The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update

doi:10.1111/all.15214

Practice Guideline

. 2022 Jul;77(7):1961-1990.

doi: 10.1111/all.15214. Epub 2022 Feb 3.

The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update

Marcus Maurer^{1

2}, Markus Magerl^{1

2}, Stephen Betschel³, Werner Aberer⁴, Ignacio J Ansotegui⁵, Emel Aygören-Pürsün⁶, Aleena Banerji⁷, Noémi-Anna Bara⁸, Isabelle Boccon-Gibod⁹, Konrad Bork¹⁰, Laurence Bouillet⁹, Henrik Balle Boysen¹¹, Nicholas Brodszki¹², Paula J Busse¹³, Anette Bygum^{14

15}, Teresa Caballero¹⁶, Mauro Cancian¹⁷, Anthony Castaldo¹¹, Danny M Cohn¹⁸, Dorottya Csuka¹⁹, Henriette Farkas¹⁹, Mark Gompels²⁰, Richard Gower²¹, Anete S Grumach²², Guillermo Guidos-Fogelbach²³, Michihiro Hide^{24

25}, Hye-Ryun Kang²⁶, Allen Phillip Kaplan²⁷, Constance Katelaris²⁸, Sorena Kiani-Alikhan²⁹, Wei-Te Lei³⁰, Richard Lockey³¹, Hilary Longhurst³², William R Lumry³³, Andrew MacGinnitie³⁴, Alejandro Malbran³⁵, Inmaculada Martinez Saguer³⁶, Juan José Matta³⁷, Alexander Nast³⁸, Dinh Nguyen³⁹, Sandra A Nieto-Martinez⁴⁰, Ruby Pawankar⁴¹, Jonathan Peter^{42

43}, Grzegorz Porebski⁴⁴, Nieves Prior⁴⁵, Avner Reshef⁴⁶, Marc Riedl⁴⁷, Bruce Ritchie⁴⁸, Farrukh Rafique Sheikh⁴⁹, William B Smith⁵⁰, Peter J Spaeth⁵¹, Marcin Stobiecki⁴⁴, Elias Toubi⁵², Lilian Agnes Varga¹⁹, Karsten Weller^{1

2}, Andrea Zanichelli⁵³, Yuxiang Zhi⁵⁴, Bruce Zuraw⁵⁵, Timothy Craig⁵⁶

Affiliations

¹ Institute of Allergology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
² Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany.
³ University of Toronto, Toronto, ON, Canada.
⁴ Department of Dermatology, Medical University of Graz, Graz, Austria.
⁵ Department of Allergy & Immunology, Hospital Quironsalud Bizkaia, Bilbao, Spain.
⁶ Center for Children and Adolescents, University Hospital Frankfurt, Frankfurt, Germany.
⁷ Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁸ Romanian Hereditary Angioedema Expertise Centre, Mediquest Clinical Research Center, Sangeorgiu de Mures, Romania.
⁹ National Reference Center for Angioedema (CREAK), Angioedema Center of Reference and Excellence (ACARE), Grenoble Alpes University Hospital, Grenoble, France.
¹⁰ Department of Dermatology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
¹¹ HAE International (HAEi), Skanderborg, Denmark.
¹² Department of Pediatric Immunology, Childrens Hospital, Skåne University Hospital, Lund, Sweden.
¹³ Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁴ Clinical Institute, University of Southern Denmark, Odense, Denmark.
¹⁵ Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
¹⁶ Allergy Department, Hospital Universitario La Paz, IdiPaz, CIBERER U754, Madrid, Spain.
¹⁷ Department of Systems Medicine, University Hospital of Padua, Padua, Italy.
¹⁸ Department of Vascular Medicine, Amsterdam UMC/University of Amsterdam, Amsterdam, The Netherlands.
¹⁹ Department of Internal Medicine and Haematology, Hungarian Angioedema Center of Reference and Excellence, Semmelweis University, Budapest, Hungary.
²⁰ Clinical Immunology, North Bristol NHS Trust, Bristol, UK.
²¹ Marycliff Clinical Research, Principle Research Solutions, Spokane, Washington, USA.
²² Clinical Immunology, Centro Universitario FMABC, Sao Paulo, Brazil.
²³ Instituto Politécnico Nacional SEPI-ENMH, Mexico City, Mexico.
²⁴ Department of Dermatology, Hiroshima Citizens Hospital, Hiroshima, Japan.
²⁵ Department of Dermatology, Hiroshima University, Hiroshima, Japan.
²⁶ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
²⁷ Division of Pulmonary, Critical Care, Allergy and Immunology, Medical university of South Carolina, Charleston, South Carolina, USA.
²⁸ Department of Medicine, Campbelltown Hospital and Western Sydney University, Sydney, NSW, Australia.
²⁹ Department of Immunology, Barts Health NHS Trust, London, UK.
³⁰ Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Mackay Memorial Hospital, Hsinchu, Taiwan.
³¹ Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
³² Department of Immunology, Auckland District Health Board and Department of Medicine, University of Auckland, Auckland, New Zealand.
³³ Internal Medicine, Allergy Division, University of Texas Health Science Center, Dallas, Texas, USA.
³⁴ Division of Immunology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³⁵ Unidad de Alergia, Asma e Inmunología Clínica, Buenos Aires, Argentina.
³⁶ Pediatrics, Haemophilia Centre Rhine Main (HZRM), Moerfelden-Walldorf, Germany.
³⁷ H. Especialidades C.M.N.SXXI, I.M.S.S., México City, Mexico.
³⁸ Department of Dermatology, Venereology and Allergology, Division of Evidence-Based Medicine Charité - Universitätsmedizin Berlin, corporate member of Free University of Berlin, Humboldt University of Berlin, and Berlin Institute of Health, Berlin, Germany.
³⁹ Respiratory, Allergy and Clinical Immunology Unit, Internal Medicine Department, Vinmec Healthcare System, College of Health Sciences, VinUniversity, Hanoi, Vietnam.
⁴⁰ Genetic Unit of Nutrition, National Institute of Pediatrics, Mexico City, Mexico.
⁴¹ Department of Pediatrics, Nippon Medical School, Tokyo, Japan.
⁴² Division of Allergy and Clinical Immunology, University of Cape Town, Cape Town, South Africa.
⁴³ Allergy and Immunology Unit, University of Cape Town Lung Institute, Cape Town, South Africa.
⁴⁴ Department of Clinical and Environmental Allergology, Jagiellonian University Medical College, Krakow, Poland.
⁴⁵ Allergy, Hospital Universitario Severo Ochoa, Madrid, Spain.
⁴⁶ Angioderma Center, Barzilai University Medical Center, Ashkelon, Israel.
⁴⁷ Division of Rheumatology, Allergy and Immunology, University of California San Diego, La Jolla, California, USA.
⁴⁸ Departments of Medicine and Medical Oncology, University of Alberta, Edmonton, AB, Canada.
⁴⁹ Section of Adult Allergy & Immunology, Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
⁵⁰ Clinical Immunology and Allergy, Royal Adelaide Hospital, Adelaide, SA, Australia.
⁵¹ Institute of Pharmacology, University of Bern, Bern, Switzerland.
⁵² Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Affiliated with Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
⁵³ Department of Internal Medicine, ASST Fatebenefratelli Sacco, Ospedale Luigi Sacco-University of Milan, Milan, Italy.
⁵⁴ Department of Allergy and Clinical Immunology, Bejing Union Medical College Hospital & Chinese Academy of Medical Sciences, Bejing, China.
⁵⁵ University of California, San Diego, San Diego, California, USA.
⁵⁶ Departments of Medicine and Pediatrics, Penn State University, Hershey, Pennsylvania, USA.

PMID: 35006617
DOI: 10.1111/all.15214

Practice Guideline

The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update

Marcus Maurer et al. Allergy. 2022 Jul.

. 2022 Jul;77(7):1961-1990.

doi: 10.1111/all.15214. Epub 2022 Feb 3.

Authors

Affiliations

¹ Institute of Allergology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
² Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany.
³ University of Toronto, Toronto, ON, Canada.
⁴ Department of Dermatology, Medical University of Graz, Graz, Austria.
⁵ Department of Allergy & Immunology, Hospital Quironsalud Bizkaia, Bilbao, Spain.
⁶ Center for Children and Adolescents, University Hospital Frankfurt, Frankfurt, Germany.
⁷ Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁸ Romanian Hereditary Angioedema Expertise Centre, Mediquest Clinical Research Center, Sangeorgiu de Mures, Romania.
⁹ National Reference Center for Angioedema (CREAK), Angioedema Center of Reference and Excellence (ACARE), Grenoble Alpes University Hospital, Grenoble, France.
¹⁰ Department of Dermatology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
¹¹ HAE International (HAEi), Skanderborg, Denmark.
¹² Department of Pediatric Immunology, Childrens Hospital, Skåne University Hospital, Lund, Sweden.
¹³ Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁴ Clinical Institute, University of Southern Denmark, Odense, Denmark.
¹⁵ Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
¹⁶ Allergy Department, Hospital Universitario La Paz, IdiPaz, CIBERER U754, Madrid, Spain.
¹⁷ Department of Systems Medicine, University Hospital of Padua, Padua, Italy.
¹⁸ Department of Vascular Medicine, Amsterdam UMC/University of Amsterdam, Amsterdam, The Netherlands.
¹⁹ Department of Internal Medicine and Haematology, Hungarian Angioedema Center of Reference and Excellence, Semmelweis University, Budapest, Hungary.
²⁰ Clinical Immunology, North Bristol NHS Trust, Bristol, UK.
²¹ Marycliff Clinical Research, Principle Research Solutions, Spokane, Washington, USA.
²² Clinical Immunology, Centro Universitario FMABC, Sao Paulo, Brazil.
²³ Instituto Politécnico Nacional SEPI-ENMH, Mexico City, Mexico.
²⁴ Department of Dermatology, Hiroshima Citizens Hospital, Hiroshima, Japan.
²⁵ Department of Dermatology, Hiroshima University, Hiroshima, Japan.
²⁶ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
²⁷ Division of Pulmonary, Critical Care, Allergy and Immunology, Medical university of South Carolina, Charleston, South Carolina, USA.
²⁸ Department of Medicine, Campbelltown Hospital and Western Sydney University, Sydney, NSW, Australia.
²⁹ Department of Immunology, Barts Health NHS Trust, London, UK.
³⁰ Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Mackay Memorial Hospital, Hsinchu, Taiwan.
³¹ Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
³² Department of Immunology, Auckland District Health Board and Department of Medicine, University of Auckland, Auckland, New Zealand.
³³ Internal Medicine, Allergy Division, University of Texas Health Science Center, Dallas, Texas, USA.
³⁴ Division of Immunology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³⁵ Unidad de Alergia, Asma e Inmunología Clínica, Buenos Aires, Argentina.
³⁶ Pediatrics, Haemophilia Centre Rhine Main (HZRM), Moerfelden-Walldorf, Germany.
³⁷ H. Especialidades C.M.N.SXXI, I.M.S.S., México City, Mexico.
³⁸ Department of Dermatology, Venereology and Allergology, Division of Evidence-Based Medicine Charité - Universitätsmedizin Berlin, corporate member of Free University of Berlin, Humboldt University of Berlin, and Berlin Institute of Health, Berlin, Germany.
³⁹ Respiratory, Allergy and Clinical Immunology Unit, Internal Medicine Department, Vinmec Healthcare System, College of Health Sciences, VinUniversity, Hanoi, Vietnam.
⁴⁰ Genetic Unit of Nutrition, National Institute of Pediatrics, Mexico City, Mexico.
⁴¹ Department of Pediatrics, Nippon Medical School, Tokyo, Japan.
⁴² Division of Allergy and Clinical Immunology, University of Cape Town, Cape Town, South Africa.
⁴³ Allergy and Immunology Unit, University of Cape Town Lung Institute, Cape Town, South Africa.
⁴⁴ Department of Clinical and Environmental Allergology, Jagiellonian University Medical College, Krakow, Poland.
⁴⁵ Allergy, Hospital Universitario Severo Ochoa, Madrid, Spain.
⁴⁶ Angioderma Center, Barzilai University Medical Center, Ashkelon, Israel.
⁴⁷ Division of Rheumatology, Allergy and Immunology, University of California San Diego, La Jolla, California, USA.
⁴⁸ Departments of Medicine and Medical Oncology, University of Alberta, Edmonton, AB, Canada.
⁴⁹ Section of Adult Allergy & Immunology, Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
⁵⁰ Clinical Immunology and Allergy, Royal Adelaide Hospital, Adelaide, SA, Australia.
⁵¹ Institute of Pharmacology, University of Bern, Bern, Switzerland.
⁵² Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Affiliated with Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
⁵³ Department of Internal Medicine, ASST Fatebenefratelli Sacco, Ospedale Luigi Sacco-University of Milan, Milan, Italy.
⁵⁴ Department of Allergy and Clinical Immunology, Bejing Union Medical College Hospital & Chinese Academy of Medical Sciences, Bejing, China.
⁵⁵ University of California, San Diego, San Diego, California, USA.
⁵⁶ Departments of Medicine and Pediatrics, Penn State University, Hershey, Pennsylvania, USA.

PMID: 35006617
DOI: 10.1111/all.15214

Abstract

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast-feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.

Keywords: C1 inhibitor; DELPHI; disease control; guideline; hereditary angioedema; management.

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References

REFERENCES

1. Rosen FS, Pensky J, Donaldson V, Charache P. Hereditary angioneurotic edema: two genetic variants. Science. 1965;148(3672):957-958.
1. Donaldson VH, Evans RR. A biochemical abnormality in herediatry angioneurotic edema: absence of serum inhibitor of C' 1-Esterase. Am J Med. 1963;35:37-44.
1. Nussberger J, Cugno M, Amstutz C, Cicardi M, Pellacani A, Agostoni A. Plasma bradykinin in angio-oedema. Lancet. 1998;351(9117):1693-1697.
1. Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2017 revision and update. Allergy. 2018;73(8):1575-1596.
1. Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema - the 2017 revision and update. World Allergy Organization J. 2018;11:5.

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[1] Rosen FS, Pensky J, Donaldson V, Charache P. Hereditary angioneurotic edema: two genetic variants. Science. 1965;148(3672):957-958.

[2] Rosen FS, Pensky J, Donaldson V, Charache P. Hereditary angioneurotic edema: two genetic variants. Science. 1965;148(3672):957-958.

[3] Donaldson VH, Evans RR. A biochemical abnormality in herediatry angioneurotic edema: absence of serum inhibitor of C' 1-Esterase. Am J Med. 1963;35:37-44.

[4] Donaldson VH, Evans RR. A biochemical abnormality in herediatry angioneurotic edema: absence of serum inhibitor of C' 1-Esterase. Am J Med. 1963;35:37-44.

[5] Nussberger J, Cugno M, Amstutz C, Cicardi M, Pellacani A, Agostoni A. Plasma bradykinin in angio-oedema. Lancet. 1998;351(9117):1693-1697.

[6] Nussberger J, Cugno M, Amstutz C, Cicardi M, Pellacani A, Agostoni A. Plasma bradykinin in angio-oedema. Lancet. 1998;351(9117):1693-1697.

[7] Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2017 revision and update. Allergy. 2018;73(8):1575-1596.

[8] Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2017 revision and update. Allergy. 2018;73(8):1575-1596.

[9] Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema - the 2017 revision and update. World Allergy Organization J. 2018;11:5.

[10] Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema - the 2017 revision and update. World Allergy Organization J. 2018;11:5.

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The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update

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The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update

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