Clinical phenotypes and molecular endotypes of chronic urticaria: Linking clinical expression to underlying immune mechanisms

Chronic urticaria (CU) is a biologically heterogeneous inflammatory skin disease characterized by recurrent wheals and/or angioedema. Despite its uniform clinical presentation, the disease encompasses diverse clinical phenotypes and molecular endotypes driven by distinct immune mechanisms. Integrating these patterns is essential for transitioning from empirical management toward precision medicine. This review explores the convergence of observable clinical phenotypes and underlying molecular endotypes to refine diagnosis and guide stratified therapeutic strategies. A comprehensive literature review was conducted, focusing on clinical clusters (eg, pediatric, elderly, and ethnic variations), immunological drivers (type I autoallergy and type IIb autoimmunity), and emerging targeted therapies. Linking clinical phenotypes with molecular endotypes enables a more personalized approach to CU management. Future directions include the validation of point-of-care biomarkers and the utilization of digital phenotyping to achieve disease modification and long-term remission.