Testing Algorithm for Blastomycosis

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

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

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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

Show Text Description

Approximate blastomycosis-endemic areas

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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.

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Approximate areas with the presence of Blastomyces in the world

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.

Additional Resources

• Clinical Testing Guidance for Coccidioidomycosis, Histoplasmosis, and Blastomycosis in Patients With Community-Acquired Pneumonia for Primary and Urgent Care Providers | Clinical Infectious Diseases | Oxford Academic (oup.com)
• Webinar Thursday, September 21, 2023 – Algorithms for Diagnosing the Endemic Mycoses Blastomycosis, Coccidioidomycosis, and Histoplasmosis (cdc.gov)
• Three Cases of Community-Acquired Pneumonia (medscape.com)