A translational approach to improve therapeutics in atopic dermatitis and beyond

Atopic dermatitis (AD) and alopecia areata are highly prevalent inflammatory skin/hair conditions. While previously not fully understood and limited in treatment options, AD is currently undergoing a therapeutic revolution. Our increased understanding of the underlying immunologic and barrier dysregulations and disease heterogeneity across its spectrum is facilitating hypothesis-driven therapeutic development. Early transcriptomic analyses in AD skin and blood have identified disease-specific biomarkers and uncovered immune and barrier abnormalities that may contribute to disease pathogenesis. From these findings, various therapeutic targets were then proposed and investigated in clinical trials, leading to the Food and Drug Administration approval of several biologics and small molecule drugs that are now widely used in the clinical setting. Molecular phenotyping of patient samples before and after treatment has further elucidated the specific immunomodulatory effect of each therapeutic, as well as the relative contributions of various immune pathways to disease pathogenesis. This bench-to-bedside cyclical approach has rapidly broadened our understanding of AD and enabled the rapid expansion of the AD therapeutic pipeline. In this brief review, we detail how molecular and blood profiling studies in AD laid the foundation for a therapeutic revolution, discuss currently approved and potential therapeutics for AD resulting from this bench-to-bedside approach, and highlight how this translational approach is being applied to advancing the therapeutic pipeline of alopecia areata.