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 Th2 inflammatory cascade conversely proposes that protecting the same barrier and promoting adequate interactions with other organs, like 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 AD patients, including the most relevant filaggrin gene mutations, the recent discovery of the role of the transient receptor potential vanilloid 1 (TRPV1), 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 TCI, along with pioneering trials proposed to change their current use (PACI and SEAL). We provide an overview of the novel therapies that enhance the skin barrier, like probiotics and prebiotics topical application, read-through drugs, direct and indirect FLG replacement, and IL and JAK inhibitors. Lastly, we discuss the newer strategies for preventing and treating food allergies in the form of epicutaneous immunotherapy (EPIT) and the experimental use of single-dose of adeno-associated virus (AAV) vector gene immunotherapy.