What blood test is used to diagnose a mold-related illness in a patient presenting with respiratory issues, allergic reactions, or skin rashes?

Blood Testing for Mold-Related Illness

The primary blood tests for mold-related illness are serum galactomannan (GM) and (1→3)-β-D-glucan for invasive aspergillosis in high-risk immunocompromised patients, while serum antigen-specific IgG/IgA antibody testing should NOT be relied upon solely for diagnosing hypersensitivity pneumonitis or mold allergy. 1

Blood Tests for Invasive Mold Infections (Aspergillosis)

Galactomannan Testing

• Serum galactomannan is recommended as an accurate marker for invasive aspergillosis (IA) in adult and pediatric patients with hematologic malignancy or hematopoietic stem cell transplant (HSCT) 1
• GM testing is NOT recommended for routine screening in solid organ transplant recipients or patients with chronic granulomatous disease 1
• GM should not be used for blood screening in patients already receiving mold-active antifungal therapy or prophylaxis, as sensitivity drops significantly 1

(1→3)-β-D-Glucan Testing

• Serum (1→3)-β-D-glucan assays are recommended for diagnosing invasive aspergillosis in high-risk patients (hematologic malignancy, allogeneic HSCT), but this test is NOT specific for Aspergillus and can be positive with other fungal infections 1
• This test has high negative predictive value, making it useful for discontinuing empirical antifungal therapy when negative 2

PCR Testing

• Blood-based PCR for Aspergillus remains controversial with no consensus recommendation for routine clinical use due to lack of standardized, validated commercial assays 1
• When PCR is used, it should be interpreted carefully on a case-by-case basis in conjunction with other diagnostic tests and clinical context 1

Blood Tests for Mold Allergy and Hypersensitivity

Serum Antigen-Specific IgG/IgA Testing

• Guidelines explicitly recommend NOT relying solely on serum antigen-specific IgG or IgA testing to confirm or rule out hypersensitivity pneumonitis (HP) 1
• Major limitations include lack of standardized antigen preparations, lack of standardized immunoassay techniques, variable diagnostic cutoff thresholds, and validation only in limited populations 1
• Detection of serum IgG/IgA may suggest putative mold exposure when history is questionable (e.g., musty odor without visible mold), but lacks data supporting it as a reproducible diagnostic tool 1
• In one study, 60% of subjects with positive precipitins reported no exposure, while 32% with negative precipitins had identifiable exposure, demonstrating poor correlation 1

Serum IgE Testing (Skin Testing Preferred)

• For allergic rhinitis and asthma related to mold, skin prick testing to fungal antigens (Alternaria, Aspergillus, Penicillium, Cladosporium) is the first-line test, not blood testing 3
• Serum-specific IgE can be measured as an alternative when skin testing is not feasible 3
• Approximately 3-10% of the European population shows mold sensitization 3

Critical Limitations and Pitfalls

What Blood Tests CANNOT Do

• There are no uniformly accepted, valid serologic tests to assess mold exposure levels in environmental mold exposure cases 3
• Blood tests for mycotoxins have no validated methods for clinical diagnostics 4
• Serum antibody assays for endemic mycoses (blastomycosis) have significant cross-reactivity with other fungal infections, particularly histoplasmosis 1

When Blood Tests Are Inadequate

• For suspected invasive mold infections, tissue biopsy with histopathology and culture provides higher diagnostic yield than blood tests alone 2
• Blood cultures are positive in less than 50% of hematogenously disseminated candidiasis cases 2
• The sensitivity of fungal antigen tests (β-D-glucan or galactomannan) is particularly low in patients already receiving antifungal agents 2

Recommended Diagnostic Approach by Clinical Scenario

For Respiratory Symptoms with Environmental Mold Exposure

• Document temporal relationship between symptoms and damp environments 3
• Perform skin prick testing to mold allergens as first-line (not blood testing) 3
• Consider serum-specific IgE only if skin testing unavailable 3
• Do NOT order serum IgG/IgA precipitins as a standalone test 1

For Suspected Invasive Aspergillosis (Immunocompromised Patients)

• Order serum galactomannan if patient has hematologic malignancy or HSCT (not on mold-active prophylaxis) 1
• Order serum (1→3)-β-D-glucan recognizing it is non-specific 1
• Combine multiple diagnostic methods including chest CT, bronchoscopy with BAL, and tissue biopsy when feasible 1, 2
• Consider molecular diagnostics (PCR) only in specialized centers with validated assays 1, 2

For Suspected Hypersensitivity Pneumonitis

• Do NOT rely on serum precipitins (IgG/IgA) alone for diagnosis 1
• Integrate high-resolution CT findings with clinical history and exposure assessment 1
• Consider bronchoscopy with BAL for lymphocyte analysis if diagnosis remains uncertain 1