Testing Algorithm for Blastomycosis

Community-Acquired Pneumonia

What to know

  • Blastomycosis is an invasive fungal disease that often presents as community-acquired pneumonia in primary and urgent care settings.
  • Blastomycosis cannot be reliably distinguished from other causes of respiratory illness by signs or symptoms alone.
  • Clinicians in urgent care and outpatient settings can use this algorithm to help make determinations about clinical testing.
Map showing the spread of Blastomycosis within the U.S.

When to consider testing for blastomycosis

Blastomycosis is an invasive fungal disease that often presents as community-acquired pneumonia in primary and urgent care settings. It is less common than coccidioidomycosis and histoplasmosis except in certain hyperendemic areas, such as northern Minnesota and Wisconsin. It is endemic in parts of the U.S. and the world. 

Blastomycosis cannot be reliably distinguished from other causes of respiratory illness by signs or symptoms alone. Thus, patients are commonly misdiagnosed and inappropriately treated with antibiotics—up to 2.5 courses of antibacterial medications are given on average before proper diagnosis.1.

Consider testing patients with community-acquired pneumonia who:

  • Live in or recently traveled to an endemic area (maps below) and
  • Have not improved with at least one course of empiric antibiotics.

Visual algorithm

PDF version

If a patient lives in or has recently traveled to a blastomycosis-endemic area and has:

A flowchart to show the diagnosis of blastomycosis
A flowchart to show the diagnosis of blastomycosis

1a. CAP of unknown etiology not responding to a course of empiric antibiotics

or

1b. Initial CAP visit if:

  1. Skin lesions present* or
    1. *Skin lesions could be indicative of late disease or traumatic inoculation rather than acute pulmonary blastomycosis.
  2. Link to known blastomycosis outbreak

2. Consider enzyme immunoassay (EIA) urine antigen testing

  1. Antigen positive
    1. Probable acute pulmonary blastomycosis
      1. Blastomyces antigen tests have extensive cross-reactivity with Histoplasma. However, both infections are typically treated in a similar manner for most clinical manifestations
  2. Antigen negative
    1. Consider alternative diagnosis
    2. If there is a high degree of suspicion:
      1. Consider consulting infectious disease or pulmonary
      2. Additional testing:
        1. Sputum or bronchoalveolar lavage (BAL) culture and microscopy; skin biopsy (if lesion exists) for histopathology; or serologic antibody tests. Evaluation of other non-pulmonary manifestations in the bone, genitourinary tract, and central nervous system may be helpful in diagnosis.
        2. If the additional testing is positive, then probable acute pulmonary blastomycosis.
          1. Blastomyces antigen tests have extensive cross-reactivity with Histoplasma. However, both infections are typically treated in a similar manner for most clinical manifestations
        3. If additional testing is negative, then consider alternate diagnosis

Approximate blastomycosis-endemic areas

Approximate areas with the presence of Blastomyces worldwide
Approximate areas with the presence of Blastomyces within the U.S.

These areas include midwestern, south central, and southeastern states, especially:

  • Around the Ohio and Mississippi River Valleys, Great Lakes, and Saint Lawrence River.
  • Northern Wisconsin and Minnesota, where it may be hyperendemic.
Map showing approximate area with the presence of Blastomyces in the U.S.
Approximate areas with the presence of Blastomyces in the world
Health Care Providers: Clinical Overview of Blastomycosis

Additional considerations

Clinicians may also consider testing for blastomycosis on an initial presentation of community-acquired pneumonia with one of the following:

  • Abnormal skin lesions
  • Link to known blastomycosis outbreak

How to test for blastomycosis

Consider ordering an enzyme immunoassay (EIA) urine antigen test initially for blastomycosis diagnosis. EIA urine antigen tests may have the highest sensitivity of noninvasive tests and the quickest turnaround time. If the EIA urine antigen is negative, clinicians should consider alternative diagnoses. Alternatively, if a high degree of suspicion remains, additional diagnostic options include sputum or bronchoalveolar lavage (BAL) culture and microscopy as well as skin biopsies (if lesion exists) for microscopy. Evaluation of other non-pulmonary manifestations in the bone, genitourinary tract, and central nervous system may be helpful in diagnosis. Available serologic antibody tests are reported to have low sensitivity, though they may be a useful adjunct diagnostic test when an antigen test is negative or when trying to differentiate blastomycosis from histoplasmosis (e.g., if done in combination with Histoplasma antibody testing). Consultation with specialists in infectious diseases or pulmonology may be considered if a high degree of suspicion remains as well.

Blastomyces antigen tests have extensive cross-reactivity with Histoplasma. Both infections are treated the same way in most clinical manifestations.

Clinicians should refer to the Infectious Diseases Society of America's blastomycosis treatment guidelines or an infectious disease physician when determining therapy after a positive result.

Tests for Blastomycosis
Test Sensitivity Specificity Populations studied
Antibody tests
Complement fixation (CF) antibody 9%–57% 30%–100% Adult populations, outbreak settings
Immunodiffusion (ID) antibody 28%–65% 100% Adult populations, outbreak settings
Antigen Tests
EIA urine antigen 76%–93% High (but does cross-react with Histoplasma) Adult populations
EIA serum antigen 56%–82% High (but does cross-react with Histoplasma) Adult populations
Other Tests
Histopathology 81% 100% Adult populations
Cytology 38%–97% 100% Adult populations, pregnancy
  • Alpern JD, Bahr NC, Vazquez-Benitez G, Boulware DR, Sellman JS, Sarosi GA. Diagnostic Delay and Antibiotic Overuse in Acute Pulmonary Blastomycosis. Open Forum Infect Dis. 2016;3(2):ofw078. doi:10.1093/ofid/ofw078