Guided Gradual Egg-Tolerance Induction in Hen's Egg Allergic Children Tolerating Baked Egg: A Prospective Randomized Trial.

Background: Over the last few years, studies have shown that the majority of egg allergic children tolerate baked egg (e.g., cake), and that consuming baked egg accelerates the resolution of egg allergy. However, few prospective studies demonstrate the step-wise reintroduction of egg at home after developing baked egg tolerance. Although this could have a positive impact on the children's quality of life and nutrition. Additionally, research supporting the theoretical concept that heating in the presence or absence of wheat causes reduced allergenicity of egg proteins is limited. Objective: To investigate the clinically most favorable duration of gradual egg-tolerance induction in baked egg tolerant children at home, with regard to complete raw egg tolerance. Methods: Baked egg tolerant children above 12 months of age were randomly assigned to a short- or long arm protocol. In the short arm, egg-tolerance induction was studied over 18 months compared to 30 months in the long arm. Children were guided through this protocol involving the step-wise introduction of increasingly allergenic forms of egg starting with baked egg offered as cake, followed by hard-boiled egg, omelet/waffle/pancake, soft-boiled egg, and finally raw egg. We hereby designed this protocol based on the influence of thermal processing in the presence or absence of wheat on egg proteins, as investigated by ELISA, SDS-PAGE, and immunoblotting. At inclusion, children either passed an in-hospital cake challenge or had ovomucoid sIgE ≤1.2 kUA/L, which was considered safe for introduction at home. Results: Gel electrophoresis revealed that the ovalbumin band became weaker with heating, while the ovomucoid band remained stable. In accordance, the IgE-binding to ovalbumin decreased with extensive heating, as opposed to ovomucoid. However, heating in the presence of wheat led to a decreased IgE reactivity to ovomucoid. Of the 78 children in the intention-to-treat group, 39 were randomized to each arm. Fifty-eight children reached the raw egg tolerance endpoint, of which 80% were in the short arm and 69% in the long arm. Within the short arm, the median time to raw egg tolerance was 24 months (95% CI, 21-27 months) compared to 30 months (95% CI, 28-32 months) in the long arm (p = 0.005). No grade IV reactions or cases of eosinophilic esophagitis were observed. The short arm was considered to be non-inferior to the long arm. Conclusion: Our gradual short arm protocol appears to be safe and allows clinicians to guide baked egg tolerant children toward raw egg tolerance at home. The allergenicity of the egg proteins was affected by heating temperature and duration, as well as the presence of wheat.

A Clinical Perspective on the Dietary Therapies for Pediatric Eosinophilic Esophagitis: The Gap Between Research and Daily Practice.

Pediatric eosinophilic esophagitis (ped-EoE) is an immune-mediated pathology affecting 34 per 100.000 children. It is characterized by an esophageal inflammation caused by an immune response towards food antigens that come into contact with the esophageal lining. Depending on the age of the child, symptoms can vary from abdominal pain, vomiting and failure to thrive to dysphagia and food impaction. The diagnosis of this chronic disease is based on the symptoms of esophageal dysfunction combined with an infiltration of more than 15 eosinophils per high-power field and the exclusion of secondary causes. The treatment modalities include the 3Ds: Drugs, allergen avoidance by Diet and/or esophageal Dilation. In this review we focused on the efficacy of dietary approaches in ped-EoE, which currently include the elemental diet (amino acid-based diet), the empiric elimination diet and the allergy test-directed elimination diet. Although several reviews have summarized these dietary approaches, a lack of consistency between and within the elimination diets hampers its clinical use and differences in subsequent reintroduction phases present a barrier for dietary advice in daily clinical practice. We therefore conducted an analysis driven from a clinician's perspective on these dietary therapies in the management of ped-EoE, whereby we examined whether these variations within dietary approaches, yet considered to be similar, could result in significant differences in dietary counseling.

Immunological Outcomes of Allergen-Specific Immunotherapy in Food Allergy.

IgE-mediated food allergies are caused by adverse immunologic responses to food proteins. Allergic reactions may present locally in different tissues such as skin, gastrointestinal and respiratory tract and may result is systemic life-threatening reactions. During the last decades, the prevalence of food allergies has significantly increased throughout the world, and considerable efforts have been made to develop curative therapies. Food allergen immunotherapy is a promising therapeutic approach for food allergies that is based on the administration of increasing doses of culprit food extracts, or purified, and sometime modified food allergens. Different routes of administration for food allergen immunotherapy including oral, sublingual, epicutaneous and subcutaneous regimens are being evaluated. Although a wealth of data from clinical food allergen immunotherapy trials has been obtained, a lack of consistency in assessed clinical and immunological outcome measures presents a major hurdle for evaluating these new treatments. Coordinated efforts are needed to establish standardized outcome measures to be applied in food allergy immunotherapy studies, allowing for better harmonization of data and setting the standards for the future research. Several immunological parameters have been measured in food allergen immunotherapy, including allergen-specific immunoglobulin levels, basophil activation, cytokines, and other soluble biomarkers, T cell and B cell responses and skin prick tests. In this review we discuss different immunological parameters and assess their applicability as potential outcome measures for food allergen immunotherapy that may be included in such a standardized set of outcome measures.