Advances in the pathophysiology of atopic dermatitis revealed by novel therapeutics and clinical trials.

Atopic dermatitis (AD) is an inflammatory skin disease arising from a complex interplay of genetic, immune, and environmental factors. The development and successful marketing of the anti-IL-4/IL-13 monoclonal antibody, dupilumab, and the topical nonsteroidal phosphodiesterase 4 (PDE4) inhibitor, crisaborole, as well as the Janus kinase (JAK) inhibitor, delgocitinib, have brought hope for developing new therapeutic agents. The efficacy of these treatments contributes to our understanding of the pathophysiology of AD. Dupilumab modulates the Th2-related immune response, demonstrating that IL-4 and IL-13 contribute to epidermal hyperplasia, skin homeostasis, and innate immune responses on the skin surface in AD. The effectiveness of crisaborole reveals that PDE4 contributes to Th2 and Th17/Th22 inflammation and lesional skin barrier dysfunction, while delgocitinib shows that JAK-associated signaling is essential for the inflammatory reaction in AD. This review provides a brief overview of recent research on therapeutic monoclonal antibodies and small biologic molecules for AD and what these treatments reveal about AD pathophysiology.