Different Paths, One Goal: Milk Ladders in IgE- and Non-IgE-Mediated Cow's Milk Protein Allergy-A Narrative Review

Cow's milk protein allergy (CMPA) is one of the most common food allergies in early childhood. Although a strict elimination diet effectively prevents allergic symptoms, it does not promote the development of tolerance to cow's milk proteins (CMPs). The milk ladder is a stepwise approach to the reintroduction of CMPs, starting with extensively heated forms and gradually progressing to unheated cow's milk, according to the individual tolerance levels. The rationale for this approach lies in the reduced allergenicity of heated forms, mainly due to the food matrix effect. The milk ladder was originally developed to gradually expand the diet in children with non-IgE-mediated CMPA. However, recent evidence suggests that it can also be applied in IgE-mediated CMPA to accelerate tolerance development. In children with high-risk IgE-mediated CMPA, this approach may be more challenging. Even minor recipe modifications, particularly those affecting composition or heating conditions, can alter the allergenicity of heated foods. Moreover, barriers to reintroducing food allergens, including parental anxiety or the child's food aversion, may be more pronounced in this group. Although for high-risk patients, reintroduction is usually performed in hospital settings, increasing evidence indicates that, in selected cases, it may also be safely conducted at home. Several emerging strategies, including early low-dose exposure and oral immunotherapy, show promise in further enhancing tolerance development. Despite these challenges, early reintroduction of CMPs appears to play a crucial role in modulating the immune response and promoting tolerance. This review provides the summary of evidence and practical insights into the implementation of the milk ladder in children with IgE-mediated CMPA.