Differentiating the cellular and humoral components of neuromuscular blocking agent-induced anaphylactic reactions in patients undergoing anaesthesia

Aalberse, Rob C.; Budde, Ilona Kleine; Mulder, Maxim J.H.L.; Stapel, S. O.; Paulij, Wilma P.; Leynadier, F.; Hollmann, Marcus W.

doi:10.1093/bja/aer028

Cited by 16 publications

(13 citation statements)

References 23 publications

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“…This suggests that skin tests with rocuronium might not indicate IgE-mediated allergy, while skin tests to succinylcholine, a drug not acting on the MRGPRX2 receptor but sharing the QA epitope with rocuronium, could be more reliable for true NMBA IgE hypersensitivity. It also shows that IgE to rocuronium might be of lesser clinical relevance, as shown in other studies [43,52]. However, whether skin test with NMBA at correct concentrations may still be of value for IgE-mediated hypersensitivity, remains matter of debate.…”

Section: Perioperative Anaphylaxis Due To Nmba Revisedmentioning

confidence: 58%

“…In a study investigating the cellular and humoral components of NMBA-induced anaphylactic reactions, the correlation between skin test reactivity to rocuronium and IgE to rocuronium was low. In contrast, striking correlation between IgE to rocuronium and skin test reactivity to succinylcholine was found ( p < 0.001) [52]. This suggests that skin tests with rocuronium might not indicate IgE-mediated allergy, while skin tests to succinylcholine, a drug not acting on the MRGPRX2 receptor but sharing the QA epitope with rocuronium, could be more reliable for true NMBA IgE hypersensitivity.…”

Section: Perioperative Anaphylaxis Due To Nmba Revisedmentioning

confidence: 99%

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

Spoerl

Nigolian

Czarnetzki

et al. 2017

IJMS

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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.

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Section: Perioperative Anaphylaxis Due To Nmba Revisedmentioning

confidence: 58%

Section: Perioperative Anaphylaxis Due To Nmba Revisedmentioning

confidence: 99%

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

Spoerl

Nigolian

Czarnetzki

et al. 2017

IJMS

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“…In some conditions, such as bacterial colonization, or more extreme situations, such as CD4 deficiency, IgE can be produced in the absence of T cell help [35]. These B cells produce “natural” antibodies with a broad specificity and may be the precursors of isotype-switched B cells producing antibodies to glycans such as the antibodies to the galactose-alpha-1,3 galactose epitope [36, 37] and low-molecular compounds such as quaternary ammonium compounds related to muscle relaxants [38, 39] and drugs like pholcodine [40–43]. …”

Section: Update On the Major Conclusion Of The Ige-reporter-mouse Stmentioning

confidence: 99%

The Developmental History of IgE and IgG4 Antibodies in Relation to Atopy, Eosinophilic Esophagitis, and the Modified TH2 Response

Aalberse

Platts-Mills

Rispens

2016

Curr Allergy Asthma Rep

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A common reaction from anyone confronted with allergy is the question: what prevents universal allergy? We will discuss recent findings in the mouse system that have provided us with clues on why allergy is not more common. We will also address one crucial aspect of atopic allergy in humans, which is absent in most mouse model systems, an IgG/IgE ratio <10. We consider the typical mouse IgE response to be more closely related to the “modified TH2” response in humans. We will discuss the similarities and differences between the IgE and IgG4 response to allergens and an update on the IgG4 B cell, partly derived from studies on eosinophilic esophagitis and IgG4-related diseases.

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“…2 -4 Immunoglobulin E (IgE) antibodies to rocuronium have been reported in 48% of serum samples from patients with allergies to neuromuscular blocking agents, although only a small proportion of such IgEpositive patients will actually develop anaphylaxis. 5 6 We report three cases of suspected sugammadex-induced hypersensitivity reactions occurring between July 2010 and June 2011. These events developed immediately after the administration of sugammadex, with varying degrees of severity.…”

mentioning

confidence: 99%

Three cases of suspected sugammadex-induced hypersensitivity reactions

Godai

Hasegawa-Moriyama

Kuniyoshi

et al. 2012

British Journal of Anaesthesia

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Neuromuscular blocking agents have been implicated in 60-70% of anaphylactic events associated with anaesthesia. We report two cases of probable hypersensitivity reaction to sugammadex and an additional suspected but less supported case of possible immune-mediated reaction or other adverse reaction. The patients were given a bolus of sugammadex 100 mg immediately before extubation. In all three patients, a possible allergic reaction was suspected within 4 min of sugammadex administration, but with different degrees of severity. Skin testing was positive in two of these patients. Hypersensitivity to sugammadex unaccompanied by cardiovascular or respiratory symptoms might be missed during the course of anaesthesia. Careful monitoring for possible allergic responses is required in patients who have received sugammadex.

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Differentiating the cellular and humoral components of neuromuscular blocking agent-induced anaphylactic reactions in patients undergoing anaesthesia

Abstract: Our results indicate that NMBA-related anaphylaxis requires not only IgE NMBA reactivity, but also altered cellular reactivity in the patient. The latter may be demonstrable by testing basophils from the patient, a skin test with (steroidal) NMBA, or both.

Cited by 16 publications

References 23 publications

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

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

The Developmental History of IgE and IgG4 Antibodies in Relation to Atopy, Eosinophilic Esophagitis, and the Modified TH2 Response

Three cases of suspected sugammadex-induced hypersensitivity reactions

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