Cold Urticaria: From Wheals to Anaphylaxis

Cold urticaria (ColdU) is characterized by wheals, angioedema, or both, which are triggered by exposure to cold. A subset of patients experiences cold-induced anaphylaxis (ColdA), a potentially life-threatening systemic reaction. The pathogenesis of ColdU remains incompletely understood, but mast cell activation plays a central role. Most hypotheses are decades old and require further investigations. ColdU and ColdA are clinically diagnosed and typically supported by cold stimulation testing (CST). However, standard CST methods may yield negative results despite a clear clinical history. ColdU is classified into typical and atypical forms based on CST responses. ColdA occurs more frequently in patients with mucosal angioedema involving the oropharynx. It is most commonly triggered by full-body cold exposure, such as swimming. Diagnostic workup should include a detailed history, CST, and evaluation for underlying conditions, particularly in patients with clinical signs and symptoms extending beyond the skin. First-line treatment involves second-generation H₁-antihistamines, often needed at increased doses for disease control. Omalizumab has shown efficacy in clinical trials and case reports for refractory cases. Adrenaline is the first-line therapy for ColdA; high-risk patients should be prescribed autoinjectors and receive proper training in their use. This review provides an overview of the pathophysiology, classification, diagnostic procedures, and management of ColdU and ColdA, emphasizing clinical variability and unmet research needs.