Clinical practice guideline for H1 antihistamine-resistant Chronic Spontaneous Urticaria

Chronic spontaneous urticaria (CSU), characterized by recurrent wheals and/or angioedema persisting for more than 6 weeks, represents a substantial clinical challenge. Although international guidelines endorse second-generation H1-antihistamines (sgAHs) as first-line therapy, up to 50% of patients remain refractory even at quadruple doses, significantly compromising quality of life and mental well-being. Notably, standardized guidelines for managing H1 antihistamine-resistant CSU are currently lacking. To address this gap, we aimed to develop an evidence-based clinical practice guideline for the diagnosis, assessment, and step-wise treatment of H1 antihistamine-resistant CSU. A multidisciplinary panel conducted a systematic literature review and through multiple rounds of group discussions, both offline and online, to draft recommendations. Evidence was graded using the Oxford CEBM 2011 system and recommendations assigned GRADE strengths. This guideline provides a standardized, personalized treatment algorithm for H1 antihistamine-resistant CSU, aiming to improve clinical efficacy, reduce socioeconomic burden, and direct future research toward validating novel agents such as JAK inhibitors and optimizing long-term outcomes.