The Efficacy and Safety of Stepwise Oral Food Challenge in Children With Cow’s Milk Allergy

To assess the safety and efficacy of graded oral food challenge (OFC) in pediatric patients with cow’s milk (CM) allergy.Included in the study were 927 pediatric patients with a median age of 3.2 years who underwent a CM-OFC between 2017 and 2021 in Kumamoto Prefecture, western Japan.Target challenge doses were classified as low (1-10 mL or <33–330 mg of unheated CM protein), medium (≥10 mL but <100 mL), or full (≥100 mL or ≥3300 mg CM protein). Target doses were divided into 2 to 3 doses administered every 30 to 60 minutes. A positive OFC was the development of obvious symptoms within a few hours after dosing. Participants who previously reacted to low doses of CM or who had markedly elevated CM serum immunoglobulin E (IgE) levels (>100 kU/L) underwent very low-dose OFC using baked milk or less than or equal to 1 mL CM. Positive results were advised to continue exposure to the previously tolerated amount of CM and then rechallenged 12 months later.Two hundred ten children (22.7%) had positive OFC; 69 children (7.4%) developed anaphylaxis, with lower doses of OFC causing more anaphylaxis than higher doses. Allergic reactions developed in 48.6% of children who underwent very low-dose OFC and 32.8% of children who underwent low-dose OFC. Children with IgE levels 0.70 to 17.49 kU/L had significantly increased positive OFC results (P > .001). The low-dose group was more likely to include children who eliminated CM (P > .001), had a history of anaphylaxis induced by CM (P > .001), and had higher total IgE (P = .033) and CM-specific (P > .001) IgE levels. Multivariate analysis indicated that in the low-dose OFC group, higher CM-specific IgE levels (P = .034), younger age (P = .005), and complete elimination of CM (P = .002) were associated with positive OFC results.This article suggests that a stepwise OFC protocol may allow for the safe reintroduction of CM, even in patients with elevated CM-specific IgE or a prior history of anaphylaxis to CM. Initiating these challenges at a younger age, preferably infancy, with very low starting doses may enhance safety and promote the development of CM tolerance over time.CM allergy is one of the most common food allergies, particularly in early childhood. CM allergy is often challenging for patients and families to manage due to its widespread presence in food products. Social and dietary restrictions lead to a major impact on quality of life. The authors of this study support early stepwise reintroduction of CM in OFC to help patients eventually tolerate CM.