100373 - “Refractory Chronic Spontaneous Urticaria to Conventional Treatment: Challenges and Therapeutic Strategies”

Background

Chronic spontaneous urticaria (CSU) is a mast cell–driven disorder characterized by recurrent wheals and/or angioedema lasting longer than six weeks. Despite guideline-based management, 10–50% of patients remain uncontrolled on high-dose second-generation H1-antihistamines (AH1). Omalizumab (OMZ) is recommended as second-line therapy, while cyclosporine is reserved for refractory cases. Recently, dupilumab has emerged as a novel therapeutic option, expanding the treatment landscape of CSU.

Objective

To describe the therapeutic challenges and clinical evolution of pediatric-onset CSU refractory to multiple lines of treatment, highlighting the role of dupilumab.

Case Presentation

An 8-year-old girl developed, after an infectious episode, daily intensely pruritic generalized wheals (UAS7: 50), associated with bilateral eyelid angioedema, abdominal pain, and nausea. Treatment with cetirizine was escalated to fourfold dosing, combined with short courses of oral corticosteroids during angioedema flares.

Baseline investigations showed normal blood count and inflammatory markers, positive antinuclear antibodies (ANA 1:80), total IgE 97 kU/L, and a positive TAB (autologous serum) suggesting an autoimmune phenotype. Due to persistent disease activity, OMZ 300 mg every 4 weeks was administered for 14 months, achieving only a transient partial response. Given the autoimmune background and autoimmunity family history, rheumatologic assessment identified a heterozygous variant of uncertain significance in the RELA gene, also detected in the asymptomatic mother.

Cyclosporine (30 mg/day) was initiated 21 months after disease onset, inducing complete remission maintained for 12 months. Relapse occurred three months after treatment withdrawal. Dupilumab 300 mg every two weeks was subsequently started, leading to rapid and sustained clinical remission, with excellent tolerability to date.

Conclusion

Severe refractory CSU represents an unmet therapeutic challenge. While cyclosporine remains an effective option, safety concerns limit long-term use. Dupilumab may offer a safe and effective alternative even in patients with low total IgE levels and suspected type IIb autoimmune CSU, supporting its emerging role in treatment-refractory disease.