Risk factors for systemic reactions in typical cold urticaria: Results from the COLD‐CE study

Abstract

Background Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold‐induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU. Methods An international, cross‐sectional study COLD‐CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold‐induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms. Results Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold‐induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes. Conclusion ColdA is common in typical ColdU. High‐risk patients require education about their condition and how to use an adrenaline autoinjector.

Adrenaline autoinjector is underprescribed in typical cold urticaria patients

“…1 Cold-induced anaphylaxis (ColdA), which may result in fatality, 2 is common in typical cold urticaria (ColdU), and risk factors for ColdA have recently been identified for the first time. 3 As of now, it is largely unclear how often patients with ColdU (i) receive adrenaline treatment and (ii) are provided with an AAI. 2 A study by Gernez et al in the USA showed that 48% of allergy and immunology specialists prescribe an AAI to ColdU patients less than 10% of the time.…”

“…Less than 10% of patients with ColdA received adrenaline and less than 40% of them have an AAI. ColdU patients need to be screened by specialists and non-specialists to identify those with ColdA risk factors (Table 2), 3 which may also include underlying clonal mast cell disorder. 6 Prescribing an AAI to patients at risk of ColdA needs to be com- Note: Data are given as no.…”

Development of the Cold Urticaria Activity Score

“…3,8,9 About 40% of ColdU patients develop systemic reactions, such as vertigo, nausea, hypotension, dyspnea, or anaphylaxis, in addition to wheals or angioedema. 8,10 Many ColdU patients experience a severe impairment in their quality of life, as they frequently avoid outdoor activities or contact with cold water, such as swimming 11 but can also experience symptoms in daily activities such as preparation of cold food, wet cleaning, and skin contact with cool objects, for example, toilet seats.…”

“…The spectrum of reactions to these triggers varies widely, ranging from mild localized whealing to dangerous generalized and systemic reactions and potentially life‐threatening angioedema 3,8,9 . About 40% of ColdU patients develop systemic reactions, such as vertigo, nausea, hypotension, dyspnea, or anaphylaxis, in addition to wheals or angioedema 8,10 11 but can also experience symptoms in daily activities such as preparation of cold food, wet cleaning, and skin contact with cool objects, for example, toilet seats.…”

“…Typical ColdU is diagnosed by a positive standardized cold stimulation test (CST), performed with an ice cube or TempTest ® 1,2 . By contrast, atypical ColdUs are characterized by either negative results or atypical responses to standardized CSTs 2,3,10 . ColdU is classified as primary in the absence of an underlying disease.…”