotic infection caused by dimorphic fungi. The disease is rare in cats, and reports on imaging findings with central nervous system (CNS) involvement are limited. Magnetic resonance imaging (MRI) was performed antemortem in three feline patients. Imaging findings that may allow prioritization of intracranial blastomycosis over other differential diagnoses included focal or multifocal intra-axial mass lesions with dural contact, lesion hypointensity on T2-weighted images and diffusion-weighted imaging/apparent diffusion coefficient map (DWI/ADC), strong and homogeneous contrast enhancement of the lesion(s), concurrent meningeal enhancement, marked perilesional edema and mass-effect, and ocular abnormalities. One cat was managed successfully and had a recurrence of CNS blastomycosis more than 4.5 years after the initial diagnosis. Repeat MRI at that point revealed both new and persistent (chronic) abnormalities.

Blastomycosis, caused by Blastomyces spp., is an endemic mycosis capable of causing significant disease throughout the body. Higher rates of infection are seen in the Mississippi and Ohio River valleys, the Great Lakes region of the United States and Canada, much of Africa, and, to a lesser extent, in India and the Middle East. Limited reporting inhibits our true understanding of the geographic distribution of blastomycosis. An estimated 50% of those infected remain asymptomatic. Of those who present with symptomatic disease, pulmonary involvement is most common, while the most common extrapulmonary sites are the skin, bones, genitourinary system, and central nervous system. Itraconazole is the standard therapy for mild-moderate disease. Data for other azoles are limited. Amphotericin is used for severe disease, and corticosteroids are occasionally used in severe disease, but evidence for this practice is limited. Despite increasing incidence and geographic reach in recent years, there are still significant knowledge gaps in our understanding of blastomycosis. Here, we provide an updated review of the epidemiology, clinical presentations, and diagnostic and therapeutic approaches for this infection. We also discuss areas needing further research.

UNASSIGNED: Blastomyces spp, the etiologic agents of blastomycosis, are endemic dimorphic fungi that require prolonged antifungal therapy, which can be complicated by adverse drug effects. Isavuconazonium sulphate (ISA) is a triazole with in vitro and in vivo activity against Blastomyces spp, but there is a paucity of clinical data supporting its use for treatment of blastomycosis.
UNASSIGNED: This retrospective case series identified 14 patients with blastomycosis at least partially treated with ISA at the University of Wisconsin between 2015 and 2019. Treatment duration and outcomes were documented. In addition, 29 clinical isolates of Blastomyces spp between 2004 and 2017 were tested for minimum inhibitory concentrations against ISA and other antifungals.
UNASSIGNED: Fourteen patients were treated with a median of 255 days of ISA accounting for 68% of total therapy. Half (7 of 14) of the patients were immunocompromised, 11 of 14 (79%) were proven cases of blastomycosis, 7 of 14 (50%) had central nervous system (CNS) involvement, and 11 of 14 (79%) were cured. Antifungal susceptibility testing showed a consistently low minimum inhibitory concentration to ISA ≤ 0.015 mcg/mL.
UNASSIGNED: This case series supports the efficacy and safety for ISA in the treatment of blastomycosis with or without CNS disseminated, especially when alternative triazoles cannot be used.

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This retrospective multicenter cohort study assessed temporal changes in the severity and mortality rate of blastomycosis in Quebec, Canada, and identified risk factors for death in patients with blastomycosis in 1988-2016. The primary outcome was 90-day all-cause deaths. Among 185 patients, 122 (66%) needed hospitalization and 30 (16%) died. We noted increases in the proportion of severe cases, in age at diagnosis and in the proportion of diabetic and immunocompromised patients over time. Independent risk factors for death were age (adjusted odds ratio [aOR] 1.04, 95% CI 1.00-1.07), immunosuppression (aOR 4.2, 95% CI 1.5-11.6), and involvement of >2 lung lobes (aOR 5.3, 95% CI 1.9-14.3). There was no association between the Blastomyces genotype group and all-cause mortality. The proportion of severe cases of blastomycosis has increased in Quebec over the past 30 years, partially explained by the higher number of immunosuppressed patients.

Laboratory diagnosis of blastomycosis relies on a combination of methods, including antigen detection. We assessed the performance of analyte-specific reagents from Gotham Biotech (Portland, ME) for quantitative detection of Blastomyces dermatitidis galactomannan (GM) in urine using an enzyme immunoassay (EIA) compared to the Blastomyces quantitative EIA from MiraVista Diagnostics (Indianapolis, IN). Residual urine from 232 unique patients previously tested by the MiraVista assay was evaluated using the Gotham EIA, which showed 97.4% (74/76), 100% (156/156), and 99.1% (230/232) positive, negative, and overall agreement, respectively. Correlation between the quantitative B. dermatitidis antigen levels by the Gotham and MiraVista EIAs was low (R2 = 0.20). Medical records were available for 36 of the 232 patients, among whom four had confirmed blastomycosis and both the Gotham and MiraVista EIAs were positive. Nine of these patients had histoplasmosis, and the Gotham and MiraVista EIAs yielded negative results in 44.4% (4/9) and 22.2% (2/9) of cases, respectively. Both assays were negative in the remaining 23 patients. After laboratory implementation of the Gotham EIA, chart reviews were performed on the first 50 unique patients (51 samples) tested by the assay in our hospital. Among these, 3/50 (6%) samples were positive by the Gotham EIA, including two samples from a patient with culture-confirmed blastomycosis and one from a patient with histoplasmosis (also positive by the MiraVista Blastomyces EIA). All remaining patients were negative by the Gotham EIA and had alternative diagnoses. Our findings show comparable performance between the Gotham and MiraVista quantitative EIAs for detection of B. dermatitidis GM in urine.