Ethan Bendayan,1 Alexandre Ton That,1 Catherine Keying Zhu,2 Elena Netchiporouk,2,3, Moshe Ben-Shoshan4, 1Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada; 2Division of Dermatology, Department of Medicine, McGill University Health Centre, Montreal, QC, Canada; 3Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC, Canada; 4Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, McGill University, Montreal, QC, CanadaThese authors contributed equally to this workCorrespondence: Ethan Bendayan, Faculty of Medicine and Health Sciences, McGill University, 1001 Decarie Boulevard, Montreal, Quebec, H4A 3J1, Canada, Email ethan.bendayan@mail.mcgill.caAbstract: Chronic urticaria (CU) is a mast cell-driven condition presenting with recurrent wheals (hives), angioedema, or both for over 6 weeks. It encompasses chronic spontaneous urticaria (CSU), in which hives occur without specific external triggers, and chronic inducible urticaria (CIndU), in which stimuli, such as physical factors, reliably induce hives. Differentiating CIndU from CSU may be challenging yet crucial. Patients may have unrecognized triggers or may have both CSU and CIndU, rendering diagnosis and management challenging. Drawing on current guidelines, randomized control trials, observational studies, and other recent studies, this narrative review discusses the subtypes of CSU and CIndU, emphasizing clinical distinctions, diagnosis, and treatment implications. Key diagnostic clues to identify CIndU include the reproducibility of symptoms followed by defined stimuli and a positive response to provocation testing. In contrast, CSU diagnosis should be centered on clinical history. Biomarkers may be helpful to establish a diagnosis of autoimmune CSU but are rarely ordered in routine practice. Treatment is outlined according to current guidelines and evidence, noting that while second-generation H1-antihistamines are first-line for all CU patients, patients with CIndU often require trigger avoidance and occasionally off-label therapies (eg, omalizumab) for adequate control. In addition, this review discusses emerging treatments for CU, such as dupilumab, Bruton’s tyrosine kinase (BTK) inhibitors, and barzolvolimab, which reflect the rapidly evolving therapeutic landscape. This review provides a practical guide for clinicians to differentiate and manage CSU and CIndU, by identifying key differences between CSU and CIndU based on current evidence.Keywords: chronic urticaria, chronic inducible urticaria, chronic spontaneous urticaria, provocation testing
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