Chronic Spontaneous Urticaria: Pathophysiological Mechanisms, Emerging Biomarkers, and Therapeutic Advances

Chronic urticaria (CU) is a mast cell-driven inflammatory skin disorder characterized by recurrent wheals, angioedema, or both lasting more than six weeks, often resulting in significant impairment of quality of life. Although CU has traditionally been regarded as a predominantly histamine-mediated condition, evidence accumulated over the past decade has redefined chronic spontaneous urticaria (CSU) as a complex immune-mediated disease with marked biological heterogeneity. Distinct pathogenic mechanisms involving autoimmune pathways, dysregulated mast cell activation, and chronic inflammatory networks have been identified, providing a mechanistic basis for disease persistence, variable severity, and therapeutic refractoriness. This review synthesizes current concepts in CSU pathophysiology, with emphasis on mast cell biology, autoimmune endotypes, and inflammatory amplification mechanisms. We further discuss emerging biomarkers with potential relevance for disease stratification and treatment prediction, as well as established and novel therapeutic strategies targeting key pathogenic pathways. By integrating mechanistic insights with clinical implications, this review highlights the transition toward endotype-driven and biomarker-guided management of chronic urticaria.