Standard Cold Stimulation Test May Miss 1 in 3 Patients With Cold Urticaria: Study
Germany: A new study has revealed that about 1 in 3 patients with cold urticaria (ColdU) had a negative standard cold stimulation test despite having convincing clinical symptoms. Patients with positive testing had a greater disease burden, including more frequent breathing difficulties and cardiovascular symptoms.
The findings were published in The Journal of Allergy and Clinical Immunology: In Practice by Dorothea Terhorst-Molawi, MD, Institute of Allergology, Charité-Universitätsmedizin Berlin, Germany, and colleagues. The researchers examined the clinical characteristics of patients with ColdU whose symptoms were not confirmed by standard cold stimulation testing (SCST).
ColdU causes recurrent hives or angioedema following exposure to cold. Typical ColdU is generally confirmed when SCST produces whealing within 10 minutes at the stimulated area of the forearm following exposure to an ice cube or TempTest. However, the characteristics of patients with clinically suspected ColdU but negative SCST results have remained unclear.
The international cross-sectional COLD-CE study included 364 patients with ColdU recruited from 11 GA²LEN UCARE centres. Researchers collected detailed clinical histories and performed SCST, followed by comparisons between patients with positive and negative test results and multivariable analyses to identify factors associated with SCST-negative disease.
Key findings:
- SCST was negative in 121 patients (33.2%) and positive in 243 (66.8%).
- Patients with SCST-negative ColdU were younger and developed the condition at an earlier age.
- A family history of ColdU and concomitant chronic spontaneous urticaria (CSU) were more common among SCST-negative patients.
- SCST-positive patients reported a greater number of cold triggers and more frequently experienced oropharyngeal mucosal angioedema, breathing difficulties, and cardiovascular symptoms.
- SCST-negative ColdU remained independently associated with a family history of the disease, fewer cold triggers, an obligatory sensation of cold before symptoms developed, and concomitant CSU.
- The adjusted odds ratio was 2.47 for family history, 0.66 for each additional cold trigger, 3.85 for obligatory cold sensation and 2.23 for concomitant CSU.
The study had several limitations, including its cross-sectional design, specialised-centre recruitment, potential recall and information bias from patient-reported data, and residual confounding. The moderate sample size and variability across centres may have affected some associations. Modified cold stimulation testing was not systematically performed, so the proportion of SCST-negative patients who might respond to alternative testing remains unknown. False-negative results may also have resulted from inadequate cooling, exposure duration, or testing at unaffected sites.
Overall, the findings suggest that a negative standard cold stimulation test should not by itself exclude ColdU. In patients with a convincing clinical history, clinicians should reassess cold triggers, affected sites, disease activity, and treatment status and consider modified cold provocation testing when appropriate.
Reference:
Terhorst-Molawi, D., Ahsan, D. M., Fomina, D., Salameh, P., Altrichter, S., Andrenova, G., Bauer, A., Borzova, E., Dinevski, D., Giménez-Arnau, A. M., Gonçalo, M., Gutsche, A., Holm, J. G., Khoshkhui, M., Klyucharova, A., Kocatürk, E., Košnik, M., Kulthanan, K., Makris, M., . . . Bizjak-Suran, M. (2026). Cold Urticaria With Negative Standard Cold Stimulation Testing: Results From the COLD-CE Study. The Journal of Allergy and Clinical Immunology: In Practice. https://doi.org/10.1016/j.jaip.2026.08.022
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