D1.306 - Cold-induced urticaria: Phenotypic characterization and risk factors for cold-induced anaphylaxis

Cold-induced urticaria (ColdU) is a chronic, inducible urticaria causing wheals and/or angioedema after cold exposure. Cold-induced anaphylaxis (ColdA) occurs in 17–37% of patients. Our aim was to phenotypically characterize ColdU patients and identify risk factors associated with ColdA.

We conducted a retrospective descriptive study including all patients diagnosed with ColdU between 2022 and 2025 in our Allergy Unit. Demographic, clinical, and diagnostic variables were collected. ColdA was defined by mucocutaneous involvement and ≥1 of the following: gastrointestinal symptoms, lower respiratory tract involvement, cardiovascular compromise, or neurological manifestations.

A total of 67 patients were included (67.2% female), median age at symptom onset of 15.5 years (IQR 8-37). Concomitant forms of urticaria were identified in 20.9% of patients, mainly cholinergic urticaria (42.9%), followed by chronic spontaneous urticaria (35.7%) and dermographism (21.4%). Allergic comorbidities were present in 67.2% of patients, most frequently rhinoconjunctivitis (73.3%) and asthma (35.6%). One patient required omalizumab.

Median baseline tryptase levels were 4.5 µg/L (IQR 3–6), eosinophil counts 200 x 10³cells/µL (IQR 132–300), and total IgE levels 83 IU/ml (IQR 44–279). No positive cryoglobulins were detected.

The ice cube test was positive in 43.5% of tested patients, while the TempTest showed a low positivity rate (6.0%).

ColdA occurred in 11.9% of patients, with cold water immersion as the main trigger (66.7%). During the anaphylactic episodes, generalized urticaria predominated over localized involvement (77.8% vs 11.1%), and cardiovascular symptoms occurred in 77.8%.

When comparing patients with and without ColdA, ice cube test positivity was significantly more frequent in the ColdA group (p < 0.05). TempTest positivity trended higher in ColdA (50% vs 4.5%), althought differences were not statistically significant.

No significant differences were found in other clinical variables (Table 1). 

In this cohort, ColdA occurred in a clinically relevant proportion of patients with ColdU, being cold water immersion the main trigger. A positive ice cube test was significantly associated with the presence of anaphylaxis, reinforcing its usefulness in clinical risk assessment. Additionally, the predominance of generalized urticaria during episodes suggests its potential as a clinical marker for a high-risk phenotype.