Revaccination outcomes among adolescents and adults with suspected hypersensitivity reactions following COVID-19 vaccination: A Canadian immunization research network study.

BACKGROUND: COVID-19 vaccination has been associated with anaphylaxis and hypersensitivity reactions. Infectious disease physicians and allergists in the Canadian Special Immunization Clinic (SIC) Network developed guidance for evaluating patients with adverse events following immunization (AEFI) including suspected hypersensitivity. This study evaluated management and adverse event recurrence following subsequent COVID-19 vaccinations. METHODS: Individuals aged 12 years and older enrolled at participating SICs before February 28, 2023 who were referred for suspected or diagnosed hypersensitivity reaction following COVID-19 vaccination, or for prevaccination assessment of suspected allergy to a COVID-19 vaccine component were included. De-identified clinical assessments and revaccination data, captured in a centralized database, were analyzed. The Brighton Collaboration case definition (BCCD) for anaphylaxis (2023 version) was applied. RESULTS: The analysis included 206 participants from 13 sites: 26 participants referred for pre-vaccination assessment and 180 participants referred for adverse events following COVID-19 vaccination (15/180 [8.3%] with BCCD confirmed anaphylaxis, 84 [46.7%] with immediate hypersensitivity symptoms not meeting BCCD, 33 [18.3%] with other diagnosed hypersensitivity reactions, and 48 [26.7%] participants with a final diagnosis of non-hypersensitivity AEFI). Among participants referred for AEFIs following COVID-19 vaccination, 166/180 (92.2%) were recommended for COVID-19 revaccination after risk assessment, of whom 158/166 (95.2%) were revaccinated (all with a COVID-19 mRNA vaccine). After revaccination, 1/15 (6.7%) participants with prior anaphylaxis, 1/77 (1.3%) with immediate hypersensitivity not meeting criteria for anaphylaxis and 1/24 (4.2%) with other physician diagnosed hypersensitivity developed recurrent AEFI symptoms that met the BCCD for anaphylaxis. All 26 participants referred pre-vaccination, including 9 (34.6%) with history of polyethylene glycol-asparaginase reactions, were vaccinated without occurrence of immediate hypersensitivity symptoms. CONCLUSIONS: Most individuals in this national cohort who experienced a hypersensitivity event following COVID-19 vaccination and were referred for specialist review were revaccinated without AEFI recurrence, suggesting that specialist evaluation can facilitate safe revaccination.

A Patient Charter for Chronic Urticaria.

Chronic urticaria (CU) is the recurring development of wheals (aka "hives" or "welts"), angioedema, or both for more than 6 weeks. Wheals and angioedema occur with no definite triggers in chronic spontaneous urticaria, and in response to known and definite physical triggers in chronic inducible urticaria. Approximately 1.4% of individuals globally will have CU during their lifetime. The itching and physical discomfort associated with CU have a profound impact on daily activities, sexual function, work or school performance, and sleep, causing significant impairment in a patient's physical and mental quality of life. CU also places a financial burden on patients and healthcare systems. Patients should feel empowered to self-advocate to receive the best care. The voice of the patient in navigating the journey of CU diagnosis and management may improve patient-provider communication, thereby improving diagnosis and outcomes. A collaboration of patients, providers, advocacy organizations, and pharmaceutical representatives have created a patient charter to define the realistic and achievable principles of care that patients with CU should expect to receive. Principle (1): I deserve an accurate and timely diagnosis of my CU; Principle (2): I deserve access to specialty care for my CU; Principle (3): I deserve access to innovative treatments that reduce the burden of CU on my daily life; Principle (4): I deserve to be free of unnecessary treatment-related side-effects during the management of my CU; and Principle (5): I expect a holistic treatment approach to address all the components of my life impacted by CU. The stated principles may serve as a guide for healthcare providers who care for patients with CU and translate into better patient-physician communication. In addition, we urge policymakers and authors of CU treatment guidelines to consider these principles in their decision-making to ensure the goals of the patient are achievable.

A multicenter chart review of patient characteristics, treatment, and outcomes in hereditary angioedema: unmet need for more effective long-term prophylaxis.

BACKGROUND: Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, recurring subcutaneous or submucosal swelling. Without effective therapy, HAE can negatively impact patients' quality of life. Management of HAE includes on-demand treatment of attacks and short- and long-term prophylaxis (LTP) to prevent attacks. Newer therapies may be more tolerable and effective in managing HAE; however, therapies such as androgens are still widely used in some countries owing to their relative ease of access and adequate disease control for some patients. This study evaluated the characteristics, treatment patterns, clinical outcomes, and healthcare resource utilization of a multinational cohort of patients with HAE, with a focus on understanding reasons for recommending or discontinuing available therapies. METHODS: A retrospective chart review was conducted at 12 centers in six countries and included data from patients with HAE type 1 or 2 who were ≥ 12 years of age at their first clinical visit. The relationship between LTP use and attack rates was evaluated using a multivariable Poisson regression model. Data were collected between March 2018 and July 2019. RESULTS: Data from 225 patients were collected (62.7% female, 86.2% White, 90.2% type 1); 64.4% of patients had their first HAE-related visit to the center prior to or during 2014. Treatment patterns varied between countries. Overall, 85.8% of patients were prescribed on-demand treatment and 53.8% were prescribed LTP, most commonly the androgen danazol (53.7% of patients who used LTP). Plasma-derived C1 inhibitor (Cinryze®) was used by 29.8% of patients for LTP. Patients who received LTP had a significantly lower rate of HAE attacks than patients who did not receive any LTP (incidence rate ratio (95% confidence interval) 0.90 (0.84-0.96)). Androgens were the most commonly discontinued therapy (51.3%), with low tolerability cited as the most frequent reason for discontinuation (50.0%). CONCLUSIONS: Overall, findings from this study support the use of LTP in the prevention of HAE attacks; a lower rate of attacks was observed with LTP compared with no LTP. However, the type of LTP used varied between countries, with tolerability and accessibility to specific treatments playing important roles in management decision-making.

Transitioning subcutaneous immunoglobulin 20% therapies in patients with primary and secondary immunodeficiencies: Canadian real-world study.

BACKGROUND: Real-world data on transitioning to Immune Globulin Subcutaneous (Human) 20% solution (Ig20Gly) are limited. This study aimed to assess infusion parameters and experience of patients with primary (PID) or secondary immunodeficiencies (SID) transitioning to Ig20Gly in clinical practice in Canada. METHODS: Patients with PID or SID who received subcutaneous immunoglobulin (SCIG) for ≥ 3 months before transitioning to Ig20Gly were eligible for this multicenter (n = 6), phase 4, non-interventional, prospective, single-arm study. Ig20Gly infusion parameters, dosing, and adverse events were collected from patient medical records at Ig20Gly initiation and 3, 6, and 12 months post-initiation. Patient satisfaction and quality of life were assessed 12 months post-initiation using validated questionnaires. RESULTS: The study included 125 patients (PID, n = 60; SID, n = 64; PID + SID, n = 1). Median volume per infusion was 30.0 ml at initiation, and 40.0 ml at 6 and 12 months post-initiation. Most patients administered Ig20Gly weekly and used two infusion sites (primarily abdomen). At each time point, median infusion duration was ≤ 1 h. At 12 months, 61% of infusions were administered via a pump and 39% manually. Headache and infusion-site reactions were the most reported adverse events of interest. Patients expressed overall satisfaction with Ig20Gly at 12 months post-initiation, with all respondents indicating they would like to continue Ig20Gly. CONCLUSIONS: This study provides a detailed description of Ig20Gly infusion parameters, tolerability, and quality of life in clinical practice among patients with PID or SID switching to Ig20Gly from another SCIG and confirms the feasibility of infusing Ig20Gly via pump or manual administration. Trial registration NCT03716700, Registered 31 August 2018, https://clinicaltrials.gov/ct2/show/NCT03716700.

Demographic and clinical characteristics of patients with hereditary angioedema in Canada.

BACKGROUND: Data on the clinical and demographic features of Canadian patients with hereditary angioedema (HAE) are lacking. OBJECTIVE: To describe the clinical and demographic features in a large Canadian HAE cohort and compare them with patients with HAE in other countries. METHODS: An online questionnaire was distributed to the members of 2 Canadian HAE patient groups to collect information on demographics and HAE clinical characteristics. All participants 18 years of age or older with HAE type I or II were eligible. Frequency, location, prodromes, and triggers of HAE attacks, including types of HAE treatment, were characterized. RESULTS: Among the 90 participants who completed the online survey, 57% self-identified as having HAE type 1 and 26% HAE type II. The average diagnostic delay was 11 years. In the preceding 6 months, 24% of the participants had no attacks and 35% experienced greater than 5 attacks. The most frequently affected regions of the body were the abdomen (83%), arms orlegs (63%), face (41%), and larynx or throat (41%). Approximately 87% of the participants reported having access to C1 inhibitor at home, and 69% reported using it for long-term prophylaxis. CONCLUSION: Canadian patients with HAE share common clinical characteristics with patients with HAE in other countries. They had a delay in HAE diagnosis and a high burden of disease, as indicated by the high frequency of attacks in the preceding 6 months. This study provides a better understanding of the demographic and clinical characteristics of Canadian patients with HAE.

Impact of lanadelumab in hereditary angioedema: a case series of 12 patients in Canada.

BACKGROUND: Hereditary angioedema (HAE) is a rare autosomal dominant disease resulting in recurring episodes of swelling, leading to considerable patient morbidity and mortality. Lanadelumab is a plasma kallikrein inhibitor that is approved as 1st line therapy in Canada for long term prophylaxis of HAE attacks. OBJECTIVE: To describe our clinical findings from a case series of adult patients with HAE type 1/2 who have been initiated on lanadelumab. METHODS: A chart review of HAE type 1/2 patients at three academic centers in Canada was undertaken with demographic and clinical data extracted. Patients were included if they had been receiving lanadelumab for at least 6 months. Patients with other causes of angioedema were excluded. RESULTS: 12 patients meeting enrollment criteria were identified. Compared to pre-lanadelumab, patients had mean reductions of 72% and 62% in attack rate and treated attack rate respectively. 3 patients reported complete remission from attacks after starting lanadelumab. Most patients had significant improvements in HAE impact on social outings. CONCLUSION: Our case series findings support the 2019 International/Canadian HAE guideline that lanadelumab is an effective therapy for long term prophylaxis. In our patient population, initiation of lanadelumab improved disease control, minimized the burden of treatment and improved HAE impact on social outings.

Quality of life in patients with hereditary angioedema in Canada.

BACKGROUND: Hereditary angioedema (HAE) is associated with decreased quality of life (QoL), which has typically been measured using a generic non-disease-specific questionnaire. OBJECTIVE: We aimed to assess the QoL in patients with HAE type I and II in Canada using a previously validated HAE-specific questionnaire. METHODS: An online questionnaire was sent to the members of two Canadian HAE patient groups to collect data on demographics, HAE clinical course, and QoL scores. All patients 18 years of age or older with HAE type I or II were eligible. The impact of the available clinical factors on the QoL scores was evaluated. Multiple linear regression was performed using clinically relevant factors to predict HAE QoL outcome. RESULTS: Among the 72 patients in the study, the mean total HAE QoL score was 102 (±23) (SD) on a scale of 25 to 135, with higher scores indicating better QoL. Although the total QoL scores correlated positively with patients' level of satisfaction and perceived control (P < .001 for both), it correlated negatively with the number of acute attacks (P = .03). Yet, the types of treatment did not have an impact on the QoL. Predictors, including sex, comorbidities, and the number of attacks, only explained 12% of the variance in the total QoL scores. CONCLUSION: HAE continues to impair QoL in Canadian patients despite receiving recommended treatment. Although the frequency of attacks affects QoL, patients' experience with their HAE care also affects QoL substantially. The study highlights the importance of considering patients' experience with their HAE care as physicians develop an appropriate management plan.

Correction to: The International/Canadian Hereditary Angioedema Guideline.

[This corrects the article DOI: 10.1186/s13223-019-0376-8.].

Development of the Hereditary Angioedema Rapid Triage Tool.

BACKGROUND: Patients with hereditary angioedema (HAE) present to the emergency department (ED), where their symptoms are often incorrectly attributed to common allergic and gastrointestinal conditions, resulting in major delays in diagnosis and treatment. OBJECTIVE: To develop a rapid triage HAE (Hereditary AngioEdema Rapid Triage [HAE-RT]) tool for ED settings. METHODS: A mixed-methods approach was used in 3 phases: Phase 1: A literature review on the current management of patients with HAE in the ED. Phase 2: A Delphi study with HAE specialists (N = 9) and Patient Advocacy Group Members (N = 3) to reach consensus on the predictor variables (PVs) to be included in the HAE-RT tool. Phase 3: A retrospective chart review to assess the performance of the PVs for HAE. RESULTS: The literature review informed the final list of PVs included in the HAE-RT prototype. Nine experts participated in the Delphi study. Of 8 identified HAE-specific PVs, 3 reached consensus: (1) absence of urticaria, (2) recurrent abdominal pain/swelling, and (3) lack of response to allergic-directed therapy. The retrospective study included 107 patients (N = 66 with HAE; N = 41 non-HAE). Patients with HAE were more likely to have a family history of HAE (71%; P < .0001), previous recurrent angioedema (96%; P < .002), and previous recurrent abdominal pain (77%; P < .0001), and only 6% responded to allergy treatments (P < .0001). The HAE-RT tool had 98% sensitivity and specificity. CONCLUSIONS: Expert consensus led to the identification and prioritization of variables that when incorporated into an HAE-RT tool were associated with a high level of sensitivity and specificity when applied to known patients.

The International/Canadian Hereditary Angioedema Guideline.

This is an update to the 2014 Canadian Hereditary Angioedema Guideline with an expanded scope to include the management of hereditary angioedema (HAE) patients worldwide. It is a collaboration of Canadian and international HAE experts and patient groups led by the Canadian Hereditary Angioedema Network. The objective of this guideline is to provide evidence-based recommendations, using the GRADE system, for the management of patients with HAE. This includes the treatment of attacks, short-term prophylaxis, long-term prophylaxis, and recommendations for self-administration, individualized therapy, quality of life, and comprehensive care. New to the 2019 version of this guideline are sections covering the diagnosis and recommended therapies for acute treatment in HAE patients with normal C1-INH, as well as sections on pregnant and paediatric patients, patient associations and an HAE registry. Hereditary angioedema results in random and often unpredictable attacks of painful swelling typically affecting the extremities, bowel mucosa, genitals, face and upper airway. Attacks are associated with significant functional impairment, decreased health-related quality of life, and mortality in the case of laryngeal attacks. Caring for patients with HAE can be challenging due to the complexity of this disease. The care of patients with HAE in Canada, as in many countries, continues to be neither optimal nor uniform. It lags behind some other countries where there are more organized models for HAE management, and greater availability of additional licensed therapeutic options. It is anticipated that providing this guideline to caregivers, policy makers, patients, and advocates will not only optimize the management of HAE, but also promote the importance of individualized care. The primary target users of this guideline are healthcare providers who are managing patients with HAE. Other healthcare providers who may use this guideline are emergency and intensive care physicians, primary care physicians, gastroenterologists, dentists, otolaryngologists, paediatricians, and gynaecologists 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.

The diagnosis of hereditary angioedema with C1 inhibitor deficiency: a survey of Canadian physicians and laboratories.

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease resulting in random and unpredictable attacks of swelling. The swelling in C1-INH-HAE is a result of impaired regulation of bradykinin production. The fact that the array of tests needed to diagnose HAE is not always available to the treating physicians is challenging for them and their patients. METHODS: The data for this article were extracted from two distinct surveys. The first survey was conducted among HAE treating physicians and aimed to determine the availability and utilization of the various assays performed to help the diagnosis of C1-INH-HAE. The second survey was conducted with the various laboratories across Canada that performs the assays used in the diagnosis of HAE. The aim of this survey was to determine the availability and profile of the various assays used in the diagnosis of C1-INH-HAE in Canada, thereby ultimately bringing a rational basis for the biological testing. RESULTS: C1-INH functional assay was widely available in Canada (93%), but was only offered by a small numbers of hospitals meaning that there could be longer delays in the analysis of these samples that may explain why the physicians expressed a lower level of confidence in this assay (59%). Antigenic C1-INH was available to the vast majority of the physicians treating C1-INH-HAE (93%) and was considered reliable by 96% of the respondents. Antigenic C4 was found available to all Canadian physicians and, although with limited specificity, was considered very reliable by all the participants. This study revealed that 81% of physicians were able to order the antigenic C1q and the confidence in this assay was moderate (70%). Concerning genetic testing, the survey revealed that most of the CHAEN members never had to or couldn't order this test. CONCLUSION: This study highlights the need for improved education and knowledge exchange, about biological assays available to Canadian physicians and their performance in proper diagnosis of C1-INH-HAE to improve confidence and access to relevant tests.

Canadian physician survey on the medical management of hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is a rare disease that has significant morbidity and may be potentially fatal because of airway obstruction. OBJECTIVE: To determine practice patterns in physicians treating HAE. METHODS: A survey was designed to determine HAE practice patterns among Canadian physicians. These physicians were identified by sending the survey to members of 3 physician organizations (Canadian Hereditary Angioedema Network, Canadian Society of Clinical Immunology and Allergy, and Canadian Hematology Society). RESULTS: Thirty-six physicians responded to the survey. Thirty-four physicians were included in the analysis. Most referrals to HAE-treating physicians were from family and emergency department physicians. The most common sites of swelling reported by patients to physicians were facial, peripheral, and abdominal. A mean of 53.9% of patients with type 1 and 2 HAE and 53.4% of patients with HAE with normal C1 esterase inhibitor were undergoing long-term prophylaxis. A mean of 41.9%, 19.4%, and 93.5% of respondents had some patients taking danazol, tranexamic acid, and C1-esterase inhibitor, respectively. Most physicians believed that severity and frequency of attacks were the most important determinants in deciding when to use prophylaxis. A mean of 88.2% of physicians used C1-esterase inhibitor to treat acute attacks and 79.4% used icatibant. All respondents were aware of HAE guidelines. CONCLUSION: Physicians are using guidelines to support their practice and using agents suggested by guidelines with confidence. C1 inhibitor is being used widely for prophylaxis and treatment of acute attacks along with icatibant. However, certain special patient populations may require additional focus in future guidelines.

Insights and advances in chronic urticaria: a Canadian perspective.

In the past few years there have been significant advances which have changed the face of chronic urticaria. In this review, we aim to update physicians about clinically relevant advances in the classification, diagnosis and management of chronic urticaria that have occurred in recent years. These include clarification of the terminology used to describe and classify urticaria. We also detail the development and validation of instruments to assess urticaria and understand the impairment on quality-of-life and the morbidity caused by this disease. Additionally, the approach to management of chronic urticaria now focuses on evidence-based use of non-impairing, non-sedating H1-antihistamines given initially in standard doses and if this is not effective, in up to 4-fold doses. For urticaria refractory to H1-antihistamines, omalizumab treatment has emerged as an effective, safe option.

Canadian hereditary angioedema guideline.

Hereditary angioedema (HAE) is a disease which is associated with random and often unpredictable attacks of painful swelling typically affecting the extremities, bowel mucosa, genitals, face and upper airway. Attacks are associated with significant functional impairment, decreased Health Related Quality of Life, and mortality in the case of laryngeal attacks. Caring for patients with HAE can be challenging due to the complexity of this disease. The care of patients with HAE in Canada is neither optimal nor uniform across the country. It lags behind other countries where there are more organized models for HAE management, and where additional therapeutic options are licensed and available for use. The objective of this guideline is to provide graded recommendations for the management of patients in Canada with HAE. This includes the treatment of attacks, short-term prophylaxis, long-term prophylaxis, and recommendations for self-administration, individualized therapy, quality of life, and comprehensive care. It is anticipated that by providing this guideline to caregivers, policy makers, patients and their advocates, that there will be an improved understanding of the current recommendations regarding management of HAE and the factors that need to be considered when choosing therapies and treatment plans for individual patients. The primary target users of this guideline are healthcare providers who are managing patients with HAE. Other healthcare providers who may use this guideline are emergency physicians, gastroenterologists, dentists and otolaryngologists, 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.

2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema.

BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. OBJECTIVE: To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010). METHODS: The Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'angioédème héréditaire (RCAH) http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring) held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review. RESULTS: This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. CONCLUSIONS: Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.

Hereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema.

BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) in 2004. OBJECTIVE: To ensure that this consensus remains current. METHODS: In collaboration with the Canadian Network of Rare Blood Disorder Organizations, we held the second Canadian Consensus discussion with our international colleagues in Toronto, Ontario, on February 3, 2006, and reviewed its content at the Fifth C1 Inhibitor Deficiency Workshop in Budapest on June 2, 2007. Papers were presented by international investigators, and this consensus algorithm approach resulted. RESULTS: This consensus algorithm outlines the approach recommended for the diagnosis, therapy, and management of HAE, which was agreed on by the authors of this report. This document is only a consensus algorithm approach and continues to require validation. As such, participants agreed to make this a living 2007 algorithm, a work in progress, and to review its content at future international HAE meetings. CONCLUSIONS: There is a paucity of double-blind, placebo-controlled trials on the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Controlled trials currently under way will provide further insight into the management of HAE. As with our Canadian 2003 Consensus, this 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of HAE was formed through the meeting and agreement of patient care professionals along with patient group representatives and individual patients.

Canadian 2003 International Consensus Algorithm For the Diagnosis, Therapy, and Management of Hereditary Angioedema.

C1 inhibitor deficiency (hereditary angioedema [HAE]) is a rare disorder for which there is a lack of consensus concerning diagnosis, therapy, and management, particularly in Canada. European initiatives have driven the approach to managing HAE with 3 C1-INH Deficiency Workshops held every 2 years in Hungary starting in 1999, with the third Workshop having recently been held in May 2003. The European Contact Board has established a European HAE Registry that will hopefully advance our knowledge of this disorder. The Canadian Hereditary Angioedema Society/Société d'Angioédème Héréditaire du Canada organized a Canadian International Consensus Conference held in Toronto, Ontario, Canada, on October 24 to 26, 2003, to foster consensus between major European and North American HAE treatment centers. Papers were presented by investigators from Europe and North America, and this consensus algorithm approach was discussed. There is a paucity of double-blind placebo-controlled trials in the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Enclosed is the consensus algorithm approach recommended for the diagnosis, therapy, and management of HAE and agreed to by the authors of this article. This document is only a consensus algorithm approach and requires validation. As such, participants agreed to make this a living 2003 algorithm (ie, a work in progress) and agreed to review its content at future international HAE meetings. The consensus, however, has strength in that it was arrived at by the meeting of patient-care providers along with patient group representatives and individual patients reviewing information available to date and reaching agreement on how to approach the diagnosis, therapy, and management of HAE circa 2003. Hopefully evidence to support approaches to the management of HAE will approach the level of meta-analysis of randomized controlled trials in the near future.