Global frequency, diagnosis, and treatment of hereditary angioedema with normal C1 inhibitor
Background: Hereditary angioedema (HAE) is a rare genetic disease, most frequently associated with deficiency or dysfunction in the C1 inhibitor protein. HAE with normal C1 inhibitor (HAE-nC1INH) lacks standardized diagnostic tests, limiting precise prevalence estimates and development of specific t...
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2025-08-01
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| Series: | Journal of Allergy and Clinical Immunology: Global |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772829325000475 |
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| author | Markus Magerl, MD Marc A. Riedl, MD, MS Luisa Karla Arruda, MD, PhD Andrea Bauer, MD, MPH Alejandro Berardi, MD Jonathan A. Bernstein, MD Laurence Bouillet, MD, PhD Matthew Buckland, PhD Thomas Buttgereit, MD Danny M. Cohn, MD, PhD Timothy Craig, DO Roberta F. Criado, MD, PhD Aurélie Du-Thanh, MD, PhD Olivier Fain, MD Margarida Gonçalo, MD, PhD Jens Greve, MD Anete Sevciovic Grumach, MD, PhD Mar Guilarte, MD, PhD Constance Katelaris, MD, PhD Tamar Kinaciyan, MD Elena A. Latysheva, MD Ramon Lleonart, MD Oscar Calderón Llosa, MD Eli Mansour, MD, PhD Vesna Grivcheva-Panovska, MD, PhD Claudio Parisi, MD Nelson Augusto Rosario Filho, MD, PhD Amélia Spínola Santos, MD Petra Staubach, MD Anna Valerieva, MD, PhD Solange Oliveira Rodrigues Valle, MD, PhD Sherry Danese, MBA Julie Ulloa Paul K. Audhya, MD, MBA Marcus Maurer, MD |
| author_facet | Markus Magerl, MD Marc A. Riedl, MD, MS Luisa Karla Arruda, MD, PhD Andrea Bauer, MD, MPH Alejandro Berardi, MD Jonathan A. Bernstein, MD Laurence Bouillet, MD, PhD Matthew Buckland, PhD Thomas Buttgereit, MD Danny M. Cohn, MD, PhD Timothy Craig, DO Roberta F. Criado, MD, PhD Aurélie Du-Thanh, MD, PhD Olivier Fain, MD Margarida Gonçalo, MD, PhD Jens Greve, MD Anete Sevciovic Grumach, MD, PhD Mar Guilarte, MD, PhD Constance Katelaris, MD, PhD Tamar Kinaciyan, MD Elena A. Latysheva, MD Ramon Lleonart, MD Oscar Calderón Llosa, MD Eli Mansour, MD, PhD Vesna Grivcheva-Panovska, MD, PhD Claudio Parisi, MD Nelson Augusto Rosario Filho, MD, PhD Amélia Spínola Santos, MD Petra Staubach, MD Anna Valerieva, MD, PhD Solange Oliveira Rodrigues Valle, MD, PhD Sherry Danese, MBA Julie Ulloa Paul K. Audhya, MD, MBA Marcus Maurer, MD |
| author_sort | Markus Magerl, MD |
| collection | DOAJ |
| description | Background: Hereditary angioedema (HAE) is a rare genetic disease, most frequently associated with deficiency or dysfunction in the C1 inhibitor protein. HAE with normal C1 inhibitor (HAE-nC1INH) lacks standardized diagnostic tests, limiting precise prevalence estimates and development of specific treatment guidelines. Objective: This study sought to describe the global frequency, diagnostic pathway, and current treatment patterns of HAE-nC1INH. Methods: Board-certified HAE-treating physicians from accredited Angioedema Centers of Reference and Excellence (ACAREs) were invited to complete a 27-item online survey between December 2022 and April 2023. Results: Thirty physicians from 30 ACAREs across 15 countries reported a mean of 71 (range, 11-148) patients with HAE assessed/treated within the previous 12 months. On average, physicians estimated 24% (range, 2-44%) of patients with HAE were diagnosed with HAE-nC1INH, most of whom were adults (88%). To diagnose HAE-nC1INH, physicians most commonly assessed family history and plasma C4 levels (90% each), and C1 function and quantitative levels (87% each). On-demand and prophylactic treatment patterns varied widely across countries, with an average (range) of 56% (33-100%) of patients receiving on-demand treatment only, and 37% (0-67%) receiving both on-demand and prophylactic treatment. Physicians identified the greatest unmet needs in HAE-nC1INH management as treatment specifically indicated for this patient population and availability of an oral treatment. Conclusion: HAE-nC1INH may be more prevalent than previously reported. Importantly, our findings revealed varying diagnostic and treatment approaches. Validated, accessible diagnostic biomarkers and clinical outcomes derived from rigorous clinical trials assessing mechanistically based treatments would advance understanding and management of HAE-nC1INH. |
| format | Article |
| id | doaj-art-075d58bdf5a74ba885febacccd90db83 |
| institution | DOAJ |
| issn | 2772-8293 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Allergy and Clinical Immunology: Global |
| spelling | doaj-art-075d58bdf5a74ba885febacccd90db832025-08-20T03:00:25ZengElsevierJournal of Allergy and Clinical Immunology: Global2772-82932025-08-014310044610.1016/j.jacig.2025.100446Global frequency, diagnosis, and treatment of hereditary angioedema with normal C1 inhibitorMarkus Magerl, MD0Marc A. Riedl, MD, MS1Luisa Karla Arruda, MD, PhD2Andrea Bauer, MD, MPH3Alejandro Berardi, MD4Jonathan A. Bernstein, MD5Laurence Bouillet, MD, PhD6Matthew Buckland, PhD7Thomas Buttgereit, MD8Danny M. Cohn, MD, PhD9Timothy Craig, DO10Roberta F. Criado, MD, PhD11Aurélie Du-Thanh, MD, PhD12Olivier Fain, MD13Margarida Gonçalo, MD, PhD14Jens Greve, MD15Anete Sevciovic Grumach, MD, PhD16Mar Guilarte, MD, PhD17Constance Katelaris, MD, PhD18Tamar Kinaciyan, MD19Elena A. Latysheva, MD20Ramon Lleonart, MD21Oscar Calderón Llosa, MD22Eli Mansour, MD, PhD23Vesna Grivcheva-Panovska, MD, PhD24Claudio Parisi, MD25Nelson Augusto Rosario Filho, MD, PhD26Amélia Spínola Santos, MD27Petra Staubach, MD28Anna Valerieva, MD, PhD29Solange Oliveira Rodrigues Valle, MD, PhD30Sherry Danese, MBA31Julie Ulloa32Paul K. Audhya, MD, MBA33Marcus Maurer, MD34Angioedema Center of Reference and Excellence (ACARE), Institute of Allergology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany; Corresponding author: Markus Magerl, MD, Campus Benjamin Franklin, Hindenburgdamm 27, Institut für Allergieforschung, 12203 Berlin, Germany.Division of Allergy and Immunology, University of California—San Diego, La Jolla, CalifClinical Hospital of Ribeirão Preto Medical School, University of São Paulo, São Paulo, BrazilDepartment of Dermatology, University Allergy Center, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, GermanyInstituto de Asma, Alergia y Enfermedades Respiratorias, Corrientes, ArgentinaUniversity of Cincinnati College of Medicine, Division of Rheumatology, Allergy and Immunology and Bernstein Allergy Group and Clinical Research Center, Cincinnati, OhioFrench National Reference Center for Angioedema (CREAK), Grenoble Alpes University, Grenoble, FranceBarts Health NHS Trust, London, United KingdomAngioedema Center of Reference and Excellence (ACARE), Institute of Allergology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, GermanyAmsterdam UMC Location AMC, Amsterdam, The NetherlandsPenn State University, University Park, PaAlergo Skin, Santo André, BrazilMontpellier University Hospital, Montpelier, FranceSorbonne Université, service de médecine interne, AP-HP, Hôpital St Antoine, Paris, FranceClínica de Dermatologia, University Hospital, Coimbra Local Health Unit, and Faculty of Medicine, University of Coimbra, Coimbra, PortugalDepartment of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center, Ulm, GermanyClinical Immunology, University Center Faculty of Medicine ABC, Santo André, BrazilAllergy Department, Hereditary Angioedema Reference Center (CSUR-74), Vall d’Hebron Research Unit (VHIR), Hospital Universitari Vall d’Hebron, Barcelona, SpainCampbelltown Hospital and Western Sydney University, Campbelltown, AustraliaDepartment of Dermatology, ACARE, Medical University of Vienna, Vienna, AustriaPirogov Russian National Research Medical University, Moscow, RussiaHospital Universitari de Bellvitge, Barcelona, SpainSANNA–Clínica el Golf, San Isidro, PeruUniversidade Estadual de Campinas (UNICAMP), Campinas, BrazilACARE North Macedonia, PHI University Clinic of Dermatology, Ss Cyril and Methodius Skopje University, Skopje, Republic of North MacedoniaHospital Italiano de Buenos Aires, Buenos Aires, ArgentinaFederal University of Parana, Curitiba, BrazilACARE, Hereditary Angioedema Unit, Immunoallergology Department, Unidade Local de Saúde de Santa Maria, Faculdade de Medicina da Universidade de Lisboa, Lisbon, PortugalHautklinik und Poliklinik Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz, GermanyDepartment of Allergology, Medical University of Sofia, University Hospital “Alexandrovska,” Sofia, BulgariaClementino Fraga Filho University Hospital Federal University of Rio de Janeiro, Rio de Janeiro, BrazilOutcomes Insights, Agoura Hills, CalifOutcomes Insights, Agoura Hills, CalifKalVista Pharmaceuticals Inc, Cambridge, MassAngioedema Center of Reference and Excellence (ACARE), Institute of Allergology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, GermanyBackground: Hereditary angioedema (HAE) is a rare genetic disease, most frequently associated with deficiency or dysfunction in the C1 inhibitor protein. HAE with normal C1 inhibitor (HAE-nC1INH) lacks standardized diagnostic tests, limiting precise prevalence estimates and development of specific treatment guidelines. Objective: This study sought to describe the global frequency, diagnostic pathway, and current treatment patterns of HAE-nC1INH. Methods: Board-certified HAE-treating physicians from accredited Angioedema Centers of Reference and Excellence (ACAREs) were invited to complete a 27-item online survey between December 2022 and April 2023. Results: Thirty physicians from 30 ACAREs across 15 countries reported a mean of 71 (range, 11-148) patients with HAE assessed/treated within the previous 12 months. On average, physicians estimated 24% (range, 2-44%) of patients with HAE were diagnosed with HAE-nC1INH, most of whom were adults (88%). To diagnose HAE-nC1INH, physicians most commonly assessed family history and plasma C4 levels (90% each), and C1 function and quantitative levels (87% each). On-demand and prophylactic treatment patterns varied widely across countries, with an average (range) of 56% (33-100%) of patients receiving on-demand treatment only, and 37% (0-67%) receiving both on-demand and prophylactic treatment. Physicians identified the greatest unmet needs in HAE-nC1INH management as treatment specifically indicated for this patient population and availability of an oral treatment. Conclusion: HAE-nC1INH may be more prevalent than previously reported. Importantly, our findings revealed varying diagnostic and treatment approaches. Validated, accessible diagnostic biomarkers and clinical outcomes derived from rigorous clinical trials assessing mechanistically based treatments would advance understanding and management of HAE-nC1INH.http://www.sciencedirect.com/science/article/pii/S2772829325000475Hereditary angioedemanormal C1INHprevalencediagnosticstreatmentmanagement |
| spellingShingle | Markus Magerl, MD Marc A. Riedl, MD, MS Luisa Karla Arruda, MD, PhD Andrea Bauer, MD, MPH Alejandro Berardi, MD Jonathan A. Bernstein, MD Laurence Bouillet, MD, PhD Matthew Buckland, PhD Thomas Buttgereit, MD Danny M. Cohn, MD, PhD Timothy Craig, DO Roberta F. Criado, MD, PhD Aurélie Du-Thanh, MD, PhD Olivier Fain, MD Margarida Gonçalo, MD, PhD Jens Greve, MD Anete Sevciovic Grumach, MD, PhD Mar Guilarte, MD, PhD Constance Katelaris, MD, PhD Tamar Kinaciyan, MD Elena A. Latysheva, MD Ramon Lleonart, MD Oscar Calderón Llosa, MD Eli Mansour, MD, PhD Vesna Grivcheva-Panovska, MD, PhD Claudio Parisi, MD Nelson Augusto Rosario Filho, MD, PhD Amélia Spínola Santos, MD Petra Staubach, MD Anna Valerieva, MD, PhD Solange Oliveira Rodrigues Valle, MD, PhD Sherry Danese, MBA Julie Ulloa Paul K. Audhya, MD, MBA Marcus Maurer, MD Global frequency, diagnosis, and treatment of hereditary angioedema with normal C1 inhibitor Journal of Allergy and Clinical Immunology: Global Hereditary angioedema normal C1INH prevalence diagnostics treatment management |
| title | Global frequency, diagnosis, and treatment of hereditary angioedema with normal C1 inhibitor |
| title_full | Global frequency, diagnosis, and treatment of hereditary angioedema with normal C1 inhibitor |
| title_fullStr | Global frequency, diagnosis, and treatment of hereditary angioedema with normal C1 inhibitor |
| title_full_unstemmed | Global frequency, diagnosis, and treatment of hereditary angioedema with normal C1 inhibitor |
| title_short | Global frequency, diagnosis, and treatment of hereditary angioedema with normal C1 inhibitor |
| title_sort | global frequency diagnosis and treatment of hereditary angioedema with normal c1 inhibitor |
| topic | Hereditary angioedema normal C1INH prevalence diagnostics treatment management |
| url | http://www.sciencedirect.com/science/article/pii/S2772829325000475 |
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