April 05, 2022

3 min read


Disclosures:
Bizjak reports a speaker and advisory board role with Novartis. Maurer reports speaker/advisory roles with or research funding from Allakos, Aralez Bio, ArgenX, AstraZeneca, Celldex Therapeutics, Centogene, CSL Behring, Foundation for Advanced Education in the Sciences, Genentech, GI Innovation, Innate Pharma, Kyowa Kirin, LEO Pharma, Lilly, The Menarini Group, Merck, Moxie Systems, Novartis, Roche, Sanofi/Regeneron, Third Harmonic Bio, UCB and Uriach. Please see the study for all other authors’ relevant financial disclosures.


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Patients with typical cold urticaria should be screened for cold-induced anaphylaxis risks and prescribed adrenaline autoinjectors, according to a study published in Allergy.

“Intramuscular adrenaline is the first-line treatment for anaphylaxis, and a delay in its administration is a risk factor for anaphylaxis-related death,” Mojca Bizjak, MD, a dermatology and dermatological allergology specialist with the University Clinic of Respiratory and Allergic Diseases Golnik Slovenia, and Marcus Maurer, MD, professor of dermatology and allergy at Charité – Universitätsmedizin Berlin, told Healio in a statement.


Man uses epinephrine autoinjector

Source: Adobe Stock

High-risk patients with typical cold urticaria (ColdU) require an adrenaline autoinjector (AAI), Bizjak and Maurer said, but exactly which patients should carry one has been undefined. Predictors for cold-induced anaphylaxis have been ill defined as well, they continued.

Mojca Bizjak

“Some researchers suggested that all patients with ColdU should be provided with an adrenaline autoinjector, but this strategy could lead to high health care costs and trigger unnecessary anxiety in patients who have a low risk for life-threatening reactions,” Bizjak and Maurer said.

The researchers studied 412 patients with ColdU and whealing in response to local cold stimulation testing. Forty of these patients (10%) had concomitant chronic spontaneous urticaria, leaving 372 (median age, 36 years; 69% female; 91% adults) with standalone ColdU.

Calling it a clinical emergency, the researchers defined cold-induced anaphylaxis as an acute cold-induced involvement of the skin and/or visible mucosal tissue and cardiovascular manifestations, difficulty breathing or gastrointestinal symptoms.

“Health care professionals should be familiar with its recognition, treatment and prevention,” Bizjak and Maurer said.

Cold-induced anaphylaxis occurred among 145 (39%) patients, but only 12 (8%) received adrenaline treatment and only 54 (37%) had an AAI. Of the 48 patients (13%) who experienced hypotension, eight (17%) received adrenaline and five (10%) received adrenaline and had an AAI prescription.

The researchers also found cold-induced anaphylaxis to be more common in temperate countries compared with cold climates (44% vs. 21%; P < .001), with AAI prescriptions more common in temperate countries (30% vs. 15%; P = .011).

There was no significant difference in cold-induced anaphylaxis frequency between temperate and tropical countries (44% vs. 42%), although temperate countries saw more AAI prescriptions (30% vs. 12%; P = .038).

Marcus Maurer

“Cold-induced anaphylaxis induced by complete cold water immersion, such as activities in the ocean, is linked to clinical characteristics of patients living in temperate climates, but cold-induced anaphylaxis induced by exposure to cold air was more common in countries with a tropical climate,” Bizjak and Maurer said.

Also, 107 patients (29%) were diagnosed with cold-induced anaphylaxis triggered by complete cold water immersion, such as at beaches, yet only eight (8%) received adrenaline treatment by medical personnel or by self-administration.

Patients with oropharyngeal/laryngeal symptoms received AAI prescriptions more often than those who did not have these symptoms (37% vs. 20%; P = .001).

“More than a third of patients with typical ColdU had experienced cold-induced anaphylaxis, but our data may overrepresent severe ColdU compared with that occurring in the community because patients were evaluated at tertiary care centers known to evaluate more severe patients,” Bizjak and Maurer said.

Based on these findings, the researchers called cold-induced anaphylaxis undertreated, saying it should be approached and treated like other anaphylaxis types.

Specialists and nonspecialists alike should screen patients with ColdU to identify those with risk factors for cold-induced anaphylaxis, the researchers continued, such as a previous systemic reaction to a Hymenoptera sting, generalized wheals, angioedema, oropharyngeal or laryngeal symptoms, itchy earlobes and concomitant asthma.

Patients with these risk factors should get an AAI prescription and advice about how they can avoid relevant cold triggers. These patients also should receive a written treatment plan and AAI training .

“We provide clinically useful instructions to improve patient care in a regular clinical setting,” Bizjak and Maurer said.

Plus, the researchers said that AAIs should be accessible at public beaches and that lifeguards and emergency teams should be educated about cold-induced anaphylaxis.

“We do not know how many deaths from drowning have actually occurred due to this cause,” Bizjak and Maurer said.

Also, the researchers said consideration should be given to add cold-induced anaphylaxis to the list of indications for AAI.

“Adrenaline autoinjectors should be carried as a first-aid measure by patients at risk for cold-induced anaphylaxis, but only 39% of our patients who had already experienced cold-induced anaphylaxis due to immersion in open waters carry it,” Bizjak and Maurer said. “We need to spread the knowledge.”

The researchers are continuing to analyze their data and plan on reporting additional results in future publications in addition to researching other chronic inducible urticaria subtypes such as cholinergic urticaria, symptomatic dermographism and solar urticaria.

“The next big steps for ColdU are to identify and characterize the cellular and molecular drivers of ColdU and to help with the development of more effective treatment options,” Bizjak and Maurer said. “Patients with ColdU need to be taken seriously. We are obliged and can improve their care and protection.”

For more information:

Mojca Bizjak, MD, can be reached at [email protected].

Marcus Maurer, MD, can be reached at [email protected].

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