Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis ...and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2), by providing guidance on common and important clinical issues, such as: 1) How should HAE be diagnosed? 2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? 3) What are the goals of treatment? 4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast feeding women? 5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.
Mastocytosis is a complex disorder affecting various organs. The diagnostic workup can be challenging and requires a multidisciplinary approach including the use of uncommon tests. To assess ...mastocytosis management around the globe, we conducted the first worldwide online survey for physicians.
A 21-item questionnaire was sent out to the members of the World Allergy Organization (WAO), the Global Allergy and Asthma European Network (GA2LEN), the Urticaria (UCARE) and Angioedema (ACARE) Centers of Reference and Excellence, the German Society of Allergology and Clinical Immunology (DGAKI), and the European Mast Cell and Basophil Research Network (EMBRN) in April-June 2021.
Across 628 respondents from 79 countries 87.7% and 9.7% of physicians were allergists/clinical immunologists and/or dermatologists. Participating physicians were from all regions of the world (Europe, EU: 41.6%; North America, NA: 24.8%; Latin America, LA: 14.5%; Asia-Pacific, AP: 12.6%; and Africa/Middle East, AME: 6.5%). Only 2.2% of respondents worked at Specialized Mastocytosis Centers (SMCs) in NA or EU. Physicians reported caring for four patients with mastocytosis per year, with higher numbers in EU and AP (five/year) compared to LA (two/year). Dermatologists and physicians who work at SMCs reported higher patient numbers (15/year and 80/year, respectively). Suspicion of mastocytosis in the allergology and dermatology community is commonly driven by anaphylaxis (82.9%), mastocytosis skin lesions (82.1%), or elevated tryptase levels (76.6%). Osteoporosis and gastrointestinal symptoms less often prompted suspicion of mastocytosis (21.4% and 49.9%, respectively). WHO-diagnostic criteria and classification, regardless of the region, are only used by about 50% of physicians, with higher rates for SMCs (83.3%). Serum tryptase, bone marrow biopsy, and KIT D816V mutation analysis are included in the diagnostic workup by 90.9%, 61.5%, and 58.4% of physicians, respectively. The biggest challenges for the management of mastocytosis are the lack of more effective treatment options (51.1%), missing multidisciplinary networks (47.1%), and the lack of experience of specialists from other disciplines (39.0%).
The diagnostic workup for mastocytosis differs from consensus recommendations and varies between regions. This may be improved by establishing active multidisciplinary networks, increasing access to diagnostic procedures, consistently applying WHO criteria, and developing new Mastocytosis Centers of Reference and Excellence.
Hereditary angioedema (HAE), a potentially life-threatening genetic disorder due to C1 inhibitor deficiency in most cases, is characterized by sudden and/or recurrent attacks of angioedema ...(subcutaneous/submucosal swellings). The global World Allergy Organization (WAO)/European Academy of Allergy and Clinical Immunology (EAACI) International guideline for HAE management is comprehensive, but the implementation of this guideline may require regional adaptation considering the diversity in disease awareness, type of medical care systems, and access to diagnostics and treatment. The aim of this Delphi initiative was to build on the global guideline and provide regional adaptation to address the concerns and specific needs in the Middle East.
The Consensus panel comprised 13 experts from the Middle East (3 from the United Arab Emirates, 3 from Saudi Arabia, 2 from Lebanon, 2 from Kuwait, 2 from Oman and 1 from Qatar) who have more than 2 decades of experience in allergy and immunology and are actively involved in managing HAE patients. The process that was carried out to reach the consensus recommendation included: 1.) A systematic literature review for articles related to HAE management using Ovid MEDLINE. 2.) The development of a questionnaire by an internationally acclaimed expert, with 10 questions specific to HAE management in the Middle East. 3.) Experts received the questionnaire via email individually and their answers were recorded (email/interview). 4.) A virtual consensus meeting was organized to discuss the questionnaire, make amends if needed, vote, and achieve consensus.
The questionnaire comprised 10 questions, each with 2 or more statements/recommendations on which the regional experts voted. A consensus was reached based on a 70% agreement between the participants. The key highlights include: 1) HAE experts in the Middle East emphasized the importance of a positive family history for arriving at a diagnosis of HAE. 2) The number of episodes per month or per 6-month period and severity should be used, together with other markers, to determine the need for prophylaxis. 3) Disease status should be monitored by periodic visits and the use of patient-reported outcome measures such as the angioedema activity score and the angioedema control test. 4) Attenuated androgens and tranexamic acid may be considered for long-term prophylaxis, if lanadelumab, C1-Inhibitor or berotralstat are not available.
This consensus recommendation may help to educate healthcare practitioners in the Middle East and unify their approach to the diagnosis and management of HAE.
During that year, she experienced occasional diarrhea, which spontaneously resolved. Because the skin pigmentation was continually increasing, the patient underwent 12 days of inpatient diagnostics ...and treatment at age 48 years. ...initial treatment of 4 shots, she has continued receiving similar shots as maintenance therapy once every 4 weeks to the present day. Since completion of the initial 4 biweekly treatment shots, no further wheal formation or pruritus has occurred, and there have been no more attacks of vertigo or nausea (Fig 1).
Rationale To evaluate the efficacy and safety of two doses of subcutaneous, plasma-derived C1 inhibitor (C1-INH) with the dispersing agent, recombinant human hyaluronidase (rHuPH20) to prevent ...angioedema attacks in patients with hereditary angioedema (HAE) with C1-INH deficiency.
Methods In this randomized, double-blind, dose-ranging, crossover study, patients >=12 years of age with a confirmed diagnosis of HAE were randomly assigned to receive subcutaneous injections of 1000 ...U C1-INH with 24,000 U rHuPH20 (treatment A) or 2000 U C1-INH with 48,000 U rHuPH20 (treatment B) every 3 or 4 days for 8 weeks and then crossed over to the other treatment for another 8-week period.
Disease burden is particularly high in Chronic Spontaneous Urticaria (CSU) patients with angioedema, and patients whose signs and symptoms are inadequately controlled by H1-antihistamines need new ...treatment options. Here we report an exploratory analysis, from the ligelizumab Phase 2b study, investigating angioedema occurrence in patients with CSU and describe the changes in angioedema following treatment with ligelizumab, omalizumab, or placebo.
Data from the ligelizumab Phase 2b core (ligelizumab 72 mg, 240 mg, omalizumab 300 mg and placebo) and extension study (ligelizumab 240 mg) were used. Changes in Weekly Angioedema Activity Score (AAS7), the Dermatology Life Quality Index (DLQI), and Weekly Urticaria Activity Score (UAS7) among each time point were analyzed for each treatment arm.
From a total of 297 patients analyzed, 165 (55.6%) reported angioedema occurrence at baseline, with mean AAS7 ranging 30.6—42.2 across treatment arms. At Week 12 of the core study 87.5%, 84.6%, 75.0%, and 61.0% of patients were angioedema free for ligelizumab 72 mg, 240 mg, omalizumab 300 mg, and placebo arms, respectively. In CSU patients with angioedema at baseline, the largest change from baseline in AAS7 score was observed with ligelizumab 72 mg (−31.9) at week 16 in the core study. Patients with angioedema had a higher mean DLQI at baseline (14.9—16.1) vs. patients without angioedema (10.6—12.0). In patients with angioedema, low AAS7 was significantly associated with complete response on UAS7 (UAS7 = 0) and complete normalization of DLQI (DLQI 0—1).
In the Phase 2b study, ligelizumab effectively reduced angioedema and urticaria symptoms, and improved health related quality of life in patients with moderate-to-severe CSU.
NCT02477332; NCT02649218.
...many allergic patients exhibit high levels of circulating antigen-specific IgE but never have anaphylaxis, whereas other subjects with low concentrations of specific IgE in the blood can ...experience anaphylactic shock.1 Endothelin-1 (ET-1), a 21-amino-acid naturally occurring peptide with potent vasoconstrictor activity, has been reported to exacerbate certain allergic reactions in rodents. MCs are thought to represent a critical effector cell in IgE-dependent anaphylaxis.1 Prior functional assays and expression analyses of various MC populations demonstrated that ETA can be expressed by connective tissue-type MCs, including peritoneal MCs.5,6,9 However, immature bone marrow-derived cultured mouse mast cells (BMCMCs), which have some similarities to mucosal-type MCs, are largely unresponsive to ET-1 and have very low levels of receptor expression.6 We confirmed, using flow cytometric analysis, the substantial expression of ETA and weak expression of ETB on C57BL/6 mouse peritoneal MCs (Fig 1, A), as well as the absence of detectable surface ETB and very weak expression of ETA on C57BL/6 mouse BMCMCs (Fig 1, B).
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