D2.346 - When cold triggers anaphylaxis

Background

Cold-induced urticaria (CIndU) is a rare form of chronic inducible urticaria, particularly uncommon in the pediatric population and associated with an increased risk of systemic reactions, including anaphylaxis. This condition can severely impact quality of life (QoL) and interfere with normal child development.

Case Presentation

A 15-year-old female was referred to our Allergy Department for recurrent pruritic wheals triggered by cold exposure, including cold seawater, swimming pools, cold showers, cold wind, and abrupt temperature changes. Symptoms began in the summer of 2022 after sea swimming and progressively worsened despite on-demand and daily second-generation H1-antihistamines (AH). In 2023, she developed a systemic reaction characterized by generalized urticaria, tremors, dizziness and presyncope following cold seawater exposure, consistent with anaphylaxis, leading to prescription of an adrenaline auto-injector.

The ice cube test was positive after 5 minutes, confirming the diagnosis of CIndU. Total IgE was 711kU/L.

A stepwise therapeutic approach was implemented, including up-dosing second-generation AH up to four times the licensed dose. Despite maximal AH therapy, Urticaria Activity Score over 7 days (UAS7) remained persistently elevated, indicating inadequate disease control.

Over time, the disease had a significant impact on patient’s quality of life (QoL), with inability to participate in aquatic activities throughout the year, frequent absence from physical education classes due to cold-induced flares, and avoidance of social activities. Symptoms occurred several times per week, and her parents expressed concern about her mental health and overall psychological well-being.

Given AH-refractory disease, significant QoL impairment, and persistently elevated UAS7 scores, off-label treatment with omalizumab was initiated after approval by the Hospital Pharmacy and Therapeutics Committee. After the third monthly dose of subcutaneous omalizumab (300 mg), the patient achieved optimal disease control, with marked symptom reduction and no adverse events. AH were gradually tapered, and disease control was sustained.

Discussion/Conclusion

This case highlights the importance of early diagnosis of CIndU, assessment of systemic risk, and stepwise therapeutic escalation. Although not currently approved in national guidelines in Portugal, omalizumab represents an effective and well-tolerated option in pediatric patients with severe, antihistamine-refractory CIndU and significant QoL impairment.