Cold urticaria what we know and what we do not know

Cold urticaria is a subtype of chronic inducible urticaria, characterized by wheals and/or angioedema that occur after cold exposure. It constitutes a challenging clinical problem due to the risk of cold-induced anaphylaxis, its long duration, and diagnostic difficulties with atypical cold urticaria. The classification of cold urticaria includes typical and atypical subtypes. Recent studies and guidelines have progressed its understanding and management.

It is thought to involve the formation of autoallergens and IgE to these autoallergens induced by cold, which provoke a release of mediators from skin mast cells.

It is known that cold-induced wheals develop on rewarming and resolve within an hour and that anaphylaxis can occur. Its diagnosis is based on the patient’s history and cold stimulation testing. Other tests include searching for underlying infections, to be done if the patient has a relevant record. The management of cold urticaria includes avoiding cold, using nonsedating antihistamines, and, if needed, omalizumab.

Questions unanswered include cold urticaria epidemiology, underlying pathomechanisms, clinical heterogeneity, and treatment outcomes.

An international multicenter observational prospective study COLD-CE is being conducted to globally improve the understanding of cold urticaria and cold anaphylaxis, with their pathophysiology representing a research priority. Oropharyngeal angioedema and/or cold anaphylaxis in cold urticaria require further studies of innovative agents. The use of genomic, postgenomic, and machine learning approaches is the next frontier in research leading to novel therapeutic targets.