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The fact that genetic and environmental factors could trigger disruption of the epithelial barrier and subsequently initiate a T H 2 inflammatory cascade conversely proposes that protecting the same barrier and promoting adequate interactions with other organs, such as the gut, may be crucial for lowering the risk and preventing atopic diseases, particularly, food allergies. In this review, we provide an overview of structural characteristics that support the epithelial barrier hypothesis in patients with atopic dermatitis, including the most relevant filaggrin gene mutations, the recent discovery of the role of the transient receptor potential vanilloid 1, and the role involvement of the microbiome in healthy and damaged skin. We present experimental and human studies that support the mechanisms of allergen penetration, particularly the dual allergen exposure and the outside-in, inside-out, and outside-inside-outside hypotheses. We discuss classic skin-targeted therapies for food allergy prevention, including moisturizers, steroids, and topical calcineurin inhibitors, along with pioneering trials proposed to change their current use (Prevention of Allergy via Cutaneous Intervention and Stopping Eczema and ALlergy). We provide an overview of the novel therapies that enhance the skin barrier, such as probiotics and prebiotics topical application, read-through drugs, direct and indirect FLG replacement, and interleukin and janus kinases inhibitors. Last, we discuss the newer strategies for preventing and treating food allergies in the form of epicutaneous immunotherapy and the experimental use of single-dose of adeno-associated virus vector gene immunotherapy., Competing Interests: Disclosures Dr Ciaccio receives research grant support from the National Institutes of Health (NIH), Food Allergy Research & Education (FARE), and Paul and Mary Yovovich and has served as a medical consultant/advisor for Genentech, Novartis, Siolta, Clostrabio, and FARE. Dr Chinthrajah reports receiving grants from National Institute of Allergy and Infectious Diseases (NIAID), CoFAR, Regeneron, Stanford Maternal and Child Health Research Institute, and FARE and is an advisory board member at Alladapt Therapeutics, Novartis, Genentech, Allergenis, Intrommune Therapeutics, and IgGenix. Dr Chan reports receiving grant from NIAID and NIH. Prof Leung reports receiving grants from Genentech, Incyte Corporation, and Sanofi-Genzyme; nonfinancial support from Aslan Pharmaceuticals; and personal fees from Leo Pharmaceuticals. Dr Marshall reports receiving research grant support from NIH. Prof Nadeau reports receiving grants from NIAID; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Environmental Health Sciences (NIEHS); and FARE; receiving stock options from IgGenix, Seed Health, ClostraBio, Cour, and Alladapt; serving as an advisor at Cour Pharma; serving as a consultant for Excellergy, Red tree ventures, Before Brands, Alladapt, Cour, Latitude, Regeneron, and IgGenix; serving as a co-founder of Before Brands, Alladapt, Latitude, and IgGenix; serving as National Scientific Committee member at Immune Tolerance Network (ITN) and NIH clinical research centers; and having patents including, “Mixed allergen composition and methods for using the same,” “Granulocyte-based methods for detecting and monitoring immune system disorders,” and “Methods and Assays for Detecting and Quantifying Pure Subpopulations of White Blood Cells in Immune System Disorders.” Dr Radulovic reports receiving grant from NIAID and NIH. Prof Lack reports receiving grant from NIAID/NIH; having personal fees and stock options from DBV Technologies; having stock options from Mission MightyMe; and serving as a scientific consultant/advisor for Novartis, Sanofi-Genzyme, Regeneron, ALK-Abello, Reckitt Mead Johnson, and Lurie Children's Hospital. Dr Sindher receives research grant support from NIH, FARE, CoFAR, DBV, AIMMUNE, and Regeneron and has served as an advisor for Genentech. Prof Brough reports receiving grant from NIAID and NIH and receiving speaker honoraria from DBV Technologies, GlaxoSmithKline, and Sanofi. The remaining authors have no conflicts of interest to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Allergist-immunologists use serologic peanut allergy testing to maximize test sensitivity and specificity while minimizing cost and inconvenience. Recent advances toward this goal include a better understanding of specific IgE (sIgE) and component testing, epitope-sIgE assays, and basophil activation testing. Predicting reaction severity with serologic testing is challenged by a range of co-factors that influence reaction severity, such as the amount and form of any allergen consumed and comorbid disease. In 2020, the Allergy Immunology Joint Task Force on Practice Parameters recommended Ara h 2-sIgE as the most cost-effective diagnostic test for peanut allergy because of its superior performance, when compared with skin prick testing and serum IgE. Basophil activation testing, a functional test of allergic response not evaluated in the Joint Task Force on Practice Parameters guideline, is a promising option for both allergy diagnosis and prognosis. Similarly, epitope-sIgE testing may improve prediction of reaction thresholds, but further validation is needed. Despite advances in food allergy testing, many of these tools remain limited by cost, accessibility, and feasibility. In addition, there is a need for further research on how atopic dermatitis may be modifying serologic food allergy severity assessments. Given these limitations, allergy test selection requires a shared decision-making approach so that a patient's values and preferences regarding financial impact, inconvenience, and psychological effects are considered in the context of clinician expertise on the timing and use of optimized testing., Competing Interests: Disclosures Dr Golden is a consultant for Novartis, Aquestive, and Kokua and has received clinical trials support from Genentech, Novartis, Pfizer, GlaxoSmithKline, Merck, Regeneron, and AstraZeneca. Dr Brough reports receiving research grants from the NIH (NIAAD) and speaker fees from DBV Technologies. Dr Santos reports receiving grants from Medical Research Council (MR/M008517/1; MC/PC/18052; and MR/T032081/1), Food Allergy Research and Education, the Immune Tolerance Network/National Institute of Allergy and Infectious Diseases (NIAID and NIH), Asthma UK (AUK-BC-2015-01), BBSRC, Rosetrees Trust, and the NIHR through the Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust, during the conduct of the study; receiving personal fees from Thermo Scientific, Nutricia, Infomed, Novartis, Allergy Therapeutics, and Buhlmann; and receiving research support from Buhlmann and Thermo Fisher Scientific through a collaboration agreement with King's College London. Dr Shaker is a member and co-chair of the Joint Task Force on Practice Parameters; serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice; is an associate editor of Annals of Allergy, Asthma & Immunology; serves on the board of directors of the American Academy of Allergy, Asthma, and Immunology (views expressed are his own); and has participated in research that has received funding from DBV. Dr Conway has no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures Dr Marshall reports research grant support from National Institutes of Health (NIH). Dr Leung reports grants from Genentech, Incyte Corporation, and Sanofi-Genzyme, nonfinancial support from Aslan Pharmaceuticals, and personal fees from Leo Pharmaceuticals. Professor Lack reports grant from National Institute of Allergy and Infectious Diseases (NIAID)/NIH, personal fees and stock options from DBV Technologies, and stock options from Mission MightyMe; and has served as a scientific consultant/advisor for Novartis, Sanofi-Genzyme, Regeneron, ALK-Abello, Reckitt Mead Johnson, and Lurie Children's Hospital. Dr Sindher receives research grant support from NIH, Food Allergy Research & Education (FARE), CoFAR, DBV, AIMMUNE and Regeneron and has served as an advisor for Genentech. Dr Ciaccio receives research grant support from the NIH, FARE, and Paul and Mary Yovovich and has served as a medical consultant/advisor for Genentech, Novartis, Siolta, Clostrabio, and FARE. Dr Chan reports grant from NIAID/NIH. Professor Nadeau reports grants from NIAID, National Heart, Lung, and Blood Institute, National Institute of Environmental Health Sciences, and FARE; stock options from IgGenix, Seed Health, ClostraBio, Cour, Alladapt; advisor at Cour Pharma; consultant for Excellergy, Red Tree Ventures, Before Brands, Alladapt, Cour, Latitude, Regeneron, and IgGenix; cofounder of Before Brands, Alladapt, Latitude, and IgGenix; National Scientific Committee member at Immune Tolerance Network, and NIH clinical research centers; and patents include “Mixed allergen com-position and methods for using the same,” “Granulocyte-based methods for detecting and monitoring immune system disorders,” and “Methods and Assays for Detecting and Quantifying Pure Subpopulations of White Blood Cells in Immune System Disorders.” Professor Brough reports grant from NIAID/NIH and speaker honoraria from DBV Technologies, GSK, and Sanofi.