Non-IgE-Dependent Hypersensitivity to Rocuronium Reversed by Sugammadex: Report of Three Cases and Hypothesis on the Underlying Mechanism

Spoerl, David; D''Incau, Stéphanie; Roux‐Lombard, Pascale; Harr, Thomas; Czarnetzki, Christoph

doi:10.1159/000446182

Cited by 31 publications

(24 citation statements)

References 28 publications

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“…However, vitamin K 1 itself does not induce pseudoallergy; the trigger may be the solubilizer. Perioperatively administered rocuronium can induce pseudoallergy via the non-IgE mediated Mas-related G protein-coupled receptor member X2, which activates mast cell degranulation [69]. …”

Section: Drug-induced Pseudoallergymentioning

confidence: 99%

Drug-Induced Pseudoallergy: A Review of the Causes and Mechanisms

Zhang

Li²,

Shi³

et al. 2017

Pharmacology

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Adverse drug reactions occur frequently and can trigger pseudoallergy, which has become a serious threat to public health. Pseudoallergy is a typical non-immune anaphylactic reaction characterized by the independence of antigen-specific immune responses. In the clinic, pseudoallergy is often elicited by the first dose of medication, and here lies its unpredictability and occasional lethal outcome. However, the mechanisms of pseudoallergy are not well understood. This review focusses on the causes and mechanisms of pseudoallergy induced by drugs. Two categories of mechanisms will be considered, namely, (1) complement activation-related pseudoallergy and (2) mast cell activation-related pseudoallergy. The factors that induce pseudoallergy include opioid drugs, complement activation-related pseudoallergenic drugs, nonsteroidal anti-inflammatory drugs and traditional Chinese medicine injections.

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Section: Drug-induced Pseudoallergymentioning

confidence: 99%

Drug-Induced Pseudoallergy: A Review of the Causes and Mechanisms

Zhang

Li²,

Shi³

et al. 2017

Pharmacology

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“…The neuromuscular blocking agent rocuronium may cause IgE-mediated anaphylaxis as well as non-IgE-mediated hypersensitivity reactions that can be reversed by sugammadex, suggesting a non-IgE-mediated MRGPRX2- (Mas-related G-protein-coupled receptor member X2) triggered mast cell degranulation induced by rocuronium [92]. In cases of rare, immediate-type reactions to heparins that can be identified by skin prick testing, alternative therapies with unfractionated heparins or fondaparinux have been recommended [93].…”

Section: Drug Hypersensitivity: the Triad Of Pathomechanism Diagnostmentioning

confidence: 99%

Recent Advances in Clinical Allergy and Immunology

Simon

2018

Int Arch Allergy Immunol

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Allergic diseases are of great concern because of their high prevalence, which is still rising in several regions, their impact on patients’ physical and psychological health, the huge burden they place on patients’ quality of life, as well as the socioeconomic consequences that they cause. Recent research has provided new data on both genetic and environmental risk factors of atopic/allergic diseases. The application of new technologies such as “omics” has allowed a better understanding of the pathogenesis and has helped with the identification of therapeutic targets. Immense progress has been made in developing and applying novel, targeted therapies, for example for asthma and urticaria. Intensive efforts are being made to find biomarkers that help to classify patients, to identify their potential responsiveness to specific therapies, and to monitor the disease severity. Based on recent insights in the pathogenesis of food allergy and drug hypersensitivity, novel strategies for diagnostics, allergen avoidance, and induction of tolerance have been developed. Here, we summarize important findings in the field of clinical allergy and immunology with a special focus on asthma, allergic rhinitis, atopic dermatitis, food allergy, urticaria, angioedema, and drug hypersensitivity.

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“…The most important hypotheses for these false-positive sIgE results are an elevated total IgE [65] and intake of the opiate antitussive pholcodine [70]. Alternatively, as recently stressed by Spoerl et al [3], IDHR to NMBA such as rocuronium might occur independently from IgE/FcεRI cross-linking and relate to MRGPRX2-mediated activation of mast cells [2] and, therefore, not be depicted by sIgE assays.…”

Section: Neuromuscular Blocking Agentsmentioning

confidence: 99%

“…Today, two distinct types of IgE-mediated bovine gelatin allergy are recognized: genuine gelatin allergy that results from sensitization to the protein part of the molecule; and gelatin allergy resulting from a sensitization to a glycan moiety of the molecule, i.e. galactose-α [1, 3] -galactose (α-gal) [95–97], as first described by Chung et al [98] and Commins et al [99]. To our knowledge, there are no studies that have determined the diagnostic accuracy of sIgE gelatin.…”

Section: Miscellaneousmentioning

confidence: 99%

“…Unfortunately, only a few drug-specific IgE (drug-sIgE) assays are available, and most of them have not been thoroughly validated. Furthermore, IDHR might not per se involve IgE/high-affinity IgE receptor (FcεRI)-cross-linking, but may also result from alternative pathways, such as a ligation of the Mas-related G-protein receptor MRGPRX2 [2, 3], that cannot be detected by an sIgE antibody assay. The development and validation of cellular tests such as basophil activation tests (BAT) might, somewhat, hold promise in such cases.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Diagnosis of Immediate Drug Hypersensitivity Anno 2017: Potentials and Limitations

et al. 2017

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BackgroundFor most physicians, quantification of drug-specific immunoglobulin E (drug-sIgE) antibodies constitutes the primary in vitro measure to document immediate drug hypersensitivity reactions (IDHR). Unfortunately, this is often insufficient to correctly identify patients with IgE-mediated IDHR and impossible for non-IgE-mediated IDHR that result from alternative routes of basophil and mast cell activation. In these difficult cases, diagnosis might benefit from cellular tests such as basophil activation tests (BAT).AimThe aim was to review the potential and limitations of quantification of sIgE and BAT in diagnosing IDHR. The utility of quantification of serum tryptase is discussed.MethodsA literature search was conducted using the key words allergy, basophil activation, CD63, CD203c, diagnosis, drugs, hypersensitivity, flow cytometry, specific IgE antibodies; this was complemented by the authors’ own experience.ResultsThe drugs that have been most studied with both techniques are β-lactam antibiotics and curarizing neuromuscular blocking agents (NMBA). For sIgE morphine, data are available on the value of this test as a biomarker for sensitization to substituted ammonium structures that constitute the major epitope of NMBA, especially rocuronium and suxamethonium. For the BAT, there are also data on non-steroidal anti-inflammatory drugs (NSAIDs) and iodinated radiocontrast media. For β-lactam antibiotics, sensitivity and specificity of sIgE varies between 0 and 85% and 52 and 100%, respectively. For NMBA, sensitivity and specificity varies between 38.5 and 92% and 85.7 and 100%, respectively. Specific IgE to morphine should not be used in isolation to diagnose IDHR to NMBA nor opiates. For the BAT, sensitivity generally varies between 50 and 60%, whereas specificity attains 80%, except for quinolones and NSAIDs.ConclusionsAlthough drug-sIgE assays and BAT can provide useful information in the diagnosis of IDHR, their predictive value is not absolute. Large-scale collaborative studies are mandatory to harmonize and optimize test protocols and to establish drug-specific decision thresholds.

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Non-IgE-Dependent Hypersensitivity to Rocuronium Reversed by Sugammadex: Report of Three Cases and Hypothesis on the Underlying Mechanism

Cited by 31 publications

References 28 publications

Drug-Induced Pseudoallergy: A Review of the Causes and Mechanisms

Drug-Induced Pseudoallergy: A Review of the Causes and Mechanisms

Recent Advances in Clinical Allergy and Immunology

In Vitro Diagnosis of Immediate Drug Hypersensitivity Anno 2017: Potentials and Limitations

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