Endemic mycosis caused by Blastomyces dermatitidis, presenting with pulmonary, cutaneous, and bone disease in the Mississippi/Ohio River valleys and Great Lakes region.
Also known as: Blastomyces dermatitidis, Gilchrist disease, North American blastomycosis
Overview
Systemic mycosis caused by the dimorphic fungi Blastomyces dermatitidis and Blastomyces gilchristii, acquired by inhalation of conidia from moist soil and decomposing organic matter. Disease ranges from subclinical infection to acute or chronic pneumonia, with frequent extrapulmonary dissemination to skin, bone, genitourinary tract, and central nervous system.
Epidemiology
Endemic to the Mississippi and Ohio River valleys, the Great Lakes region, and parts of southeastern Canada. Sporadic and outbreak cases also reported in upstate New York, Minnesota, Wisconsin, and northern Ontario. Most cases occur in adults engaged in outdoor activities (hunting, fishing, construction) near waterways.
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Risk factors
- Outdoor exposure in endemic regions: hunting, fishing, camping, forestry, excavation
- Proximity to rivers, lakes, and wooded waterways
- Immunocompromised state — although blastomycosis can affect previously healthy hosts
- HIV infection, solid organ transplantation, TNF-alpha inhibitor therapy
- Pregnancy (associated with severe disease)
- Diabetes mellitus, COPD
Pathophysiology
Inhaled conidia are deposited in alveoli where they convert to the yeast phase. Yeasts are partially resistant to neutrophil killing and elicit pyogranulomatous inflammation. Lymphohematogenous dissemination is common, with predilection for skin, bones, prostate, and CNS. Cell-mediated immunity controls infection but does not eliminate it; reactivation is possible.
Clinical presentation
Symptoms
- Acute pulmonary: fever, productive cough, pleuritic chest pain, dyspnea, myalgias
- Chronic pulmonary: insidious cough, weight loss, low-grade fever, hemoptysis (mimics TB or malignancy)
- Cutaneous: painless verrucous or ulcerative lesions with heaped-up borders and microabscesses
- Osteoarticular: indolent bone pain, draining sinuses, contiguous soft tissue abscess
- Genitourinary: prostatitis, epididymitis, dysuria
- CNS: headache, focal deficits, meningeal signs (uncommon outside immunocompromised hosts)
Signs / physical exam
- Skin: verrucous, crusted, or ulcerated lesions, often on face/extremities
- Lung: focal consolidation, mass-like opacity, or diffuse pneumonia
- Lytic bone lesions on imaging, often with adjacent soft tissue abscess
- Prostate tenderness or enlargement on exam
Classic findings
Chronic pneumonia and a verrucous skin lesion in a midwestern hunter or outdoor worker. Broad-based budding yeast on KOH preparation of sputum or skin lesion is pathognomonic.
Differential diagnosis
- Bacterial pneumonia — Acute lobar consolidation, response to antibiotics; failure to respond should prompt fungal workup in endemic exposure
- Tuberculosis — Chronic cough, upper-lobe cavitation, weight loss; AFB testing and fungal stains both needed in endemic areas
- Lung cancer — Mass-like lesion, weight loss; biopsy distinguishes; blastomycosis can mimic malignancy on PET
- Squamous cell skin carcinoma — Cutaneous blastomycosis produces verrucous, ulcerated, heaped-up lesions that mimic SCC; biopsy with fungal stains essential
- Histoplasmosis — Overlapping geography; intracellular small yeasts versus broad-based budding large yeasts on histology
- Coccidioidomycosis — Southwest US geography, spherules with endospores on histology
- Cryptococcosis — Encapsulated narrow-based budding yeast; CNS predilection in HIV; India ink and CrAg distinguish
Diagnostic workup
Diagnostic criteria
Definitive diagnosis by culture or by visualization of characteristic broad-based budding yeast on direct microscopy or histopathology. Antigen testing supports diagnosis when culture is pending.
Labs
- Direct microscopy (KOH) of sputum, BAL, or tissue showing broad-based budding yeast (8-15 microm with thick refractile cell wall)
- Fungal culture (gold standard but slow, 2-4 weeks)
- Histopathology with GMS or PAS stain
- Urine and serum Blastomyces antigen (high sensitivity, cross-reacts with Histoplasma)
- Blastomyces serology has limited sensitivity and specificity
- CBC, BMP, LFTs
Imaging
- Chest x-ray and CT: lobar consolidation, mass-like opacity, miliary or reticulonodular pattern, cavitation
- Bone imaging (radiograph, CT, MRI) for suspected osteomyelitis
- MRI brain with contrast for CNS involvement
- Genitourinary imaging if prostatitis or epididymitis suspected
Treatment
First-line
- Mild to moderate pulmonary or extrapulmonary disease (non-CNS): itraconazole 200 mg PO TID for 3 days then BID for 6-12 months
- Moderate to severe pulmonary, disseminated, or immunocompromised: liposomal amphotericin B 3-5 mg/kg/day IV for 1-2 weeks, then itraconazole 200 mg PO BID for at least 12 months
- CNS blastomycosis: liposomal amphotericin B 5 mg/kg/day for 4-6 weeks, then azole — fluconazole, voriconazole, or itraconazole — for at least 12 months and until CSF normalizes
- Bone and joint disease: total 12 months of itraconazole following induction
- Pregnancy: liposomal amphotericin B (azoles are teratogenic)
Second-line / adjunct
- Voriconazole — preferred for CNS disease due to CSF penetration
- Posaconazole or isavuconazole for refractory or intolerant patients
- Therapeutic drug monitoring of itraconazole trough (>1 microg/mL)
- Surgical drainage of large abscesses, debridement of osteomyelitis
Complications
- ARDS — acute respiratory distress syndrome from severe pulmonary blastomycosis (high mortality)
- Chronic cavitary lung disease, hemoptysis
- Disseminated skin, bone, and genitourinary disease
- CNS abscess and meningitis
- Treatment-related: amphotericin nephrotoxicity, infusion reactions; azole hepatotoxicity and drug interactions
PANCE pearls
- Broad-based budding yeast on KOH or histopathology is pathognomonic for Blastomyces — distinguishes from narrow-based Cryptococcus and small intracellular Histoplasma.
- Suspect blastomycosis in midwestern hunters or outdoor workers with chronic pneumonia plus skin lesions that look like squamous cell carcinoma.
- ARDS is a feared early complication and carries mortality up to 50-80%.
- Voriconazole has the best CSF penetration among azoles and is preferred for CNS blastomycosis after amphotericin induction.
- Antigen testing cross-reacts with histoplasmosis — culture or histopathology is still needed for species confirmation.
References
- IDSA 2008 — Clinical Practice Guidelines for the Management of Blastomycosis (Chapman et al., Clin Infect Dis 2008)
- CDC — CDC — Blastomycosis: epidemiology, clinical features, and laboratory testing
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