J Allergy Clin Immunol Pract. 2026 Aug 25:S2213-2198(26)00702-6. doi: 10.1016/j.jaip.2026.08.022. Online ahead of print.
ABSTRACT
BACKGROUND: Cold urticaria (ColdU) is defined by recurrent wheals and/or angioedema after cold exposure. Typical ColdU is confirmed by positive standard cold stimulation testing (SCST), defined as whealing within 10 minutes over the stimulated area on the volar forearm after provocation with an ice cube and/or TempTest®. SCST-negative ColdU remains insufficiently characterized.
OBJECTIVE: To characterize SCST-negative ColdU and identify factors independently associated with it.
METHODS: We analyzed 364 patients with ColdU from the international, cross-sectional COLD-CE study across 11 GA2LEN UCARE centers. Detailed clinical history was obtained, SCST performed, and group comparisons and logistic regression were conducted.
RESULTS: Of 364 patients, 121 (33.2%) had SCST-negative and 243 (66.8%) had SCST-positive ColdU. Compared with SCST-positive ColdU, SCST-negative patients were younger (P = .004), had earlier onset (P = .002), and more often had a positive family history of ColdU (P = .005), and concomitant chronic spontaneous urticaria (CSU; P < .001). SCST-positive ColdU was associated with more reported cold triggers (P < .001), mucosal angioedema involving the oropharynx (P = .009), difficulty breathing (P < .001), and cardiovascular symptoms (P = .001). In multivariable analysis, SCST-negative ColdU remained independently associated with family history of ColdU (adjusted odds ratio [aOR], 2.47; 95% confidence interval [CI], 1.12-5.43), fewer reported cold triggers (aOR per trigger, 0.66; 95% CI, 0.55-0.79), obligatory feeling of cold for symptom development (aOR, 3.85; 95% CI, 2.03-7.32), and concomitant CSU (aOR, 2.23; 95% CI, 1.13-4.37).
CONCLUSION: SCST-negative ColdU is common and clinically distinct from SCST-positive ColdU.
PMID:42641985 | DOI:10.1016/j.jaip.2026.08.022