Skip to main content

Advertisement

Log in

Sulfonamide allergy and cross-reactivity

  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Concerns about cross-allergenicity between sulfonamide antibiotics and nonantibiotic sulfonamide-containing drugs continue to complicate pharmacotherapy. Several elegant investigations have demonstrated unequivocal lack of interaction between the sulfonamide group and either cellular or humoral immunity. The immunologic determinant of type I immunologic responses to sulfonamide antibiotics is the N1 heterocyclic ring, and nonantibiotic sulfonamides lack this structural feature. Many non-type I hypersensitivity responses to sulfonamide antibiotics are attributable to reactive metabolites that cause either direct cytotoxicity or humoral or cellular responses. Metabolite formation is stereospecific to the N4 amino nitrogen of the sulfonamide antibiotics, a structure not found on any nonantibiotic sulfonamide drugs. Cellular immune responses to sulfonamide antibiotics are responsible for many non-immunoglobulin E-mediated dermatologic reactions; however, the stereospecificity of T-cell response renders cross-reactivity between sulfonamide antibiotics and nonantibiotics highly unlikely. Apparent cross-reactivity responses to sulfonamide-containing drugs likely represent multiple concurrent, rather than linked, drug hypersensitivities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Tilles S: Practical issues in the management of hypersensitivity reactions: sulfonamides. South Med J 2001, 94:817–824.

    PubMed  CAS  Google Scholar 

  2. Kucera C, Greenberger P: Adverse drug reactions: treatment and prevention. Hosp Med 1996, 32:11–24.

    Google Scholar 

  3. Sullivan TJ, Ong RC, Gilliam LK: Studies of the multiple drug allergy syndrome. J Allergy Clin Immunol 1989, 83:270.

    Article  Google Scholar 

  4. Patterson R, Bello AE, Lefkowith J: Immunologic tolerability profile of celecoxib. Clin Ther 1999, 21:2065–2079.

    Article  PubMed  CAS  Google Scholar 

  5. Alfirevic A, Stalford AC, Viklar FJ, et al.: Slow acetylator phenotype and genotype in HIV-positive patients with sulfamethoxazole hypersensitivity. Br J Clin Pharmacol 2003, 55:158–165.

    Article  PubMed  CAS  Google Scholar 

  6. Bukhalo M, Zeitouni NC, Cheney RT: Leukocytoclastic vasculitis induced by use of glyburide: a case of possible cross-reaction of a sulfonamide and a sulfonylurea. Cutis 2003, 3:235–238.

    Google Scholar 

  7. Klinder KP, Harbilas JW, Johns TE: Drug-induced hematologic disorders. In Pharmacotherapy: A Pathophysiologic Approach, edn 5. Edited by Dipiro J, et al., New York: McGraw-Hill; 2002:1783–1795.

    Google Scholar 

  8. Kuby J, ed: Hypersensitivity reactions in immunology. In Immunology, edn 3. Philadelphia: W.H. Freeman and Co.; 1997:413–439.

  9. Leyva L, Torres MJ, Posadas S, et al.: Anticonvulsant-induced toxic epidermal necrolysis: monitoring the immunologic response. J Allergy Clin Immunol 2000, 105:157–165.

    Article  PubMed  CAS  Google Scholar 

  10. Fritsch PO, Sidoroff A: Drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis. Am J Clin Dermatol 2000, 1:349–360.

    Article  PubMed  CAS  Google Scholar 

  11. Cribb AE, Lee B, Trepanier L, Spielberg SP: Adverse reactions to sulphonamide and sulphonamide-trimethoprim antimicrobials: clinical syndromes and pathogenesis. Adverse Drug React Toxicol Rev 1996, 15:9–10.

    PubMed  CAS  Google Scholar 

  12. Roychowdhury S, Svensson CK: Mechanisms of drug-induced delayed type hypersensitivity reactions in the skin. AAPS J 2005, 7:E834–E846.

    Article  PubMed  CAS  Google Scholar 

  13. Kano Y, Inaoka M, Sakuma K, Shiohara T: Virus reactivation and intravenous immunoglobulin (IVIG) therapy of drug-induced hypersensitivity syndrome. Toxicology 2005, 209:165–167.

    Article  PubMed  CAS  Google Scholar 

  14. Hashimoto K, Yasukawa M, Tohyama M: Human herpesvirus 6 and drug allergy. Curr Opin Allergy Clin Immunol 2003, 3:255–260.

    Article  PubMed  CAS  Google Scholar 

  15. Harle DG, Baldo BA, Wells JV: Drugs as allergens: detection and combining site specificities of IgE antibodies to sulfamethoxazole. Mol Immunol 1988, 25:1347–1354.

    Article  PubMed  CAS  Google Scholar 

  16. Knowles S, Shapiro L, Shear N: Should celecoxib be contraindicated in patients who are allergic to sulfonamides? Revisiting the meaning of “sulfa” allergy. Drug Saf 2001, 24:239–247.

    Article  PubMed  CAS  Google Scholar 

  17. Carrington DM, Earl HS, Sullivan TJ: Studies of human IgE to a sulfonamide determinant. J Allergy Clin Immunol 1987, 79:442–447.

    Article  PubMed  CAS  Google Scholar 

  18. Hansbrough JR, Wedner HJ, Chaplin DD: Anaphylaxis to intravenous furosemide. J Allergy Clin Immunol 1987, 80:538–541.

    Article  PubMed  CAS  Google Scholar 

  19. Verdel BM, Souverein PC, Egberts AC, Leufkens HG: Difference in risks of allergic reaction to sulfonamide drugs based on chemical structure. Ann Pharmacother 2006, 40:1040–1046.

    Article  PubMed  CAS  Google Scholar 

  20. Ernst EJ, Egge JA: Celecoxib-induced erythem a multiforme with glyburide cross-reactivity. Pharmacotherapy 2002, 22:637–640.

    Article  PubMed  Google Scholar 

  21. Curtis BR, Mcfarland JG, Wu GG, et al.: Antibodies in sulfonamide-induced immune thrombocytopenia recognize calcium-dependent epitopes on the glycoprotein IIb/IIIa complex. Blood 1994, 84:176–183.

    PubMed  CAS  Google Scholar 

  22. Bedard K, Smith S, Cribb A: Sequential assessment of an antidrug antibody response in a patient with a systemic delayed-onset sulphonamide hypersensitivity syndrome reaction. Br J Dermatol 2000, 142:253–258.

    Article  PubMed  CAS  Google Scholar 

  23. Gruchalla RS: Diagnosis of allergic reactions to sulfonamides. Allergy 1999, 54:28–32.

    Article  PubMed  Google Scholar 

  24. Friedmann PS, Lee MS, Friedmann AC, Barnetson RS: Mechanisms in cutaneous drug hypersensitivity reactions. Clin Exp Allergy 2003, 33:861–872.

    Article  PubMed  CAS  Google Scholar 

  25. Hess DA, Sisson ME, Suria H, et al.: Cytotoxicity of sulfonamide reactive metabolites: apoptosis and selective toxicity of CD8(+) cells by the hydroxylamine of sulfamethoxazole. FASEB J 1999, 13:1688–1698.

    PubMed  CAS  Google Scholar 

  26. Gruchalla RS, Pesenko RD, Do TT, Skiest DJ: Sulfonamide-induced reactions in desensitized patients with AIDS—the role of covalent protein haptenation by sulfamethoxazole. J Allergy Clin Immunol 1998, 101:371–378.

    Article  PubMed  CAS  Google Scholar 

  27. Wulferink M, Dierkes S, Gleichmann E: Cross-sensitization to haptens: formation of common haptenic metabolites, T cell recognition of cryptic peptides, and true T cell cross-reactivity. Eur J Immunol 2002, 32:1338–1348.

    Article  PubMed  CAS  Google Scholar 

  28. Farrell J, Naisbitt DJ, Drummond NS, et al.: Characterization of sulfamethoxazole and sulfamethoxazole metabolite-specific T-cell responses in animals and humans. J Pharmacol Exp Ther 2003, 306:229–237.

    Article  PubMed  CAS  Google Scholar 

  29. Schnyder B, Burkhart C, Schnyder-Frutig K, et al.: Recognition of sulfamethoxazole and its reactive metabolites by drug-specific CD4 + T cells from allergic individuals. J Immunol 2000, 164:6647–6654.

    PubMed  CAS  Google Scholar 

  30. Kaur C, Sarkar R, Kanwar A: Fixed drug eruption to rofecoxib with cross-reactivity to sulfonamides [letter]. Dermatology 2001, 203:351.

    Article  PubMed  CAS  Google Scholar 

  31. Sarkar R, Kaur C, Kanwar A: Extensive fixed drug eruption to nimesulide with cross-sensitivity to sulfonamides in a child. Pediatr Dermatol 2002, 6:553–554.

    Article  Google Scholar 

  32. Nassif A, Bensussan A, Boumsell L, et al.: Toxic epidermal necrolysis: effector cells are drug-specific cytotoxic T cells. J Allergy Clin Immunol 2004, 114:1209–1215.

    Article  PubMed  CAS  Google Scholar 

  33. Johnson KK, Green DL, Rife JP, Limon L: Sulfonamide cross-reactivity: fact or fiction? Ann Pharmacother 2005, 39:290–301.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carolyn C. Brackett PharmD, BCPS.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brackett, C.C. Sulfonamide allergy and cross-reactivity. Curr Allergy Asthma Rep 7, 41–48 (2007). https://doi.org/10.1007/s11882-007-0029-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-007-0029-8

Keywords

Navigation