Effectiveness and Safety of Pharmacological Treatments for Chronic Inducible Urticaria: A Narrative Synthesis

Background: Several treatments for chronic inducible urticaria (CIndU) have been studied, but reviews covering all subtypes are limited. Objectives: Our goal is to synthesize the effectiveness and safety of available therapies across all CIndU subtypes. Methods: We performed a review of PubMed and Scopus databases to identify studies reporting treatment data on cold urticaria, symptomatic dermographism, solar urticaria, delayed-pressure urticaria, exercise-induced urticaria, cholinergic urticaria and mixed subtypes. No studies were identified that specifically focused on heat, aquagenic, or contact urticaria; however, these subtypes are encompassed within certain studies examining mixed subtypes. Results: Our search yielded 36 studies. Second-generation H1-antihistamines as first-line treatment provided significant symptom control in most CIndU subtypes, with updosing to four times the standard dose showing greater effectiveness than standard doses. Omalizumab was highly effective as second-line treatment for antihistamine-refractory patients, although relapse after discontinuation was common. In delayed-pressure urticaria dapsone and high-dose intravenous immunoglobulin yielded good responses. Narrowband UVB benefited symptomatic dermographism and solar urticaria but with high relapse rates. Emerging mast cell-depleting therapies (barzolvolimab, lirentelimab) showed promising effectiveness, while the interleukin-1 inhibitor rilonacept failed to demonstrate clinical benefit. Across the 36 studies, adverse events were generally low for most treatments, with higher incidence reported with barzolvolimab. Conclusions: Updosed antihistamines are more effective than standard doses in controlling CIndU symptoms without a significant increase in adverse events. Omalizumab at 150–300 mg every 4 weeks is effective for antihistamine-refractory CIndU, though it is off-label. Relapse after treatment cessation is frequent, highlighting the need for personalized long-term strategies. Novel endotype-specific treatments require dedicated CIndU trials, as current evidence is largely extrapolated from chronic spontaneous urticaria.