BackgroundThere is currently considerable uncertainty regarding what the predictors of the severity of diagnostic or accidental food allergic reactions are, and to what extent the severity of such reactions can be predicted.ObjectiveTo identify predictors for the severity of diagnostic and accidental food allergic reactions and to quantify their impact.MethodsThe study population consisted of children with a double‐blind, placebo‐controlled food challenge (DBPCFC)–confirmed food allergy to milk, egg, peanut, cashew nut, and/or hazelnut. The data were analyzed using multiple linear regression analysis. Missing values were imputed using multiple imputation techniques. Two scoring systems were used to determine the severity of the reactions.ResultsA total of 734 children were included. Independent predictors for the severity of the DBPCFC reaction were age (B = 0.04, P = .001), skin prick test ratio (B = 0.30, P < .001), eliciting dose (B = −0.09, P < .001), level of specific immunoglobulin E (B = 0.15, P < .001), reaction time during the DBPCFC (B = −0.01, P = .004), and severity of accidental reaction (B = 0.08, P = .015). The total explained variance of this model was 23.5%, and the eliciting dose only contributed 4.4% to the model. Independent predictors for more severe accidental reactions with an explained variance of 7.3% were age (B = 0.03, P = .014), milk as causative food (B = 0.77, P < .001), cashew as causative food (B = 0.54, P < .001), history of atopic dermatitis (B = −0.47, P = .006), and severity of DBPCFC reaction (B = 0.12, P = .003).ConclusionsThe severity of DBPCFCs and accidental reactions to food remains largely unpredictable. Clinicians should not use the eliciting dose obtained from a graded food challenge for the purposes of making risk‐related management decisions.

This study describes the role of two STAT6 gene variants in food allergy using data of patients and their parents who underwent double‐blind placebo‐controlled food challenges (DBPCFCs). After quality control, 369 trios were analysed including 262 children (71.0%) with food allergy. Associations were tested by the Family based association test. The A alleles of both SNPs were associated with food allergy (P = .036 and P = .013 for rs324015 and rs1059513, respectively). Furthermore, these A alleles were associated with peanut allergy, higher sIgE levels to both peanut and cow's milk, more severe symptoms and higher eliciting doses during peanut and cow's milk DBPCFCs (all P < .05). In silico analysis indicates that the identified risk variants increase STAT6 expression which stimulates the differentiation of CD4 +  T cells to the Th2 subset. In conclusion, STAT6 variants may be involved in the pathophysiology of food allergy and their role seems to be independent of the allergenic food.

Food allergy is a potentially life-threatening disease with a detrimental effect on the quality of life of caregivers and children. A case series of double-blind, placebo-controlled food challenges (DBPCFC) with four peanut allergic patients by Grimshaw et al, suggested that a lower fat content of the peanut matrix reduced the amount of peanut required to elicit a reaction in three of the four subjects. These three subjects also had more severe symptoms in the food challenge using a high-fat peanut matrix. 5 However, due to the small number of subjects, only a descriptive evaluation of the results was possible and thus no definite conclusions could be drawn from this study.So far, the current evidence suggests that the qualities of the food matrix may play an important role in the severity of the allergic reaction. However, to the best of the authors' knowledge, no previous study has shown an association between the fat content of a matrix and the clinical allergic response. A previous study from our centre with hen's egg challenges failed to find such an association. 6The aim of this study was to examine possible matrix effects of a high-and low-fat content food matrix during DBPCFCs with peanut by comparing the severity and eliciting doses (EDs) of challenge reactions.All positive diagnostic peanut DBPCFCs performed at the Beatrix's Children's Hospital in the University Medical Center Groningen between 2002 and 2014 were included. Food challenges were excluded if they were performed with any other than the two most frequently used recipes (11 cases excluded). In children with repeated DBPCFCs, only the first test was included (37 cases excluded). Fourteen cases were excluded because the challenge recipe was not specified.DBPCFCs were performed as part of routine clinical care and according to previously published protocols. 7,8 The recipes used were peanut in cookies and peanut in gingerbread, with a fat content of 23.9% and 5.9%, respectively. The contents of the recipes are shown in Table 1. The dosing scheme for the two recipes was --