Immunoglobulin-E–mediated cow’s milk allergy (IgE-CMA) is the one of the most frequent IgE-mediated food allergy in children in industrialized countries and may cause life-threatening anaphylaxis. The natural history of CM IgE-mediated food allergy is favourable for most children. However, the clinical outcome of CMA seems worse than previously described, with less chance of recovery after the age of 3. 1 Avoidance is currently the only management approach for children with food allergies, along with educating carers about rescue treatment. However, quality of life is altered especially for children affected by ubiquitous allergens, and avoidance does completely rule out the risk of anaphylaxis due to accidental exposure. 2 In this context, oral immunotherapy (OIT) may be a promising alternative. 3 However, its main goal is to protect patients against low-threshold anaphylactic reactions, and it can cause severe adverse effects requiring the use of epinephrine. 3 Using baked milk is thought to improve the safety of cow’s milk OIT, as heating food is known to reduce the allergenicity of conformational epitopes. 4 Cow’s milk proteins (MP) are also altered by their interactions with other substances in the food matrix. 4 However, Nowak-Wegrzyn et al4 have shown that heated milk reactive subjects possessed IgE antibodies that still bound caseins after boiling. Moreover, as highlighted by Goldberg et al, 5 it remains to be determined whether baked milk OIT can induce tolerance to raw milk.

Another side of the debate is the administration schedule. Most of them consist of an initial rush up-dosing phase over 1 day in a hospital setting, followed by a maintenance phase at the same dose. However, these schedules may convey a high risk of adverse reactions due to intensive escalation. In this context, we prospectively evaluated the efficacy and the safety of two OIT protocols in a cohort of children with persistent IgE-CMA: a cluster schedule starting immediately with raw milk (with a presumed higher risk of side-effects) versus a slowprogression schedule starting with baked milk and then less and less heated milk over time (with a presumed lower risk of side-effects).