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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Question 1Infectious DiseaseMedium
A 52-year-old previously healthy hunter from Minnesota is admitted with biopsy-confirmed pulmonary and cutaneous blastomycosis. He has moderate pulmonary involvement with a peak oxygen requirement of 2 L by nasal cannula and several verrucous skin lesions but no CNS involvement. His liver and renal function are normal and he is hemodynamically stable. Which of the following is the most appropriate first-line management?
AObservation with serial imaging
BOral itraconazole for 6-12 months
COral fluconazole for 4 weeks
DTopical terbinafine to skin lesions
Reveal answer & full explanation
Correct answer: B — Oral itraconazole for 6-12 months
AObservation with serial imaging
BOral itraconazole for 6-12 months✓
COral fluconazole for 4 weeks
DTopical terbinafine to skin lesions
Why Oral itraconazole for 6-12 months is correct
The Infectious Diseases Society of America (IDSA) recommends oral itraconazole 200 mg twice daily for 6-12 months as first-line therapy for mild-to-moderate non-CNS blastomycosis
Itraconazole has excellent activity against Blastomyces dermatitidis, good tissue penetration, and proven cure rates exceeding 90% in non-severe disease
Serum drug levels should be monitored after 2 weeks to confirm therapeutic concentrations
Why the others are wrong
A) Observation with serial imaging — observation is inappropriate because untreated blastomycosis carries substantial morbidity and mortality with risk of dissemination to bone, GU tract, and CNS
C) Oral fluconazole for 4 weeks — fluconazole has weaker in vitro and clinical activity against Blastomyces and is reserved for CNS disease as part of step-down therapy or when itraconazole cannot be used; a 4-week course is inadequate regardless
D) Topical terbinafine to skin lesions — topical antifungals do not address the systemic and pulmonary infection driving cutaneous dissemination; blastomycotic skin lesions reflect hematogenous spread and require systemic therapy
Additional high-yield points
For severe pulmonary, disseminated, or CNS disease: liposomal amphotericin B is given for 1-2 weeks followed by itraconazole step-down therapy
Question 2Infectious DiseaseMedium
A 28-year-old male has a 3-week history of progressive dyspnea, non-productive cough, and low-grade fever. He was treated with azithromycin 5 days ago without improvement. He moved from Ohio to Arizona 3 months ago. CXR shows bilateral hilar adenopathy and diffuse reticulonodular infiltrates. Serum LDH is elevated. Bronchoscopy BAL shows broad-based budding yeast with a thick, double-contoured cell wall on Grocott methenamine silver (GMS) stain. Which of the following is the most likely diagnosis?
ABlastomycosis
BCoccidioidomycosis
CPneumocystis jirovecii pneumonia
DHistoplasmosis
Reveal answer & full explanation
Correct answer: A — Blastomycosis
ABlastomycosis✓
BCoccidioidomycosis
CPneumocystis jirovecii pneumonia
DHistoplasmosis
Why Blastomycosis is correct
The GMS finding of broad-based budding yeast with a thick, double-contoured cell wall is the pathognomonic feature of Blastomyces dermatitidis.
Blastomyces is endemic to the Ohio and Mississippi River valleys, the Great Lakes region, and parts of Canada — consistent with this patient's origin in Ohio.
It is a dimorphic fungus: mold at 25°C, yeast at 37°C.
Broad-based budding means the parent and daughter cells are similar in size and connected by a wide base — distinguishing it from other endemic mycoses.
Pulmonary disease is often progressive and refractory to antibacterials, with potential dissemination to skin (verrucous/ulcerative lesions), bone, genitourinary tract, and CNS.
Why the others are wrong
Coccidioidomycosis — Right-concept-wrong-geography anchoring on the patient's current desert-Southwest location; GMS shows spherules packed with endospores, not broad-based budding yeast.
Pneumocystis jirovecii pneumonia — Confused-with another GMS-staining organism; PJP shows cup/helmet-shaped cysts without budding and typically occurs in immunocompromised hosts (HIV, transplant).
Histoplasmosis — Shares the Ohio/Mississippi endemic region (geographic anchoring), but Histoplasma yeasts are small, intracellular, and narrowly budding, lacking the thick double-contoured wall.
Additional high-yield points
IDSA treatment for mild-to-moderate pulmonary blastomycosis: itraconazole 200 mg TID x3 days loading, then 200 mg BID x6-12 months.
Severe blastomycosis (ARDS, immunocompromised): liposomal amphotericin B 3-5 mg/kg/day x1-2 weeks then itraconazole step-down.
CNS blastomycosis: liposomal amphotericin B 5 mg/kg/day x4-6 weeks then voriconazole or itraconazole.
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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.
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)
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