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      World allergy organization anaphylaxis guidance 2020

      research-article
      a , , b , c , d , e , f , g , h , i , j , K , l , m , n , o , 1 , p , 1
      The World Allergy Organization Journal
      World Allergy Organization
      Anaphylaxis, Acute systemic allergic reaction, Adrenaline, Cofactors, Epinephrine, Guidance, Guidelines, Antihistamines, Glucocorticoids, Food allergy, Venom allergy, Drug allergy, ACE, Angiotensin converting enzyme, BAT, basophil activation test, CAST, cellular allergen stimulation test, EAI, epinephrine auto-injectors, IgE, immunoglobulin E, IgG, immunoglobulin G, FcεRI, IgE high-affinity receptor, MRGPRX2, Mas-related G-protein coupled receptor member X2, NSAIDs, nonsteroidal anti-inflammatory drugs

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          Abstract

          Anaphylaxis is the most severe clinical presentation of acute systemic allergic reactions. The occurrence of anaphylaxis has increased in recent years, and subsequently, there is a need to continue disseminating knowledge on the diagnosis and management, so every healthcare professional is prepared to deal with such emergencies. The rationale of this updated position document is the need to keep guidance aligned with the current state of the art of knowledge in anaphylaxis management. The World Allergy Organization (WAO) anaphylaxis guidelines were published in 2011, and the current guidance adopts their major indications, incorporating some novel changes. Intramuscular epinephrine (adrenaline) continues to be the first-line treatment for anaphylaxis. Nevertheless, its use remains suboptimal. After an anaphylaxis occurrence, patients should be referred to a specialist to assess the potential cause and to be educated on prevention of recurrences and self-management. The limited availability of epinephrine auto-injectors remains a major problem in many countries, as well as their affordability for some patients.

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          Most cited references146

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          Identification of a mast cell specific receptor crucial for pseudo-allergic drug reactions

          Mast cells are primary effectors in allergic reactions, and may have significant roles in diseases by secreting histamine and various inflammatory and immunomodulatory substances 1,2 . While classically they are activated by IgE antibodies, a unique property of mast cells is their antibody-independent responsiveness to a range of cationic substances, collectively called basic secretagogues, including inflammatory peptides and drugs associated with allergic-type reactions 1,3 . Roles for these substances in pathology have prompted a decades-long search for their receptor(s). Here we report that basic secretagogues activate mouse mast cells in vitro and in vivo through a single receptor, MrgprB2, the orthologue of the human G-protein coupled receptor (GPCR) MrgprX2. Secretagogue-induced histamine release, inflammation, and airway contraction are abolished in MrgprB2 null mutant mice. Further, we show that most classes of FDA-approved peptidergic drugs associated with allergic-type injection-site reactions also activate MrgprB2 and MrgprX2, and that injection-site inflammation is absent in mutant mice. Finally, we determine that MrgprB2 and MrgprX2 are targets of many small molecule drugs associated with systemic pseudo-allergic, or anaphylactoid, reactions; we show that drug-induced symptoms of anaphylactoid responses are significantly reduced in knockout mice, and we identify a common chemical motif in several of these molecules that may help predict side effects of other compounds. These discoveries introduce a mouse model to study mast cell activation by basic secretagogues and identify MrgprX2 as a potential therapeutic target to reduce a subset of drug-induced adverse effects.
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            Anaphylaxis – a 2020 Practice Parameter Update, Systematic Review and GRADE Analysis

            Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care.
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              The pathophysiology of anaphylaxis

              Anaphylaxis is a severe, systemic hypersensitivity reaction that is rapid in onset and characterized by life-threatening airway, breathing, and/or circulatory problems, and that is usually associated with skin and mucosal changes. Because it can be triggered in some people by minute amounts of antigen (e.g. certain foods or single insect stings), anaphylaxis can be considered the most aberrant example of an imbalance between the cost and benefit of an immune response. This review will describe current understanding of the immunopathogenesis and pathophysiology of anaphylaxis, focusing on the roles of IgE and IgG antibodies, immune effector cells, and mediators thought to contribute to examples of the disorder. Evidence from studies of anaphylaxis in humans will be discussed, as well as insights gained from analyses of animal models, including mice genetically deficient in the antibodies, antibody receptors, effector cells, or mediators implicated in anaphylaxis, and mice which have been “humanized” for some of these elements. We also will review possible host factors which may influence the occurrence or severity of anaphylaxis. Finally, we will speculate about anaphylaxis from an evolutionary perspective, and argue that, in the context of severe envenomation by arthropods or reptiles, anaphylaxis may even provide a survival advantage.

                Author and article information

                Contributors
                Journal
                World Allergy Organ J
                World Allergy Organ J
                The World Allergy Organization Journal
                World Allergy Organization
                1939-4551
                30 October 2020
                October 2020
                30 October 2020
                : 13
                : 10
                : 100472
                Affiliations
                [a ]Allergy Section, Department of Internal Medicine, Hospital Vall d’Hebron, and ARADyAL research network, Barcelona, Spain
                [b ]Department of Allergy and Immunology, Hospital Quironsalud Bizkaia, Bilbao, Spain
                [c ]Department of Allergy, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Kanagawa, Japan
                [d ]Pediatric Allergy and Immunology Unit, Ain Shams University, Cairo, Egypt
                [e ]Servicio de Alergia, Hospital Clınico San Carlos, IdISSC, Madrid, Spain
                [f ]Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
                [g ]Division of Medicine, Academy of Medicine of Rio de Janeiro, Rio de Janeiro, Brazil
                [h ]Division of Pulmonary, Allergy and Sleep Medicine, Department of Medicine, Mayo Clinic, Jacksonville, Florida, USA
                [i ]Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
                [j ]Allergy and Clinical Immunology Department, Centro Médico Docente La Trinidad and Clinica El Ávila, Caracas, Venezuela
                [K ]Asthma Center and Allergy Unit, Verona University and General Hospital, Verona, Italy
                [l ]Allergy and Respiratory Research Group, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK
                [m ]Hospital Sírio Libanês, Brazil andUniversity Hospital of Montpellier, São Paulo, Montpellier, and Sorbonne Université, INSERM Paris, France, and WHO Collaborating Centre on Scientific Classification Support Montpellier, and WHO ICD-11 Medical and Scientific Advisory Committee Geneva, Switzerland
                [n ]Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore
                [o ]National Heart Lung Institute, Imperial College London and Discipline of Paediatrics and Child Health, School of Medicine, University of Sydney, Sydney, Australia
                [p ]Department of Dermatology and Allergology, Charite-Universitätsmedizin, Berlin, Germany
                Author notes
                []Corresponding author. Allergy Section, Department of Internal Medicine, Hospital Vall d’Hebron, Passeig Vall d’Hebron 119-129, 08035, Barcelona, Spain. vcardona@ 123456vhebron.net
                [1]

                These authors contributed equally to the work.

                Article
                S1939-4551(20)30375-6 100472
                10.1016/j.waojou.2020.100472
                7607509
                33204386
                3371f63c-01d3-40ab-9405-f5dd039cba84
                © 2020 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 16 August 2020
                : 3 September 2020
                Categories
                Position Paper

                Immunology
                anaphylaxis,acute systemic allergic reaction,adrenaline,cofactors,epinephrine,guidance,guidelines,antihistamines,glucocorticoids,food allergy,venom allergy,drug allergy,ace, angiotensin converting enzyme,bat, basophil activation test,cast, cellular allergen stimulation test,eai, epinephrine auto-injectors,ige, immunoglobulin e,igg, immunoglobulin g,fcεri, ige high-affinity receptor,mrgprx2, mas-related g-protein coupled receptor member x2,nsaids, nonsteroidal anti-inflammatory drugs

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