Cow's milk allergy (CMA) in children: identification of allergologic tests predictive of food allergy

F. Bellini, G. Ricci, D. Remondini, A. Pession

Oral food challenge (OFC) is still considered the gold standard for diagnosis of food allergy (FA). Skin prick test (SPT) and specific IgE (sIgE) tests are very useful but limited in their predictive accuracy. End point test (EPT) has been recently considered to determine the starting dose to induce oral desensitization. Allergometric tests combined may discriminate children at higher risk of reactions during OFC. We considered 94 children referred to our Allergy and Immunology Pediatric Department between January 2009 and December 2011 with CMA. Cutaneous allergometric skin tests (SPT and EPT) were periodically performed on all 94 children with CMA; sIgE levels against cow's milk proteins (CMP) alfa-lactalbumin, beta-lactoglobulin and casein were periodically evaluated through blood samples every 6-12 months. During the period of the study, 26/94 (27.6%) children underwent more than once OFC.
We collected 135 OFC compared with clinical presentation: 49/135 (36.2%) OFC were performed shortly after the onset of symptoms directly related to spontaneous intake of milk, to confirm suspicion of FA; 86/135 (63.7%) OFC were performed to evaluate the acquisition of tolerance. Of these, 52/86 (60.4%) OFC resulted positive, 34/86 (39.5%) were negative.
The 3D EPT has the best ratio sensitivity (SE) / positive predictive value (PPV), SE 83%, specificity (SP) 58.3%, PPV 89.3%, negative predictive value (NPV) 45.1%. EPT 6D and 7D have the best PPV (100%) with a low NPV (respectively 22.2% and 21.2%). We obtained that a mean fresh milk wheal diameter > 12 mm was predictive of 97% OFC, but only 32/101 (31.6%) allergic children presented this value. The tests with a wheal diameter < 5 were performed on younger children, all of which were less than 9 months old; only 5 other tests performed on less than 9 months olds resulted in the others subgroups (1 in > 12 mm wheal and 4 in the group between 6-11 mm). We also found that 95% of children with 4D EPT wheal diameter < 6 mm resulted tolerant.
This cut off could be useful to decide which children have a lower risk of reactions during the OFC. EPT is more useful than SPT especially for children < 1 year of age being a less operator dependent test, and it could be helpful to discriminate between children with the highest risk to develop anaphylaxis following an OFC (> 5D positive EPT) and children with lowest risk (> 2D positive EPT), but it can't replace OFC, that currently remains the gold standard in the diagnosis of FA. We also underline that in allergic children younger than 9 months old, the values of SPT with fresh milk is much lower than in older children, so that it's better to separate this group of age when we try to predict the evolution of OFC through the evaluation with EPT. A validation of such results in a prospective study could maybe be useful to confirm the outcome of our data in the predictivity of OFC.
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