Targeting Mast Cells in Chronic Spontaneous Urticaria

This review focuses on the pathophysiology, diagnostic approach, and current and emerging treatments of chronic spontaneous urticaria (CSU), with an emphasis on mast-cell mediated mechanisms and therapeutic targets.

CSU is a mast-cell mediated disease involving both immunoglobulin E (IgE) and non-IgE mediated pathways, thus targeting mast cells and their downstream mediators can provide therapeutic benefit. Emerging therapies such as dupilumab, Bruton's tyrosine kinase (BTK) inhibitors, anti-KIT antibodies, Janus kinase (JAK) inhibitors, Mas-related G protein-coupled receptor X2 (MRGPRX2) inhibitors, interleukin (IL)-17 and IL-5 inhibitors, anti-thymic stromal lymphopoietin (TSLP) monoclonal antibodies, and mast cell silencers, as well as lifestyle changes such as low-histamine diets, are under investigation for antihistamine- refractory disease. While current international guidelines recommend second-generation H1-antihistamines as first-line treatments of CSU, novel treatments targeting mast-cell mediated pathways show promise for refractory disease. Recent advancements in targeted therapies and biomarkers may improve treatment personalization and response.