Drug allergy to local anesthetics: a variety of diagnostic strategies
DOI: 10.32364/2587-6821-2020-4-1-42-47
L.L. Lazarenko1,2, D.V. Shabanov3, T.P. Ses’4, T.G. Fedoskova3, A.A. Totolyan1,4
1Pasteur Research Institute of Epidemiology and Microbiology, St. Petersburg,
Russian Federation
2I.I. Mechnikov North-Western State Medical University, St. Petersburg, Russian Federation
3NRC Institute of Immunology, Moscow, Russian Federation
4I.P. Pavlov First St. Petersburg State Medical University, St. Petersburg, Russian Federation
Most patients referring to allergists for drug allergy report that local anesthetics are the main causative agents. Local anesthetics can provide a myriad of adverse reactions, i.e., allergic, pseudo-allergic, and toxic. In many patients, toxic effects of preservatives or adrenaline account for local anesthetic intolerance. This paper reviews published data and authors’ experience with various local anesthetic allergy tests, both in vivo (skin tests, provocation tests, saliva allergy tests) and in vitro (allergen-specific IgE and IgG measurement, basophil activation test etc.). Positive skin tests were revealed in 5.4%, specific IgE in 2.9%, and specific IgG in 3%. Measurement of allergy mediators in saliva is a promising tool since in situ fixation of allergic reaction and objectification of the results by highly-sensitive laboratory tests are provided. The choice of laboratory test depends on reaction development term and expected pathogenic mechanism. However, none of the laboratory tests is absolutely reliable in terms of verifying allergy to local anesthetics. A combination of various in vivo and vitro tests improves the efficacy of diagnostic strategies. Despite numerous laboratory tests, allergen-specific IgE and IgG tests and basophil activation test are currently commercially available only.
Keywords: drug allergy, drug hypersensitivity, local anesthetics, diagnostics, in vivo tests, in vitro tests, specific IgE, specific IgG, basophil activation test, skin tests, provocation tests.
For citation: Lazarenko L.L., Shabanov D.V., T.P. Ses’ et al. Drug allergy to local anesthetics: a variety of diagnostic strategies. Russian Medical Review. 2020;4(1):42–47. DOI: 10.32364/2587-6821-2020-4-1-42-47.
About the authors:
1,2Lyudmila L. Lazarenko — MD, PhD, allergist and immunologist, ORCID iD 0000-0002-5324-7395;
3Dmitriy V. Shabanov — MD, PhD, researcher, ORCID iD 0000-0003-2342-8678;
4Tat’yana P. Ses’ — MD, PhD, Professor, ORCID iD 0000-0001-7903-0023;
3Tat’yana G. Fedoskova — MD, PhD, Professor, Head of the Laboratory, ORCID iD 0000-0003-1456-3923;
1,4Areg A. Totolyan — MD, PhD, Professor, Academician of the Russian Academy of Sciences, Director, ORCID iD 0000-0003-4571-8799.
1Pasteur Research Institute of Epidemiology and Microbiology. 14, Mira str., St. Petersburg, 197101, Russian Federation.
2I.I. Mechnikov North-Western State Medical University. 41, Kirochnaya str., St. Petersburg, 191015, Russian Federation.
3NRC Institute of Immunology. 24, Kashirskoe road, Moscow, 115478, Russian Federation.
4I.P. Pavlov First St. Petersburg State Medical University. 6–8, L’va Tolstogo str., St. Petersburg, 197022, Russian Federation.
Contact information: Lyudmila L. Lazarenko, e-mail: lazarenko@list.ru. Financial Disclosure: no authors have a financial or property interest in any material or method mentioned. There is no conflict of interests. Received 02.03.2020.
2. Хаитов Р.М., Ильина Н.И. Национальное руководство: Аллергология и иммунология. М.; 2009. [Khaitov R.M., Ilyina N.I. National guideline: Allergology and immunology. M.; 2009 (in Russ.)].
3. Lirk P., Hollmann M.W., Strichartz G. The science of local anesthesia: basic research, clinical application, and future directions. Anesth Analg. 2018;126(4):1381–1392. DOI: 10.1213/ANE.0000000000002665.
4. Kirksey M.A., Haskins S.C., Cheng J., Liu S.S. Local anesthetic peripheral nerve block adjuvants for prolongation of analgesia: a systematic qualitative review. PLoS One. 2015;10(9): e0137312. DOI: 10.1371/journal.pone.0137312.
5. El-Boghdadly K., Pawa A., Chin K.J. Local anesthetic systemic toxicity: current perspectives. Local Reg Anesth. 2018;11:35. DOI: 10.2147/LRA.S154512.
6. Shah J., Votta-Velis E.G., Borgeat A. New local anesthetics. Best Pract Res Clin Anaesthesiol. 2018;32(2):179–185. DOI: 10.1016/j.bpa.2018.06.010.
7. Ильина Н.И., Латышева Т.В., Мясникова Т.Н. и др. Лекарственная аллергия. Методические рекомендации для врачей (часть 2). Российский аллергологический журнал. 2013;(6):25–40. [Ilyina N.I., Latysheva T.V., Myasnikova T.N. et al. Drug allergy. Guidelines for doctors (part 2). Rossiyskiy allergologicheskiy zhurnal. 2013;(6):25–40 (in Russ.)].
8. Pichler W.J., Hausmann O. Classification of drug hypersensitivity into allergic, pi, and pseudo-allergic forms. Int Arch Allergy Immunol. 2016;171(3–4):166–179. DOI: 10.1159/000453265.
9. Мясникова Т.Н., Романова Т.С., Хлудова Л.Г., Латышева Т.В. Диагностика лекарственной аллергии: современный взгляд на проблему. РМЖ. 2018;126(1):28–32. [Myasnikova T.N., Romanova T.S., Khludova L.G., Latysheva T.V. Diagnosis of drug allergy: a modern view of the problem. RMJ. 2018;126(1):28–32 (in Russ.)].
10. Brockow K., Garvey L.H., Aberer W. et al. Skin test concentrations for systemically administered drugs — an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy. 2013;68(6):702–712. DOI: 10.1111/all.12142.
11. Адо А.Д., Прошина Ю.А., Лусс Л.В., Бондарева Г.П. и др. Тест торможения естественной миграции лейкоцитов in vivo для специфической диагностики лекарственной аллергии. Практическое пособие по клинической иммунологии и аллергологии. Под ред. Р.М. Хаитова. М.: ТОРУС ПРЕСС; 2005. [Ado A.D., Proshina Yu.A., Luss L.V., Bondareva G.P. et al. Test of inhibition of natural migration of leukocytes in vivo for specific diagnosis of drug allergy. Practical guide to clinical immunology and allergology. Ed. R.M. Khaitov. М.: ТORUS PRESS; 2005 (in Russ.)].
12. Lazarenko L.L. Buccal provocative test in saliva for determination of hypersensitivity to dental materials. Allergy. 2017;72:705.
13. Романова Т.В. Особенности диагностики in vivo лекарственной аллергии, протекающей по замедленному типу. Дис. … канд. мед. наук. М.; 2019. [Romanova T.V. Diagnostic features of in vivo delayed-type drug allergy. Thesis. М.; 2019 (in Russ.)].
14. Torres M.J., Romano A., Celik G. et al. Approach to the diagnosis of drug hypersensitivity reactions: similarities and differences between Europe and North America. Clin Transl Allergy. 2017;7(1):7. DOI: 10.1186/s13601-017-0144-0.
15. Mayorga C., Ebo D.G., Lang D.M. et al. Controversies in drug allergy: in vitro testing. J Allergy Clin Immunol. 2019;143(1):56–65. DOI: 10.1016/j.jaci.2018.09.022.
16. Mayorga C., Celik G., Rouzaire P. et al. In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy. 2016;71(8):1103–1134. DOI: 10.1111/all.12886.
17. Berroa F., Lafuente A., Javaloyes G. et al. The usefulness of plasma histamine and different tryptase cut-off points in the diagnosis of peranaesthetic hypersensitivity reactions. Clin Exp Allergy. 2014;44(2):270–277. DOI: 10.1111/cea.12237.
18. Ebo D.G., Leysen J., Mayorga C. et al. The in vitro diagnosis of drug allergy: status and perspectives. Allergy. 2011;66(10):1275–1286. DOI: 10.1111/j.1398-9995.2011.02661.x.
19. Ebo D.G., Faber M., Elst J. et al. In vitro diagnosis of immediate drug hypersensitivity during anesthesia: a review of the literature. J Allergy Clin Immunol Pract. 2018;6(4):1176–1184. DOI: 10.1016/j.jaip.2018.01.004.
20. Fontaine C., Mayorga C., Bousquet P.J. et al. Relevance of the determination of serum-specific IgE antibodies in the diagnosis of immediate $β$-lactam allergy. Allergy. 2007;62(1):47–52. DOI: 10.1111/j.1398-9995.2006.01268.x.
21. Lazarenko L. Detection of IgE- and IgG-antibodies to local anaesthetics and dental materials. What is the diagnostic value? Allergy Eur J Allergy Clin Immunol. 2012;67:128.
22. Totolyan A., Lazarenko L. Monitoring of IgE — Antibodies in dental allergy. Allergy Eur J Allergy Clin Immunol. 2011;66:161–162.
23. Lazarenko L. Allergy in Dental Practice: Myth or Reality? In: British Society for Allergy and Clinical Immunology Annual Meeting 8–10 July, 2013 Telford International Centre, UK. Telford; 2013.
24. Лазаренко Л.Л., Сесь Т.П. Гуморальный иммунный ответ при непереносимости протезных материалов и местных анестетиков. Медицинская иммунология. 2015;17(S):100. [Lazarenko L.L., Sess T.P. Humoral immune response with intolerance to prosthetic materials and local anesthetics. Medical immunology. 2015;17(S):100 (in Russ.)].
25. Sanz M.L., Gamboa P., De Weck A.L. A new combined test with flowcytometric basophil activation and determination of sulfidoleukotrienes is useful for in vitro diagnosis of hypersensitivity to aspirin and other nonsteroidal anti-inflammatory drugs. Int Arch Allergy Immunol. 2005;136(1):58–72. DOI: 10.1159/000082586.
26. Sanz M.L., Gamboa P.M., Mayorga C. Basophil activation tests in the evaluation of immediate drug hypersensitivity. Curr Opin Allergy Clin Immunol. 2009;9(4):298–304. DOI: 10.1097/ACI.0b013e32832d5311.
27. Hausmann O.V., Gentinetta T., Bridts C.H., Ebo D.G. The basophil activation test in immediate-type drug allergy. Immunol Allergy Clin North Am. 2009;29(3):555–566. DOI: 10.1016/j.iac.2009.04.011.
28. Hoffmann H.J., Santos A.F., Mayorga C. et al. The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease. Allergy. 2015;70(11):1393–1405. DOI: 10.1111/all.12698.
29. Бычкова Н.В. Возможности лаборатории в диагностике лекарственной гиперчувствительности. Российский иммунологический журнал. 2019;13(22):181–185. [Bychkova N.V. Laboratory capabilities in the diagnosis of drug hypersensitivity. Russian immunological journal. 2019;13(22):181–185 (in Russ.)].
30. Pichler W.J., Tilch J. The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy. 2004;59(8):809–820. DOI: 10.1111/j.1398-9995.2004.00547.x.
31. Mayorga C., Doña I., Perez-Inestrosa E. et al. The value of in vitro tests to diminish drug challenges. Int J Mol Sci. 2017;18(6):1222. DOI: 10.3390/ijms18061222.
32. Roujeau J.-C., Albengres E., Moritz S. et al. Lymphocyte transformation test in drug-induced toxic epidermal necrolysis. Int Arch Allergy Immunol. 1985;78(1):22–24. DOI: 10.1159/000233856.
33. Orasch C.E., Helbling A., Zanni M.P. et al. T-cell reaction to local anaesthetics: relationship to angioedema and urticaria after subcutaneous application-patch testing and LTT in patients with adverse reaction to local anaesthetics. Clin Exp allergy J Br Soc Allergy Clin Immunol. 1999;29(11):1549–1554. DOI: 10.1046/j.1365-2222.1999.00693.x.
34. Beeler A., Zaccaria L., Kawabata T. et al. CD69 upregulation on T cells as an in vitro marker for delayed-type drug hypersensitivity. Allergy. 2008;63(2):181–188.
35. Porebski G., Gschwend-Zawodniak A., Pichler W.J. In vitro diagnosis of T cell-mediated drug allergy. Clin Exp Allergy. 2011;41(4):461–470. DOI: 10.1111/j.1365-2222.2011.03701.x.
36. Tapia B., Padial A., Sánchez-Sabaté E. et al. Involvement of CCL27-CCR10 interactions in drug-induced cutaneous reactions. J Allergy Clin Immunol. 2004;114(2):335–340. DOI: 10.1016/j.jaci.2004.04.034.
37. Martin M., Wurpts G., Ott H. et al. In vitro detection and characterization of drug hypersensitivity using flow cytometry. Allergy. 2010;65(1):32–39. DOI: 10.1111/j.1398-9995.2009.02143.x.
38. Lochmatter P., Beeler A., Kawabata T.T. et al. Drug-specific in vitro release of IL-2, IL-5, IL-13 and IFN-γ in patients with delayed-type drug hypersensitivity. Allergy. 2009;64(9):1269–1278. DOI: 10.1111/j.1398-9995.2009.01985.x.
39. Zawodniak A., Lochmatter P., Yerly D. et al. In vitro detection of cytotoxic T and NK cells in peripheral blood of patients with various drug-induced skin diseases. Allergy. 2010;65(3):376–384. DOI: 10.1111/j.1398-9995.2009.02180.x.
40. Blanca M., Torres M.J., Leyva L. et al. Expression of the skin-homing receptor in peripheral blood lymphocytes from subjects with nonimmediate cutaneousallergic drug reactions. Allergy. 2000;55(11):998–1004. DOI: 10.1034/j.1398-9995.2000.00628.x.
41. Cornejo-Garcia J.A., Fernandez T.D., Torres M.J. et al. Differential cytokine and transcription factor expression in patients with allergic reactions to drugs. Allergy. 2007;62(12):1429–1238. DOI: 10.1111/j.1398-9995.2007.01542.x.
42. Zhang F.-R., Liu H., Irwanto A. et al. HLA-B* 13: 01 and the dapsone hypersensitivity syndrome. N Engl J Med. 2013;369(17):1620–1628. DOI: 10.1056/NEJMoa1213096.
43. Hung S.-I., Chung W.-H., Liou L.-B. et al. HLA-B* 5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci. 2005;102(11):4134–4139. DOI: 10.1073/pnas.0409500102.
This work is licensed under a Creative Commons «Attribution» 4.0 License.
