Search

Angioedema can occur in the absence of urticaria and can be broadly divided into three main categories: mast cell-mediated (e.g., histamine), non-mast-cell-mediated (bradykinin-induced) and idiopathic angioedema. Non-mast-cell-mediated angioedema is largely driven by bradykinin. Bradykinin-induced angioedema can be hereditary, acquired or drug-induced, such as with angiotensin-converting enzyme (ACE) inhibitors. Although bradykinin-mediated angioedema can be self-limited, it can cause significant morbidity and laryngeal involvement may lead to fatal asphyxiation. The mainstays of management for angioedema are: (1) to avoid specific triggers (if possible and where known) and (2) treatment with medication (if indicated). For hereditary angioedema (HAE), there are specifically licensed treatments that can be used for the management of attacks, or for prophylaxis in order to prevent attacks. In this article, the authors will review the causes, diagnosis and management of angioedema. Key take-home messages: Angioedema can occur in the absence of urticaria, with ACE inhibitor-induced and idiopathic/spontaneous angioedema being the most common causes. ACE inhibitors should be discontinued in any individual who presents with angioedema without urticaria as this condition is associated with life-threatening upper airway angioedema. Idiopathic/spontaneous angioedema responds well to prophylactic antihistamines (which may be increased to fourfold the standard dosing); however, more advanced treatment, such as omalizumab, may be needed. In some acute situations, oral corticosteroids may be required. HAE and AAE are rare disorders also characterized by angioedema in the absence of urticaria; they result from a deficiency or dysfunction of the C1-INH (a plasma protease inhibitor that regulates several proinflammatory pathways) and can be associated with life-threatening upper airway swelling. The diagnosis of HAE and AAE should include the assessment of C4, C1q, and C1-INH function and antigenic levels. The management of HAE and AAE involves an approach to acute treatment, short-term and long-term prophylaxis that is evidence-based and follows current guideline recommendations. All patients suspected of having HAE or AAE should be referred to, and managed by, a specialist with expertise in these conditions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Because C1-INH levels can be falsely low in the first year of life, confirmatory testing should be done after age 1 year.[3],[4] Resources for patients and health care professionals A patient organization, HAE Canada (https://haecanada.org/), provides resources for patients and caregivers. Hereditary angioedema should be considered in the differential diagnosis of any patient presenting with unexplained abdominal pain and recurrent episodes of angioedema (particularly if asymmetric in nature) without urticaria. Hereditary angioedema (HAE) is a rare autosomal dominant disorder characterized by recurrent episodes of painful (and usually asymmetric) swelling without urticaria that leads to substantial morbidity and even mortality (in the case of laryngeal involvement) if left untreated. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]