TOPLINE

About 1 in 3 patients with cold urticaria (ColdU) tested negative on the standard cold stimulation test (SCST) despite having convincing symptoms; those who tested positive had a greater clinical burden, including more frequent breathing difficulties and cardiovascular symptoms.

METHODOLOGY

• Researchers conducted an observational study to better understand patients with ColdU who test negative on SCST, a group that remains poorly characterized. 
• The study analyzed 364 patients (median age, 36 years; 67% women) with ColdU from 11 urticaria centers across nine countries between 2019 and 2021. 
• All participants underwent SCST using an ice cube test, a thermoelectric device called TempTest, or both, applied to the forearm for 5 minutes; skin responses were assessed 10 minutes later, with a palpable wheal at the test site indicating a positive result.
• Participants were classified as SCST-positive or SCST-negative based on test results; those with negative results but a convincing history of cold-induced symptoms, supported by photographs, were considered to have SCST-negative ColdU.
• Researchers compared clinical characteristics, trigger profiles, comorbidities, and treatment responses between the two groups.

TAKEAWAY

• About 33.2% of patients had SCST-negative ColdU, and they were younger (median age, 31.0 vs 39.0 years) and had an earlier disease onset (22.0 vs 30.0 years; P < .01 for both) than those with SCST-positive ColdU.
• Patients with SCST-positive ColdU had higher rates of cutaneous angioedema (59.7% vs 47.1%), breathing difficulty (28.4% vs 10.7%), cardiovascular symptoms (31.7% vs 15.7%), and mucosal angioedema due to ingestion of cold food or drinks (37.9% vs 24.0%; P ≤ .05 for all) than those with SCST-negative ColdU.
• Those with SCST-negative ColdU were 2.47 times more likely to have a family history of cold urticaria, 34% less likely to report each additional cold trigger, 3.85 times more likely to report an obligatory feeling of cold before symptoms, and 2.23 times more likely to have concomitant chronic spontaneous urticaria (all P ≤ .05).
• Good efficacy with standard-dose antihistamines was reported more often for SCST-negative than for SCST-positive ColdU, and adrenaline autoinjectors were prescribed more often for SCST-positive than for SCST-negative ColdU (both P ≤ .001).

IN PRACTICE

"Negative standard testing should not exclude ColdU but should prompt review of triggers, symptomatic sites, disease activity, treatment status, and modified provocation testing," the authors wrote.

SOURCE

Mojca Bizjak-Suran, MD, PhD, with the University Clinic of Respiratory and Allergic Diseases Golnik in Golnik, Slovenia, was the corresponding author of the study, which was published online on August 24 in The Journal of Allergy and Clinical Immunology: In Practice.

LIMITATIONS

The cross-sectional design prevented the assessment of causality or long-term outcomes. Modified cold stimulation testing and specific nonclassical SCST response patterns were not collected systematically. Reliance on patient-reported history for symptoms, triggers, and treatment responses may have introduced recall bias.

DISCLOSURES

This research did not receive any specific grant from funding agencies. Several authors reported financial ties with multiple pharmaceutical companies, including consulting and advisory roles, speaker honoraria, and research support. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.