Clinical and molecular aspects of managing chronic spontaneous urticaria: identifying endotypes, phenotypes, and determinants of treatment response and resistance

Chronic spontaneous urticaria (CSU) is a clinically heterogeneous, mast cell-driven inflammatory disease in which disease expression, treatment response, and resistance are determined by distinct but overlapping immunopathogenic mechanisms. Growing evidence supports the existence of two principal molecular endotypes: type I (autoallergic) CSU, mediated by autoreactive IgE antibodies against self-antigens such as thyroid peroxidase and interleukin-24, and type IIb (autoimmune) CSU, characterized by IgG (and less frequently IgA or IgM) autoantibodies directed against IgE or its high-affinity receptor FcεRI. These endotypes differ substantially in biomarker profiles, clinical severity, and therapeutic…