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Abstract

We thank Van Gasse et al1Van Gasse A.L. Vito S. Faber M.A. Hagendorens M.M. Didier E.G. An alternative explanation for immediate hypersensitivity reactions to opioids.J Allergy Clin Immunol Pract. 2017; 5: 1806Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar for their interest in our paper2Li P.H. Ue K.L. Wagner A. Rutkowski R. Rutkowski K. Opioid hypersensitivity: predictors of allergy and role of drug provocation testing.J Allergy Clin Immunol Pract. 2017; 5: 1601-1606Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar and discussing the role of Mas-related G protein-coupled receptors in the pathomechanism of opioid allergy. Their activation might indeed explain certain aspects of opioid hypersensitivity reactions. Our pragmatic, “real-life” study focused on the clinical predictors of opioid hypersensitivity and the importance of drug provocation testing (DPT). We fully appreciate the need for safe, precise, and less time-consuming testing methods than DPT. However, despite tremendous progress in the recent years, there are still inherent practical limitations of basophil activation tests (BAT), including the need for fresh basophils (which are not easily transported or stored) and the possibility of nonresponder basophils in up to 10% to 20% of patients.3Mangodt E.A. Van Gasse A.L. Bastiaensen A. Decuyper I.I. Uyttebroek A. Faber M. et al.Flow-assisted basophil activation tests in immediate drug hypersensitivity: two decades of Antwerp experience.Acta Clin Belg. 2016; 71: 19-25Crossref PubMed Scopus (17) Google Scholar, 4Santos A.F. Lack G. Basophil activation test: food challenge in a test tube or specialist research tool?.Clin Transl Allergy. 2016; 6: 10Crossref PubMed Scopus (70) Google Scholar, 5Mayorga C. Celik G. Rouzaire P. Whitaker P. Bonadonna P. Rodrigues-Cernadas J. et al.In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper.Allergy. 2016; 71: 1103-1134Crossref PubMed Scopus (204) Google Scholar, 6Mukai K. Gaudenzio N. Gupta S. Vivanco N. Bendall S.C. Maecker H.T. et al.Assessing basophil activation by using flow cytometry and mass cytometry in blood stored 24 hours before analysis.J Allergy Clin Immunol. 2017; 139: 889-899.e11Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar BAT may be falsely negative if there is a significant delay between the index reaction and testing. It has been recommended that it should be performed within 3 years of reaction.5Mayorga C. Celik G. Rouzaire P. Whitaker P. Bonadonna P. Rodrigues-Cernadas J. et al.In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper.Allergy. 2016; 71: 1103-1134Crossref PubMed Scopus (204) Google Scholar Moreover, BAT might be nondiagnostic if patients are allergic to drug intermediates or hapten-carrier complexes rather than the pure index drug itself.7Steiner M. Harrer A. Himly M. Basophil reactivity as biomarker in immediate drug hypersensitivity reactions—potential and limitations.Front Pharmacol. 2016; 7: 171Crossref PubMed Scopus (19) Google Scholar Furthermore, the facilities and expertise for such tests are still not routinely available. At the current time, BAT is unfortunately not a practical option outside the research setting. Finally, despite the promise of novel in vitro diagnostic methods, many of them have not been standardized and have unknown predictive value—especially in opioid allergy with substantial underdiagnosis and heterogeneity of clinical manifestations.2Li P.H. Ue K.L. Wagner A. Rutkowski R. Rutkowski K. Opioid hypersensitivity: predictors of allergy and role of drug provocation testing.J Allergy Clin Immunol Pract. 2017; 5: 1601-1606Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar These testing methods cannot replace drug provocation tests without further validation studies. In conclusion, although BAT may help to risk stratify or guide the decision for opioid DPT in the future, it requires future studies and validation. The underutilization of DPT remains evident and often leads to the avoidance of an incorrect drug or missing other culprits of drug hypersensitivity. At present, no in vitro or in vivo tests can substitute or obviate the need for DPT in the clinical evaluation of opioid allergy. An alternative explanation for immediate hypersensitivity reactions to opioidsThe Journal of Allergy and Clinical Immunology: In PracticeVol. 5Issue 6PreviewWe read the publication on opioid hypersensitivity by Li et al1 with great interest. It clearly highlights the difficulties and uncertainties associated with a correct diagnosis of genuine IgE/FcεRI opioid allergy. The authors finally state that, for the time being, there is no in vitro nor in vivo test that enables us to differentiate between usually clinically indistinguishable IgE/FcεRI-dependent and non-IgE/FcεRI-dependent reactions with absolute certainty. However, we would like to draw attention to the Mas-related G protein coupled receptor X2 (MRGPRX2) as an alternative explanation of their findings and challenge their statement regarding the value of in vitro tests in “opioid allergy.” The Mas-related G protein-coupled receptors (Mrgprs) comprise a subfamily of receptors named after the first discovered member, Mas. Full-Text PDF