Executive summary of the EAACI guidelines on diagnosis of IgE‐mediated food allergy

It has been almost one decade since the first and last EAACI Food Allergy Guidelines were published.1 These have recently been updated and include two modules, one on diagnosis and another one on management of IgE-mediated food allergy—this editorial focuses on the first module about diagnosis, which is published in this issue of Allergy.2 The EAACI guidelines on diagnosis of IgE-mediated food allergy have been developed by a large group of multinational and multidisciplinary group of experts. The present editorial provides an overview of the progress made in food allergy diagnostics over the last 10 years and of the new key recommendations for best clinical practice in 2023, and highlights research priorities and upcoming challenges in terms of implementation of the guidelines in clinical practice. The prevalence of food allergy continues to rise, in both children and adults, impacting communities around the world. The effect on individuals who experience symptoms to foods is never trivial and sometimes the need for excessive exclusion of foods has adverse health, social and psychological consequences for the patient and their family.3, 4 Infants and young children are particularly vulnerable from a nutritional standpoint and so it is vital to ensure that a robust diagnosis is made in a timely manner to mitigate any effects on growth and avoid the development of aversive eating behaviours.5, 6 An accurate diagnosis is therefore vital, but results can be difficult to interpret as IgE sensitization does not equate with clinical allergy. Additional diagnostic challenges may arise in older children, adolescents and adults sensitized to aeroallergens, which cross-react with some foods, and the clinician needs to differentiate primary from secondary food allergy. Similar issues can also occur in individuals with atopic dermatitis, or in certain ethnic groups who may have raised total IgE levels and allergen-specific IgE sensitization that is clinically irrelevant. Misdiagnosis can lead to exclusion of a food, and other associated foods. Conversely, potentially severe or even fatal reactions can occur, if the trigger food has been wrongly identified and exposure to the culprit food is not avoided. Similarly, removing a previously tolerated food from the diet due to a positive allergy test can result in clinical food allergic reactions, as IgE sensitization in the absence of continued consumption can lead to development of food allergy. Since the systematic review of the literature up until October 2012 done to inform the 2014 EAACI Food Allergy Guidelines,7 significant advances have revolutionized allergy diagnostics. Not only our understanding of the use of traditional allergy tests, such as skin prick testing (SPT) and specific IgE has improved, but also advances in the standardization of allergen extracts, innovation with molecular IgE and cellular tests, along with the more widespread availability of multiplex assays have been achieved. Molecular Allergology (MA) has significantly evolved and can enhance the precision of allergy diagnostics. This is especially true for some foods, such as peanut, hazelnut, cashew nut, and sesame.8 Molecular IgE tests have increasingly become an integral part of clinical practice in allergy centers worldwide. In addition to IgE binding tests, functional assays have emerged as valuable tools for food allergy diagnosis. Among these, the basophil activation test (BAT) stands out: initially used in the research setting and still with limited availability outside specialized centers, the BAT has been accumulating evidence and gaining popularity as an important test when other allergy tests yield equivocal results.9 Taken together, these developments have enhanced accuracy, efficiency, and personalized treatment approaches in food allergy diagnosis. These advances have become evident in the new systematic review of the literature performed in preparation for update of the EAACI Guidelines on Food Allergy Diagnosis.10 With broad and open criteria to search for evidence on accuracy of allergy tests to diagnose IgE-mediated food allergy, for any food and any test, we were able to conduct informative meta-analyses on the diagnostic performance of the test-food combination for which there were enough studies. We also conducted meta-analyses looking at diagnostic performance of tests for different age groups and different geographical locations as these factors are known to influence the performance of allergy tests. We built reference tables with cut-offs for tests on which the meta-analyses were based, including optimal cut-offs and maximal sensitivity and specificity cut-offs, as reported by the authors. These cut-offs can be used as a reference to make clinical decisions in patient populations and clinical settings similar to the ones from which these were originated. Highly sensitive tests are useful to exclude food allergy if results are below the cut-offs. Highly specific tests are useful to rule in food allergy if results are above the cut-off. Optimal cut-offs are often used to make decision about whether to challenge patients but should be considered carefully in light of their associate sensitivity and specificity. To conclude, an accurate diagnosis of food allergy is essential, particularly in the context of a rising prevalence and rising awareness about atopic diseases, and food allergy specifically. The current EAACI Guidelines on Food Allergy Diagnosis will be followed by EAACI Guidelines on Management of IgE-mediated Food Allergy. We aim to update these guidelines by 2028, or earlier if important evidence emerges. Dissemination and implementation of the updated EAACI Food Allergy Guidelines will be crucial to ensure prompt identification of the disease and optimization of the care of patients living with food allergies. AFS, IS and CR wrote the first version of the editorial. All authors critically reviewed the manuscript and approved its final version. The authors would like to thank the group of experts and Jeanette Kobler from the EAACI Headquarters team for giving their time and expertise to the EAACI Food Allergy Guideline project. There is no specific funding related to this publication. A.F. Santos reports grants from Medical Research Council (MR/M008517/1; MC/PC/18052; MR/T032081/1), Food Allergy Research and Education (FARE), the Immune Tolerance Network/National Institute of Allergy and Infectious Diseases (NIAID, NIH), Asthma UK (AUK-BC-2015-01), BBSRC, Rosetrees Trust and the NIHR through the Biomedical Research Centre (BRC) award to Guy's and St Thomas' NHS Foundation Trust, during the conduct of the study; personal fees from Thermo Scientific, Nutricia, Infomed, Novartis, Allergy Therapeutics, Buhlmann, as well as research support from Buhlmann and Thermo Fisher Scientific through a collaboration agreement with King's College London. Susanne Halken reports personal fees from ALK, Mead Johnson, Viatris, GSK, outside the submitted work. G. Du Toit reports grants and personal fees from Aimmune, DBV, Novartis, personal fees from FARE, grants from NIH-NIAID, outside the submitted work. G. Roberts reports research funding from National Institute of Health and Food Standards Agency. President of British Society of Allergy and Clinical Immunology. C. A. Akdis has received research grants from the Swiss National Science Foundation, European Union (EU CURE, EU Syn-Air-G), Novartis Research Institutes, (Basel, Switzerland), Stanford University (Redwood City, Calif), Seed Health (Boston, USA) and SciBase (Stockholm, Sweden); is the Co-Chair for EAACI Guidelines on Environmental Science in Allergic diseases and Asthma; Chair of the EAACI Epithelial Cell Biology Working Group is on the Advisory Boards of Sanofi/Regeneron (Bern, Switzerland, New York, USA), Stanford University Sean Parker Asthma Allergy Center (CA, USA), Novartis (Basel, Switzerland), Glaxo Smith Kline (Zurich, Switzerland), Bristol-Myers Squibb (New York, USA), Seed Health (Boston, USA) and SciBase (Stockholm, Sweden); and is the Editor-in-Chief of Allergy. A.Muraro declared the receipt of consultation or speakers fees for Viatris, Aimmune, DVB Technologies, Nestlè Health Sciences, ALK, Stallergenes, Novartis, Sanofi Regeneron. I. Skypala declared the receipt of honoraria from ThermoFisher, Royal College of General Practitioners and Touch Independent Medical Education. Data sharing is not applicable to this article as no new data were created or analyzed in this study.