Management of atopy with dupilumab and omalizumab in CADINS disease
Management of atopy with dupilumab and omalizumab in CADINS disease
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.
CADINS, CARD11, atopic dermatitis, dupilumab, eczema, omalizumab, urticaria
Diaz-Cabrera, Natalie M.
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Bauman, Bradly M.
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Iro, Mildred A.
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Dabbah-Krancher, Gina
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Molho-Pessach, Vered
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Zlotogorski, Abraham
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Shamriz, Oded
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Dinur-Schejter, Yael
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Sharon, Tatyana dubnikov
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Stepensky, Polina
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Tal, Yuval
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Eisenstein, Eli m.
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Pietzsch, Leonora
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Schuetz, Catharina
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Abreu, Damien
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Coughlin, Carrie C.
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Cooper, Megan A.
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Milner, Joshua D.
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Williams, Anthony
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Armoni-Weiss, Gil
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Snow, Andrew l.
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Leiding, Jennifer W.
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17 January 2024
Diaz-Cabrera, Natalie M.
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Bauman, Bradly M.
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Iro, Mildred A.
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Dabbah-Krancher, Gina
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Molho-Pessach, Vered
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Zlotogorski, Abraham
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Shamriz, Oded
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Dinur-Schejter, Yael
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Sharon, Tatyana dubnikov
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Stepensky, Polina
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Tal, Yuval
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Eisenstein, Eli m.
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Pietzsch, Leonora
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Schuetz, Catharina
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Abreu, Damien
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Coughlin, Carrie C.
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Cooper, Megan A.
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Milner, Joshua D.
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Williams, Anthony
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Armoni-Weiss, Gil
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Snow, Andrew l.
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Leiding, Jennifer W.
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Diaz-Cabrera, Natalie M., Bauman, Bradly M., Iro, Mildred A., Dabbah-Krancher, Gina, Molho-Pessach, Vered, Zlotogorski, Abraham, Shamriz, Oded, Dinur-Schejter, Yael, Sharon, Tatyana dubnikov, Stepensky, Polina, Tal, Yuval, Eisenstein, Eli m., Pietzsch, Leonora, Schuetz, Catharina, Abreu, Damien, Coughlin, Carrie C., Cooper, Megan A., Milner, Joshua D., Williams, Anthony, Armoni-Weiss, Gil, Snow, Andrew l. and Leiding, Jennifer W.
(2024)
Management of atopy with dupilumab and omalizumab in CADINS disease.
Journal of Clinical Immunology, 44 (2), [48].
(doi:10.1007/s10875-023-01636-y).
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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JOCI-D-23-00155_R1
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Management of CADINS JCI 2024
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Accepted/In Press date: 2 December 2023
Published date: 17 January 2024
Keywords:
CADINS, CARD11, atopic dermatitis, dupilumab, eczema, omalizumab, urticaria
Identifiers
Local EPrints ID: 489261
URI: http://eprints.soton.ac.uk/id/eprint/489261
ISSN: 0271-9142
PURE UUID: f056db9e-e00f-4d11-a4e1-3c17c7745459
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Date deposited: 18 Apr 2024 16:50
Last modified: 19 Apr 2024 01:54
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Contributors
Author:
Natalie M. Diaz-Cabrera
Author:
Bradly M. Bauman
Author:
Gina Dabbah-Krancher
Author:
Vered Molho-Pessach
Author:
Abraham Zlotogorski
Author:
Oded Shamriz
Author:
Yael Dinur-Schejter
Author:
Tatyana dubnikov Sharon
Author:
Polina Stepensky
Author:
Yuval Tal
Author:
Eli m. Eisenstein
Author:
Leonora Pietzsch
Author:
Catharina Schuetz
Author:
Damien Abreu
Author:
Carrie C. Coughlin
Author:
Megan A. Cooper
Author:
Joshua D. Milner
Author:
Gil Armoni-Weiss
Author:
Andrew l. Snow
Author:
Jennifer W. Leiding
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