Hereditary angioedema: beyond international consensus - circa December 2010 - The Canadian Society of Allergy and Clinical Immunology Dr. David McCourtie Lecture

<p>Abstract</p> <p>Background</p> <p>The 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema was published earlier this year in this Journal (Bowen et al. <it>Allergy, Asthma & Clinical Immunology </it>2010, 6:24 - <url>http://www.aacijournal.com/content/6/1/24</url>). Since that publication, there have been multiple phase III clinical trials published on either prophylaxis or therapy of hereditary angioedema and some of these products have changed approval status in various countries. This manuscript was prepared to review and update the management of hereditary angioedema.</p> <p>Objective</p> <p>To review approaches for the diagnosis and management of hereditary angioedema (HAE) circa December 2010 and present thoughts on moving from HAE management from international evidence-based consensus to facilitate more local health unit considerations balancing costs, efficacies of treatments, and risk benefits. Thoughts will reflect Canadian and international experiences.</p> <p>Methods</p> <p>PubMed searches including hereditary angioedema and diagnosis, therapy, management and consensus were reviewed as well as press releases from various pharmaceutical companies to early December 2010.</p> <p>Results</p> <p>The 2010 International Consensus Algorithms for the Diagnosis, Therapy and Management of Hereditary Angioedema is reviewed in light of the newly published phase III Clinical trials for prevention and therapy of HAE. Management approaches and models are discussed.</p> <p>Conclusions</p> <p>Consensus approach and double-blind placebo controlled trials are only interim guides to a complex disorder such as HAE and should be replaced as soon as possible with large phase IV clinical trials, meta analyses, data base registry validation of approaches including quality of life and cost benefit analyses, safety, and head-to-head clinical trials investigating superiority or non-inferiority comparisons of available approaches. Since not all therapeutic products are available in all jurisdictions and since health care delivery approaches and philosophy vary between countries, each health care delivery sector will likely devise their own algorithms based on local practicalities for implementing evidence-based guidelines and standards for HAE disease management. Quality-of-life and cost affordability benefit conclusions will likely vary between countries and health care units. Data base registries for rare disorders like HAE should be used to detect early adverse events for new therapies and to facilitate phase IV clinical trials and encourage superiority and non-inferiority comparisons of HAE management approaches.</p

Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults: a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden.

Objectives. To establish the prevalence of remaining beta-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later. Design. Population-based cohort study. Setting. Nationwide from all Departments of Medicine and Endocrinology in Sweden. Subjects. A total of 312 young (15-34 years old) adults diagnosed with diabetes during 1987-88. Main outcome measure. Plasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved beta-cell function was defined as measurable C-peptide levels. Three islet antibodies - cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies - were measured. Results. Amongst 269 islet antibody positives (ab+) at diagnosis, preserved beta-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m-2, respectively; P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively; P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively; P = 0.007) at diagnosis compared with ab+ without remaining beta-cell function. Amongst the 241 patients without detectable beta-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up. Conclusions. Sixteen per cent of patients with autoimmune type 1 diabetes had remaining beta-cell function 8 years after diagnosis whereas 5.8% with beta-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up

Classification, diagnosis, and approach to treatment for angioedema: Consensus report from the Hereditary Angioedema International Working Group

Angioedema is defined as localized and self-limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

HAE therapies: past present and future

Advances in understanding the pathophysiology and mechanism of swelling in hereditary angioedema (HAE) has resulted in the development of multiple new drugs for the acute and prophylactic treatment of patients with HAE. This review will recap the past treatment options, review the new current treatment options, and discuss potential future treatment options for patients with HAE

HAE international home therapy consensus document

Hereditary angioedema (C1 inhibitor deficiency, HAE) is associated with intermittent swellings which are disabling and may be fatal. Effective treatments are available and these are most useful when given early in the course of the swelling. The requirement to attend a medical facility for parenteral treatment results in delays. Home therapy offers the possibility of earlier treatment and better symptom control, enabling patients to live more healthy, productive lives. This paper examines the evidence for patient-controlled home treatment of acute attacks ('self or assisted administration') and suggests a framework for patients and physicians interested in participating in home or self-administration programmes. It represents the opinion of the authors who have a wide range of expert experience in the management of HAE

The international WAO/EAACI guideline for the management of hereditary angioedema – the 2017 revision and update

Abstract Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up-to-date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2). The key clinical questions covered by these recommendations are: 1) How should HAE-1/2 be defined and classified?, 2) How should HAE-1/2 be diagnosed?, 3) Should HAE-1/2 patients receive prophylactic and/or on-demand treatment and what treatment options should be used?, 4) Should HAE-1/2 management be different for special HAE-1/2 patient groups such as pregnant/lactating women or children?, and 5) Should HAE-1/2 management incorporate self-administration of therapies and patient support measures? This article is co-published with permission in Allergy and the World Allergy Organization Journal

Gesättigte Fettsäuren und das Risiko für koronare Herzerkrankungen

Aufgabenstellung: Die Reduktion der Aufnahme gesättigter Fettsäuren wird seit Jahrzehnten empfohlen, um das Risiko für koronare Herzerkrankungen zu senken. Von 2006 bis 2010 wurden mehrere Studien publiziert, die keinen Zusammenhang zwischen der Zufuhr gesättigter Fettsäuren und dem Risiko für koronare Herzerkrankungen fanden. Ziel der vorliegenden Arbeit war es, anhand von Studien den aktuellen Wissensstand zur Wirkung von gesättigten Fettsäuren auf das Risiko für koronare Herzerkrankungen aufzuzeigen. Vorgehensweise: Ausgangspunkt war die 2006 erschienene, evidenzbasierte Leitlinie der Deutschen Gesellschaft für Ernährung (DGE) „Fettkonsum und Prävention ausgewählter ernährungsmitbedingter Krankheiten“. Über die Datenbank PubMed wurde nach Meta-Analysen und Reviews aus dem Zeitraum 2006 bis einschließlich 2010 recherchiert. Die Ergebnisse der sechs ausgewählten Übersichtsarbeiten wurden dargestellt, eingeordnet und diskutiert. Wesentliche Ergebnisse: Fünf Meta-Analysen bzw. Reviews von Kohortenstudien zeigen konsistent keinen signifikanten Zusammenhang zwischen der Aufnahme gesättigter Fettsäuren und dem Risiko für koronare Herzerkrankungen. Eine gepoolte Analyse aus Kohortenstudien und Ergebnisse aus randomisierten kontrollierten Studien beurteilen den teilweisen Ersatz von gesättigten Fettsäuren durch mehrfach ungesättigte Fettsäuren als risikomindernd. Die Evidenz aus Interventionsstudien konnte nicht abschließend eingeordnet werden. Folgerungen: Eine Überarbeitung der Leitlinie erscheint sinnvoll, da sich die Evidenzlage seit 2006 verändert hat. Durch eine Überarbeitung könnte der aktuelle Wissensstand zur Thematik gesättigte Fettsäuren und Risiko für koronare Herzerkrankung erschöpfend analysiert werden. Auf dieser Basis sollten dann die geltenden Ernährungsempfehlungen in Bezug auf gesättigte Fette dahingehend überprüft werden, ob sie das Kriterium „evidenz-basiert“ erfüllen.Objective: Reduced saturated fatty acid consumption has been recommended for dec-ades to lower the risk of coronary heart disease. Several studies have been published from 2006 to 2010 which found no associations between the intake of saturated fatty acids and coronary heart disease. By screening studies this paper aims to give an overview of the current knowledge regarding the effects of saturated fatty acids on coronary heart disease. Methods: A guideline that was published in 2006 by the DGE (German Association for Nutrition) functioned as a starting point: “Consumption of dietary fat and prevention of selected nutrition related diseases.”6 Search for Meta-analyses and reviews was conducted by the database PubMed for the period from 2006 through December 2010. The results from the six selected papers were described, classified and discussed. Main Results: Five Meta-analyses e.g. reviews of cohort studies consistently showed no significant association between intake of saturated fatty acids and coronary heart disease. One pooled analysis of cohort studies and results from randomized controlled trials con-cluded a risk reducing effect from a partial substitution of saturated fatty acids by polyunsaturated fatty acids. The evidence originating from randomized controlled trials could not be conclusively determined. Conclusions: Due to the growing knowledge since 2006, a revision of the DGE-guideline appears reasonable. Through this work the current evidence in regard to saturated fatty acids and risk of coronary heart disease could be conclusively analyzed. On this basis, the existing dietary recommendations in relation to saturated fatty acids should be verified whether they meet the criterion "evidence based"