D1.313 - Clinical Characteristics of Chronic Urticaria Patients With and Without Flares With Systemic Symptoms

Chronic urticaria (CU) is currently not classified within mast cell activation syndromes (MCAS); however, a subset of patients experience recurrent systemic flares during the disease, presenting with gastrointestinal, respiratory, and cardiovascular symptoms that fulfill clinical criteria for anaphylaxis in the absence of identifiable triggers. These episodes pose a diagnostic and therapeutic challenge, as it is unclear whether they belong to the chronic urticaria spectrum or reflect mast cell activation–related disease.This study aimed to characterize CU patients with systemic flares and to identify factors associated with recurrent episodes.

In this retrospective study conducted at a tertiary allergy and immunology center, patients diagnosed with chronic idiopathic urticaria between 2015 and 2025 were evaluated. The study population was defined by the availability of baseline serum tryptase measurements, yielding a final cohort of 70 patients. Patients were categorized according to the presence or absence of systemic flares fulfilling clinical criteria for anaphylaxis without identifiable triggers. Clinical features, treatment modalities, and laboratory parameters were compared between groups. In a secondary analysis, patients with systemic flares were further stratified according to single versus recurrent episodes.

Seventy patients (64.0% female; median age 39.3 years) were included. Systemic flares occurred in 36 patients (51%), most commonly presenting as moderate anaphylaxis (86.1%). Compared with patients without systemic flares, basophil and lymphocyte counts were higher, whereas total IgE levels and aeroallergen sensitization rates did not differ. In multivariable analysis, higher lymphocyte counts were independently associated with systemic flares (OR 3.35; 95% CI 1.31–8.56; p = 0.012). Baseline serum tryptase levels were not significantly associated with systemic flares (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). Among patients with recurrent flares, 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 distinct subgroup of patients with chronic urticaria who experience systemic flares fulfilling anaphylaxis criteria and exhibit well-controlled cutaneous disease with antihistamines, a lower need for omalizumab, and higher peripheral lymphocyte counts. Gastrointestinal symptoms represent an important risk factor for recurrent systemic flares in CU. Patients with gastrointestinal involvement and recurrent flares—particularly in the absence of identifiable triggers—should be carefully evaluated for underlying mast cell activation.