Failure of introduction of food allergens after negative oral food challenge tests in children

Our study shows a high failed introduction rate for milk, egg, hazelnut and peanut. Twenty-eight percent of the children failed to introduce the challenged food. Eigenmann et al. determined the proportion of failed introductions by questioning 73 patients after a negative FC test with different kinds of food. Failed introduction was reported in 25.4 % of the cases (18/71) [3], which is comparable with the test results of our study. The study of van Erp et al. determined the proportion of failed introduction in 103 children with a negative peanut challenge test. Introduction failed in 32 % of the children [9]. Flammarion et al. examined the consumption of the food after a negative FC test. They investigated the frequency of recurrent allergic reactions during introduction and its consequences on daily life for 67 children who underwent a total 110 FC tests. In this study, a successful introduction rate of 83 % has been reported [4]. Finally, Dambacher et al. have reported a successful introduction rate of 81 % (60 out of 74) for children with a cow’s milk allergy [1]. The high successful introduction rate of these latter two studies compared to our study might be due to the kind of allergen tested. The percentage of negative FC test with milk and egg are higher in the study of Flammarion et al. compared with our study. The study of Dambacher et al. included only negative FC tests with milk in contrast to our study with negative FC tests with milk, egg, peanut and hazelnut. To take the kind of allergen tested into account is important, because our study demonstrated that 43 (40.2 %) FC tests with peanut and hazelnut were followed by a failed introduction in comparison with 9 (11.4 %) of the milk and egg FC tests. Moreover, even after correction of age, the FC test for peanut showed significantly lower successful introduction than for milk and egg. The lower successful introduction for peanut and hazelnut could be caused by frequent publicity on the subject, which enhances awareness and fear for peanut allergy, as in daily life traces of peanut are difficult to avoid in the diet [3].

Indeed, successful introduction was associated with a significantly lower age. The successful introduction rate for boys was higher than that for girls. A significant (p = 0.026) higher rate of introduction for boys compared to girls was also reported by Eigenmann et al. [3]. We did not find an increase of the successful introduction rate after an OFC test in comparison with a DBPCFC test.

Symptoms during introduction at home had a significant influence on failed introduction, in one fourth of the children. This factor is also reported by van Erp et al., Eigenmann et al. and Flammarion et al. [3, 4, 9]. Adverse events during introduction after a negative FC test have been documented for failure in 12.7 % of the cases by Eigenmann et al. and in 5.5 % by Flammarion et al. A possible explanation for the relatively high occurrence of symptoms during introduction at home might be that the introduction dose was higher than the final dose of the FC test. All FC tests were performed with a recipe described in the study by Vlieg-Boerstra et al. [9]. The term failed introduction is thus debatable; the children who experienced symptoms during introduction might react to a higher eliciting dose than used in the challenge. Consequently, an open challenge with higher doses at the department should be performed to identify susceptibility to higher doses and at the same time convincing for the child and parent that the allergen is not harmful. Another reason for the more frequently occurring symptoms during introduction at home could be the differences in intrinsic and extrinsic factors between clinic and home and the food matrix [8].

Furthermore, the child and/or the parents of the child should be informed by the clinician at forehand about the indication for the FC test and the consequences of the outcome of the FC test. After the negative challenge, dietary advice is recommended, with explanation about reasons why and methods how, to introduce the food, as the introduction rate also depended on the given advice. A clear cut introduction scheme should be given to the parent or child, and a follow-up appointment to evaluate the success of introduction is mandatory. Most importantly, the parent and/or child need firstly to be convinced that the challenge results is negative, otherwise the chance that they will introduce the allergen in their diet is small. Taking fear away to ingest the food at home is important for the chance of a successful introduction. Failed introduction may lead to incomplete diets, missing essential nutrients and a lower quality of life [6].

Moreover, there is a chance of developing an acute allergic reaction after long time elimination [5]. The time period between challenge and introduction appeared also to be of great importance. This finding is not described in earlier studies and might be a useful recommendation for daily practice. We recommend to introduce the relevant food within 1 week after challenging the patient.

This is the largest study on the introduction rates of food after a negative FC test. As a result, we had the unique opportunity to investigate many influencing factors on the introduction rate. However, the retrospective design is a limitation of this study. Time span between food challenge and completion of the questionnaire is wide. It is obvious that children challenged in the end of 2012 filled out the questionnaire more correctly than children challenged in 2008. The multivariate model in the study of van Erp et al. showed that long interval between FC test and questionnaires was significantly associated with introduction failure in children with a suspected peanut allergy [9].

The questionnaire is not validated, and associations are mostly investigated with univariate analysis, because of the relative small groups.

In summary, we found a high rate of failed introduction after a negative food challenge. Fear is an important factor, most likely caused by assumed symptoms during the FC tests and symptoms during introduction of the food at home. For a successful introduction of food after a negative challenge, we recommend a higher total dose of the food in the challenge and a clear dietary advice with 1 week follow-up to guide introduction of challenged food.