Clinical Reviews in Allergy & Immunology

, Volume 24, Issue 2, pp 137–147 | Cite as

Anaphylactic and anaphylactoid reactions to aspirin and other NSAIDs

  • Eva A. Berkes


Aspirin and non-steroidal antiinflammatory drugs (NSAIDs) may cause anaphylactic or anaphylactoid reactions. Constitutively-expressed cyclooxygenase (COX-1) inhibition is likely to be responsible for the cross-reactions and side effects associated with these drugs, as well as the anaphylactoid reactions sometimes seen in aspirin-sensitive respiratory disease. Though anaphylactic and anaphylactoid reactions may be clinically indistinguishable, they involve different mechanisms. Anaphylactic reactions are due to immediate hypersensitivity involving cross-linking of drug-specific IgE. Regardless of COX selectivity pattern, NSAIDs may function as haptens capable of inducing allergic sensitization. Unlike anaphylaxis, anaphylactoid reactions are most likely related to inhibition of COX-1 by NSAIDS. Thus, an anaphylactoid reaction caused by a particular COX-1 inhibiting NSAID will occur with a chemically unrelated NSAID which also inhibits COX-1 enzymes. Selective COX-2 inhibitors appear to be safe in patients with a history of NSAID-related anaphylactoid reactions but can function as haptens, with resulting sensitization and anaphylaxis upon next exposure. This article will discuss the mechanisms, prevalence and population-based studies of anaphylactic and anaphylactoid reactions caused by aspirin and NSAIDs. The evaluation and management of patients suspected of having experienced an anaphylactic or anaphylactoid reaction to aspirin or other NSAIDs will also be reviewed.

Index Entries

Aspirin non-steroidal antiinflammatory drugs (NSAID) anaphylaxis anaphylactoid cyclooxygenase 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jones, R. (2001), Nonsteroidal antiinflammatory drug prescribing: past, present and future. Am. J. Med. 110, 4S-7S.PubMedCrossRefGoogle Scholar
  2. 2.
    Mengle-Gaw, L. J. S. B. Nonsteroidal antiinflammatory drugs, in Clinical Immunology: Principles and Practice Rich, F. T. R. R., Shearer, W. T., Kotzin, B. L., and Schroeder, H. W., eds., Mosby, New York, 2001, pp. 107.1–107.10.Google Scholar
  3. 3.
    Stevenson, D. D. (2001), Anaphylactic and anaphylactoid reactions to aspirin and nonsteroidal antiinflammatory drugs. Immunology and Allergy Clinics of North America 21, 745–768.Google Scholar
  4. 4.
    Stevenson, D. (1998), Adverse reactions to nonsteroidal antiinflammatory drugs. N. American Clinics Allergy and Immunology 18:4, 773–798.CrossRefGoogle Scholar
  5. 5.
    Stevenson, D., Sanchez-Borges, M., and Szczeklik, A. (2001), Classification of allergic and pseudoallergic reactions to drugs that inhibit cyclooxygenase enzymes. Ann. Allergy Asthma Immunol. 87, 177–180.PubMedGoogle Scholar
  6. 6.
    DeJarnatt, A. C. G. J. (1992), Basic mechanism of anaphylaxis and anaphylactoid reactions. Immunology and Allergy Clinics of North America 12, 501–515.Google Scholar
  7. 7.
    Czerniawska-Mysik, G. and Szczeklik, A. (1981), Idiosyncrasy to pyrazolone drugs. Allergy 36, 381–384.PubMedCrossRefGoogle Scholar
  8. 8.
    Krilis, S., Gregson, R. P., and Basten, A. (1981), Investigation of the possible involvement of IgE antisalicylol antibodies in patients with urticaria. Int. Arch. Allergy Appl. Immunol. 64, 293–300.PubMedGoogle Scholar
  9. 9.
    Vidal, C. (1997), Parcetamol (acetaminophen) hypersensitivity. Annals of Allergy, Asthma and Immunology.Google Scholar
  10. 10.
    Szczeklik, A. (1986), Analgesics, allergy and asthma. Drugs 4, 148–163.Google Scholar
  11. 11.
    DeWeck, A. L. (1971), Immunologic effects of aspirin anhydride, a contaminant of commercial acetylsalicylic acid preparations. Int. Arch. Allergy 41, 393–400.Google Scholar
  12. 12.
    Phills, J. and Perelmutter, L. (1974), IgE mediated allergic type reactions to aspirin. Acta Allergol., 29, 474–490.PubMedGoogle Scholar
  13. 13.
    Daxun, Z., Becker, W. M., Schulz, K. H., and Schlaak, M. (1993), Sensitivity to aspirin: a new serologic diagnostic method. J. Investigational Allergol. Clin. Immunol. 3, 72–78.Google Scholar
  14. 14.
    Blanca, M., Perez, E., Garcia, J. J., Miranda, A., Terrados, S., Vega, J. M., et al. (1989), Angioedema and IgE antibodies to aspirin: a case report. Ann. Allergy 62, 295–298.PubMedGoogle Scholar
  15. 15.
    Quiralte, J., Blanco, C., Castillo, R., Ortega, N., and Carrillo, T. (1997), Anaphylactoid reactions due to nonsteroidal antiinflammatory drugs: clinical and crossreactivity studies. Ann. Allergy Asthma Immunol. 78, 293–296.PubMedGoogle Scholar
  16. 16.
    Van Diem, L. and Grilliat, J. P. (1990), Anaphylactic shock induced by parcetamol. Eur. J. Clin. Pharmacol. 38, 389–390.PubMedCrossRefGoogle Scholar
  17. 17.
    Fernandez-Rivas, M., de la Hoz, B., and Cuevas, M. (1993), Hypersensitivity reactions to anthranilic acid derivatives. Ann. Allergy 71, 515–518.PubMedGoogle Scholar
  18. 18.
    Rake, G. W., Jr., and Jacobs, R. L. (1983), Anaphylactoid reactions to tolmetin and zomepirac. Ann. Allergy 50, 323–325.PubMedGoogle Scholar
  19. 19.
    Jett, G. K. and Wilson, E. (1984), Anaphylactic reaction associated with sulindac. Ann. Emerg. Med. 13, 462–464.PubMedCrossRefGoogle Scholar
  20. 20.
    Strom, B. L., Carson, J. L., and Morse, M. L. (1987), The effect of indication on hypersensitivity reactions associated with zomepirac sodium and other non steroidal antiinflammatory drugs. Arthritis Rheum. 30, 1142–1148.PubMedCrossRefGoogle Scholar
  21. 21.
    Kemp S. F., Lockey, R. F., Wolf, B. L., and Lieberman, P. (1995), Anaphylaxis: a review of 266 cases. Arch. Intern. Med. 155, 1749–1754.PubMedCrossRefGoogle Scholar
  22. 22.
    Liberman, P. Anaphylaxis and anaphylactoid reactions, in Allergy: Principles and Practice, Middleton, E. J., Reed, C. E., Ellis, E. F., Adkinson, N. F., Jr., Yunginer, J. W., and Busse, W. W., eds., vol. 2, 5th ed. Mosby St. Louis, 1998, pp. 1079–1092.Google Scholar
  23. 23.
    Szczeklik, A. and Stevenson, D. D. (1999), Aspirininduced asthma: advances in pathogenesis and management. J. Allergy Clin. Immunol. 104, 5–13.PubMedCrossRefGoogle Scholar
  24. 24.
    Hayllar, J. and Bjarnason, I. (1995), NSAIDs, Cox-2 inhibitors, and the gut. Lancet 346, 521–522.PubMedCrossRefGoogle Scholar
  25. 25.
    Stevenson, D. D. (1993), Challenge procedures in detection of reactions to aspirin and nonsteroidal antiinflammatory drugs [editorial; comment]. Ann. Allergy 71, 417–418.PubMedGoogle Scholar
  26. 26.
    Bosso, J. V., Schwartz, L. B., and Stevenson, D. D. (1991), Tryptase and histamine release during aspirin-induced respiratory reactions. J. Allergy Clin. Immunol. 88, 830–837.PubMedCrossRefGoogle Scholar
  27. 27.
    Stevenson, D. D., Arroyave, C. M., Bhat, K. N., and Tan, E. M. (1976), Oral aspirin challenges in asthmatic patients: a study of plasma histamine. Clin. Allergy 6, 493–505.PubMedCrossRefGoogle Scholar
  28. 28.
    Sladek, K. and Szczeklik, A. (1993), Cysteinyl leukotrienes overproduction and mast cell activation in aspirin-provoked bronchospasm in asthma. Eur. Respir. J. 6, 391–399.PubMedGoogle Scholar
  29. 29.
    Stevenson, D. D. (1988), Oral challenges to detect aspirin and sulfite sensitivity in asthma. NE and Regional Allergy Proceedings 9, 135–142.Google Scholar
  30. 30.
    Ferreri, N. R., Howland, W. C., Stevenson, D. D., and Spiegelberg, H. L. (1988), Release of leukotrienes, prostaglandins, and histamine into nasal secretions of aspirin-sensitive asthmatics during reaction to aspirin. Am. Rev. Resp. Dis. 137, 847–854.PubMedGoogle Scholar
  31. 31.
    Anderson, J. A. (1992), Allergic reactions to drugs and biological agents. JAMA 268, (20), 2844–2857.PubMedCrossRefGoogle Scholar
  32. 32.
    Strom, B. L., Carson, J. L., and Schinnar, R. (1988) The effect of indication on the risk of hypersensitivity reactions associated with tolmetin sodium versus other nonsteroidal antiinflammatory drugs. J. Rheumatol. 15, 659–699.Google Scholar
  33. 33.
    Van der Klauw, M. M., Stricker, B. H., and Herings, R. M. (1993), Population based case-cohort study of drug-induced anaphylaxis. Br J. Clin. Pharmacol. 35, 400–408.PubMedGoogle Scholar
  34. 34.
    Scala, E., Giani, M., Pirrotta, L., Guerra, E. C., Locanto, M., De Pita, O., et al. (2001), Selective severe anaphylactic reaction due to ketorolac tromethamine without nonsteroidal antiinflammatory drug intolerance. J. Allergy Clin. Immunol. 107, 557.PubMedCrossRefGoogle Scholar
  35. 35.
    Levy, M. B. and Fink, J. N. (2001), Anaphylaxis to celecoxib. Ann. Allergy Asthma Immunol. 87, 72–73.PubMedCrossRefGoogle Scholar
  36. 36.
    Rossi, A.C.K.D. (1982), Tolmetin-induced anaphylactoid reactions. N. Engl. J. Med. 307(8), 499–500.PubMedCrossRefGoogle Scholar
  37. 37.
    Van Puijenbroek, E. P. E. A., Meyboom, R. H., and Leufkens, H. G. (2002), Different risks for NSAID-induced anaphylaxis. Ann. Pharmacother. 36(1), 24–29.PubMedCrossRefGoogle Scholar
  38. 38.
    Szczeklik, A., Gryglewski, R. J., and Czerniawska-Mysik, G. (1977), Clinical patterns of hypersensitivity to nonsteroidal antiinflammatory drugs and their pathogenesis. J. Allergy Clin. Immunol. 60(5), 276–284.PubMedCrossRefGoogle Scholar
  39. 39.
    Settipane, R. A., Shrank, P. J., Simon, R. A., Mathison, D. A., Christensen, S. C., and Stevenson, D. D. (1995), Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects. J. Allergy Clin. Immunol. 96, 480–485.PubMedCrossRefGoogle Scholar
  40. 40.
    Stevenson, D. D., Hougham, A., Schrank, P., Goldlust, B., and Wilson, R. (1990), Disalcid crosssensitivity in aspirin sensitive asthmatics. J. Allergy Clin. Immunol. 86, 749–758.PubMedCrossRefGoogle Scholar
  41. 41.
    Stevenson, D. and Simon, R. A. (2001), Lack of crossreactivity between rofecoxib and aspirin in aspirin sensitive asthmatic patients. J. Allergy Clin. Immunol. 108, 47–51.PubMedCrossRefGoogle Scholar
  42. 42.
    Dahlen, B., Szczeklik, A., and Murray, J. J. (2001), Celecoxib in patients with asthma and aspirin intolerance. N. Engl. J. Med. 344, 142.PubMedCrossRefGoogle Scholar
  43. 43.
    Schellenberg, R. and Isserow, S. H. (2001), Anaphylactoid reaction to a cyclooxygenase-2 inhibitor in a patient who had a reaction to a cyclooxygenase-1 inhibitor. N. Engl. J. Med. 345, 1856.PubMedCrossRefGoogle Scholar
  44. 44.
    Vane, J. R. (2000), The fight against rheumatism: from willow bark to COX-1 sparing drugs. J. Physiol. Pharmacol. 51(4 Pt 1), 573–586.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  • Eva A. Berkes
    • 1
  1. 1.Sarasota Allergy and Asthma Specialty ClinicSarasota

Personalised recommendations