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Int. J. Mol. Sci. 2017, 18(6), 1223; doi:10.3390/ijms18061223

Reclassifying Anaphylaxis to Neuromuscular Blocking Agents Based on the Presumed Patho-Mechanism: IgE-Mediated, Pharmacological Adverse Reaction or “Innate Hypersensitivity”?

1
Division of Clinical Immunology and Allergy, Department of Medical Specialties, University Hospital and Faculty of Medicine, University of Geneva, rue Gabrielle-Perret-Gentil 4, CH-1205 Geneva, Switzerland
2
Department of Anesthesiology, University Hospital and Faculty of Medicine, University of Geneva, rue Gabrielle-Perret-Gentil 4, CH-1205 Geneva, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editors: Johannes Haybaeck and Werner Pichler
Received: 12 April 2017 / Revised: 1 June 2017 / Accepted: 2 June 2017 / Published: 7 June 2017
(This article belongs to the Special Issue Drug Hypersensitivity)
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Abstract

Approximately 60% of perioperative anaphylactic reactions are thought to be immunoglobulin IgE mediated, whereas 40% are thought to be non-IgE mediated hypersensitivity reactions (both considered non-dose-related type B adverse drug reactions). In both cases, symptoms are elicited by mast cell degranulation. Also, pharmacological reactions to drugs (type A, dose-related) may sometimes mimic symptoms triggered by mast cell degranulation. In case of hypotension, bronchospasm, or urticarial rash due to mast cell degranulation, identification of the responsible mechanism is complicated. However, determination of the type of the underlying adverse drug reaction is of paramount interest for the decision of whether the culprit drug may be re-administered. Neuromuscular blocking agents (NMBA) are among the most frequent cause of perioperative anaphylaxis. Recently, it has been shown that NMBA may activate mast cells independently from IgE antibodies via the human Mas-related G-protein-coupled receptor member X2 (MRGPRX2). In light of this new insight into the patho-mechanism of pseudo-allergic adverse drug reactions, in which as drug-receptor interaction results in anaphylaxis like symptoms, we critically reviewed the literature on NMBA-induced perioperative anaphylaxis. We challenge the dogma that NMBA mainly cause IgE-mediated anaphylaxis via an IgE-mediated mechanism, which is based on studies that consider positive skin test to be specific for IgE-mediated hypersensitivity. Finally, we discuss the question whether MRGPRX2 mediated pseudo-allergic reactions should be re-classified as type A adverse reactions. View Full-Text
Keywords: drug allergy; perioperative anaphylaxis; pseudo-allergy; adverse drug reaction; mast cell; histamine; Mas-related G-protein coupled receptor member X2 drug allergy; perioperative anaphylaxis; pseudo-allergy; adverse drug reaction; mast cell; histamine; Mas-related G-protein coupled receptor member X2
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MDPI and ACS Style

Spoerl, D.; Nigolian, H.; Czarnetzki, C.; Harr, T. Reclassifying Anaphylaxis to Neuromuscular Blocking Agents Based on the Presumed Patho-Mechanism: IgE-Mediated, Pharmacological Adverse Reaction or “Innate Hypersensitivity”? Int. J. Mol. Sci. 2017, 18, 1223.

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