Drug-induced anaphylaxis: prevalence, risk factors, triggers

Cover Page
Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access


Currently, there is a tendency to increase the prevalence of drug-induced anaphylaxis. Medicines occupy a leading position among the causes of the development of anaphylactic reactions in the adult group of patients and second place in children, the most significant in this matter are non-steroidal anti-inflammatory drugs, antibacterial drugs and X-ray contrast agents. The risk of developing of drug anaphylaxis in most cases is not predictable, while the frequency of severe and fatal reactions is extremely high. This article presents an analysis of current data regarding the prevalence, possible risk factors, and triggers of drug anaphylaxis.

Restricted Access

Natalia V Esakova

Academician Yu.E. Veltishchev Research Clinical Institute of Pediatrics N.I. Pirogov Russian National Research Medical University

Email: env007@rambler.ru

Alexander Nikolaevich Pampura

Academician Yu.E. Veltishchev Research Clinical Institute of Pediatrics N.I. Pirogov Russian National Research Medical University

  1. Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Bock SA, Branum A et al. Second symposium on the definition and management of anaphylaxis: summary report - Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117:391-397. DOI: 10.1016/j. jaci.2005.12.1303.
  2. Montanez MI, Mayorga C, Bogas G, Barrionuevo E, Fernandez-Santamaria R et al. Epidemiology, Mechanisms, and Diagnosis of Drug-Induced Anaphylaxis. Front Immunol. 2017;8:614. doi: 10.3389/fimmu.2017.00614.
  3. Liew WK, Williamson E, Tang ML. Anaphylaxis fatalities and admissions in Australia. J Allergy Clin Immunol. 2009;123(2):434-442. doi: 10.1016/j.jaci.2008.10.049.
  4. 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):1318-1328. doi: 10.1016/j.jaci.2014.08.018.
  5. Wood RA, Camargo CA Jr, Lieberman P, Sampson HA, Schwartz LB, Zitt M et al. Anaphylaxis in United States: the prevalence and characteristics of anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133(2):461-467. doi: 10.1016/j.jaci.2013.08.016.
  6. Huang F, Chawla K, Jarvinen KM, Nowak-Węgrzyn A. Anaphylaxis in a New York City pediatric emergency department: triggers, treatments, and outcomes. J Allergy Clin Immunol. 2012;129(1):162-168. doi: 10.1016/j.jaci.2011.09.018
  7. Clark S, Wei W, Rudders SA, Camargo CA Jr. Risk factors for severe anaphylaxis in patients receiving anaphylaxis treatment in US emergency departments and hospitals. J Allergy Clin Immunol. 2014;134(5):1125-1130. DOI: 10.1016/j. jaci.2014.05.018.
  8. Brown SG, Stone SF, Fatovich DM, Burrows SA, Holdgate A, Celenza A. Anaphylaxis: clinical patterns, mediator release, and severity. J Allergy Clin Immunol. 2013;132(5):1141-1149. doi: 10.1016/j.jaci.2013.06.015.
  9. Banerji A, Rudders S, Clark S, Wei W, Long AA, Camargo CA Jr. Retrospective study of drug-induced anaphylaxis treated in the emergency department or hospital: patient characteristics, management, and 1-year follow-up. J Allergy Clin Immunol Pract. 2014;2(1):46-51. doi: 10.1016/j.jaip.2013.08.012.
  10. Stafforini DM, McIntyre TM, Zimmerman GA, Prescott SM. Platelet-activating factor, a pleiotrophic mediator of physiological and pathological processes. Crit Rev Clin Lab Sci. 2003;40(6):643-672. doi: 10.1080/714037693.
  11. Vadas P, Gold M, Liss G, Smith C, Yeung J. PAF acetylhy-drolase deficiency predisposes to fatal anaphylaxis. J Allergy Clin Immunol. 2003;11:S206.
  12. Vadas P, Perelman B, Liss G. Platelet-activating factor, histamine, and tryptase levels in human anaphylaxis. J Allergy Clin Immunol. 2013;131:144-149. DOI: 10.1016/j. jaci.2012.08.016.
  13. Brown SG, Stone SF, Fatovich DM, Burrows SA, Holdgate A, Celenza A. Anaphylaxis: clinical patterns, mediator release, and severity. J Allergy Clin Immunol. 2013;132(5):1141-1149. doi: 10.1016/j.jaci.2013.06.015.
  14. Kruse S, Mao XQ, Heinzmann A, Blattmann S, Roberts MH, Braun S. The Ile198Thr and Ala379Val variants of plasmatic PAF-Acetylhydrolase impair catalytical activities and are associated with atopy and asthma. Am J Hum Genet. 2000;66(5):1522-1530. doi: 10.1086/302901.
  15. Esakova NV, Saakyan EK, Kondratieva NS, Kokaeva ZG, Nesterova AP, Golovatenko-Abramov PK et al. Platelet-Activating Factor-Acetylhydrolase Gene (PLA2G7) Expression in Children with a History of Food Anaphylaxis. J Allergy Ther. 2015;6:211. doi: 10.4172/2155-6121.1000211.
  16. Bertelsen K, Dalgaard JB. Death due to penicillin. 16 Danish cases with autopsies. Nord Med. 1965;73:173-177.
  17. Idsoe O, Guthe T, Willcox RR, de Weck AL. Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock. Bull World Health Organ. 1968;38(2):159-188.
  18. Bonadonna P, Pagani M, Aberer W, Bilo MB, Brockow K, Oude Elberink H et al. Drug hypersensitivity in clonal mast cell disorders: ENDA/EAACI position paper. Allergy. 2015;70(7):755-763. doi: 10.1111/all.12617.
  19. Lang DM, Alpern MB, Visintainer Pf, Smith ST Elevated risk of anaphylactoid reaction from radiographic contrast media is associated with both beta-blocker exposure and cardiovascular disorders. Arch Intern Med. 1993;153(17):2033-2040.
  20. Nassiri M, Babina M, Dolle S, Edenharter G, Rueff F, Worm M. Ramipril and metoprolol intake aggravate human and murine anaphylaxis: evidence for direct mast cell priming. J Allergy Clin Immunol. 2015;135(2):491-499. DOI: 10.1016/j. jaci.2014.09.004.
  21. Stoevesandt J, Hain J, Stolze I, Kerstan A, Trautmann A. Angiotensin-converting enzyme inhibitors do not impair the safety of Hymenoptera venom immunotherapy build-up phase. Clin Exp Allergy. 2014;44(5):747-755. DOI: 10.1111/ cea.12276.
  22. Ramirez E, Cabanas R, Laserna LS, Fiandor A, Tong H, Prior N. Proton pump inhibitors are associated with hyper sensitivity reactions to drugs in hospitalized patients: a nested casecontrol in a retrospective cohort study. Clin Exp Allergy. 2013;43(3):344-352. doi: 10.1111/cea.12034.
  23. Kuruvilla M, Khan DA. Anaphylaxis to drugs. Immunol Allergy Clin North Am. 2015;35(2):303-319. DOI: 10.1016/j. iac.2015.01.008.
  24. Blanca-Lopez N, Soriano V, Garcia-Martin E, Canto G, Blanca M. NSAID-induced reactions: classification, prevalence, impact, and management strategies. J Asthma Allergy. 2019;12:217-233. doi: 10.2147/JAA.S164806.
  25. Riemer AB, Gruber S, Pali-Scholl I, Kinaciyan T, Untersmayr E, Jensen-Jarolim E. Suppression of gastric acid increases the risk of developing immunoglobulin E-mediated drug hypersensitivity: human diclofenac sensitization and a murine sensitization model. Clin Exp Allergy. 2010;40(3):486-493. doi: 10.1111/j.1365-2222.2009.03363.x.
  26. Himly M, Jahn-Schmid B, Pittertschatscher K, Pittertschatscher K, Bohle B, Grubmayr K et al. IgE-mediated immediate-type hypersensitivity to the pyrazolone drug pro-pyphenazone. J Allergy Clin Immuno.l 2003;111(4):882-888. doi: 10.1067/mai.2003.163.
  27. Quiralte J, Blanco C, Delgado J, Ortega N, Acntara M, Castillo R et al. Challenge-based clinical patterns of223 Spanish patients with nonsteroidal anti-inflammatory-drug-induced-re-actions. J Investig Allergol Clin Immunol. 2007;17(3):182-188.
  28. Gonzalez-Perez A, Aponte Z, Vidaurre CF, Garcia Rodriguez LA. Anaphylaxis epidemiology in patients with and patients without asthma: a United Kingdom database review. J Allergy Clin Immunol. 2010;125(5):1098-1104.
  29. Weiss ME, Adkinson NF. Immediate hypersensitivity reactions to penicillin and related antibiotics. Clin Allergy. 1988;18(6):515-540. doi: 10.1111/j.1365-2222.1988. tb02904.x.
  30. Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Arch Intern Med. 2001;161(1):15-21. doi: 10.1001/archinte.161.1.15.
  31. Levine BB, Zolov DM. Prediction of penicillin allergy by immunological tests. J Allergy. 1969;43(4):231-244. doi: 10.1016/0021-8707(69)90066-5.
  32. Macy E, Ngor EW Safely diagnosing clinically significant penicillin allergy using only penicilloyl-poly-lysine, penicillin, and oral amoxicillin. J Allergy Clin Immunol Pract. 2013;1:258-263. doi: 10.1016/j.jaip.2013.02.002.
  33. Blanca M, Torres MJ, Garcia JJ, Romano A, Mayorga C, de Ramon E et al. Natural evolution of skin test sensitivity in patients allergic to beta-lactam antibiotics. J Allergy Clin Immunol. 1999;103(5 Pt 1):918-924. doi: 10.1016/s0091-6749(99)70439-2.
  34. Torres MJ, Ariza A, Mayorga C, Dona I, Blanca-Lopez N, Rondon C et al. Clavulanic acid can be the component in amoxicillin-clavulanic acid responsible for immediate hypersensitivity reactions. J Allergy Clin Immunol. 2010;125(2):502-505. doi: 10.1016/j.jaci.2009.11.032.
  35. Romano A, Gueant-Rodriguez RM, Viola M, Amoghly F, Gaeta F, Nicolas JP et al. Diagnosing immediate reactions to cephalosporins. Clin Exp Allergy. 2005;35(9):1234-1242. doi: 10.1111/j.1365-2222.2005.02317.x.
  36. Chen Z, Baur X, Kutscha-Lissberg F, Merget R. IgE-mediated anaphylactic reaction to imipenem. Allergy. 2000;55(1):92-93. doi: 10.1034/j.1398-9995.2000.00360.x.
  37. Iglesias Cadarso A, Saez Jimenez SA, Vidal Pan C, Rodriguez Mosquera M. Aztreonam-induced anaphylaxis. Lancet. 1990;336(8717):746-747. doi: 10.1016/0140-6736(90)92238-d.
  38. Romano A, Viola M, Gueant-Rodriguez RM, Gaeta F, Valluzzi R, Gueant JL. Brief communication: tolerability of meropenem in patients with IgE-mediated hypersensitivity to penicillins. Ann Intern Med. 2007;146(4):266-269. doi: 10.7326/0003-4819-146-4-200702200-00005.
  39. Romano A, Gaeta F, Valluzzi RL, Caruso C, Rumi G, Bousquet PJ. IgE-mediated hypersensitivity to cephalosporins: cross-reactivity and tolerability of penicillins, monobactams, and carbapenems. J Allergy Clin Immunol. 2010;126(5):994-999.
  40. Bijl AM, Van der Klauw MM, Van Vliet AC, Stricker BH. Anaphylactic reactions associated with trimethoprim. Clin Exp Allergy. 1998;28(4):510-512. doi: 10.1046/j.1365-2222.1998.00258.x.
  41. Swamy N, Laurie SA, Ruiz-Huidobro E, Khan DA. Successful clarithromycin in a multiple macrolid e-allergic patient. Ann Allergy Asthma Immunol. 2010;105(6):489-490.
  42. Renaudin JM, Beaudouin E, Ponvert C, Demoly P, Moneret-Vautrin DA. Severe drug-induced anaphylaxis: analysis of 333 cases recorded by the Allergy Vigilance Network from 2002 to 2010. Allergy. 2013;68(7):929-937. doi: 10.1111/all.12168.
  43. Blanca-Lopez N, Ariza A, Dona I, Mayorga C, Montanez MI. Hypersensitivity reactions to fluoroquinolones: analysis of the factors involved. Clin Exp Allergy. 2013;43(5):560-567.
  44. Wong JT, Ripple RE, MacLean JA, Marks DR, Bloch KJ. Vancomycin hypersensitivity: synergism with narcotics and “desensitization” by a rapid continuous intravenous protocol. J Allergy Clin Immunol. 1994;94(2): 189-194. doi: 10.1016/0091-6749(94)90039-6.
  45. Kim MH, Lee SY, Lee SE, Yang MS, Jung JW, Park CM et al. Anaphylaxis to iodinated contrast media: clinical characteristics related with development of anaphylactic shock. PLoS One. 2014;9(6):e100154. doi: 10.1371/journal.pone.0100154.
  46. Brockow K, Romano A, Aberer W, Bircher AJ, Barbaud A, Bonadonna P et al. Skin testing in patients with hypersensitivity reactions to iodinated contrast media - a European multicenter study. Allergy. 2009;64(2):234-241. doi: 10.1111/j.1398-9995.2008.01832.x.
  47. Jung JW, Kang HR, Kim MH, Lee W, Min KU, Han MH et al. Immediate hypersensitivity reaction to gadolinium-based MR contrast media. Radiology. 2012;264(2):414-422. doi: 10.1148/radiol.12112025.
  48. Greenberger PA, Patterson R, Radin RC. Two pretreatment regimens for high-risk patients receiving radiographic contrast media. J Allergy Clin Immunol. 1984;74(4):540-543. doi: 10.1016/0091-6749(84)90391-9.
  49. Davenport MS, Cohan RH, Caoili EM, Ellis JH. Repeat contrast medium reactions in premedicated patients: frequency and severity. Radiology. 2009;253(2):372-379. DOI: 10.1148/ radiol.2532090465.
  50. Gandhi S, Litt D, Chandy M, Nguyen BM, Jindal NL, Tarlo SM et al. Successful rapid intravenous desensitization for radioiodine contrast allergy in a patient requiring urgent coronary angiography. J Allergy Clin Immunol Pract. 2014;2(1):101-102. doi: 10.1016/j.jaip.2013.06.016.
  51. Harle Dg, Baldo BA, Coroneos Nj, Fisher MM. Anaphylaxis following administration of papaveretum. Case report: implication of IgE antibodies that react with morphine and codeine, and identification of an allergenic determinant. Anesthesiology. 1989;71(4):489-494.
  52. Gonzalez P, de la Sen ML, Venegas I, Ramon A, Soriano V, Cueva B et al. Immediate hypersensitivity to heparins: a cross-reactivity study. J Investig Allergol Clin Immunol. 2014;24(5):367-368.
  53. Kishimoto TK, Viswanathan K, Ganguly T, Elankumaran S, Smith S, Pelzer K et al. Contaminated heparin associated with adverse clinical events and activation of the contact system. N Engl J Med. 2008;358(23):2457-2467. doi: 10.1056/NE-JMoa0803200.
  54. Dona I, Blanca-Lopez N, Torres MJ, Garcia-Campos J, Garcia-Nunez I, Gomez 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.
  55. Bonadonna P, Lombardo C, Bortolami O, Bircher A, Scherer K, Barbaud A et al. Hypersensitivity to proton pump inhibitors: diagnostic accuracy of skin tests compared to oral provocation test. J Allergy Clin Immunol. 2012;130(2):547-549. doi: 10.1016/j.jaci.2012.04.048.
  56. Mertes PM, Alla F, Trechot P, Auroy Y, Jougla E; Groupe d’Etudes des Reactions Anaphylactoides Peranesthesiques. Anaphylaxis during anes-thesia in France: an 8 year national survey. J Allergy Clin Immunol. 2011;128(2):366-373. doi: 10.1016/j.jaci.2011.03.003.
  57. Laxenaire MC. Epidemiology of anesthetic anaphylactoid reactions. Fourth multicenter survey (July 1994 - December 1996). Ann Fr Anesth Reanim. 1999;18(7):796-809. doi: 10.1016/S0750-7658(00)88460-9.
  58. Janas-Naze A, Osica P. The incidence of lidocaine allergy in dentists: an evaluation of 100 general dental practitioners. Int J Occup Med Environ Health. 2019;32(3):333-339. doi: 10.13075/ijomeh.1896.01235.
  59. Berkun X Ben-Zvi A, Levy X Galili D, Shalit M. Evaluation of adverse reactions to local anesthetics: Experience with 236 patients. Ann Allergy Asthma Immunol. 2003;91:342-345.
  60. Laxenaire MC, Charpentier C, Feldman L. Anaphylactoid reactions to colloid plasma substitutes: incidence, risk factors, mechanisms. A French multicenter prospective study. Ann Fr Anesth Reanim. 1994;13(3):301-310. doi: 10.1016/S0750-7658(94)80038-3.


Abstract - 141

PDF (Russian) - 5




  • There are currently no refbacks.

Copyright (c) 2020 Russian Allergological Journal

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies