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Cow's milk-specific immunoglobulin E levels as predictors of clinical reactivity in the follow-up of the cow's milk allergy infants


M. Carmen García-Ara, C/Alfredo Marqueríe 18, 4°C, 28034 Madrid, Spain. E-mail:


Background IgE-mediated cow's milk proteins (CMPs) allergy shows a tendency to disappear with age. The sooner tolerance is detected, the earlier the substitute diets can be suspended and the quicker family emotional hardship is alleviated.

Objective To analyse the specific IgE levels to cow's milk and its proteins, which help to separate tolerant from no tolerant children in the follow-up of infants with allergy to cow's milk.

Patients and methods Sixty-six infants diagnosed with IgE-mediated allergy to CMPs were included in this prospective follow-up study. Periodic reassessments were carried out every 6 months until they were 2-years old and then, annually, until tolerance arose or until the last reassessment in which tolerance had not been achieved. Non-tolerant infants were followed, at least, for a period of 3 years. In each visit, the same skin tests and determination of specific IgE (CAP System FEIA) for milk and its proteins were carried out. The open challenge test was repeated unless a clear transgression to milk, which came to be positive, had taken place within the previous 3 months in each of the follow-up visits. Specific IgE levels to milk and its proteins, in different moments of the follow-up were analysed by means of the receiver-operating characteristic curve to predict clinical reactivity.

Results Throughout the follow-up 45 (68%) infants became tolerant. The follow-up mean for tolerant infants was 21.2 months whereas for non-tolerant infants it was 58 months. The specific IgE levels which were predictors of the clinical reactivity (positive predictive value (PPV)geqslant R: gt-or-equal, slanted90%), grew as the age of the infants increased: 1.5, 6 and 14 kUA/L for milk in the age range 13–18 and 19–24 months and in the third year, respectively. Specific IgE levels to casein: 0.6, 3 and 5 kUA/L, respectively, predicted clinical reactivity (PPVgeqslant R: gt-or-equal, slanted90%) in the different analysed moments of the follow-up. The cut-off points: 2.7, 9 and 24 kUA/L for milk and 2, 4.2 and 9 kUA/L for casein, respectively, predicted clinical reactivity with an accuracy geqslant R: gt-or-equal, slanted95% corresponding to a specificity of 90%.

Conclusions Monitorization of specific IgE concentration for milk and casein by means of the CAP system in allergic children to CMPs allows us to predict, to a high degree of probability, clinical reactivity. Age factor must be taken into account to evaluate the specific IgE levels which are predictors of tolerance or clinical reactivity.