Diagnosis of Allergic Bronchopulmonary Aspergillosis: A Case-Based Approach

Sahajal Dhooria; Ritesh Agarwal

Disclosures

Future Microbiol. 2014;9(10):1195-1208. 

In This Article

What Investigations Are Used for Screening of ABPA?

Aspergillus fumigatus-specific IgE levels and Aspergillus skin test (AST) are the investigations most commonly used for diagnosing sensitization to A. fumigatus (defined as asthma with immediate cutaneous hypersensitivity to A. fumigatus or elevated specific IgE levels). Let us examine the utility of each of them in the diagnosis of ABPA.

A. fumigatus-specific IgE Levels

In 1974, Patterson et al. identified the presence of IgE antibodies directed toward A. fumigatus in the sera of patients with ABPA, and proposed this investigation as the most specific test in diagnosis of ABPA.[23] We now know that presence of A. fumigatus-specific IgE antibodies is not specific (specificity: 69–78%) for ABPA as they are also seen in Aspergillus-sensitized asthma, albeit at a lower level. However, A. fumigatus-specific IgE is probably the most sensitive test in diagnosis of ABPA. In a latent class analysis, A. fumigatus specific IgE level >0.35 kilo units of antibodies per liter (kUA/l) showed 100% sensitivity in the diagnosis of ABPA in three different models.[8] Although a cutoff value more than that of the pooled serum samples from patients with Aspergillus-sensitized asthma was proposed,[24,25] the clinical significance of this cutoff is not known. Clearly, more studies from different geographical regions are needed for defining a cutoff for A. fumigatus-specific IgE levels. At present, a value of 0.35 kUA/l, as agreed upon by the recently convened expert group meeting, might be accepted as the cutoff for a positive result.[7]

Aspergillus Skin Test

The presence and degree of cutaneous reactivity acts as a surrogate marker for sensitization within target organs, that is, lung in case of ABPA.[26] Skin testing for determining Aspergillus sensitization is performed by introducing a small quantity of A. fumigatus antigen (commercial or locally prepared) into the epidermis either by skin prick test (SPT), and if negative, followed by an intradermal injection.[21] The outcome of skin test is influenced by the relative concentration of the allergens in the extract and proper performance of the skin test.[27] A positive Type I reaction is typical of ABPA and represents the presence of A. fumigatus-specific IgE antibodies. Intradermal skin tests are more sensitive than SPT for the diagnosis of Aspergillus sensitization. In a meta-analysis, intradermal tests fared better than SPT for the detection of Aspergillus sensitization in bronchial asthma (28.7 vs 24.8%, p = 0.002); however, the prevalence did not vary with the type of antigen used (commercial or indigenous).[21] A positive skin test, similar to A. fumigatus-specific IgE, is not pathognomonic of ABPA as 28% of asthmatics have a positive AST, and of these only 40% are diagnosed with ABPA.[21] There is an association, albeit weak between Aspergillus sensitization (without ABPA) and severity of asthma.[28] In fact, patients who manifest severe asthma, fungal sensitization and in whom ABPA is excluded are classified as severe asthma with fungal sensitization.[29–32]

AST has been recommended as the preferred test for screening asthmatic patients for ABPA.[3,33] However, a positive skin test is probably not the gold standard for Aspergillus sensitization in the context of ABPA. In a recent study, Aspergillus skin testing (intradermal method using an indigenous antigen) had sensitivity ranging between 88 and 94% for the diagnosis of ABPA in asthmatics (vs 100% for A. fumigatus-specific IgE).[8] Thus, one in ten patients of ABPA can be potentially missed if AST is used as the screening test for ruling out ABPA (Box 3). Therefore, we recommend that all patients with persistent asthma be routinely investigated with an A. fumigatus specific IgE to rule out ABPA. An AST may be performed if specific IgE assay is not available; however, the clinician should understand that up to 6–12% of patients could be potentially missed if skin test is used as a screening modality.[8]

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