IgE-Mediated Allergies

Diagnostic Approaches

IgE-mediated allergies manifest with a diverse range of clinical symptoms, which often affect multiple organ systems in the body. These manifestations can vary from skin reactions to respiratory, gastrointestinal, cardiovascular and neurological symptoms. Clinical manifestations of IgE-mediated allergies are shown in Table 2-1.

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Three forms of tests are commonly used for the diagnosis of IgE-mediated allergies:

• Skin prick tests
• Serum IgE assays
• Oral food challenge (OFC)

Immediate hypersensitivity skin testing (IHST) is a method that uses a device coated with allergen extract or fresh food to scratch the surface of the skin, allowing the allergen to penetrate. If the individual is allergic to a specific food, a reaction characterized by redness, swelling and itching will occur at the site within approximately 15 minutes. The size of the wheal (swelling) and flare (redness) produced is measured and compared to a control to determine the presence of an allergic reaction. The test is considered positive if the diameter of the wheal caused by the food allergen is ≥3 mm larger than the one observed with the negative control. Serum specific IgE (sIgE) assays measure circulating antibody levels using the fluorescence enzyme labelling technique. In this method, the patient's serum is exposed to a surface-fixed allergen, to which food-specific IgE from the patient attaches. A fluorescently labeled anti-IgE antibody is then used to identify the food-specific IgE.

Although IHST and sIgE assays have a high sensitivity (>90%) and are valuable for identifying potential food allergens, the specificity of both tests can be quite low (<50%). These tests do not differentiate between sensitization and true allergies, which can potentially misdirect practitioners and lead to an inaccurate diagnosis. Furthermore, these tests do not indicate allergy severity. The severity scales often reported with these tests are misleading and should not be used in test interpretation. Serum sIgE food panels are frequently overused due to their accessibility and perceived convenience, often being ordered indiscriminately by healthcare providers without considering the patient's clinical history or symptoms. This overuse stems from a desire for quick diagnostic answers; however, serum sIgE food panels are unreliable due to their high rate of false positives. The use of sIgE panels can lead to misdiagnosis or overdiagnosis, leaving patients with harmful physical and/or psychological effects, financial strain and opportunity costs (Figure 2-1).

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Oral food challenge, ideally performed in a double-blind, placebo-controlled manner, is the gold standard for diagnosing food allergies. During an OFC, the patient consumes gradually increasing amounts of the suspected allergen to provoke any potential allergic reactions. This controlled exposure allows clinicians to observe and evaluate the patient's response, distinguishing between true allergies and other conditions. To ensure the reliability of the test, patients must discontinue all medications that could interfere with the results before the OFC is conducted. It is important to note that OFC can lead to anaphylaxis. Therefore, it is up to the clinician to decide whether the patient should undergo an OFC test, based on the clinical history, physical examination and previous test results.

As mentioned earlier, skin prick tests and serum IgE assays lack the necessary specificity and therefore may yield false results, while OFC are time-consuming, costly and carry the risk of triggering severe allergic reactions. The need for better diagnostic modalities led to the development of promising novel promising tests, including serologic tests which measure epitope-specific IgE levels, the basophil activation test (BAT) and the mast cell activation test (MAT). Epitope-specific IgE testing offers higher specificity and reduced cross-reactivity compared to whole allergen testing. However, it may produce false negatives due to a smaller IgE-binding region and potential omission of crucial conformational epitopes. To address this, additional testing for IgE specific to other allergen components enhances diagnostic accuracy and ensures comprehensive evaluation of allergic sensitivities. The BAT and MAT assess all components of the allergic reaction, offering results that closely reflect the patient's allergic status. Recent studies have confirmed the high sensitivity and specificity of BAT, demonstrating its accuracy in diagnosing food allergies, predicting the severity and threshold of allergic reactions, and identifying patients who react to low doses of allergens. The MAT has shown lower sensitivity than the BAT; however, the MAT can be a valuable diagnostic tool for patients with nonresponding basophils.