Update on the Pathogenesis and Therapy of Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a common inflammatory skin disorder characterized by recurrent eczematous lesions and intense itch. Although it most often starts in infancy and affects children, it is also highly prevalent in adults. In this article, the main aspects of AD have been updated, with a focus on the pathogenetic and therapeutic aspects. The pathogenesis of AD is complex, and it is evident that a strong genetic predisposition, epidermal dysfunction, skin microbiome abnormalities, immune dysregulation, and the neuroimmune system are critical in AD development. Mutations in the genes associated with disrupted epidermal barrier, exaggerated pathological inflammation and inadequate antimicrobial peptides can promote enhanced Th2 inflammation and mediate pruritus. Current understanding of etiology highlights gut microbial diversity, NK cell deficiency, and different immunological phenotype with age and race. For topical anti-inflammatory treatment for mild-to-severe AD, phosphodiesterase 4 inhibitors (PDE-4), JAK inhibitors, and microbiome transplantation with Roseomonas mucosa provided more management selections. The treatment of moderate-to-severe AD has been limited to merely symptomatic and relatively nonspecific immunosuppressive approaches. In-depth understanding of the pathogenesis of AD has led to the development of innovative and targeted therapies, such as biologic agents targeting interleukin (IL)-4, IL-13 and JAK/STAT inhibitors. Other potential therapeutic agents for AD include agents targeting the T helper (Th) 22 and Th17/IL23 pathway. Antipruritic therapy and complementary probiotics therapy have also been reviewed.