Advances in targeted therapies for chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is a common dermatologic disorder marked by significant patient heterogeneity. Existing treatment strategies often fall short of adequately addressing patients' clinical needs. In the past decade, insights into the pathophysiology of CSU have catalyzed the development of novel targeted therapies, which can be categorized into three main approaches: targeting mast cells, targeting cytokines, and targeting Janus kinase (JAK) signaling. Mast cell-targeted strategies focus on surface receptors (e.g., activating receptors, the KIT receptor governing mast cell proliferation/survival, and inhibitory receptors) and intracellular pathways such as Bruton's tyrosine kinase (BTK). Cytokine-targeted therapies aim at specific mediators including IL-4, thymic stromal lymphopoietin (TSLP), IL-17, IL-23, and IL-5. Regarding JAK-targeted therapy, besides approved JAK inhibitors, several novel agents, including dual-target inhibitors, are under investigation. This review systematically delineates recent advances in targeted therapies for CSU, comparing the features and clinical potential of different agents, to inform evidence-based and personalized management of this condition.