Feasibility and Reaction Thresholds of Double-Blind, Placebo-Controlled Peanut and Nut Food Challenges Using Gingerbread Matrix

Introduction: Double-blind, placebo-controlled food challenges are an important tool in diagnosing food allergies. PRACTALL recommends a dose-escalation schedule of 3-3,000 mg of food protein and a top dose of at least 2,000 mg to avoid false-negative results. This retrospective observational study tests the thresholds and feasibility using a previously published gingerbread matrix. Methods: Data of food provocations with peanuts and nuts in children from 2015 to 2019 in the Reinier de Graaf Hospital were analyzed. We performed the food challenge following a schedule of 1, 3, 10, 30, 100, 300, 1,000, and 3,000 mg allergen protein. The feasibility of ingestion of the gingerbread matrix was determined by analyzing the amount of consumed gingerbread. Results: 513 food challenges performed in 365 children (median age 6.9 years) were analyzed. Forty percent (204/513) of the food challenges were positive. Fifteen children already reacted at 1 mg protein (7%), 3 with a grade 3 reaction. The median cumulative amount of gingerbread matrix the children could eat on 1 day was 130.3 g. The median cumulative amount of allergen protein eaten was 2,585 mg; only 49% reached the minimum desired cumulative amount of 3,500 mg allergen protein. Despite that, there were no reported reactions at home in the 86% who introduced the allergen after a negative challenge. Conclusion: Seven percent of the children react on a starting dose of 1 mg of food protein. Therefore, when using the PRACTALL guidelines, early responders can be expected. Ingestion of a cumulative dose of 3,500 mg to reach a false-negative rate of maximum 5% is not feasible in most children using the gingerbread matrix. However, the cumulative dose may be reduced without increasing false-negative results, making challenges with the gingerbread matrix feasible for all age groups.