C1 inhibitor (C1-INH) deficiency presents in congenital (hereditary angioedema, HAE) or acquired forms. There are three variants of hereditary angioedema (HAE): HAE-C1-INH Type I with low C1-INH protein and function (85% of cases; autosomal dominant); HAE-C1-INH Type II with normal protein but low function (15% of cases; autosomal dominant); and HAE Type III hereditary angioedema with normal C1 inhibitor protein and function (estrogen-dependent inherited form found mostly in females; some with defects in coagulation factor XII, HAE-FXII; others of unknown defect, HAE-Unknown) [
1,
2]. Acquired angioedema (AAE) is most frequently associated with lymphoproliferative and autoimmune disorders and with some medications including ACE inhibitors and plasmin activators [
3,
4]. Patients with HAE may experience recurrent soft tissue swellings, intestinal swellings, and abdominal pains, and may have life-threatening swellings of the airway. The incidence of HAE is estimated at 1:10,000 to 1:50,000. Risk of dying from airway obstruction is not clear but deaths from this complication if left untreated are not uncommon [
1,
5].
In Canada, Jeanne Burnham organized the HAE patient organization and Scientific Advisory Committee interested in advancing the standard of care for HAE in Canada and from this grew the Canadian Hereditary Angioedema Society (CHAES)/Société d'angioédème héréditaire du Canada (SAHC) established in 2001. This group recently disbanded and evolved into an informal network of HAE physicians with patient advisory input, the
Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'Angioédème Héréditaire (RCAH) -
http://www.haecanada.com. The first meeting of CHAEN/RCAH took place together with the Canadian Society of Allergy and Clinical Immunology/La Société canadienne d'allergie et d'immunologie clinique (CSACI/SCAIC) in Edmonton, Alberta, Canada September 2007 and its second meeting in Toronto, Ontario, Canada May 16
th, 2010 along with the Canadian HAE Consensus 2010 Conference
http://www.haecanada.com/m.php?p=ehome. In 2002, we proposed to coordinate therapy for HAE in Canada modeled after the hemophilia experience in Canada [
6]. CHAES/SAHC organized an international HAE consensus meeting held in Toronto, Ontario, Canada October 2003 and from this came the first Canadian International Consensus for the diagnosis, therapy, and management of HAE [
7]. The 2003 Toronto HAE Consensus meeting was held under the sponsorship of the Canadian Hematology Society and was the first meeting of the Network of Rare Blood Disorder Organizations (NRBDO;
http://www.hemophilia.ca/en/about-the-chs/collaboration/network-of-rare-blood-disorder-organizations/) for Canada, and was updated in 2007 [
1] through the NRBDO, the 6
th International C1-INH Deficiency Workshop and the 2010 Canadian HAE Consensus Conference being held in Toronto, Ontario, Canada May 15
th and 16
th, 2010 sponsored by CHAEN/RCAH, the Canadian Society of Allergy and Clinical Immunology, the University of Calgary, and funded by an unrestricted educational grant from CSL Behring
http://www.haecanada.com/m.php?p=ehome. The updated Canadian Consensus will be submitted to the Journal:
Allergy Asthma and Clinical Immunology, the official Journal of the CSACI/SCAIC [
8];
http://www.aacijournal.com/.
Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'Angioédème Héréditaire (RCAH)
CHAEN/RCAH is an informal organization modeled after the Association of Hemophilia Clinic Directors of Canada
http://www.ahcdc.ca/. Currently, the Chair is Dr. Tom Bowen, University of Calgary
http://tbowen@pol.net and the Vice-Chair Western Canada is Dr. Bruce Ritchie, University of Alberta and the Vice-Chair Eastern Canada is Dr. Jacques Hebert, Laval University. The CHAEN/RCAH website is:
http://www.haecanada.com/ and the CHAEN/RCAH Webmaster is John Brosz. CHAEN/RCAH Clinic Directors collaborate with the HAE International Medical Advisory Panel
http://www.haei.org/?q=node/290 and attempt to harmonize with their global initiatives including data registry and promotion of research. Our CHAEN/RCAH Clinic Directors Group and Patient Advisory Committee will work to prevent duplication of activities, minimize overlap of efforts, and work towards exchange of data base registry data in an unlinked fashion with international groups and push for open publication of treatment protocols. CHAEN/RCAH tries to meet every two years (first meeting was in conjunction with the Canadian Society of Allergy and Clinical immunology, Edmonton, September 2007). We try to update the Canadian HAE Consensus protocols, involve the CHAEN/RCAH Patient Advisory Group, involve the CHAEN/RCAH Clinic medical and paramedical staff, and foster research in HAE management in Canada. People wishing to be involved in various aspects of CHAEN/RCAH should contact Dr. Tom Bowen,
http://tbowen@pol.net.
Home therapy
Again modeling the Hemophilia Home Care program, some HAE patients receive home care self or assisted administration on demand. Example of self or assisted administration may be found on the CHAEN/RCAH website:
http://haecanada.com/infusion/ (see Appendix 1). Other home therapy information and standards of care are reviewed by Dr. Hilary Longhurst [
11,
12]. In centres where home therapy has not yet been instituted, implementation of such HAE home therapy can be most rapidly accomplished by partnering with the local Hemophilia Home Care Clinic. We hope Comprehensive Care Clinics for HAE and other rare blood disorders will become established across Canada in parallel and partnership with Hemophilia clinics and Rare Blood Disorder clinics across Canada. Patients with rare disorders such as blood disorders receive optimum care through such Comprehensive Care Clinics and teams specialized in management of such complex disorders.
Summary
We believe management of HAE in Canada has improved over the past decade thanks to the efforts of first the Canadian Hereditary Angioedema Society (CHAES)/Société d'angioédème héréditaire du Canada (SAHC) and then the Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'Angioédème Héréditaire (RCAH)
http://www.haecanada.com. CHAEN/RCAH has a patient advisory group that has evolved from the original CHAES/SAHC and it is hoped that the HAE Patient Group will again formally organize and replace the current patient advisory committee of CHAEN/RCAH (this is being worked on by Barbara Mako, current Patient Advisory Group Chair). Clinical research in diagnosis, therapy, and management continues in HAE clinics in Canada and it hoped more clinics will join CHAEN/RCAH and become involved in such clinical research. Comprehensive Care Clinics for HAE are slowly developing and we hope these will continue to evolve and collaborate with the National Rare Blood Disorders Organization (NRBDO) and the NRBDO clinics evolving there. Until new therapeutic products become licensed in Canada, use of these is under clinical trial studies or available through Health Canada Special Access Program. We are excited that the first licensing of a therapeutic product has finally occurred in 2010 (Berinert
®) and anxiously wait licensing of other therapeutic options for HAE patients. CHAEN/RCAH members will remain involved in the ongoing development of international consensus approach and evidence based guidelines for HAE management.
We should remember: "It can be done - It must be done for the sake of our patients" (Tom Bowen).