Plain Language SummaryStepwise oral food challenge (OFC) tests begin with low doses of allergens, progressing to full doses. This is one of the strategies used to avoid anaphylactic reactions to the reintroduction of allergens. We previously reported the safety and efficacy of hen egg OFC. In this study, we discuss it for cow’s milk (CM) allergy. We included 927 children (median age, 3.2 years) who underwent CM-OFC between 2017 and 2021. The target challenge dose was classified as low (<10 mL), middle (≥10 mL but <100 mL), or full. When the participants reacted to low doses, they underwent very low-dose OFC using baked milk or <1 mL of CM. Positive reactions developed in 210 cases (22.7%), including 69 anaphylactic reactions (7.4%). A lower target dose resulted in more positive OFC results and anaphylaxis. Multivariate analysis indicated that only in low-dose OFCs, higher CM-specific IgE (CM-sIgE) levels, younger age, and complete CM elimination were associated with positive OFC results. Food ladders, an approach to reintroduce allergens, are becoming increasingly popular. Although we believe that OFC is a safer strategy to reintroduce CM to children with CM allergy, our CM-OFCs appeared to develop more anaphylactic reactions than milk ladders. The stepwise OFC reintroduced small amounts of CM, even in cases with high CM-sIgE levels or a history of anaphylaxis. Performing CM-OFC at a younger age, preferably from infancy, with very low doses, similar to milk ladders, may facilitate the safe reintroduction of CM.
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