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Management of Atopy with Dupilumab and Omalizumab in CADINS Disease
Natalie M Diaz-Cabrera1, Bradly M Bauman2,3, Mildred A Iro4
1Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL, USA.
Insights
Biologic therapies dupilumab and omalizumab effectively treated severe atopic dermatitis and chronic spontaneous urticaria in patients with CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease, reducing the need for other medications.
Area of Science:
- Immunology
- Genetics
- Dermatology
Background:
- Loss-of-function (LOF) pathogenic variants in the CARD11 gene cause CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease.
- CADINS disease presents with severe atopic manifestations, recurrent infections, and autoimmunity.
- Existing treatments for severe atopy in CADINS patients are often insufficient.
Purpose of the Study:
- To assess the efficacy and tolerability of dupilumab and omalizumab in treating severe atopic symptoms in patients with CADINS.
- To evaluate the impact of these biologic therapies on refractory atopic dermatitis and chronic spontaneous urticaria in CADINS patients.
Main Methods:
- Assessed treatment response in six CADINS patients (five treated with dupilumab, one with omalizumab) for severe atopic symptoms.
- Validated CARD11 mutations for pathogenicity using a T cell transfection assay assessing NF-κB signaling.
- Monitored symptom improvement, medication adjustments, and complications during follow-up.
Main Results:
- All six patients experienced rapid and sustained improvement in severe atopic dermatitis and chronic spontaneous urticaria.
- Patients were able to decrease or discontinue previous topical and systemic medications for atopy.
- No complications were observed during the follow-up period, indicating good tolerability.
Conclusions:
- Dupilumab and omalizumab are effective and well-tolerated treatments for severe, refractory atopic disease in patients with CADINS.
- These biologic therapies offer a promising therapeutic option for managing complex atopic manifestations in CADINS patients.
- Targeting IL-4/IL-13 (dupilumab) and IgE (omalizumab) pathways may be beneficial in CADINS, despite the underlying CARD11 defect.
Abstract:
The caspase activation and recruitment domain 11 (CARD11) gene encodes a scaffold protein required for lymphocyte antigen receptor signaling. Dominant-negative, loss-of-function (LOF) pathogenic variants in CARD11 result in CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease. Patients with CADINS suffer with severe atopic manifestations including atopic dermatitis, food allergy, and chronic spontaneous urticaria in addition to recurrent infections and autoimmunity. We assessed the response of dupilumab in five patients and omalizumab in one patient with CADINS for the treatment of severe atopic symptoms. CARD11 mutations were validated for pathogenicity using a T cell transfection assay to assess the impact on activation-induced signaling to NF-κB. Three children and three adults with dominant-negative CARD11 LOF mutations were included. All developed atopic disease in infancy or early childhood. In five patients, atopic dermatitis was severe and recalcitrant to standard topical and systemic medications; one adult suffered from chronic spontaneous urticaria. Subcutaneous dupilumab was initiated to treat atopic dermatitis and omalizumab to treat chronic spontaneous urticaria. All six patients had rapid and sustained improvement in atopic symptoms with no complications during the follow-up period. Previous medications used to treat atopy were able to be decreased or discontinued. In conclusion, treatment with dupilumab and omalizumab for severe, refractory atopic disease in patients with CADINS appears to be effective and well tolerated in patients with CADINS with severe atopy.
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