Immunoglobulin E cross-linking or MRGPRX2 activation: clinical insights from rocuronium hypersensitivity

MRGPRX2 activation in mast cells by neuromuscular blocking agents and other agonists: Modulation by Sugammadex by Nithya A. Fernandopulle et al.

“…2,7 Actually, the MRGPRX2-dependent MC-activating capacity of rocuronium could well be limited to cutaneous MCs. 4 In the current study, the authors confirm rocuronium to enhance intracellular calcium staining but this effect is not translated in degranulation. 2,6,7 Hence, our surprise that this rocuronium-sugammadex model was used to further unveil the MRGPRX2-dependent MC degranulating potential of rocuronium.…”

“…2,3 To the best of our knowledge, there has been only one clinical study to a better understanding of IgE-and MRGPRX2-mediated MC degranulation in response to NMBAs. 4 Based on the current models, the MRGPRX2-activating capacity and potency of rocuronium are left with some uncertainties. First, it appears that its MRGPRX2-activating capacity is different and difficult, if at all, predictable by its effects on its mouse orthologue.…”

“…4,8 These IgE-mediated reactions are documented by positive drug-reactive sIgE, skin tests and basophil activation tests using resting cells that do barely express MRGPRX2. 9,10 Most importantly, as MRGPRX2-dependent reactions are clinically indistinguishable from IgE-mediated reactions, 4 we wonder how the attending anaesthetist witnessing perioperative anaphylaxis could unambiguously discriminate between both pathways. Anyhow, the conclusion sugammadex cannot be recommended in the acute management of an alleged MRGPRX2-mediated rocuronium aligns with a recent consensus recommendation 11 and prior ex vivo findings in rocuronium allergic patients.…”

MRGPRX2 Activation by Rocuronium: Insights from Studies with Human Skin Mast Cells and Missense Variants

“…These findings suggest that skin reactions induced by irritative concentrations of rocuronium are a normal part of skin MC activation via MRGPRX2 and are unrelated to hypersensitivity. Furthermore, a negative rocuronium sIgE result does not rule out an IgE-mediated response to rocuronium or cross-reactivity with other drugs used in this patient [ 22 , 23 ].…”

Mechanisms of human drug-induced anaphylaxis

“…Initially, the list of drugs activating MRGPRX2 included NMBAs atracurium and rocuronium among others, but conflicting results have placed this assumption under debate. 83,84 The ability and importance of rocuronium-induced MRGPRX2 activation is under evaluation, investigating effects of MRGPRX2 mutations. 85,86 Both blood basophils and neutrophils can be studied ex vivo in the patients to improve diagnosis.…”