Serum IgE‐targeted elimination diets for treating eosinophilic esophagitis: things are not what they seem

We have eagerly read the article by Rodr ıguez-S anchez et al. (1) recently published in Allergy. The authors described an observational and descriptive (but not comparative) study carried out in adult patients suffering from eosinophilic esophagitis (EoE): Forty-three patients underwent food-specific serum IgE (sIgE) testing against the six food groups comprising an empiric six-food elimination diet (SFED) (2). Those patients with positive sIgE results (considered ≥0.1 kU/l) followed a targeted food exclusion diet (n = 26), while patients with negative results were treated with an empirical SFED (n = 17). Histological remission (<15 eos/ hpf) was achieved in 19 and 9 EoE patients, respectively. Even when the study strategy posed by the authors seems an interesting option to simplify schemes for managing EoE, we have serious concerns regarding the study concept and design, its methodology, and results, which affect the validity of the authors’ conclusions. In fact, the design of this study prevents to directly compare the effectiveness of two dietary interventions (specific sIgE-targeted elimination diet [sIgEED] and SFED), which can only be done by a well-designed longitudinal study or by a randomized clinical trial: This paper is a descriptive study that only shows the result of a common initial treatment strategy carried out in all patients and based on specific sIgE determination, followed by a latter decision node according to the results obtained. The overall ‘efficacy’ of the sIgE-ED of 73% (19/26 patients) is one of the most important misconceptions included in this paper, by committing an evident bias when the authors exclusively considered patients with positive sIgE results, and excluded those with a negative one. When the whole series of EoE patients are considered, the response rate dropped to only 44% (19/43), significantly lower to that reported for SFEDs (3). Furthermore, total sIgE levels were not considered; specific sIgE were exclusively tested for foods included in a SFED, instead to every potential food allergen, which makes all patients highly susceptible of having responded to a SFED. The additional exclusion of rice and corn in case of sIgE levels against wheat were demonstrated cannot be justified by cross-reactivity between those cereals. These facts make from this sIgE-ED not a targeted but an empirical dietary approach. The authors also claim a reduction in the cutoff point of serum IgE from 0.35 to 0.1 kU/l in order ‘to increase the sensitivity and thus to detect not only serum food-specific IgE-mediated but also non-IgE-mediated allergic reactions as well’. We really wonder how IgE-based tests are able to detect a non-IgE-mediated reaction. The fact that skin prick test results were not taken into account when designing exclusion diets provides an additional proof on the subjective use that authors made of IgE-based tests in their paper. Authors provide sensitivity and specificity figures for specific serum IgE in the 14 patients who completed the sequential food reintroduction protocol. Interestingly, whereas a larger number of patients underwent sIgE-ED compared with SFED, the ability of these tests to determine the triggering food was very low and similar to that obtained in a previous study on a full cohort of EoE patients from the same geographic region (2) (Table 1). To summarize, the conclusions made by Rodr ıgez-S anchez on the utility of sIgE-targeted elimination diet set forth a confusing scenario that should be interpreted with caution. Research efforts in EoE should be directed to assay simplified dietary strategies with a demonstrated effectiveness and to identify the true biological mediators of the immune