Clinical characteristics of chronic urticaria patients with and without systemic flares

Intraduction: Chronic urticaria (CU) is not classified as a mast cell activation syndrome; however, some patients experience systemic flares fulfilling anaphylaxis criteria without identifiable triggers, posing diagnostic and therapeutic challenges. To characterize CU patients with systemic flares and identify factors associated with recurrent episodes.

In this retrospective study at a tertiary allergy center, patients diagnosed with CU between 2015 and 2025 were screened. Among these, 192 had confirmed chronic urticaria based on disease duration and clinical evaluation. Patients with inducible urticaria subtypes associated with anaphylaxis and those with identifiable trigger-related reactions were excluded to avoid misclassification. The final cohort consisted of 70 patients, including 36 with systemic flares fulfilling clinical criteria for anaphylaxis and 34 without systemic flares.

A total of 70 patients (64.0% female; mean age 39.3±13.6 years) were included.Systemic flares occurred in 36 (51%) patients, most commonly presenting as moderate anaphylaxis (86.1%). Compared to group without systemic flares, blood basophil and lymphocyte counts were higher in the systemic-flare group. Higher lymphocyte counts were independently associated with systemic flares (OR = 3.35; 95%CI 1.31-8.56; p = 0.012), whereas baseline serum tryptase levels were not (OR = 0.77; 95%CI 0.57-1.04; p = 0.083). Patients with systemic flares were less likely to require escalation to second-line therapy with omalizumab for urticaria control (OR = 0.11; 95% CI 0.02-0.79; p = 0.028). Gastrointestinal involvement emerged as the sole independent predictor of recurrence (OR = 8.24; 95%CI 1.24-54.71; p = 0.029).

This study identifies a subgroup of patients with CU who experience systemic flares fulfilling anaphylaxis criteria, and exhibit well-controlled urticaria with antihistamines, a lower need for omalizumab, and higher peripheral lymphocyte counts. Systemic flares with gastrointestinal symptoms was a risk factor for recurrent systemic flares in CU. Our findings suggest that a subset of patients with chronic urticaria may experience recurrent systemic flares accompanied by certain clinical differences and treatment patterns compared with conventional CU, although further prospective studies are needed to better characterize this group.