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.
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
- *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
- Probable acute pulmonary blastomycosis
- Blastomyces antigen tests have extensive cross-reactivity with Histoplasma. However, both infections are typically treated in a similar manner for most clinical manifestations
- Probable acute pulmonary blastomycosis
- Antigen negative
- Consider alternative diagnosis
- If there is a high degree of suspicion:
- Consider consulting infectious disease or pulmonary
- Additional testing:
- 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.
- If the additional testing is positive, then probable acute pulmonary blastomycosis.
- If additional testing is negative, then consider alternate diagnosis
Information 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:
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
|Complement fixation (CF) antibody13,15,16||9%–57%||30%–100%||Adult populations, outbreak settings|
|Immunodiffusion (ID) antibody8,13–17||28%–65%||100%||Adult populations, outbreak settings|
|EIA urine antigen8–12||76%–93%||High (but does cross-react with Histoplasma)||Adult populations|
|EIA serum antigen8–12||56%–82%||High (but does cross-react with Histoplasma)||Adult populations|
|Cytology8,18||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
- Seitz AE, Younes N, Steiner CA, Prevots DR. Incidence and Trends of Blastomycosis-Associated Hospitalizations in the United States. Chaturvedi V, ed. PLoS ONE. 2014;9(8):e105466. doi:10.1371/journal.pone.0105466
- McDonald R, Dufort E, Jackson BR, et al. Notes from the Field: Blastomycosis Cases Occurring Outside of Regions with Known Endemicity — New York, 2007–2017. MMWR Morb Mortal Wkly Rep. 2018;67(38):1077-1078. doi:10.15585/mmwr.mm6738a8
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- Connolly P, Hage CA, Bariola JR, et al. Blastomyces dermatitidis Antigen Detection by Quantitative Enzyme Immunoassay. Clin Vaccine Immunol. 2012;19(1):53-56. doi:10.1128/CVI.05248-11
- Frost HM, Novicki TJ. Blastomyces Antigen Detection for Diagnosis and Management of Blastomycosis. Diekema DJ, ed. J Clin Microbiol. 2015;53(11):3660-3662. doi:10.1128/JCM.02352-15
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- O’Dowd TR, Mc Hugh JW, Theel ES, et al. Diagnostic Methods and Risk Factors for Severe Disease and Mortality in Blastomycosis: A Retrospective Cohort Study. J Fungi. 2021;7(11):888. doi:10.3390/jof7110888
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