Patients with chronic spontaneous urticaria (CSU) have spontaneous wheals (W), angioedema (AE), or both, for longer than 6 weeks. Clinical differences between patients with standalone W, standalone AE, and W and AE (W+AE) remain incompletely understood.

To compare W, AE, and W+AE CSU patients regarding demographics, disease characteristics, comorbidities, disease burden, and treatment response.

Baseline data from 3,698 CSU patients in the ongoing, prospective, international, multicenter, observational Chronic Urticaria REgistry (CURE) were analyzed (data cut: September 2022).

Across all CSU patients, 59%, 36%, and 5% had W+AE, W, and AE, respectively. The W+AE patients, compared with W and AE patients, showed the lowest male-to-female ratio (0.33), higher rates of concomitant psychiatric disease (17% vs 11% vs 6%, respectively), autoimmune disease (13% vs 7% vs 9%, respectively), and nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity (9% vs 5% vs 2%, respectively) and the highest disease impact. The W patients, compared with W+AE and AE patients, showed the lowest rates of concomitant hypertension (15% vs 21% vs 40%, respectively) and obesity (11% vs 16% vs 17%, respectively), the highest rate of concomitant inducible urticaria (24% vs 22% vs 6%, respectively), and shorter W duration. The AE patients, compared with W+AE and W patients, were older at disease onset, showed longer AE duration, and the best response to increased doses of H₁-antihistamines (58% vs 24% vs 31%, respectively) and omalizumab (92% vs 67% vs 60%, respectively).

Our findings provide a better understanding of CSU phenotypes and may guide patient care and research efforts that aim to link them to pathogenic drivers.