'Early Introduction' of Cow's Milk for Children with IgE-Mediated Cow's Milk Protein Allergy: A Review of Current and Emerging Approaches for CMPA Management

Abstract

IgE-mediated cow's milk protein allergy (CMPA) is one of the most prevalent food allergies in early childhood. Though the cornerstone of management involves the strict avoidance of milk products while awaiting natural tolerance, research increasingly shows that the rates of resolution are slowing down. Therefore, there is a need to explore alternative pathways to promote tolerance to cow's milk in pediatric populations. This review aims to combine and appraise the scientific literature regarding the three CMPA management methods: avoidance, the milk ladder, and oral immunotherapy (OIT) and their outcomes in terms of efficacy, safety, and immunological effects. Cow's milk (CM) avoidance virtually protects against allergic reaction until natural tolerance occurs, with hypoallergenic substitutes available in the market, but accidental ingestion represents the main issue for this strategy. Introduction to baked milk using the milk ladder was designed, with most CMPA patients successfully completing the ladder. Similar to baked milk treatment, many OIT protocols also demonstrated decreased IgE and increased IgG4 levels post protocol, as well as a reduction in wheal size diameter. Though these strategies are shown to be safe and effective in CMPA, future clinical trials should compare the safety and effectiveness of these three management strategies.

Keywords: children; cow’s milk protein allergy; immunotherapy; tolerance.

Figure 1

Natural History of CMPA tolerance according to age across studies [18,21,22,23,24,25,26,27,28,29,30,31].

Figure 2

The mechanism of the baked milk ladder. Foods on the milk ladder undergo varying degrees of heat during the baking process. The major milk allergens, casein, betalactoglobuline, and alpha-lactalbumin, are denatured to varying degrees, with casein being the most heat resistant. This baking process alters the stability of these allergens and renders them less allergenic through decreased IgE binding. Regular consumption of these baked milk products causes the increased production of IgG4, which blocks the IgE binding to the allergen. Regular consumption of these baked milk products therefore decreases IgE levels and increases IgG4 levels, allowing for increased tolerance of milk proteins as the degree of allergenicity increases through the milk ladder.

Figure 3

Rates of successful reintroduction to milk using baked milk/milk ladder protocols [40,42,45,46,51,52].

Figure 4

Describing mechanism of oral immunotherapy.

Figure 5

Phases of OIT.

Figure 6

Tolerance/desensitization achievement in treatment groups across protocols [66,67,68,69,71,72,73,74,75,76,78,79,80].