This cross-sectional study (COLD-CE) analyzed 364 patients with cold urticaria (ColdU) across 11 international GA2LEN UCARE centers to characterize those with negative standard cold stimulation testing (SCST) and identify factors independently associated with SCST-negative ColdU.
33.2% of ColdU patients (121/364) were SCST-negative. SCST-negative ColdU was independently associated with family history of ColdU (aOR 2.47), fewer cold triggers (aOR 0.66 per trigger), obligatory feeling of cold for symptom onset (aOR 3.85), and concomitant chronic spontaneous urticaria (aOR 2.23). SCST-positive ColdU carried higher rates of oropharyngeal angioedema, breathing difficulty, and cardiovascular symptoms.
- Cross-sectional design prevents causal inference or longitudinal tracking of disease course. - SCST methods (ice cube and/or TempTest) may not capture all cold exposure scenarios, potentially misclassifying some patients. - Referral bias is possible, as data came from specialized UCARE centers rather than general practice.
One in three ColdU patients may test negative on standard cold stimulation — do not rule out the diagnosis based on a negative ice cube or TempTest alone. Younger patients with a family history of ColdU, fewer identifiable triggers, and concomitant chronic spontaneous urticaria are most likely to be SCST-negative and warrant clinical diagnosis despite negative provocation testing.
