How is blastomycosis diagnosed and treated?

Diagnosis of Blastomycosis

The diagnosis of blastomycosis requires a combination of direct visualization of the organism, culture, and antigen testing, with culture being the gold standard despite its longer turnaround time.

Diagnostic Methods

Direct Visualization

• Direct microscopic examination of respiratory specimens is the most commonly used method for rapid diagnosis 1
• Respiratory specimens can be treated with:
  • Potassium hydroxide (KOH)
  • Calcofluor white
  • Papanicolaou stain
• Sensitivity ranges from 50-90% for respiratory specimens 1, 2
• Histopathological examination using methenamine silver or periodic acid-Schiff (PAS) stain is the standard for extrapulmonary disease 1

Culture

• Gold standard for definitive diagnosis
• High sensitivity: 86% from sputum and 100% from bronchial washings in patients with pulmonary disease 1
• Culture confirmation should be sought in every suspected case 1
• Major limitation: slow growth requiring up to 5 weeks for results 1

Antigen Testing

• Blastomyces urinary antigen testing has high sensitivity (92.9%) 1, 2
• Can be performed on:
  • Urine (preferred specimen)
  • Serum
  • Other body fluids
• Important limitation: significant cross-reactivity with other endemic mycoses, particularly Histoplasma capsulatum 1
• Particularly useful in cases with negative sputum cytology but subsequent positive culture 1

Serology

• Newer enzyme immunoassays (EIA) have improved sensitivity (87.8%) compared to older methods 1, 2
• Traditional serological methods (complement fixation and immunodiffusion) lack both sensitivity and specificity 1
• EIA recognizing the B. dermatitidis surface protein BAD-1 shows better performance 1
• Cross-reactivity remains an issue, with positive results observed in 6% of histoplasmosis cases 1

Diagnostic Algorithm

1. Initial evaluation:

   • Collect respiratory specimens (sputum or bronchial washings) for:
     • Direct microscopic examination with KOH or calcofluor white
     • Culture

2. Additional testing:

   • Urinary antigen testing (high sensitivity but cross-reactivity with other fungi)
   • Serum antibody testing using EIA (moderate sensitivity)
   • For extrapulmonary disease: biopsy with histopathological examination

3. Definitive diagnosis is established by:

   • Visualization of characteristic broad-based budding yeast in clinical specimens, OR
   • Isolation of B. dermatitidis in culture

Special Considerations

Immunocompromised Patients

• More likely to develop severe pulmonary infection and disseminated disease 1
• May require more aggressive diagnostic approach including:
  • Bronchoscopy with bronchoalveolar lavage
  • Tissue biopsy
  • Multiple specimen collection

Laboratory Pitfalls

• False-negative results can occur with:

  • Inadequate specimen collection
  • Single specimen examination (multiple specimens improve yield)
  • Early disease with low organism burden

• False-positive antigen results due to cross-reactivity with:

  • Histoplasmosis (most common)
  • Coccidioidomycosis
  • Paracoccidioidomycosis
  • Talaromycosis 1

Diagnostic Performance Summary

• Direct visualization: 50-90% sensitivity
• Culture: 86-100% sensitivity (gold standard)
• Urinary antigen: 92.9% sensitivity with cross-reactivity
• Serum antibody (EIA): 87.8% sensitivity

The American Thoracic Society recommends using urinary antigen testing together with clinical and epidemiological data to establish the diagnosis, particularly in immunocompromised patients 1. However, due to cross-reactivity issues, a combination of diagnostic methods is typically required for accurate diagnosis.