Allergy clinic patients’ drug hypersensitivity

Main Article Content

Karolina Frachowicz-Guerreiro
Aleksandra Wardzyńska
Marek L. Kowalski

Keywords

Anaphylaxis, B-lactams, drug hypersensitivity, drug provocation and tolerance tests, NSAIDs

Abstract

Background: Drug hypersensitivity reaction (DHR) is a common reason for an allergology consultation, during which it is not only necessary to gather a thorough medical history, but also to propose and perform diagnostic tests.


Objectives: The aim of the study was to retrospectively assess the patients with a profile of preliminary drug hypersensitivity diagnosis, the usefulness of NSAID hypersensitivity classification in outpatient practice, and to analyze the results of skin, provocation, and drug tolerance tests performed in Immunology and Allergy Clinic patients.


Methods: Around 501 medical records of patients referred to the academic allergy outpatient clinic from 2011 to 2019, and had a preliminary drug hypersensitivity diagnosis were analyzed. The diagnostic and drug tolerance tests results carried out in 269 patients of the Clinic from 2009 to 2019 were then evaluated.


Results: Among the patients referred due to suspected drug hypersensitivity, the majority (n=338, 67.5%) were believed to be hypersensitive to NSAIDs and antibiotics (n=272, 54.3%). In patients with hypersensitivity to NSAIDs, the mixed pattern was the most prevalent (n=73, 21.6%), followed by NECD (n=64, 18.9%) and NIUA (n=55, 16.3%). The second most common drug causing DHR were the antibiotics, mainly β-lactams (n=160, 58.8%), followed by macrolides (n=35, 12.9%). In hypersensitivity caused due to β-lactams, the delayed form was predominant (n=24, 15%) with manifested skin symptoms (n=74, 46.3%). Non-steroidal anti-inflammatory drugs (n=21, 42.9%), followed by antibiotics (n=11, 22.5%) were the commonest causes of anaphylaxis, as reported by 49 patients.


Conclusion: The study shows that a majority of patients with suspected drug hypersensitivity can be classified under the hypersensitivity umbrella based on their medical history, which is the basis for further diagnostic process.

Abstract 94 | PDF Downloads 63 HTML Downloads 5 XML Downloads 2

References

1. Bouvy JC, De Bruin ML, Koopmanschap MA. Epidemiology of adverse drug reactions in Europe: a review of recent obser-vational studies. Drug Saf. 2015;38(5):437–53. 10.1007/s40264-015-0281-0

2. Pouyanne P, Haramburu F, Imbs JL, Begaud B. Admissions to hospital caused by adverse drug reactions: cross sec-tional incidence study. Br Med J. 2000;320:1036. 10.1136/bmj.320.7241.1036

3. Ibia EO, Schwartz R, Wiedermann BL. Antibiotic rashes in chil-dren: a survey in a private practice setting. Arch Dermatol. 2000;136(7):849–54. 10.1001/archderm.136.7.849

4. Impicciatore P, Choonara I, Clarkson A, Provasi D, Pandolfini C, Bonati M. Incidence of adverse drug reactions in paediatric in/out-patients: a systematic review and meta-analysis of prospective studies. Br J Clin Pharmacol. 2001;52(1):77–83. 10.1046/j.0306-5251.2001.01407.x

5. Demoly P, Hillaire-Buys D. Classification and epidemiology of hypersensitivity drug reactions. Immunol Allergy Clin N Am. 2004;24(3):345–56. 10.1016/j.iac.2004.03.010

6. de Shazo RD, Kemp S. Allergic reactions to drugs and bio-logical agents. JAMA. 1997;278(22):1895–1906. 10.1001/jama.1997.03550220101014

7. Uzzaman A, Cho SH. Chapter 28: Classification of hypersen-sitivity reactions. AllergyAsthmaProc. 2012;33 Suppl 1:96–9 10.2500/aap.2012.33.3561

8. Garon SL, Pavlos RK, White KD, Brown NJ, Stone CA Jr, Phillips EJ. Pharmacogenomics of off-target adverse drug reactions. Br J Clin Pharmacol. 2017;83:1896–1911. 10.1111/bcp.13294

9. Johansson S, Hourihane J, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela T, et al. A revised nomenclature for allergy. An EAACI position statement from the EAACI nomen-clature task force. Allergy. 2001;56(9):813–24. 10.1034/j.1398-9995.2001.t01-1-00001.x

10. Johansson S, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004;113(5):832–836. 10.1016/j.jaci.2003.12.591

11. Brockow K, Romano A, Blanca M, Ring J, Pichler W, Demoly P. General considerations for skin test procedures in the diagno-sis of drug hypersensitivity. Allergy. 2002;57(1):45–51. 10.1046/j.0105-4538.2001.00001.x-i8

12. Aberer W, Bircher A, Romano A, Blanca M, Campi P, Fernandez J, et al. Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Allergy. 2003;58(9):854–63. 10.1034/j.1398-9995.2003.00279.x

13. Brzezińska-Pawłowska O., Kowalski M. L. Diagnostic approaches to immediate allergic reaction to antibiotics. Alerg Astma Immun. 2016;21(2):102–109.

14. Kowalski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs)-classification, diagnosis and management: review of the EAACI/ENDA and GA2LEN/HANNA. Allergy. 2011;66(7):818–29. 10.1111/j.1398-9995.2011.02557.x

15. Kowalski ML, Asero R, Bavbek S, Blanca M, Blanca-Lopez N, Bochenek G, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonste-roidal anti-inflammatory drugs. Allergy. 2013;68(10):1219–32. 10.1111/all.12260

16. Blumenthal KG, Peter JG, Trubiano JA, Phillips EJ. Antibiotic allergy. Lancet. 2019;393(10167):183–198. 10.1016/S0140-6736(18)32218-9

17. Stevenson DD, Kowalski ML. An epidemic of over diagnosing drug allergies. Allergy Asthma Proc. 2014;35(2):92–4. 10.2500/aap.2014.35.1015

18. Muraro A, Roberts G, Worm M, Bilo MB, Brockow K, Fernandez Rivas M, Santos AF et al. on behalf of the EAACI Food Allergy and Anaphylaxis Guidelines Group. Anaphylaxis: guide-lines from the European Academy of Allergy and Clinical Immunology. Allergy 2014; 69(8): 1026–1045. 10.1111/all.12437

19. Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol 2004;113(5):832–836. 10.1016/j.jaci.2003.12.591

20. Romano A, Atanaskovic-Markovic M, Barbaud A, Bircher AJ, Brockow K, Caubet JC, et al. Towards a more precise diag-nosis of hypersensitivity to beta-lactams-an EAACI position paper. Allergy. 2019;75(6):1300-1315. 10.1111/all.14122

21. Dona I, Blanca-Lopez N, Torres MJ, García-Campos J, García-Núñez I, Gómez F, et al. Drug hypersensitivity reactions: response patterns, drug involved, and temporal variations in a large series of patients. J Investig Allergol Clin Immunol. 2012;22(5):363–371. PMid: 23101312

22. Antunez C, Martin E, Cornejo-Garcia J A, Blanca-Lopez N, Pena RR, Mayorga C, et al. Immediate hypersensitivity reactions to penicillins and other betalactams. Curr Pharm Des. 2006;12(26): 3327–3333. 10.2174/138161206778194042

23. Jares EJ, Baena-Cagnani CE, Sanchez-Borges M, Ensina LFC, Arias-Cruz A, Gómez M, et al. Latin America Drug Allergy Interest Group. Drug-induced anaphylaxis in Latin American countries. J Allergy Clin Immunol Pract. 2015;3(5):780–788. 10.1016/j.jaip.2015.05.012

24. Blanca-Lopez N, Cornejo-Garcia JA, Perez-Alzate D, Pérez-Sánchez N, Plaza-Serón MC, Doña I, et al. Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in children and adolescents: selective reactions. J Investig Allergol Clin Immunol. 2015;25(6):385–395. PMid: 26817135.

25. Gomes E, Cardoso MF, Praça F, Gomes L, Mariño E, Demoly P. Self-reported drug allergy in a general adult Portuguese pop-ulation. Clin Exp Allergy. 2004;34(10):1597–1601. 10.1111/j.1365-2222.2004.02070.x

26. Demir S, Olgac M, Unal D, Gelincik A, Colakoglu B, Buyukozturk S. Evaluation of hypersensitivity reactions to nonsteroidal anti-inflammatory drugs according to the latest classification. Allergy Eur J Allergy Clin Immunol. 2015;70(11):1461–7. 10.1111/all.12689

27. Nissen CV, Bindslev-Jensen C, Mortz CG. Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs): classification of a Danish patient cohort according to EAACI/ENDA guide-lines. Clin Transl Allergy. 2015;3:5–10. 10.1186/s13601-015-0052-0

28. Caimmi S, Caimmi D. Bousquet P.-J. Demoly P. How Can We Better Classify NSAID Hypersensitivity Reactions?–Validation from a Large Database.Int Arch Allergy Immunol. 2012;159(3):306–312. 10.1159/000337660

29. Kowalski ML. Heterogeneity of NSAID-Exacerbated Respiratory Disease: has the time come for subphenotyping? Curr Opin Pulm Med. 2019;25(1):64–70. 10.1097/MCP.0000000000000530

30. Nissen CV, Bindslev-Jensen C, Mortz CG. Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs): Classification of a danish patient cohort according to EAACI/ENDA guide-lines. Clin Transl Allergy. 2015;5. 10.1186/s13601-015-0052-0

31. Doña I, Barrionuevo E, Salas M, Laguna JJ, Agúndez J, García-Martín E, et al. NSAIDs-hypersensitivity often induces a blended reaction pattern involving multiple organs. Sci Rep. 2018;8(1):1–9. 10.1038/s41598-018-34668-1

32. Simons FE, Ebisawa M, Sanchez-Borges M, Thong BY, Worm M, Tanno LK, et al. 2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines. World Allergy Organ J. 2015;8(1):32. 10.1186/s40413-015-0080-1

33. Jerschow E, Lin RY, Scaperotti MM, McGinn AP. Fatal anaphylaxis in the United States, 1999-2010: temporal patterns and demographic associations. J Allergy Clin Immunol. 2014;134(6):1318–28. 10.1016/j.jaci.2014.08.018

34. van der Klauw MM, Wilson JH, Stricker BH. Drug-associated anaphylaxis: 20 years of reporting in The Netherlands (1974-1994) and review of the literature. Clin Exp Allergy. 1996;26(12):1355–63. 10.1111/j.1365-2222.1996.tb00536.x

35. Leone R, Conforti A, Venegoni M, Motola D, Moretti U, Meneghelli I, et al. Drug-induced anaphylaxis: case/noncase study based on an Italian pharmacovigilance database. Drug Saf 2005;28(6):547–56. 10.2165/00002018-200528060-00006

36. Aun MV, Blanca M, Garro LS, Ribeiro MR, Kalil J, Motta AA, et al. Nonsteroidal anti-inflammatory drugs are major causes of drug-induced anaphylaxis. J Allergy Clin Immunol Pract. 2014;2(4):414–20. 10.1016/j.jaip.2014.03.014

37. Aurich S, Dölle-Bierke S, Francuzik W, Bilo MB, Christoff G, Fernandez-Rivas M, et al. Anaphylaxis in Elderly Patients-Data From the European Anaphylaxis Registry. Frontiers in immuno-logy. 2019;10:750. 10.3389/fimmu.2019.00750

38. Faria E, Rodrigues-Cernadas J, Gaspar A, Botelho C, Castro E, Lopes A, et al. Drug-induced anaphylaxis survey in Portuguese Allergy Departments. J Investig Allergol Clin Immunol. 2014;24(1):40–8. PMid: 24765880.

39. Park HK, Kang MG, Yang MS, Jung JW, Cho SH, Kang HR. Epidemiology of drug-induced anaphylaxis in a tertiary hos-pital in Korea. Allergol Int. 2017;66(4):557–562. 10.1016/j.alit.2017.02.008

40. Backstrom M, Mjorndal T, Dahlqvist R. Under-reporting of serious adverse drug reactions in Sweden. Pharmacoepidemiol Drug Saf. 2004;13(7):483–487. 10.1002/pds.962

41. Messaad D, Sahla H, Benahmed S, Godard P, Bousquet J, Demoly P. Drug provocation tests in patients with a his-tory suggesting an immediate drug hypersensitivity reac-tion. Ann Intern Med. 2004;140(12):1001–1006. 10.7326/0003-4819-140-12-200406150-00009

42. Demoly P, Hillaire-Buys D. Classification and epidemiology of hypersensitivity drug reactions. Immunol Allergy Clin North Am. 2004;24(3):345–56. 10.1016/j.iac.2004.03.010

43. Gamboa PM. The epidemiology of drug allergy-related con-sultations in Spanish Allergology Services: Alergológica-2005. J Investig Allergol Clin Immunol. 2009;19 Suppl 2: 45–50. PMid: 19530418

44. Sacco KA, Bates A, Brigham TJ, Imam JS, Burton MC. Clinical outcomes following inpatient penicillin allergy testing: A sys-tematic review and meta-analysis. Allergy. 2017;72(9):1288–1296. 10.1111/all.13168

45. Bavbek S, Celik G, Ozer F, Mungan D, Misirligil Z. Safety of selective COX-2 inhibitors in aspirin/nonsteroidal anti-inflammatory drug-intolerant patients: comparison of nime-sulide, meloxicam, and rofecoxib. J Asthma. 2004;41(1):67–75. 10.1081/JAS-120026063

46. Kowalski ML, Makowska J. Use of nonsteroidal anti-inflamma-tory drugs in patients with aspirin hypersensitivity: safety of cyclo-oxygenase-2 inhibitors. Treat Respir Med. 2006;5(6):399–406. 10.2165/00151829-200605060-00005

47. Bavbek S, Dursun AB, Dursun E, Eryilmaz A, Misirligil Z. Safety of meloxicam in aspirin-hypersensitive patients with asthma and/or nasal polyps. A challenge-proven study. Int Arch Allergy Immunol. 2007;142(1):64–9. 10.1159/000096000

48. Göksel O1, Aydin O, Misirligil Z, Demirel YS, Bavbek S. Safety of meloxicam in patients with aspirin/non-steroidal anti-inflammatory drug-induced urticaria and angioedema. J Dermatol. 2010;37(11):973–9. 10.1111/j.1346-8138.2010.00948.x

49. Senna G, Bilò MB, Antonicelli L, Schiappoli M, Crivellaro MA, Bonadonna P, et al. Tolerability of three selective cyclo-oxygenase-2 inhibitors, meloxicam, celecoxib and rofecoxib in NSAID-sensitive patients. Eur Ann Allergy Clin Immunol. 2004;36(6):215–8. PMid: 15329003

50. Li L, Laidlaw T. Cross-reactivity and tolerability of celecoxib in adult patients with NSAID hypersensitivity. J Allergy Clin Immunol Pract. 2019;7(8):2891–2893. 10.1016/j.jaip.2019.04.042