The International/Canadian hereditary angioedema guideline

Stephen Betschel¹, Karen Binkley², Rozita Borici-Mazi³, Hugo Chapdelaine⁴, Jacques Hébert⁵, Amin Kanani⁶, Paul K Keith⁷, Gina Lacuesta⁸, Susan Waserman⁷, William Yang⁹, Valerie Palda², Kelly Lang-Robertson¹⁰, Emel Aygören-Pürsün¹¹, Aleena Banerji¹², Jonathan A Bernstein¹³, Teresa Caballero¹⁴, Henriette Farkas¹⁵, Anete S Grumach¹⁶, Michihiro Hide¹⁷, Connie Katelaris^{18

19}, Hilary J Longhurst^{20

21}, Markus Magerl²², Marc Riedl²³, Andrea Zanichelli²⁴, Bruce Zuraw²³, Adil Adatia²⁵, Jean-Nicolas Boursiquot²⁶, Lori Connors⁸, Victoria Cook⁶, Michelle Cooper²⁷, Lisa Fu², Parwinder Gill²⁸, Dawn Goodyear²⁹, Amanda Jagdis⁶, Samira Jeimy³⁰, Chrystyna Kalicinsky³¹, Palinder Kamra³², Manstein Kan⁶, Harold Kim^{7

30}, Benoît Laramée³³, Erika Lee², Eric Leith², Louis Marois²⁶, Christine McCusker³⁴, Andrew O'Keefe³², Ibraheem Othman³⁵, Man-Chiu Poon²⁹, Charles St-Pierre³⁶, Peter Stepaniuk⁶, Ellie Tsai³⁷, Kelsey Uminski³⁸

Affiliations

¹ University of Toronto, Toronto, ON, Canada. Stephen.Betschel@unityhealth.to.
² University of Toronto, Toronto, ON, Canada.
³ Oxford Allergy Clinic, London, ON, Canada.
⁴ Université de Montréal, Montreal, QC, Canada.
⁵ Cliniques Lacroix, Quebec City, QC, Canada.
⁶ University of British Columbia, Vancouver, BC, Canada.
⁷ McMaster University, Hamilton, ON, Canada.
⁸ Dalhousie University, Halifax, NS, Canada.
⁹ Ottawa Allergy Research Corporation, Ottawa, ON, Canada.
¹⁰ Centre for Effective Practice, Toronto, ON, Canada.
¹¹ Goethe University Frankfurt, Frankfurt, Germany.
¹² Massachusetts General Hospital, Boston, MA, USA.
¹³ University of Cincinnati, Cincinnati, OH, USA.
¹⁴ Hospital La Paz Institute for Health Research, Madrid, Spain.
¹⁵ Semmelweis University, Budapest, Hungary.
¹⁶ Centro Universitario Faculdade de Medicina ABC, Sao Paulo, Brazil.
¹⁷ Hiroshima City Hiroshima Citizens Hospital, Hiroshima City, Japan.
¹⁸ Campbelltown Hospital, Campbelltown, NSW, Australia.
¹⁹ Western Sydney University, Richmond, NSW, Australia.
²⁰ Auckland City Hospital, Auckland, New Zealand.
²¹ University of Auckland, Auckland, New Zealand.
²² Institute of Allergology Charité, Universitätsmedizin Berlin, Berlin, Germany.
²³ University of California - San Diego, San Diego, CA, USA.
²⁴ University of Milan, Milan, Italy.
²⁵ University of Alberta, Edmonton, AB, Canada.
²⁶ Université Laval, Quebec City, QC, Canada.
²⁷ HAE Canada, Ottawa, ON, Canada.
²⁸ Dawson Road Family Medical Clinic, Guelph, ON, Canada.
²⁹ University of Calgary, Calgary, AB, Canada.
³⁰ Western University, London, ON, Canada.
³¹ University of Manitoba, Winnipeg, MB, Canada.
³² Memorial University, St John's, NL, Canada.
³³ La Polyclinique Pierre-Le Gardeur, Terrebonne, QC, Canada.
³⁴ McGill University, Montreal, QC, Canada.
³⁵ University of Saskatchewan, Regina, SK, Canada.
³⁶ L'angio-oedème héréditaire du Québec, Quebec City, QC, Canada.
³⁷ Queen's University, Kingston, ON, Canada.
³⁸ Southern Alberta Rare Blood and Bleeding Disorders Clinic, Calgary, AB, Canada.

PMID: 41606636
DOI: 10.1186/s13223-025-00999-8

Free article

Review

The International/Canadian hereditary angioedema guideline

Stephen Betschel et al. Allergy Asthma Clin Immunol. 2026.

Free article

. 2026 Jan 28.

doi: 10.1186/s13223-025-00999-8. Online ahead of print.

Authors

Affiliations

¹ University of Toronto, Toronto, ON, Canada. Stephen.Betschel@unityhealth.to.
² University of Toronto, Toronto, ON, Canada.
³ Oxford Allergy Clinic, London, ON, Canada.
⁴ Université de Montréal, Montreal, QC, Canada.
⁵ Cliniques Lacroix, Quebec City, QC, Canada.
⁶ University of British Columbia, Vancouver, BC, Canada.
⁷ McMaster University, Hamilton, ON, Canada.
⁸ Dalhousie University, Halifax, NS, Canada.
⁹ Ottawa Allergy Research Corporation, Ottawa, ON, Canada.
¹⁰ Centre for Effective Practice, Toronto, ON, Canada.
¹¹ Goethe University Frankfurt, Frankfurt, Germany.
¹² Massachusetts General Hospital, Boston, MA, USA.
¹³ University of Cincinnati, Cincinnati, OH, USA.
¹⁴ Hospital La Paz Institute for Health Research, Madrid, Spain.
¹⁵ Semmelweis University, Budapest, Hungary.
¹⁶ Centro Universitario Faculdade de Medicina ABC, Sao Paulo, Brazil.
¹⁷ Hiroshima City Hiroshima Citizens Hospital, Hiroshima City, Japan.
¹⁸ Campbelltown Hospital, Campbelltown, NSW, Australia.
¹⁹ Western Sydney University, Richmond, NSW, Australia.
²⁰ Auckland City Hospital, Auckland, New Zealand.
²¹ University of Auckland, Auckland, New Zealand.
²² Institute of Allergology Charité, Universitätsmedizin Berlin, Berlin, Germany.
²³ University of California - San Diego, San Diego, CA, USA.
²⁴ University of Milan, Milan, Italy.
²⁵ University of Alberta, Edmonton, AB, Canada.
²⁶ Université Laval, Quebec City, QC, Canada.
²⁷ HAE Canada, Ottawa, ON, Canada.
²⁸ Dawson Road Family Medical Clinic, Guelph, ON, Canada.
²⁹ University of Calgary, Calgary, AB, Canada.
³⁰ Western University, London, ON, Canada.
³¹ University of Manitoba, Winnipeg, MB, Canada.
³² Memorial University, St John's, NL, Canada.
³³ La Polyclinique Pierre-Le Gardeur, Terrebonne, QC, Canada.
³⁴ McGill University, Montreal, QC, Canada.
³⁵ University of Saskatchewan, Regina, SK, Canada.
³⁶ L'angio-oedème héréditaire du Québec, Quebec City, QC, Canada.
³⁷ Queen's University, Kingston, ON, Canada.
³⁸ Southern Alberta Rare Blood and Bleeding Disorders Clinic, Calgary, AB, Canada.

PMID: 41606636
DOI: 10.1186/s13223-025-00999-8

Abstract

This update to the 2019 Canadian Hereditary Angioedema (HAE) Guideline broadens its focus to include the management of patients with HAE worldwide, building on its established international framework. It has been developed through a collaboration of Canadian and international HAE experts and patient groups, coordinated by the Canadian Hereditary Angioedema Network. The objective is to provide evidence-based recommendations, using the Grading of Recommendations Assessment, Development and Evaluation system, for the management of patients with HAE. These include recommendations for the treatment of attacks, short-term prophylaxis, and long-term prophylaxis, as well as recommendations for self-administration, individualized therapy, health-related quality of life, and comprehensive care. New to the 2024 edition are specific recommendations for the treatment of angioedema attacks in individuals with HAE who are breastfeeding/lactating, as well as a dedicated section on shared decision-making. HAE results in spontaneous and often unpredictable attacks of painful swelling, typically affecting the extremities, bowel mucosa, genitals, face, and upper airway. These attacks are associated with significant functional impairment, reduced health-related quality of life, and in the case of laryngeal attacks, a high risk of mortality. Managing HAE is complex, and patient care in Canada, similar to many other countries, remains inconsistent and suboptimal. Care delivery lags behind nations that have implemented more structured management models for HAE, and offer broader access to a wider range of approved therapies. This guideline is intended to be used to optimize HAE management, highlight the importance of individualized care, and provide guidance to healthcare providers, policymakers, patients, and advocates. Primary target users include healthcare providers who are managing patients with HAE, as well as emergency and intensive care physicians, primary care physicians, gastroenterologists, dentists, otolaryngologists, pediatricians, hematologists, dermatologists, and gynecologists who will encounter patients with HAE and need to be aware of this condition. Hospital administrators, insurers and policy makers may also find this guideline helpful.

Keywords: Attacks; Drug therapy; Guideline; Hereditary angioedema; Lactation; Patient registry; Pediatrics; Pregnancy; Prophylaxis; Quality of life; Recommendations.

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Conflict of interest statement

Declarations. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: Details of potential conflicts of interest were elicited using the standardized ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflict of interest forms were distributed to attendees prior to their review of the manuscript, and were mandatory for all contributing authors.

References

1. Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol. 2012;130:692–7.
1. Agostoni A, Aygoren-Pursun E, Binkley KE, Blanch A, Bork K, Bouillet L, et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004;114:S51-131.
1. Zilberberg MD, Jacobsen T, Tillotson G. The burden of hospitalizations and emergency department visits with hereditary angioedema and angioedema in the United States, 2007. Allergy Asthma Proc. 2010;31:511–9.
1. Santacroce R, D’Andrea G, Maffione AB, Margaglione M, d’Apolito M. The genetics of hereditary angioedema: a review. J Clin Med. 2021
1. Zuraw BL, Sugimoto S, Curd JG. The value of rocket immunoelectrophoresis for C4 activation in the evaluation of patients with angioedema or C1-inhibitor deficiency. J Allergy Clin Immunol. 1986;78:1115–20.

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The International/Canadian hereditary angioedema guideline

Affiliations

The International/Canadian hereditary angioedema guideline

Authors

Affiliations

Abstract

Conflict of interest statement

References

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