IgE-Mediated Cow's Milk Allergy: Skin Prick Test Subtypes and Clinical Phenotypes Using Cow's Milk Hydrolysate Infant Formulas

Abstract

In 1986, Hill (Australia) classified group 1 children with cow's milk allergy (CMA) as having rapid onset, IgE-mediated reactions. In 1989, Schwartz (Rochester, NY) subtyped group 1 children (n = 75) into 1A, 1B, and 1C based on skin prick tests (SPTs) to non-hydrolyzed (CM—Similac®) and hydrolyzed CM infant formulas (Good Start®—partially hydrolyzed; Nutramigen®—extensively hydrolyzed). Our objective was to test the hypothesis that SPT subtypes 1A, 1B, and 1C represent different clinical phenotypes. Children with group 1 CMA (n = 170) were evaluated between 1989 and 2000. Clinical data analyzed included SPT subtype, signs, and symptoms after CM ingestion, age of onset, presence of other atopic conditions, serum CM-specific IgE, total serum IgE, and follow-up SPTs. Compared to 1A (n = 82), 1B (n = 58), and 1C (n = 30) had higher rates (p < 0.001) of systemic reactions to CM, higher (p < 0.001) serum-specific IgEs to CM proteins (α-lactalbumin, β-lactoglobulin, casein), higher prevalences of recurrent wheezing/asthma (1A = 23%, 1B = 41%, 1C = 57%; p < 0.001), and were 2.34 and 4.34 times more likely to have physician-diagnosed asthma. Prevalence of atopic dermatitis and mean total serum IgE were not significantly different. IgE-mediated CMA frequently is the first clinically identifiable allergic event in early life. SPT with CM and CM-hydrolysate infant formulas classifies these children into three SPT subtypes (1A, 1B, 1C) and two clinical phenotypes. 1A are "topical immediate reactors"—mild reactions, predominantly limited to contact urticaria and/or emesis. 1B and 1C, called "systemic reactors," are more highly sensitized and clinically reactive—generalized urticaria, angioedema, rhinitis, cough, stridor, and have an increased risk of asthma. Including CMA SPT subtypes and clinical phenotypes in future genetic studies might be informative in sorting out the relationships of the environment and child development to the phenotypic spectrum of asthma.