Circadian orchestration of the cutaneous microenvironment and chronotherapeutic strategies in inflammatory skin diseases

The clinical course of inflammatory skin diseases—encompassing atopic dermatitis, psoriasis, and chronic spontaneous urticaria—frequently exhibits pronounced symptomatic rhythmicity, most classically manifested as the nocturnal exacerbation of pruritus. Although previous studies have progressively elucidated the circadian mechanisms governing both the epidermal barrier and local immunity that drive lesion evolution, contemporary clinical regimens for most targeted therapeutics and biologics have yet to incorporate administration timing as a key variable for optimizing efficacy. This review systematically delineates the dynamic interactive network between skin barrier function and the immune microenvironment under the regulation of the endogenous circadian clock. Building upon this mechanistic foundation, we examine how the timing of each major drug class—topical agents, conventional systemic drugs, oral small molecules and macromolecular biologics—could be aligned with the circadian peaks of the mediators they target, and we distinguish the components of this framework that are supported by clinical data from those that remain hypotheses. Ultimately, by conceptualizing chronotherapeutic strategies for precise intervention in local microenvironmental rhythms, this article aims to provide a testable framework for future chronotherapeutic research in inflammatory skin diseases.