Annals of Allergy, Asthma & Immunology
ArticlesHereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema
Section snippets
INTRODUCTION
C1 inhibitor (C1-INH) deficiency (congenital or hereditary angioedema [HAE]) was first described by Quincke in 18821; its inheritance nature was evidenced by Osler in 18882 and further defined as autosomal dominant by Crowder and Crowder in 1917. The protein defect was described by Donaldson in 1963.3 An acquired form (acquired angioedema [AAE]) was described in 1972.4 The approach to patients who present with angioedema without urticaria was recently presented by Zingale et al.5 The incidence
PATIENT GROUP PERSPECTIVE
The HAE patient societies, including the CHAES/SAHC, have proposed establishment of comprehensive care clinics for the diagnosis, therapy, and management of HAE, including the development of home infusion and home care programs.16, 21 Similar to the presentation by Hungarian-sponsored HAE workshops in their publication,8 we think it appropriate to share the patient perspective of HAE management to help administrators reflect on the development of comprehensive care clinics for HAE. The
CLINICAL CHARACTERISTICS
HAE may present as recurrent angioedema (swelling) without urticaria (without hiving) and usually nonpruritic (without itch).23 Sometimes there is a nonpruritic serpentine erythematous rash.24 Distinguishing features of HAE are reviewed by Zingale et al5 and Bork et al.24 Swelling may affect any part of the body, including the extremities, face, trunk, gastrointestinal tract, genitourinary regions, or upper airways. Abdominal symptoms may mimic infantile colic, acute appendicitis, or other
DIAGNOSIS
Indications for testing include clinical suspicion at any age or, if the family history is positive, test at any age. Tests may not be reliable in patients younger than 1 year (false-negative and false-positive testings may occur unless using genetic typing). Testing performed in patients before the age of 1 year should be confirmed after the age of 1 year.31 A serpiginous rash is sometimes seen with the prodrome of HAE, but clinical urticaria (hives) usually make the diagnosis of HAE unlikely.
DIAGNOSTIC TESTING
If C1-INH deficiency is clinically suspected, we recommend screening with serum C4 and C1-INH proteins. C4 is normal between swelling events in only 2% of cases, so a normal C4 level should make one question the diagnosis of HAE. If there is a low index of suspicion, it may be more cost effective to screen with C4 alone (it is not necessary to screen with CH50 or C3).32 If serum C4 and C1-INH antigenic protein levels are both low and AAE not suspected, then the diagnosis is compatible with type
BASELINE LABORATORY TESTING AT DIAGNOSIS AT ANY AGE
Baseline bloodborne pathogen surveillance (hemovigilance) samples should be collected and stored at baseline and annually through national programs similar to the Canadian hemophilia hemovigilance program (Dr Bruce Ritchie: [email protected]; http://www.ahcdc.ca/BBPSP; baseline sample storing for testing for human immunodeficiency virus; human T-cell lymphoma; hepatitis B, C, and G; and future testing for possible emerging pathogens).16, 17, 22, 33 C1-INH hormone replacement (C1INHRP)
VACCINATION RECOMMENDATIONS
It is recommended that patients who may need to receive blood products receive vaccination to hepatitis B (may be in combination with a hepatitis A vaccine such as Twinrix).
MEDICATIONS TO AVOID IN PATIENTS WITH HAE
Some medications may trigger or worsen angioedema events in patients with HAE and should be avoided, including ACE-Is5, 16 and estrogen contraceptives.8, 16, 28, 29 Plasminogen activators are a theoretical risk, but the benefit may outweigh the risk.37, 38, 39
SHORT-TERM PROPHYLAXIS: MINOR MANIPULATIONS
If only mild manipulation, such as mild dental work, is required or if C1INHRP therapy is immediately available, then no prophylaxis is required. If C1INHRP therapy is not available, then danazol prophylaxis is required. Injection of local anesthetic may precipitate an attack. Figure 2 shows the HAE prophylaxis algorithm.
If considering more than mild manipulation such as dental work, danazol is recommended (even in children and in women in the last trimester of pregnancy; avoid in the first 2
SHORT-TERM PROPHYLAXIS: INTUBATION OR MAJOR PROCEDURES
C1INHRP therapy 1 hour before surgery (to be used if intubation is used; not available in all countries and currently not available in the United States). The recommended dosage is 500 U up to a weight of 50 kg (110 lb), 1,000 U for weight greater than 50 kg (110 lb) and less than 100 kg (220 lb), and 1,500 U if weight is greater than 100 kg (>220 lb). A second dose of an equal amount should be immediately available at time of surgery.8, 16, 17, 40 Repeat daily or as needed until there is no
LONG-TERM PROPHYLAXIS
If a patient experiences more than 1 severe event per month or is disabled more than 5 days per month or if the patient has a history of previous airway compromise, then consider prophylaxis with tranexamic acid, androgens, or C1INHRP therapy on demand. The number of events per year does not predict severity of the next event or whether the first or next event will be an airway event.
Attenuated androgens danazol and stanozolol (stanozolol is available in the United States through pharmacies
TREATMENT OF ACUTE HAE ATTACKS
The first-line therapy for treatment of any significant angioedema event is C1INHRP (C1INHRP administered at 500 U up to a weight of 50 kg, 1,000 U for a weight of more than 50 kg to less than 100 kg (220 lb), and 1,500 U if weight is more than 100 kg).8, 16, 17, 22, 27, 66
If C1INHRP is not available, other therapies may include increasing (usually doubling) the androgen (danazol or stanozolol) dose, tranexamic acid (Table 1), early use of adrenaline (if other therapy is not available but
BLOOD PRODUCT RISKS
Blood product infusion risks are reviewed annually by the Canadian Pediatric Society, Infectious Diseases and Immunization Committee,68 and the safety profile for pasteurized C1INHRP has been previously presented.34 We recommend patients receiving blood products should undergo annual hemosurveillance similar to the Canadian Hemophilia Program (Dr Bruce Ritchie, [email protected]).33 To date, bloodborne pathogen transmission with pasteurized C1INHRP has not been reported.16, 22, 34
COMPREHENSIVE CARE CLINICS
We recommend that a comprehensive care clinic programs be established for the diagnosis, therapy, and management of HAE similar to the model for comprehensive care of hemophilia in Canada.8, 16, 17, 19, 22, 21, 27, 64 A suggested CHAES/SAHC clinic model for HAE is included in http://www.hemophilia.ca/nrbdo/en/home.php, conference proceedings and conference recommendations,16, 18, 19, 21 and is outlined in Table 2.
DATABASE REGISTRY FOR HAE
We recommend comprehensive care clinics be encouraged to register HAE patients in national and international database registries to facilitate progress in management of this disorder. The European HAE network PREHAEAT chaired by Marco Cicardi established a European HAE Register (www.haeregister.org) and invited international collaboration in this and the International Hereditary Angioedema group (http://www.haei.org/) to facilitate advancement in HAE management. Countries are encouraged to fund
EMERGING THERAPIES
Double-blind, placebo-controlled clinical trials are under way, including human blood product C1-INH products, kallikrein inhibitor, bradykinin β2-receptor inhibitor, and recombinant C1-INH. Results of these trials should be available in the near future and should provide expanded options for therapy (http://www.hemophilia.ca/nrbdo/en/home.php, conference presentations; Fifth C1 Inhibitor Deficiency Workshop).16
ACKNOWLEDGMENTS
We thank the partners, sponsors, and the NRBDO (Canada) Meeting Organizing committee for participating in and contributing financial support to the meeting held in Toronto, Ontario, Canada, February 3, 2006, and the Fifth C1 Inhibitor Deficiency Workshop at which the consensus described herein was agreed to (listed on the Canadian Hemophilia Society Web site: http://www.hemophilia.ca/nrbdo/en/home.php, NRBDO, final program, and on the program for the Fifth C1 Inhibitor Deficiency Workshop found
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2021, Annals of Allergy, Asthma and ImmunologyCitation Excerpt :It manifests as recurrent attacks of nonpruritic and nonpitting subcutaneous or submucosal swelling. Typical areas affected are the upper airways, face, extremities, genitals, and gastrointestinal system.4 Angioedema of the throat or larynx can be life-threatening because of asphyxiation, whereas nausea, vomiting, and severe abdominal pain may result in unnecessary surgical procedures.5
Disclosures: Dr Bowen either has consultancy with or has been involved in educational programs and their organization that have required fundraising from Pharming, Jerini, Dyax-Genzyme, CSL Behring, and KOS. Dr Cicardi has consultancies with Jerini, Dyax, Lev Pharma, CSL Behring, and Pharming. Dr Zingale has consultancies with Pharming and Jerini.