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Food allergy affects a small but significant number of children and adults. Food allergy is responsible for considerable morbidity and is the commonest cause of anaphylaxis in children. One of the aims of the European Union-funded "Integrated Approaches to Food Allergen and Allergy Risk Management" (iFAAM) project was to improve our understanding of the best way to prevent the development of food allergy. Groups within the project worked on integrating the current prevention evidence base as well as generating new data to move our understanding forward. This paper from the iFAAM project is a unique addition to the literature on this topic as it not only outlines the recently published randomized controlled trials (as have previous reviews) but also summarizes two iFAAM-associated project workshops. These workshops focused on how we may be able to use dietary strategies in early life to prevent the development of food allergy and summarized the range of opinions amongst experts in this controversial area., (© 2019 John Wiley & Sons Ltd.)

Background: The conduct of oral food challenges as the preferred diagnostic standard for food allergy (FA) was harmonized over the last years. However, documentation and interpretation of challenge results, particularly in research settings, are not sufficiently standardized to allow valid comparisons between studies. Our aim was to develop a diagnostic toolbox to capture and report clinical observations in double-blind placebo-controlled food challenges (DBPCFC)., Methods: A group of experienced allergists, paediatricians, dieticians, epidemiologists and data managers developed generic case report forms and standard operating procedures for DBPCFCs and piloted them in three clinical centres. The follow-up of the EuroPrevall/iFAAM birth cohort and other iFAAM work packages applied these methods., Recommendations: A set of newly developed questionnaire or interview items capture the history of FA. Together with sensitization status, this forms the basis for the decision to perform a DBPCFC, following a standardized decision algorithm. A generic form including details about severity and timing captures signs and symptoms observed during or after the procedures. In contrast to the commonly used dichotomous outcome FA vs no FA, the allergy status is interpreted in multiple categories to reflect the complexity of clinical decision-making., Conclusion: The proposed toolbox sets a standard for improved documentation and harmonized interpretation of DBPCFCs. By a detailed documentation and common terminology for communicating outcomes, these tools hope to reduce the influence of subjective judgment of supervising physicians. All forms are publicly available for further evolution and free use in clinical and research settings., (© 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food-allergic children also have asthma, yet almost none will experience a fatal food-allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food-induced allergic reactions., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Parents and health staff perceive hen's egg allergy (HEA) as a common food allergy in early childhood, but the true incidence is unclear because population-based studies with gold-standard diagnostic criteria are lacking., Objective: To establish the incidence and course of challenge-confirmed HEA in children, from birth until the age of 24 months, in different European regions., Methods: In the EuroPrevall birth cohort study, children with a suspected HEA and their age-matched controls were evaluated in 9 countries, using a standardized protocol including measurement of HE-specific immunoglobulin E-antibodies in serum, skin prick tests, and double-blind, placebo-controlled food challenges (DBPCFC)., Results: Across Europe, 12 049 newborns were enrolled, and 9336 (77.5%) were followed up to 2 years of age. In 298 children, HEA was suspected and DBPCFC was offered. HEA by age two was confirmed in 86 of 172 challenged children (mean raw incidence 0.84%, 95% confidence interval (95% CI) 0.67-1.03). Adjusted mean incidence of HEA was 1.23% (95% CI 0.98-1.51) considering possible cases among eligible children who were not challenged. Centre-specific incidence ranged from United Kingdom (2.18%, 95% CI 1.27-3.47) to Greece (0.07%). Half of the HE-allergic children became tolerant to HE within 1 year after the initial diagnosis., Conclusions: The largest multinational European birth cohort study on food allergy with gold-standard diagnostic methods showed that the mean adjusted incidence of HEA was considerably lower than previously documented, although differences in incidence rates among countries were noted. Half of the children with documented HEA gained tolerance within 1 year postdiagnosis., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In adults, subjects sensitized to Staphylococcus aureus enterotoxins (SE) seem to have an increased risk of asthma, whereas this association is less clear in childhood and adolescence. The primary aim of the present analysis was to examine the association between sensitization to SE and asthma at the age of 20 years., Methods: The German Multicentre Allergy Study recruited 1314 healthy newborns in 1990. We analyzed data from 61 asthmatics (based on at least two criteria: physician diagnosed asthma ever, wheezing in the last 12 months, asthma medication in the last 12 months) and 122 healthy study participants at age 20. In serum, specific Immunoglobulin E (IgE) to SE and common aeroallergens were measured. The association between asthma at age 20 and sensitization to SE was estimated by logistic regression models considering allergic, socio-demographic, and lifestyle factors as potential confounders., Results: Fifty-five percent of the included participants were female. At age 20, subjects sensitized to SE were more likely to have asthma than not-sensitized subjects: raw odds ratio (OR) 2.5, 95%-confidence interval (95%CI) [1.3-4.7]; adjusted OR 1.6, 95%CI [0.8-3.4]., Conclusion: Asthmatics at age 20 were more often sensitized to SE compared to controls. Our study may indicate a moderate relationship between SE-sensitization and asthma; however, this association attenuated after adjusting for potential confounders and was no longer statistically significant. Longitudinal investigations with SE-IgE measurements at different time points in larger samples are needed to explore the temporal manner of this relationship., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cow's milk allergy (CMA) is one of the most common causes of food allergy in the first years of life. Fortunately, the majority of children with CMA develop clinical tolerance with time. However, no good individual markers exist to predict whether this will occur. Therefore, a prognosis to identify children with persistent CMA at diagnosis would be helpful., Objective: In this study, we sought to assess whether measurement of IgE to individual allergens of cow's milk (CM) would separate patients with persistent CMA from those who became clinically tolerant to CM over time., Methods: A total of 52 patients ranging from 3 months to 114 months of age with proven CMA by DBPCFC were followed over time. From these 52 patients, 32 (61.5%) patients became tolerant in the analysed time period. All patients were rechallenged at least once, some were rechallenged two or three times. Serum was analysed prior to each challenge for specific IgE, IgG and IgG4 binding to crude CM protein as well as to individual allergens of CM., Results: The individual likelihood of outgrowing CMA significantly correlates with a low level of CM-specific IgE as well as a low level of specific IgE to α-lactalbumin, β-lactoglobulin (Bos d5.0102), κ-casein and α(s1) -casein. No significant correlation was found for IgE levels to total casein, lactoferrin, β-casein and β-lactoglobulin (Bos d5.0101) as well as IgG and IgG4 levels to α-lactalbumin, β-lactoglobulin and total casein., Conclusions: CM-specific IgE is a good prognostic marker for persistence of CMA. In addition, component-resolved diagnostic showed similar results. However, in our view, the rising laboratory costs do not justify a measurement on a daily basis. Additional determination of specific IgG or IgG4 levels was not useful in predicting tolerance development in our study population., (© 2012 Blackwell Publishing Ltd.)

Background: Oral food challenge (FC) protocols are discussed with reference to starting doses, dose increments, safety, and predictability of results. The aim of this study was to evaluate the relation of eliciting allergen doses, specific IgE levels and predictive factors to the outcome of FCs in children., Methods: In 869 children (median age 1.2 years), FCs were performed with cow's milk (n = 633), hen's egg (n = 456), wheat (n = 265) and/or soy (n = 317) starting at 3-5 mg of protein. Each of the seven doses was administered every 30 min using semi-log increases. Severity of symptoms was graded from I to V. IgE was determined prior to challenges., Results: Of the children allergic to egg or milk, 9% and 10%, respectively, experienced reactions already at the first dose. Of these, 14% (egg) and 4% (milk) experienced grade IV reactions. In contrast, few children reacted to the first doses of wheat or soy, and most reactions occurred after the maximum dose. For all allergens, grade V reactions did not occur. However, grade IV reactions were seen at all eliciting doses. Elevated specific IgE level, young age and a history of atopic dermatitis were associated with a positive challenge outcome for milk or egg, and also IgE levels were associated with lower eliciting allergen doses and more severe symptoms., Conclusion: Oral FCs bear a risk of severe reactions at all dose levels. Doses of 3-5 mg protein induced symptoms in up to 10% of children allergic to milk or egg. However, food-specific IgE levels are of limited clinical value for the estimation of FC reactions., (© 2012 John Wiley & Sons A/S.)