Clinical characteristics, diagnosis, and treatment outcomes in chronic cold urticaria: Insights from a 15-year study

Cristina Coelho, Department of Allergology and Clinical Immunology, Unidade Local de Saúde Gaia/Espinho, Porto, Portugal Cláudia Maçães, Department of Allergology and Clinical Immunology, Unidade Local de Saúde Gaia/Espinho, Porto, Portugal Tomás D. Almeida, Department of Allergology and Clinical Immunology, Unidade Local de Saúde Gaia/Espinho, Porto, Portugal Susana Cadinha, Department of Allergology and Clinical Immunology, Unidade Local de Saúde Gaia/Espinho, Porto, Portugal Arminda Guilherme, Department of Allergology and Clinical Immunology, Unidade Local de Saúde Gaia/Espinho, Porto, Portugal José A. Ferreira, Department of Allergology and Clinical Immunology, Unidade Local de Saúde Gaia/Espinho, Porto, Portugal Isabel Rosmaninho, Department of Allergology and Clinical Immunology, Unidade Local de Saúde Gaia/Espinho, Porto, Portugal

Objectives: The aims are to characterize the clinical profile of CCU, evaluate diagnostic tools (particularly cold stimulation testing), review treatment outcomes and options, and highlight gaps in understanding to inform future research. Methods: A retrospective observational study was conducted including all consecutive patients followed at a tertiary allergy center who received a clinical diagnosis of CCU between January 2009 and December 2024. Demographic, clinical, diagnostic, and therapeutic data were extracted from electronic medical records using a standardized data collection form. This constituted a consecutive, non-selected sample of patients evaluated during the study period. Descriptive statistics were used to summarize patient characteristics and clinical findings. Categorical variables were compared using the Chi-square test, and a p < 0.05 was considered statistically significant. Statistical analysis was performed using IBM Statistical Package for the Social Sciences Statistics version 28. The study protocol was approved by the institutional Ethics Committee. Data were analyzed in anonymized form and, given the study design, individual informed consent was waived in accordance with applicable ethical guidelines. Results: In our cohort of 82 CCU patients (median age 37 years, 66% female), cold air (63%) and cold water exposure (62%) were the most common triggers and 7% experienced cold-induced anaphylaxis. All patients underwent cold stimulation testing to confirm the diagnosis. Most cases were idiopathic; only 2 patients (2.4%) had secondary causes (cryoglobulinemia or human immunodeficiency virus). Disease severity was mostly mild (77%), but a minority (9%) had systemic reactions, often associated with autoimmune comorbidities. Management was centered on patient education, cold avoidance, and non-sedating H1-antihistamines for symptom control. About 19% achieved complete remission during follow-up. Conclusion: While CCU is usually self-limited over the years, it can be life-threatening in severe cases. These findings highlight the need for prompt diagnosis, risk stratification, and individualized management. Ongoing research is needed to elucidate the precise pathogenesis of CCU and to optimize therapeutic strategies, particularly in severe or atypical cases.

Keywords: Chronic urticaria. Chronic cold urticaria. Physical urticaria. Anaphylaxis.