Kaplan, Allen P.Lebwohl, MarkGiménez Arnau, Anna MariaHide, MichihiroArmstrong, April W.Maurer, Marcus2023-02-202023-02-202023Kaplan A, Lebwohl M, Giménez-Arnau AM, Hide M, Armstrong AW, Maurer M. Chronic spontaneous urticaria. Focus on pathophysiology to unlock treatment advances. Allergy. 2023 Feb; 78(2): 389-401. DOI: 10.1111/all.156030105-4538http://hdl.handle.net/10230/55824Chronic spontaneous urticaria (CSU) is a debilitating skin disease characterized by intensely itchy wheals, angioedema, or both. Symptoms recur spontaneously, on a near-daily basis, over >6 weeks; many patients experience flare-ups over several years and, consequently, reduced quality of life. Differences between the inflammatory profiles of the skin of CSU patients (wheals and nonlesional sites) and healthy controls indicate that key drivers such as mast cells, eosinophils, and basophils interact, release vasoactive mediators, and prime the skin, leaving patients predisposed to symptoms. Many cytokines and chemokines involved in these inflammatory networks and their corresponding intracellular signaling cascades have been identified. These insights informed the development of therapies such as omalizumab, dupilumab, and Bruton's tyrosine kinase (BTK) inhibitors, marking a renewed focus on pathogenesis in CSU clinical research. Despite progress, current therapies provide symptomatic control but do not appear to redress the inflammatory balance in the skin permanently. A deeper understanding of CSU pathogenesis will permit a more targeted approach to developing novel treatments with curative intent. Here, we review what is known about the pathogenesis of CSU and consider how this can be used to identify rational targets to improve patient care further.application/pdfengThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License http://creativecommons.org/licenses/by-nc/4.0/, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1111/all.15603IgEAngioedemaDermatologyMast cellsUrticariainfo:eu-repo/semantics/openAccess