Histoplasmosis is a fungal infection caused by inhaling the spores of Histoplasma capsulatum, which commonly grows in soil enriched with bird or bat droppings. Diagnosis is challenging because symptoms often resemble the common flu or pneumonia and can mimic many other respiratory diseases. A definitive diagnosis requires a multi-faceted approach, combining a patient’s medical history, imaging, and detailed laboratory analysis. The process involves ruling out other conditions while searching for evidence of the fungus or the body’s reaction to it.
Initial Clinical Evaluation
The initial step involves a thorough assessment of the patient’s symptoms and background. Common symptoms of acute pulmonary histoplasmosis, such as fever, cough, headache, chills, and fatigue, are often indistinguishable from other respiratory infections. Since most people experience either no symptoms or a mild, self-limiting illness, the clinical evaluation must extend beyond current complaints.
A detailed exposure history is important for guiding the diagnosis toward a fungal cause. The provider will inquire about travel to endemic areas, such as the Ohio and Mississippi River valleys, or parts of Central and South America. Significant risk factors for exposure include occupational or recreational activities like cleaning chicken coops, exploring caves, or working with soil contaminated by guano. The patient’s immune status is also assessed, as immunocompromised individuals are at much higher risk for the severe, disseminated form of the disease.
Diagnostic Imaging
Medical imaging provides supporting evidence of the infection’s location and severity, particularly in the lungs. A chest X-ray or a computed tomography (CT) scan is commonly used to look for characteristic changes in the lung tissue. In acute infections, imaging may reveal poorly defined areas of consolidation, similar to bacterial pneumonia, or enlarged lymph nodes near the lungs (hilar or mediastinal lymphadenopathy).
CT scans are more sensitive than X-rays and can detect subtle findings, such as multiple small nodules scattered throughout the lungs, a pattern referred to as miliary histoplasmosis. For chronic or healed infections, imaging may show calcified nodules, sometimes called histoplasmomas, or calcified lymph nodes. While these findings suggest histoplasmosis, they are not exclusive and can be seen in other diseases like sarcoidosis or lung cancer, meaning imaging alone cannot confirm the diagnosis.
Identifying the Fungus Directly
Laboratory tests are employed to detect the fungus itself or its byproducts within the body. The detection of Histoplasma antigen is a rapid diagnostic method, identifying a polysaccharide component released during active infection. This test is typically performed on urine or serum samples, with urine testing showing high sensitivity, especially in severe or disseminated histoplasmosis.
Antigen detection is valuable in immunocompromised patients, providing a quick result to guide immediate treatment. The test is also useful for monitoring antifungal therapy, as decreasing antigen levels correlate with a reduction in the fungal burden. Although rapid and sensitive, the antigen test can sometimes show cross-reactivity with other endemic fungi, such as Blastomyces, requiring careful interpretation.
Fungal culture remains the traditional standard method for a definitive diagnosis, involving growing Histoplasma capsulatum from a clinical sample. The fungus can be isolated from tissue biopsies, blood, bone marrow, or respiratory secretions. A significant drawback is the time required for the fungus to grow, which can take several weeks, potentially delaying treatment. Furthermore, handling the fungus requires specific safety protocols due to the risk of airborne exposure to lab personnel.
Testing the Immune Response
Testing the body’s specific reaction to fungal exposure, known as serology, detects the presence of antibodies against Histoplasma. Serological tests are generally more useful for subacute or chronic infections, or for establishing a past infection. This is because the immune system requires two to six weeks following initial exposure to produce a detectable antibody response.
The two common serological methods are immunodiffusion (ID) and complement fixation (CF). Immunodiffusion is highly specific and detects two distinct antibodies, known as H and M bands. The presence of the M band suggests a recent or chronic infection, while the H band indicates active or progressive disease.
Complement fixation measures the overall level of antibodies, expressed as a titer. A single high titer, typically 1:32 or greater, suggests an active infection. Strong evidence of ongoing infection is a four-fold increase in titer between an acute-phase sample and a later convalescent-phase sample. Complement fixation is often more sensitive than immunodiffusion, but it is less specific and may produce false positives due to cross-reactivity. Therefore, both ID and CF tests are often ordered simultaneously to maximize accuracy.