Distinct patterns of cow's milk allergy in infancy defined by prolonged, two-stage double-blind, placebo-controlled food challenges.

BACKGROUND

The clinical manifestations of cow's milk allergy (CMA) are highly variable, and challenges usually identify only immediate, IgE mediated reactions.

OBJECTIVE

To clearly identify CMA of immediate and delayed types using a two-stage, double-blind, placebo-controlled food challenge (DBPCFC), and to prospectively compare the clinical history and analyses of specific IgE antibodies to milk in predicting outcome of DBPCFC.

METHODS

A total of 69 patients (33 girls, 36 boys) were recruited for study based on a history highly suggestive of CMA and resolution of symptoms on a bovine protein-free diet. After skin-prick tests (SPTs) and search for allergen-specific serum IgE antibodies by enzyme allergosorbent test (EAST), a two-stage DBPCFC was performed over several days.

RESULTS

Of 16 patients (mean age 36.9 months) classified as probable immediate reactors based on the history, 10 (62.5%) had a positive DBPCFC with similar patterns to historical adverse reactions (< or = 2 h after milk exposure). The other 53 (77%) patients (17.3 months) had a history of probable delayed type CMA presenting with predominantly gastrointestimal symptoms from 2 h and up to 6 days after milk exposure. Of these, 15 (28.8%) had a positive DBPCFC, again with a symptom pattern similar to the history. Sensitivity/specificity of SPT was similar to that of EAST for both immediate (70/83% and 62/83% respectively, NS) or delayed (0/97% and 0/97%) CMA confirmed by DBPCFC.

CONCLUSIONS

Using our two-stage, prolonged DBPCFC, we clearly identified two groups of children with CMA, reflecting different pathogenesis of either immediate-type IgE-dependent, or delayed-type IgE-independent allergy. Although useful in immediate reactors, IgE antibody determination cannot predict the outcome of DBPCFC in delayed reactors. A thorough clinical history was the most helpful tool to predict the type of response in challenge positive patients.