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Endotypes of Chronic Spontaneous Urticaria and Angioedema.

Dennis Wong,S. Waserman,Gordon L. Sussman

Published 2025 in Journal of Allergy and Clinical Immunology

ABSTRACT

The current understanding of chronic spontaneous urticaria (CSU) suggests that a complex network of inflammatory pathways is involved in its pathogenesis. Recent development highlighted autoimmunity as one of the key pathogenic mechanisms of CSU. Two endotypes, type I autoallergic (associated with IgE antibodies against autoantigens) and type IIb autoimmune (mediated by IgG autoantibodies against IgE or its high affinity receptor (FcεRI), have been characterized. A subpopulation of the patients has an overlap of the two endotypes. About 10% of patients with CSU presents with angioedema only. Patients with isolated mast-cell mediated angioedema have distinct clinical and demographic features and should be distinguished from bradykinin-mediated angioedema. Multiple potential biomarkers such as total IgE level and IgG anti-thyroid peroxidase have been identified, and together with the corresponding endotypes, have been linked to disease severity, duration and response to treatments. Currently, the utility of these biomarkers is limited in clinical settings given the few options of therapy. However, with the advent of novel treatments, endotyping CSU might help with tailoring treatment approach.

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