Efficacy and Safety of Egg Ladders in Children With IgE-Mediated Hen's Egg Protein Allergy

Introducing baked egg into the diet of children with hen's egg allergy has been shown to potentially accelerate the development of tolerance to raw egg. However, there is no standardised egg ladder protocol, and different scientific societies across countries recommend varying versions.

This study aims to assess the effectiveness and safety of the 4-step egg ladder (4-EL) compared to the 5-step egg ladder (5-ML) in children with IgE-mediated hen's egg allergy.

An open-label randomised trial with two parallel arms in two departments of the same academic hospital will be performed. A total of 84 children with IgE-mediated hen's egg allergy will be allocated to introduce hen's egg into their diet according to either 4-EL or 5-EL with a 6-week break period between subsequent steps. Oral food challenge (OFCs) with tested products at each subsequent step of the egg ladder will be conducted in hospital settings. The primary outcome is the percentage of children who acquire tolerance to soft-boiled hen's egg (almost raw hen's egg proteins), as determined by a negative OFC at the final step of the EL. Soft-boiled egg will be administered at the end of the observation period (18 or 24 weeks, depending on the assigned study arm). The challenge dose will consist of 0,5-1 egg for children aged 1-3 years and 1 egg for those aged 4-5 years, corresponding to a maximum total of 6 g of hen's egg proteins.

Secondary outcomes will include the percentage of children with a negative OFC to each egg ladder step; the percentage of children with anaphylaxis (both those who were treated and who were not treated with adrenaline); the percentage of children with exacerbation of atopic dermatitis; growth; compliance; and quality of life of the caregivers and parents' anxiety about adverse events during their child's OFC.

The statistical analyses will be conducted with StatsDirect. The Mann-Whitney U test will be used to compare the means of continuous variables if non-normal distribution will be assessed. Proportions will be compared with the Fisher exact test. The difference in study groups was considered significant when the P value will be \<05. The results of this study will be analyzed on the basis of intention to treat.

• The percentage of children with a negative OFC at each step of the EL protocol upon completion of the study's observation period [Time frame: 18 weeks and 24 weeks, depending on the study arm]
• The percentage of children who experienced anaphylaxis [Time frame: During the observation period (18 or 24 weeks, depending on study arm),]
• The proportion of children with anaphylaxis (grades 3-5, per 2023 WAO criteria) who required epinephrine administration. [Time frame: Measured during the observation period (18 or 24 weeks, depending on the study arm).]
• The proportion of children who experienced systemic allergic reactions (SAR) of grades 1, 2, and 3 according to the 2023 WAO grading system. [Time frame: Measured during the observation period (18 or 24 weeks, depending on the study arm).]
• In the subgroup of children with atopic dermatitis, changes in the total score of the oSCORAD index will be assessed. before and after each OFC. [Time frame: Upon completion of the observation period (18 or 24 weeks, depending on the assigned study arm).]
• Change in age-adjusted z-scores for weight and length/height, evaluated using the WHO growth charts. [Time frame: During the observation period (18 or 24 weeks, depending on study arm).]
• Change in the total score of the FAQLQ-PF. [Time frame: At the end of the observation period (18 weeks and 24 weeks, depending on the study arm) from baseline.]
• Mean difference in caregiver anxiety levels, measured by the Subjective Units of Distress Scale (SUDS) [Time frame: Prior to each OFC, between study groups at each time point (18-24 weeks, depending on the study arm).]
• The proportion of children with full adherence to the intervention protocol. [Time frame: at the end of the observation period (18 or 24 weeks, depending on the assigned study arm)]