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

Bizjak M, Kosnik M, Dinevski D, Thomsen SF, Fomina D, Borzova E, Kulthanan K, Meshkova R, Ahsan DM, Al-Ahmad M, Altrichter S, Bauer A, Brockstadt M, Costa C, Demir S, Criado RF, Ensina LF, Gelincik A, Gimenez-Arnau AM, Goncalo M, Gotua M, Holm JG, Inomata N, Kasperska-Zajac A, Khoshkhui M, Klyucharova A, Kocatuerk E, Lu R, Makris M, Maltseva N, Miljkovic J, Pasali M, Paulino M, Pesque D, Peter J, Ramon GD, Ritchie C, Valle SOR, Rudenko M, Sikora A, Lima EMS, Wagner N, Xepapadaki P, Xue X, Zhao Z, Terhorst-Molawi D, Maurer M (2021)

Publication Type: Journal article

Publication year: 2021


DOI: 10.1111/all.15194


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(R) 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.

Involved external institutions

Yokohama City University JP Japan (JP) National and Kapodistrian University of Athens GR Greece (GR) Humboldt-Universität zu Berlin DE Germany (DE) Hospital Italiano de Buenos Aires AR Argentina (AR) Autonomous University of Barcelona (UAB) / Universitat Autònoma de Barcelona ES Spain (ES) University Clinic Golnik / Klinika Golnik SI Slovenia (SI) Istanbul University / İstanbul Üniversitesi TR Turkey (TR) Mahidol University / มหาวิทยาลัยมหิดล TH Thailand (TH) Hospital e Maternidade Therezinha de Jesus BR Brazil (BR) Urticaria Centers of Reference and Excellence UCARE DE Germany (DE) Koç-Universität (KU) TR Turkey (TR) London Allergy and Immunology Centre GB United Kingdom (GB) Federal University of São Paulo / Universidade Federal de São Paulo (UNIFESP) BR Brazil (BR) Universidade de Coimbra PT Portugal (PT) Technische Universität Dresden DE Germany (DE) Ministry of Health of the Russian Federation / Министерство здравоохранения Российской Федерации RU Russian Federation (RU) University of Copenhagen DK Denmark (DK) University of Maribor (UM) / Univerza v Mariboru SI Slovenia (SI) Peking University First Hospital / 北大国际医院 CN China (CN) Centro Hospitalar Universitário Lisboa Norte (CHULN) PT Portugal (PT) Faculdade de Medicina do ABC (FMABC) BR Brazil (BR) I.M. Sechenov First Moscow State Medical University RU Russian Federation (RU) Universidade Federal do Rio de Janeiro (UFRJ) / Federal University of Rio de Janeiro BR Brazil (BR) Medical University of Silesia in Katowice / Śląski Uniwersytet Medyczny w Katowicach (SUM) PL Poland (PL) Kazan State Medical University (KSMU) RU Russian Federation (RU) University of Cape Town (UCT) ZA South Africa (ZA) Mashhad University of Medical Sciences (MUMS) IR Iran, Islamic Republic of (IR) Kuwait University KW Kuwait (KW) Smolensk State Medical University / Смоленский государственный медицинский университет RU Russian Federation (RU) Sun Yat-Sen University CN China (CN)

How to cite


Bizjak, M., Kosnik, M., Dinevski, D., Thomsen, S.F., Fomina, D., Borzova, E.,... Maurer, M. (2021). Risk factors for systemic reactions in typical cold urticaria: Results from the COLD-CE study. Allergy. https://doi.org/10.1111/all.15194


Bizjak, Mojca, et al. "Risk factors for systemic reactions in typical cold urticaria: Results from the COLD-CE study." Allergy (2021).

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