Community-Acquired Pneumonia (CAP): Clinical Testing Algorithm for Blastomycosis

This clinical testing algorithm was made in collaboration with the Mycoses Study Group Education & Research Consortium.

Patient living in or having traveled to a disease-endemic area (map below). In the United States the areas include the Midwest, South, and Northeast. Globally, the continent of Africa and India.

Patient living in or having traveled to a blastomycosis-endemic area: United States east of the Mississippi

World map showing patient living in or having traveled to a blastomycosis-endemic area - United States east of the Mississippi and much of Africa

Dark Green: Areas Blastomyces is more likely to live; gray: Potential range of Blastomyces

These maps are approximations. Blastomyces is not distributed evenly and may not be present everywhere within the shaded areas. It may also be present outside of the areas indicated.

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

1b. Initial CAP visit if:

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

2. Consider enzyme immunoassay (EIA) urine antigen testing

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
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

Information About blastomycosis

About Blastomycosis

Blastomycosis is an invasive fungal disease that often presents as community-acquired pneumonia in primary and urgent care settings; however, it is less common than coccidioidomycosis and histoplasmosis except in certain hyperendemic areas, such as northern Minnesota and Wisconsin. 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 Patients hospitalized with blastomycosis have been identified across the United States, and cases have been reported in areas thought to be outside of known endemic areas.^2–4

When to Consider Testing for Blastomycosis

Clinicians may consider testing for blastomycosis in patients with community-acquired pneumonia who have failed at least one course of empiric antibiotics and who live in or have traveled to an area where blastomycosis is thought to be endemic (midwestern, south central, and southeastern states, particularly around the Ohio and Mississippi River Valleys, the Great Lakes, and the Saint Lawrence River. Northern Wisconsin and Minnesota may be hyperendemic for Blastomyces).^2,5,6

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

Abnormal skin lesions^5,6
Link to known blastomycosis outbreak

How to Test for Blastomycosis

We recommend 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.⁷

Tests for blastocycosis
Test	Sensitivity	Specificity	Populations studied
Antibody tests
Complement fixation (CF) antibody^13,15,16	9%–57%	30%–100%	Adult populations, outbreak settings
Immunodiffusion (ID) antibody^8,13–17	28%–65%	100%	Adult populations, outbreak settings
Antigen Tests
EIA urine antigen^8–12	76%–93%	High (but does cross-react with Histoplasma)	Adult populations
EIA serum antigen^8–12	56%–82%	High (but does cross-react with Histoplasma)	Adult populations
Other Tests
Histopathology¹⁸	81%	100%	Adult populations
Cytology^8,18	38%–97%	100%	Adult populations, pregnancy