What is the significance of a Histoplasma/Blastomyces antigen (Ag) level of elevated antigenemia?

From the Guidelines

A Histoplasma/Blastomyces antigen value of 2.4 ng/mL is considered positive, indicating active infection, and treatment should be initiated promptly. According to the American Thoracic Society clinical practice guideline 1, a positive likelihood ratio of 43.2 supports the diagnosis of histoplasmosis in an immunocompromised patient.

Key Considerations

• The level of antigen correlates with the severity of illness, but a value of 2.4 ng/mL does not necessarily indicate moderate to severe disease, as the positive predictive value of an antigen level greater than 16 pg/ml was 88% for moderate to severe histoplasmosis 1.
• Treatment options include itraconazole for mild to moderate disease, and liposomal amphotericin B for severe disease, followed by itraconazole for at least 12 months 1.
• Immunocompromised patients may require lifelong suppressive therapy with itraconazole 1.

Monitoring and Follow-up

• Serial antigen testing can be useful to monitor treatment response, with decreasing values indicating effective therapy 1.
• Patients should be monitored for medication side effects, particularly hepatotoxicity with itraconazole 1.

Limitations of Testing

• The Histoplasma antigen test cross-reacts with other endemic mycoses, including blastomycosis, and clinical context and additional testing are needed to determine the specific infection 1.
• The limited commercial availability of the test may delay testing and results reporting, which can limit its utility for rapid diagnosis in severe infections 1.

From the Research

Interpretation of Histoplasma/Blastomyces Ag Value

• The given value of 2.4 ng/mL is related to the diagnosis of histoplasmosis and blastomycosis, which are fungal diseases caused by environmentally acquired infection with thermally dimorphic fungi 2, 3.
• Antigen detection in urine and serum has been shown to aid in the rapid diagnosis of blastomycosis and histoplasmosis 4.
• The use of urine antigen testing for Blastomyces has been explored, and it has been found to be a sensitive noninvasive test, with a sensitivity of 87.9% and a specificity of 97.9% 5.
• Comparison of urine antigen assays for the diagnosis of Histoplasma capsulatum infection has shown high concordance between different assays, with an overall agreement of 99% 6.

Diagnostic Considerations

• The diagnosis of blastomycosis and histoplasmosis can be difficult due to the similarity of symptoms with other diseases, and the use of antigen detection and other diagnostic tests is crucial for establishing a diagnosis 2, 3.
• The gold standard for diagnosis is culture of the organism from involved tissues, but antigen detection and histopathological identification can provide rapid diagnosis 4.
• Cross-reactivity between Histoplasma and Blastomyces urine antigen tests has been observed, with 64.0% of patients with positive Histoplasma urine antigen also testing positive for Blastomyces urine antigen 5.

Treatment and Management

• Treatment of blastomycosis and histoplasmosis typically involves the use of antifungal medications, such as amphotericin B and itraconazole, with the choice of treatment depending on the severity of the disease and the patient's immune status 2, 3.
• Itraconazole is recommended for primary therapy in mild-to-moderate infection, while amphotericin B is used for severe cases or in immunosuppressed patients 2.