Skin as the target for allergy prevention and treatment.

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.)