An Unlikely Case of Blastomycosis in an Elderly Female: A Diagnostic Challenge in a Non-endemic Region.

Blastomyces dermatitidis is a fungus typically found in the soil of endemic regions such as the Midwest, concentrating in areas like Ohio, Mississippi, and the Great Lakes area. The systemic infection caused by inhaling Blastomyces dermatitidis is known as blastomycosis. The frequency of blastomycosis in non-endemic regions is increasing for a variety of speculated reasons, such as higher rates of immunosuppressed individuals and possible climate. Due to clinician unfamiliarity, misdiagnosis of blastomycosis is common, which potentiates worsening systemic infections. This study shows the clinical course of a patient with blastomycosis in a non-endemic region, highlighting the need for education for clinicians in non-endemic areas. A 72-year-old female with a history of chronic obstructive pulmonary disease (COPD), coronary artery disease, a 47-year smoking history, and hypertension presented for outpatient management of COPD. CT three months prior to presentation showed nodular opacities in the lungs. A bronchoscopy was performed and revealed negative findings for malignancy or infection; the patient developed worsening symptoms leading to hospitalization. Subsequent testing revealed Blastomyces dermatitidis. She was promptly treated with a six to 12-month course of itraconazole with close follow-up. The study highlights the need not to rule out causes of infection based on location. Blastomycosis can resemble community-acquired pneumonia. Making the correct diagnosis is paramount, as delays can result in morbidity. Fungal cultures may be the gold standard, but due to the long culture time, there need to be other diagnostic tests like urine antigen testing. This study highlights the need to increase awareness of clinicians who experience blastomycosis patients in a non-endemic region.

Comparative genome analysis and the genome-shaping role of long terminal repeat retrotransposons in the evolutionary divergence of fungal pathogens Blastomyces dermatitidis and Blastomyces gilchristii.

Blastomyces dermatitidis and Blastomyces gilchristii are cryptic species of fungi that cause blastomycosis, an often severe disease involving pulmonary infection capable of systemic dissemination. While these species appear morphologically identical, differences exist in the genetic makeup, geographical range, and possibly the clinical presentation of infection. Here, we show genetic divergence between the cryptic species through both a Blastomyces species tree constructed from orthologous protein sequences and whole genome single nucleotide variant phylogenomic analysis. Following linked-read sequencing and de novo genome assembly, we characterized and compared the genomes of 3 B. dermatitidis and 3 B. gilchristii isolates. The B. gilchristii genomes (73.25-75.4 Mb), were ∼8 Mb larger than the B. dermatitidis genomes (64.88-66.61 Mb). Average nucleotide identity was lower between genomes of different species than genomes of the same species, yet functional classification of genes suggested similar proteomes. The most striking difference involved long terminal repeat retrotransposons. Although the same retrotransposon elements were detected in the genomes, the quantity of elements differed between the two species. Gypsy retrotransposon content was significantly higher in B. gilchristii (38.04-39.26 Mb) than in B. dermatitidis (30.85-32.40 Mb), accounting for the majority of genome size difference between species. Age estimation and phylogenetic analysis of the reverse transcriptase domains suggested that these retrotransposons are relatively ancient, with genome insertion predating the speciation of B. dermatitidis and B. gilchristii. We postulate that different trajectories of genome contraction led to genetic incompatibility, reproductive isolation and speciation, highlighting the role of transposable elements in fungal evolution.

A Case of Blastomyces dermatitidis Diagnosed Following Travel to Colorado: A Case Report and Review of Literature.

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.

Disseminated blastomycosis presenting with genitourinary abscesses.

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.

Burying Hatchets into Endemic Diagnoses: Disseminated Blastomycosis from a Potentially Novel Occupational Exposure.

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.

Blastomycosis: A Review of Mycological and Clinical Aspects.

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.

Direct Tissue PCR and Genotyping for Species Identification in a Case of Laryngeal Blastomycosis.

Otolaryngologic manifestations of infection with Blastomyces species are extremely rare and restricted geographically to recognized endemic regions. Here, we describe a case of laryngeal blastomycosis that presented as slowly progressive dysphonia. While a preliminary diagnosis was made using routine histopathology, a species identification of Blastomyces dermatitidis was made using polymerase chain reaction amplification and rapid genotyping without the need for fungal culture. All symptoms resolved following 1 month of antifungal therapy. Rapid molecular differentiation of B dermatitidis from Blastomyces gilchristii provides important insights into pathogenesis given recent recognition of differences in clinical spectra.

Case report: MRI findings with CNS blastomycosis in three domestic cats.

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-Some Progress but Still Much to Learn.

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.

The Role of Isavuconazonium Sulphate for the Treatment of Blastomycosis: A Case Series and Antifungal Susceptibility.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Risk factors of severe blastomycosis and comparison of diagnosis and outcomes between immunocompetent and immunocompromised patients.

BACKGROUND: Blastomycosis is an endemic fungal infection that causes pulmonary and systemic disease. It can occur irrespective of the patient's immune status. The risk factors associated with the severity of the disease are not well studied. METHODS: This is a retrospective study of patients admitted with blastomycosis at the University of Kentucky Hospital from 2004 to 2019. Logistic regression was used to identify variables associated with severe blastomycosis. RESULTS: A total of 76 patients were identified; 22 (28.9%) had at least one immunosuppressive condition. Pulmonary blastomycosis was reported in 49/76 (65%) of the patients and disseminated infection in 27/76 (35.5%). All diagnostic tests were not significantly different in diagnostic results in immunocompromised vs immunocompetent patients. Cultures and histopathology were positive in 56/61 (91.8%) and 54/63 (85.7%) respectively. Blastomyces or Histoplasma antigen test was positive in 13/17 (76.4%) in immunocompromised patients compared to 26/42 (61.9%) in immunocompetent patients. Immunocompromised patients were more likely to be admitted to the hospital and ICU compared to immunocompetent patients. In the multivariate analysis, pulmonary multilobar disease (RR 5.68; 95% CI 2.13-15.15), obesity (RR 2.39; 95% CI 1.26-4.51), diabetes mellitus (RR 3.50; 95% CI 1.38-8.90) and immunosuppression (RR 2.28; 95% CI 1.14-4.56) were significant independent risk factors for severe blastomycosis. Inpatient mortality proportion was higher in immunocompromised patients but not statistically significant. CONCLUSION: Pulmonary multilobar disease, obesity, diabetes mellitus and immunosuppression were risk factors associated with severe blastomycosis. Immunocompromised patients required more frequent hospitalisations compared to immunocompetent patients.

Double Take on Double Vision: Invasive Rhinosinusitis From Blastomyces dermatitidis in an Adolescent With Well-Controlled Diabetes.

Blastomyces dermatitidis is a fungus endemic to the Ohio and Mississippi river valley region and great lakes region. Exposure is typically associated with outdoor activities near streams, rivers, or moist soil. Pulmonary disease is the main manifestation, whereas dissemination is more frequently observed in immunosuppressed individuals. We herein report an uncommon case of B. dermatitidis causing invasive fungal sinusitis in a patient with well-controlled type 2 diabetes mellitus in the absence of conventional higher-risk environmental exposures. This case highlights the importance of a broad differential for invasive fungal infections in patients with diabetes, including those in endemic areas without classical exposures.

Changing Patterns of Disease Severity in Blastomyces dermatitidis Infection, Quebec, Canada.

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.

Detection of Blastomyces dermatitidis Antigen in Urine Using a Commercially Available Quantitative Enzyme Immunoassay.

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.

Serum 25-hydroxyvitamin D concentrations and mortality in dogs with blastomycosis.

Blastomycosis is a prominent fungal disease in the United States. Vitamin D status has been found to be altered in critical illness and various infectious diseases. The objectives of this study were to compare serum 25-hydroxyvitamin D (25[OH]D) concentrations in dogs with blastomycosis and healthy controls, to assess the change in serum 25(OH)D concentrations in dogs with blastomycosis after 30 days of treatment, and to determine if baseline serum 25(OH)D concentrations in dogs with blastomycosis were associated with in-hospital, 30-day, or end-of-study mortality. In this prospective cohort study, 19 dogs newly diagnosed with blastomycosis had serum 25(OH)D concentrations measured with a commercially available validated radioimmunoassay at the time of diagnosis and 30 days after start of treatment. These values were compared to 24 healthy control dogs. Serum 25(OH)D concentrations at the time of diagnosis were lower in dogs with blastomycosis (median, 203 nmol/L; range, 31-590 nmol/L) than in clinically healthy control dogs (259.5 nmol/L, 97-829 nmol/L; P = 0.01). Despite clinical improvement, there was no significant change in serum 25(OH)D concentrations from baseline to 30-day follow-up. Dogs with baseline serum 25(OH)D concentrations <180.5nmol/L had a greater odds of death during hospitalization (odds ratio [OR], 15.0; 95% confidence interval [CI], 1.4-191.3; P = 0.04) and at 30 days follow-up (OR, 30.0; 95% CI, 2.5-366.7; P = 0.006). These findings highlight the need for further studies evaluating the prognostic value of vitamin D status in dogs with blastomycosis at diagnosis and throughout treatment and remission.

Central nervous system blastomycosis clinical characteristics and outcomes.

Blastomycosis is a local or systemic infection, caused by Blastomyces dermatitidis (B. dermatitidis) or B. gilchristii. Blastomycosis has been described as "the great pretender," alluding to the fact that it manifests in a wide range of symptoms and disease severity. Central nervous system (CNS) involvement, although rare, carries significant mortality. Due to the limited published reports of CNS blastomycosis, we present an updated cohort with eight cases of proven or probable CNS blastomycosis describing presentation, diagnosis, treatment and outcomes. Headache was the most common presenting symptom. Magnetic resonance imaging (MRI) proved to be the superior imaging study. All patients in our cohort were diagnosed by histopathological staining or cultures of tissue or fluid obtained from CNS or extra-CNS lesions. All patients that received treatment with Liposomal amphrotericin B for at least 10 days followed by a prolonged azole therapy did not have relapse. Two patients with late diagnoses died during hospitalization. Our findings confirm the importance of timely diagnosis and treatment of CNS blastomycosis to improve outcomes especially with an azole that have a high CNS penetration and a good intrinsic activity for B. dermatitidis such as voriconazole.

Spontaneous resolution of blastomycosis symptoms caused by B. dermatitidis.

Given the propensity of blastomycosis to disseminate or reoccur and the inability to predict which infections will experience severe manifestations, nearly all cases of blastomycosis are treated. Although, spontaneous resolution of symptoms is referred to generally in the literature, to our knowledge an individual case of this has not been previously reported. We report the spontaneous resolution of blastomycosis symptoms in a 40 year-old Caucasian male.

[Pulmonary blastomycosis]. / Blastomycose pulmonaire.

Blastomycosis is a rare fungal disease in Africa which is often due to inhalation of "Blastomyces dermatitidis". Pulmonary blastomycosis is the most common clinical manifestation which presents with a variety of clinical features, ranging from asymptomatic to rapidly fatal. We report the case of a Tunisian patient aged 35 years with no previous medical history, hospitalized with chronic cough, bilateral basithoracic pain, fever and weight loss. Clincal examination showed fever and left paravertebral subcutaneous swelling next to the tenth thoracic vertebra (T10). Chest imaging objectified bilateral alveolar and nodular opacities with excavations in some places. Sputum stain for Koch bacillus (BK) was negative (direct examination and culture). Bronchial fibroscopy was normal. Anatomopathological examination of dorsal mass biopsy revealed blastomycosis. The diagnosis was confirmed by cultures of the biopsic fragments of the mass. Antifungal therapy with itraconazole was started with clinical and radiological improvement. This case study highlights challenges in the diagnosis of blastomycosis in our country, in particular when lesions mimick tuberculosis; hence delayed therapy.