Can Allergen-Specific IgE Antibodies Diagnose Egg Allergy Accurately?

Diagnosis of food allergy requires thorough history and physical examination, and/or skin prick tests or serum immunoassays to determine food-specific IgE (sIgE) antibodies for IgE-mediated food allergy.1 Double-blind placebo-controlled food challenges (DBPCFC) are actually still the gold standard for diagnosis.2 Many researchers endeavored to find solutions on diagnosing food allergies without food challenge tests. The traditional DBPCFC tests are time-consuming, expensive and troublesome for physician and patients. Serum immunoassays of food-sIgE has become a widely used modality to evaluate IgE-mediated food allergies.3 Higher concentrations of food-sIgE levels are correlated with an increasing likelihood of clinical allergic reactions but not generally associated with the severity.4-6 However, different predictive values are being suggested from recent studies, which might be influenced by diet, age, disease, and challenge protocol.5-7 Ethnicity or geographic location can also affect the difference in predictive values because they influence prevalence and causes of food allergies.8,9 Moreover, the absence of food-sIgE does not indicate absence of clinical reactions to food.10

The current international guidelines recommend using oral food challenges (OFC) for diagnosing food allergies.11 A single-blind or an open-food challenge can be considered diagnostic under careful medical history and physical examination, instead of DBPCFC. Recently, Atopic Dermatitis Study Group in the Korean Academy of Pediatric Allergy and Respitatory Diseases introduced an adjusted guideline for the OFC for Korean children.12 If a patient has food allergy-suspected symptoms, food-sIgE antibodies would be determined to support the diagnosis. And then, if food-sIgE levels are below the diagnostic values, we can use OFC for diagnosing specific food allergy.

In Korea, egg allergy is known as the most frequent food allergy in children,13,14 however, large well-designed epidemiological studies are lacking. We still use diagnostic decision points for egg-sIgE levels based on US studies. Namely, we diagnose patients with egg allergies based on egg-sIgE levels exceeding the diagnostic values with 95% of certainty.1 Nevertheless, we often meet patients with high egg-sIgE and no clinical symptoms and vice versa. In the current issue of Allergy, Asthma & Immunology Research, Min et al.15 reported that the sensitivity and specificity of the predictive decision point values for egg white-sIgE antibodies by ImmunoCAP were relatively low in Korean children. This study started a new challenge for Korean allergists. However, the important thing we have to remember is that sIgE tests for identifying foods can potentially provoke IgE-mediated food allergy, but alone these tests are not diagnostics of food allergies, especially in patients without clinical allergic reactions.11 So we cannot exclude the possibility that the inclusion criteria, which are infants with no experience of egg intake or with a non-specific clinical response to egg intake, may cause low sensitivity and specificity. The measurement of food-sIgE levels in patients without history of clinical symptoms related to food ingestion is discouraged. Further study will be needed to determine the predictive decision point values for food allergies, especially egg allergy.

It is known that the natural history of egg allergy has a good tolerance prognosis. Kim et al.16 reported that 41% of children had developed tolerance to egg allergy by 3 years of age and 60% by 5 years of age in Korean toddlers with atopic dermatitis. However, another study suggested a worse prognosis that 4% of children will outgrow egg allergy by 4 years of age, 12% by 6 years of age, and 37% by 10 years of age.17 These recent studies implicate that egg allergy is more persistent than the conventional wisdom and it is important to predict the prognosis of egg allergy. So some predictors have been suggested to indicate the persistence in egg allergy. Egg-sIgE of >50 kIU(A)/L can be used as a predictor for persistent egg allergy.17 High ovomucoid-sIgE (Gal d1), which is one of most important allergens in egg protein, also can be used as a predictor for persistence in egg allergy.18 On the contrary, low ovomucoid-sIgE could indicate a good prognosis of egg allergy.19 Likewise, component allergen-sIgE can be used as a prognostic marker in patients with egg allergy, not as a diagnostic marker. In this issue, Min et al.15 concludes that egg white component sIgE cannot predict the clinical reactions. Prospective studies should be determined to implicate component sIgE as a prognostic marker in Korea.

Moreover, large epidemiological cohort studies for food allergy, especially in infants, are necessary to understand the current situation and natural history immediately. Prospective clinical studies are also needed to diagnose and manage food allergies and predict their prognosis more accurately.