The natural history of milk allergy in an observational cohort

Abstract

Objective: There are few studies on the natural history of milk allergy. Most are single-site and not longitudinal, and these have not identified a means for early prediction of outcomes.

Methods: Children aged 3 to 15 months were enrolled in an observational study with either (1) a convincing history of egg allergy, milk allergy, or both with a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe atopic dermatitis (AD) and a positive SPT response to milk or egg. Children enrolled with a clinical history of milk allergy were followed longitudinally, and resolution was established by means of successful ingestion.

Results: The cohort consists of 293 children, of whom 244 were given a diagnosis of milk allergy at baseline. Milk allergy has resolved in 154 (52.6%) subjects at a median age of 63 months and a median age at last follow-up of 66 months. Baseline characteristics that were most predictive of resolution included milk-specific IgE level, milk SPT wheal size, and AD severity (all P < .001). Baseline milk-specific IgG4 level and milk IgE/IgG4 ratio were not predictive of resolution and neither was expression of cytokine-inducible SH2-containing protein, forkhead box protein 3, GATA3, IL-10, IL-4, IFN-γ, or T-bet by using real-time PCR in CD25-selected, casein-stimulated mononuclear cells. A calculator to estimate resolution probabilities using baseline milk IgE level, SPT response, and AD severity was devised for use in the clinical setting.

Conclusions: In this cohort of infants with milk allergy, approximately one half had resolved over 66 months of follow-up. Baseline milk-specific IgE level, SPT wheal size, and AD severity were all important predictors of the likelihood of resolution.

FIG 1

Kaplan-Meier analysis of milk allergy resolution over time is shown in blue, with pointwise 95% CIs shown in red.

FIG 2

Kaplan-Meier analysis representing the relationship of milk allergy resolution to baseline milk-specific IgE levels. Individual curves represent IgE levels of less than 2 kU_A/L (blue), 2 to 10 kU_A/L (red), and 10 kU_A/L or greater (green).

FIG 3

Kaplan-Meier analysis representing the relationship of milk allergy resolution to baseline milk SPT wheal size. Individual curves represent wheal sizes of less than 5 mm (blue), 5 to 10 mm (red), and greater than 10 mm (green).

FIG 4

Kaplan-Meier analysis representing the relationship of milk allergy resolution to baseline AD. Individual curves represent no/mild AD (blue) and moderate/severe AD (red).

FIG 5

This figure represents results of a composite index based on the baseline milk-specific IgE level, SPT wheal, and severity of AD, which can be used to estimate the likelihood of milk allergy resolution. For example, the lower curve (red) in this figure represents a patient with a milk-specific IgE level of 20 kU_A/L, an SPT mean wheal diameter of 7 mm, and moderate-to-severe AD, whereas the middle curve (green) represents a patient with the same IgE level and skin test score but no or mild AD. The upper curve (blue) represents another patient with a milk IgE level of 2 kU_A/L, an SPT wheal score of 4 mm, and no or mild AD.