Blastomycosis

Overview and Causative Organism
Endemic Zones and Epidemiology
Exposure and Outbreak Settings
Pulmonary Blastomycosis
Skin Manifestations
Bone, Genitourinary, and CNS Involvement
Diagnosis
Microscopy: Broad-Based Budding Yeast
Treatment
Special Populations
Key Research Papers
Featured Videos

1. Overview and Causative Organism

Blastomycosis is a systemic fungal infection caused by Blastomyces dermatitidis, a dimorphic fungus that lives in the environment as a mold but converts to a yeast form at body temperature. It is the third most common endemic mycosis in North America, after histoplasmosis and coccidioidomycosis, and is capable of causing serious illness in both healthy individuals and those with weakened immune systems.

Blastomyces dermatitidis is a thermally dimorphic fungus: in the environment (below 35°C), it grows as a filamentous mold producing conidia that become airborne when soil is disturbed. When a person inhales these spores, the organism converts to the yeast phase at human body temperature (37°C). This yeast form is characterized by large cells measuring 8 to 15 micrometers in diameter, with a distinctive thick, refractile cell wall and a single, broad-based bud — a morphological feature considered pathognomonic for Blastomyces. This broad-based budding distinguishes it from Cryptococcus neoformans, which produces narrow-based buds, and from other dimorphic fungi.

One of blastomycosis's defining clinical features is its high rate of extrapulmonary spread — even in immunocompetent patients. Approximately 25 to 40% of cases develop dissemination beyond the lungs, a rate much higher than histoplasmosis, where extrapulmonary disease predominantly affects immunocompromised individuals. This tendency to disseminate widely makes blastomycosis uniquely challenging and underlines the importance of early, accurate diagnosis and systemic antifungal treatment in all confirmed cases.

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2. Endemic Zones and Epidemiology

The geographic range of blastomycosis overlaps significantly with that of histoplasmosis — centered on the Ohio and Mississippi River Valleys — but extends further north and east, particularly into the Great Lakes region and along the Canadian border. States with the highest reported incidence include Wisconsin, Minnesota, Illinois, Michigan, Indiana, Kentucky, Tennessee, Arkansas, and Mississippi. In Canada, Ontario and Manitoba carry the greatest burden.

Unlike coccidioidomycosis, which is confined to the arid Southwest, blastomycosis favors humid environments with abundant moisture, waterways, and organic debris. The organism thrives in moist, acidic soil enriched by decaying wood and leaf litter — particularly along river banks, lake shores, and forested wetland margins. This ecological niche explains why the Great Lakes states and river-adjacent regions see disproportionately high case counts.

Blastomycosis shows a striking male predominance, likely reflecting occupational and recreational risk rather than biological susceptibility. Hunters, trappers, forestry workers, campers, and construction crews who disturb soil or handle rotting wood are at elevated risk. The disease affects all age groups, but working-age adults (30 to 60 years) are most frequently diagnosed. Dogs are also commonly infected and can serve as sentinel animals for geographic risk.

True incidence is difficult to establish because blastomycosis is not reportable in all jurisdictions and is frequently misdiagnosed as bacterial pneumonia, tuberculosis, or malignancy. Surveillance data from Wisconsin — one of the few states with mandatory reporting — suggest rates of approximately 1 to 2 cases per 100,000 population per year in hyperendemic counties, with substantially higher rates in rural areas along waterways.

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3. Exposure and Outbreak Settings

Most blastomycosis cases are sporadic, arising from individual encounters with contaminated soil or wood. However, point-source outbreaks — where a defined group shares a common exposure — have been documented repeatedly and provide important insight into the organism's ecology and infectious dose.

Classic outbreak settings include:

Camping and outdoor recreation: Groups sleeping in close proximity to decaying logs, leaf piles, or riverbank soil are at elevated risk. The Eagle River, Wisconsin outbreak in the 1980s traced 48 cases to a single beaver pond area.
Hunting and trapping: Disturbing soil while digging blinds, handling animal dens, or working near beaver dams creates aerosol exposure. Hunters in northern Wisconsin and Minnesota account for a disproportionate share of cases each autumn.
Construction and excavation: Grading, trenching, or demolition near rivers or wooded wetlands can release large numbers of conidia simultaneously, causing cluster infections among workers.
Beaver dam areas: Beaver dams create the ideal microenvironment — moist, wood-rich, shaded, acidic — for Blastomyces growth. Multiple outbreaks have been traced to specific beaver colonies along lakes and streams.

The incubation period from inhalation to symptom onset ranges from 21 to 106 days, with a median around 45 days. This long and variable incubation makes it difficult for patients and clinicians to connect current illness to a specific outdoor exposure that occurred weeks earlier. When evaluating a febrile patient with pneumonia that fails antibiotics, a careful travel and activity history reaching back three months is essential.

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4. Pulmonary Blastomycosis

Pulmonary disease is the primary manifestation of blastomycosis, resulting directly from inhalation of conidia. However, the clinical spectrum is wide — ranging from asymptomatic infection that resolves without treatment, to severe pneumonia requiring intensive care.

Acute pulmonary blastomycosis resembles bacterial pneumonia or influenza. Patients present with fever, chills, productive cough (sometimes with blood-tinged sputum), pleuritis, and myalgias. Chest radiography typically shows alveolar infiltrates in a lobar or segmental pattern, and nodules or masses are common. Because the clinical and radiographic picture so closely mimics bacterial pneumonia, patients frequently receive multiple courses of antibiotics without improvement — the failure of antibiotics to resolve a pneumonia is a critical diagnostic clue that should prompt evaluation for fungal infection.

Some patients with acute pulmonary blastomycosis improve spontaneously without antifungal treatment. This occurs most often in immunocompetent individuals with limited exposure. However, current guidelines recommend treatment for all confirmed symptomatic cases because of the unpredictable risk of subsequent dissemination or reactivation — even after apparent clinical resolution.

Chronic pulmonary blastomycosis follows an indolent course over months to years, with waxing and waning symptoms. Patients may report weight loss, fatigue, low-grade fever, and a chronic productive cough. Upper lobe involvement with fibronodular infiltrates and cavitation is common, closely mimicking pulmonary tuberculosis and chronic pulmonary aspergillosis. Many cases are initially worked up for malignancy because pulmonary masses or cavities prompt concern for lung cancer.

Acute respiratory distress syndrome (ARDS) occurs in a minority of patients but carries a high mortality rate (up to 50–89% in some series). This severe form presents with high fever, rapidly progressive hypoxia, bilateral infiltrates, and respiratory failure requiring mechanical ventilation. It is more common in immunocompromised patients but can occur in otherwise healthy individuals with heavy inoculum exposure. Rapid antifungal treatment with liposomal amphotericin B is required.

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5. Skin Manifestations

Skin disease is the most common site of extrapulmonary blastomycosis, occurring in approximately 40 to 80% of patients with disseminated infection. Skin lesions typically arise by hematogenous spread from the lungs rather than direct inoculation, though rare primary cutaneous blastomycosis from traumatic implantation has been reported.

Two primary morphologies are recognized:

Verrucous (warty) plaques are the hallmark lesion. These are indurated, crusted, heaped-up plaques with an irregular border — described as having a "warty" or "cauliflower-like" surface texture. The border is typically raised, violaceous, and well-demarcated, while the center shows central clearing and scarring as the infection spreads outward. These lesions are usually painless, despite their dramatic appearance. Common sites include the face, neck, and upper extremities — areas frequently exposed during outdoor activities. Lesions grow slowly over weeks to months and may reach several centimeters in diameter.

Ulcerative plaques appear as irregular ulcers with undermined or heaped-up edges and a purulent base. They may co-exist with verrucous lesions on the same patient.

The skin lesions of blastomycosis are frequently misdiagnosed as squamous cell carcinoma, basal cell carcinoma, keratoacanthoma, pyoderma gangrenosum, or other chronic infections such as cutaneous tuberculosis (lupus vulgaris) or leishmaniasis. The characteristic appearance in the appropriate geographic and exposure context should always prompt biopsy.

Skin biopsy is highly diagnostic. Hematoxylin and eosin (H&E) staining reveals pseudoepitheliomatous hyperplasia with suppurative granulomas in the dermis containing broad-based budding yeast. Periodic acid-Schiff (PAS) and Gomori methenamine silver (GMS) stains highlight the organisms clearly. A culture of the biopsy specimen adds confirmatory sensitivity. Clinicians should always biopsy skin lesions in patients from endemic areas and request both histopathology and fungal culture.

A critical practical point: skin-only blastomycosis must never be treated with topical antifungals alone. Even when lesions appear confined to the skin, systemic antifungal therapy is required because the skin involvement indicates hematogenous dissemination from a primary pulmonary focus.

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6. Bone, Genitourinary, and CNS Involvement

Beyond the lungs and skin, blastomycosis can involve virtually any organ system. The clinical importance of recognizing these extrapulmonary sites lies in the fact that disseminated disease requires prolonged treatment and may require specific management strategies depending on the site involved.

Bone and Joint Disease

Skeletal blastomycosis occurs in approximately 10 to 25% of disseminated cases. The organism causes lytic osteomyelitis — destructive bone lesions without the reactive sclerosis typical of bacterial osteomyelitis. The vertebrae are a common site, producing a clinical picture that mimics Pott's disease (spinal tuberculosis), with vertebral body destruction, disc space narrowing, and paravertebral cold abscess formation. Long bones, ribs, and the skull may also be involved. Sinus tracts draining from bone lesions to the skin surface can be seen. Radiographic findings include lytic lesions with well-defined borders. MRI is more sensitive than plain film for early vertebral involvement.

Genitourinary Disease

The prostate gland is a favored site in male patients, making genitourinary blastomycosis an important consideration in men with disseminated disease. Prostatic involvement can present as prostatitis — with pelvic pain, urinary symptoms, and tender prostate on examination — or as an incidental finding on imaging. Epididymitis and orchitis can also occur. In men with suspected disseminated blastomycosis, prostate culture (obtained via semen, expressed prostatic secretions, or tissue biopsy) and urinary antigen testing provide useful diagnostic yield. The prostate may act as a reservoir that complicates eradication if treatment is insufficient in duration.

Central Nervous System Disease

CNS blastomycosis is uncommon but carries a high mortality rate. It occurs most frequently in immunocompromised patients — particularly those with HIV infection or organ transplantation — but can also affect immunocompetent individuals. Manifestations include meningitis (with lymphocytic pleocytosis in the CSF), brain abscess, and spinal cord involvement (epidural abscess). Diagnosis requires lumbar puncture with CSF fungal culture, and antigen detection in CSF. Treatment requires agents with good CNS penetration (see Treatment section). Other less common sites include the adrenal glands, thyroid, liver, spleen, and the eye (chorioretinitis, endophthalmitis).

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7. Diagnosis

Diagnosis of blastomycosis requires a combination of clinical suspicion, appropriate specimen collection, and laboratory confirmation. No single test is 100% sensitive, and the approach depends on the clinical presentation and available resources.

Cultures (Gold Standard): Growth of Blastomyces dermatitidis from clinical specimens remains the definitive diagnostic method. Appropriate specimens include sputum, bronchoalveolar lavage (BAL) fluid, skin biopsy tissue, bone biopsy, prostatic secretions, and CSF. The organism grows on Sabouraud's dextrose agar or inhibitory mold agar, typically within 1 to 4 weeks at room temperature, initially forming a white-to-tan mold. Confirmation requires demonstrating thermal dimorphism — conversion to the characteristic yeast form at 37°C, or DNA probe identification of the mold culture. The slow growth of cultures means that treatment decisions often must be made before culture results are available.

Urinary Antigen Detection: The MVista Blastomyces Quantitative Antigen EIA (MiraVista Diagnostics) detects galactomannan polysaccharide antigen shed by Blastomyces in urine. Sensitivity is approximately 89 to 93% in disseminated disease and somewhat lower in localized pulmonary infection. This test can provide results within 24 to 48 hours and is particularly useful for monitoring treatment response (antigen levels fall with successful therapy). An important limitation is cross-reactivity with Histoplasma capsulatum — a positive result must be interpreted in context. The antigen test is also available for serum, though urine is more sensitive.

Serology: Complement fixation (CF) and immunodiffusion (ID) tests for Blastomyces antibodies are available but have poor sensitivity (30 to 50%) and significant cross-reactivity with histoplasmosis, aspergillosis, and coccidioidomycosis. Serology should not be relied upon to rule out blastomycosis — a negative serologic test does not exclude the diagnosis. Newer enzyme immunoassay (EIA)-based serologic methods show improved performance but are not widely standardized.

Histopathology: Tissue biopsy processed with H&E, PAS, or GMS staining allows direct visualization of the characteristic broad-based budding yeast within granulomatous inflammation. This approach is particularly valuable for skin and bone lesions, and results can be available within 24 to 48 hours (much faster than culture).

Molecular testing: PCR-based assays for Blastomyces DNA in clinical specimens and culture isolates are available at reference laboratories and are increasingly used for rapid speciation of fungal cultures. These assays can identify the organism from mold cultures in hours rather than days.

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8. Microscopy: Broad-Based Budding Yeast

Direct microscopic examination of clinical specimens is one of the most rapid and cost-effective diagnostic tools in blastomycosis. Unlike histoplasmosis, where the yeast cells are tiny and difficult to see without special stains, Blastomyces yeast forms are large enough to be identified on simple KOH preparations or Papanicolaou-stained cytology.

The key features to identify on microscopy are:

Large, round yeast cells: 8 to 15 micrometers in diameter — roughly the size of a red blood cell to twice that size. The large size immediately distinguishes them from Histoplasma (2 to 4 µm).
Thick, refractile, double-contoured cell wall: This gives the yeast a characteristic "double-wall" appearance that is distinctive even on low-power examination.
Broad-based budding: The daughter cell (blastospore) attaches to the mother cell via a wide neck — the bud base is nearly as wide as the bud itself. This is the pathognomonic feature. It stands in sharp contrast to Cryptococcus neoformans, which produces a narrow-based bud from a typically encapsulated cell.
Single bud (usually): Unlike Paracoccidioides brasiliensis, which produces multiple simultaneous buds in a "steering wheel" or "pilot wheel" pattern, Blastomyces typically produces only one bud at a time.

Appropriate specimens for direct microscopy include:

Sputum or BAL fluid: Process with 10% KOH to clear mucus and cellular debris, then examine under brightfield or phase-contrast microscopy.
Pus or wound drainage from skin lesions: Thick purulent material from the base of verrucous or ulcerative lesions often contains abundant yeast cells and can yield an immediate presumptive diagnosis.
Tissue touch preparations: Fresh biopsy tissue can be pressed onto a slide, air-dried, and stained for rapid assessment.

A positive direct microscopy result with classic broad-based budding yeast in the appropriate clinical and geographic context provides sufficient presumptive evidence to initiate antifungal treatment immediately while awaiting culture confirmation. Cytopathology review of BAL or FNA specimens by an experienced cytopathologist using Papanicolaou or Diff-Quik stain can also identify the organisms reliably.

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9. Treatment

Treatment decisions in blastomycosis are guided by disease severity, site of infection, immune status, and special circumstances such as pregnancy or CNS involvement. The Infectious Diseases Society of America (IDSA) published comprehensive management guidelines (Chapman et al., 2008) that remain the standard of care.

Mild to Moderate Pulmonary and Non-CNS Extrapulmonary Disease

Itraconazole is the first-line agent for mild to moderate pulmonary blastomycosis and for extrapulmonary disease not involving the CNS (including skin, bone, and genitourinary sites). The recommended dosing is 200 mg once or twice daily (total 200 to 400 mg/day). Treatment duration is a minimum of 6 months for pulmonary disease and 6 to 12 months for bone disease (which tends to require longer therapy). Skin-only blastomycosis — even when lesions appear confined to the skin — requires systemic itraconazole for at least 6 months.

Therapeutic drug monitoring is essential with itraconazole: drug levels vary substantially between patients and formulations. A serum itraconazole level (drawn 2 weeks after initiating therapy) should target a combined itraconazole + hydroxyitraconazole concentration of at least 1 to 2 µg/mL. Liver function tests should be monitored periodically. Important drug interactions include rifampin and phenytoin, which significantly reduce itraconazole levels.

Severe Pulmonary Disease and Disseminated Infection

Liposomal amphotericin B (AmBisome) at 3 to 5 mg/kg/day is the treatment of choice for severe or life-threatening blastomycosis, including acute respiratory failure, rapidly progressive pneumonia, and disseminated infection in immunocompromised patients. The lipid formulation is preferred over conventional amphotericin B deoxycholate due to its superior tolerability and reduced nephrotoxicity. After clinical stabilization (typically 1 to 2 weeks), treatment can be stepped down to oral itraconazole to complete a total course of at least 12 months.

CNS Blastomycosis

CNS involvement demands a specific approach because of the need for adequate drug penetration across the blood-brain barrier. Itraconazole has poor CSF penetration and is insufficient as monotherapy for CNS disease. The recommended approach is:

Induction: Liposomal amphotericin B 5 mg/kg/day for 4 to 6 weeks
Consolidation and maintenance: Fluconazole 800 mg/day (high-dose, for superior CSF penetration) or voriconazole 200 to 400 mg twice daily, continued for at least 12 months and often lifelong in immunocompromised patients

Voriconazole has emerged as a preferred alternative for CNS blastomycosis because of its excellent CNS penetration and activity against Blastomyces. Isavuconazole is an emerging option with good activity and tolerability, though clinical experience in blastomycosis is more limited.

Special Antifungal Considerations

Fluconazole has limited activity against Blastomyces at standard doses and should not be used as first-line therapy for non-CNS disease. Only at high doses (800 mg/day) is it effective, and it is then reserved for CNS consolidation or patients who cannot tolerate itraconazole.

Monitoring for relapse: Blastomycosis has a meaningful relapse rate, particularly when treatment is stopped prematurely. Clinical, radiographic, and antigen monitoring at 3-month intervals after completing therapy is recommended. A rising urine antigen level in a patient who has completed therapy should prompt re-evaluation for relapse.

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10. Special Populations

Immunocompromised Patients

Patients with HIV/AIDS (particularly CD4 counts below 200 cells/µL), solid organ transplant recipients on immunosuppression, patients receiving high-dose corticosteroids, and those undergoing cancer chemotherapy are at substantially higher risk for severe and rapidly disseminated blastomycosis. Extrapulmonary dissemination occurs more frequently and more aggressively in these patients, and CNS involvement is disproportionately common. These patients should be treated with liposomal amphotericin B for induction regardless of initial disease severity, followed by long-term itraconazole suppression. In patients with HIV, secondary prophylaxis with itraconazole is recommended until CD4 count rises and remains above 200 cells/µL on antiretroviral therapy for at least 6 months.

Pregnancy

Blastomycosis in pregnancy carries risk of transplacental spread to the fetus and can cause congenital infection. Itraconazole is contraindicated in pregnancy (teratogenic in animal studies; pregnancy category C/D). The treatment of choice for pregnant patients is liposomal amphotericin B, which does not cross the placenta in significant amounts and has the longest safety record in pregnancy among antifungals. Azoles (itraconazole, voriconazole, fluconazole at high doses) should be avoided throughout pregnancy.

Children

Pediatric blastomycosis is uncommon but has been documented, particularly in children with outdoor exposure in endemic areas. The clinical presentation mirrors that of adults. Itraconazole suspension (2 to 5 mg/kg/day) is the preferred treatment for mild-moderate disease in children, with weight-based liposomal amphotericin B for severe disease.

Cancer and Chemotherapy Patients

Patients with hematologic malignancies receiving chemotherapy can develop rapidly progressive blastomycosis with high mortality. Prompt recognition, aggressive diagnostic workup (including blood cultures and urine antigen), and early antifungal therapy with liposomal amphotericin B are essential. Blastomycosis in the neutropenic patient may not produce the typical granulomatous response, making histopathology less typical and culture recovery even more important.

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11. Key Research Papers

Additional PubMed searches for current research:

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12. Featured Videos

Featured videos on blastomycosis will appear here after the playlist is generated.

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Blastomycosis

Table of Contents

1. Overview and Causative Organism

2. Endemic Zones and Epidemiology

3. Exposure and Outbreak Settings

4. Pulmonary Blastomycosis

5. Skin Manifestations

6. Bone, Genitourinary, and CNS Involvement

Bone and Joint Disease

Genitourinary Disease

Central Nervous System Disease

7. Diagnosis

8. Microscopy: Broad-Based Budding Yeast

9. Treatment

Mild to Moderate Pulmonary and Non-CNS Extrapulmonary Disease

Severe Pulmonary Disease and Disseminated Infection

CNS Blastomycosis

Special Antifungal Considerations

10. Special Populations

Immunocompromised Patients

Pregnancy

Children

Cancer and Chemotherapy Patients

11. Key Research Papers

12. Featured Videos

Connections