Current Allergy and Asthma Reports

, Volume 5, Issue 1, pp 9–14 | Cite as

Update on beta-lactam allergy diagnosis

  • Pascal Demoly
  • Antonino Romano


Allergic reactions to penicillin and cephalosporin antibiotics are common. The mechanisms involved are heterogeneous and not yet completely understood. However, clinical and immunologic studies suggest that type I (IgE-mediated) and type IV (cellmediated) pathogenic mechanisms are involved in most immediate and non-immediate reactions, respectively. The diagnostic procedure has recently been standardized under the aegis of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interest group on drug hypersensitivity. In this review, we describe the general guidelines for evaluating subjects in whom there is suspicion of allergic reactions to β-lactams.


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References and Recommended Reading

  1. 1.
    Johansson S, Hourihane J, Bousquet J, et al.: A revised nomenclature for allergy: an EAACI position statement from the EAACI nomenclature task force. Allergy 2001, 56:813–824.PubMedCrossRefGoogle Scholar
  2. 2.
    Levine BB: Immunologic mechanisms of penicillin allergy: a haptenic model system for the study of allergic diseases of man. N Engl J Med 1966, 275:1115–1125.PubMedCrossRefGoogle Scholar
  3. 3.
    Torres MJ, Blanca M, Fernandez J, et al.: Diagnosis of immediate reactions to beta-lactam antibiotics. Allergy 2003, 58:961–972.Practical guidelines on β-lactam allergy diagnosis (when reactions occurred within the first hour after drug administration).PubMedCrossRefGoogle Scholar
  4. 4.
    Romano A, Blanca M, Torres MJ, et al.: Diagnosis of nonimmediate reactions to beta-lactam antibiotics. Allergy 2004, 59:1153–1160.Practical guidelines on β-lactam allergy diagnosis (when reactions occurred more than 1 hour after drug administration).PubMedCrossRefGoogle Scholar
  5. 5.
    Saxon A: Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann Intern Med 1987, 107:204–215.PubMedGoogle Scholar
  6. 6.
    Weiss ME, Adkinson NF: Immediate hypersensitivity reactions to penicillin and related antibiotics. Clin Allergy 1988, 18:515–840.PubMedCrossRefGoogle Scholar
  7. 7.
    Bachot N, Roujeau JC: Differential diagnosis of severe cutaneous drug eruptions. Am J Clin Dermatol 2003, 4:561–572.PubMedCrossRefGoogle Scholar
  8. 8.
    Pichler WJ: Delayed drug hypersensitivity reactions. Ann Intern Med 2003, 139:683–693.Outstanding proposal for a revision of the Gell and Coombs classification when applied to drug allergy.PubMedGoogle Scholar
  9. 9.
    Demoly P, Bousquet J: Epidemiology of drug allergy. Curr Opin Allergy Clin Immunol 2001, 1:305–310.PubMedGoogle Scholar
  10. 10.
    Primeau MN, Adkinson NF Jr: Recent advances in the diagnosis of drug allergy. Curr Opin Allergy Clin Immunol 2001, 1:337–341.PubMedGoogle Scholar
  11. 11.
    Gruchalla RS: Clinical assessment of drug-induced disease. Lancet 2000, 356:1505–1511.PubMedCrossRefGoogle Scholar
  12. 12.
    Demoly P, Kropf R, Bircher A, Pichler WJ: Drug hypersensitivity questionnaire. Allergy 1999, 54:999–1003.PubMedCrossRefGoogle Scholar
  13. 13.
    Brockow K, Romano A, Blanca M, et al.: General considerations for skin test procedures in the diagnosis of drug hypersensitivity. Allergy 2002, 57:45–51.PubMedCrossRefGoogle Scholar
  14. 14.
    Blanca M, Mayorga C, Torres MJ, et al.: Clinical evaluation of Pharmacia CAP System RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy. Allergy 2001, 56:862–870.PubMedCrossRefGoogle Scholar
  15. 15.
    Nyfeler B, Pichler WJ: The lymphocyte transformation test for the diagnosis of drug allergy: sensitivity and specificity. Clin Exp Allergy 1997, 27:175–181.PubMedCrossRefGoogle Scholar
  16. 16.
    Sanz ML, Gamboa PM, Antepara I, et al.: Flow cytometric basophil activation test by detection of CD63 expression in patients with immediate-type reactions to beta-lactam antibiotics. Clin Exp Allergy 2002, 32:277–286.PubMedCrossRefGoogle Scholar
  17. 17.
    Aberer W, Bircher A, Romano A, et al.: Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Allergy 2003, 58:854–863.PubMedCrossRefGoogle Scholar
  18. 18.
    Messaad D, Sahla H, Benahmed S, et al.: Drug provocation tests in patients with a history suggesting an immediate drug hypersensitivity reaction. Ann Intern Med 2004, 140:1001–1006.PubMedGoogle Scholar
  19. 19.
    Moore N, Biour M, Paux G, et al.: Adverse drug reaction monitoring: doing it the French way. Lancet 1985, 2:1056–1058.PubMedCrossRefGoogle Scholar
  20. 20.
    Jones JK: Criteria for journal reports of suspected drug reactions. Clin Pharm 1982, 1:554–555.PubMedGoogle Scholar
  21. 21.
    Naranjo CA, Busto U, Sellers EM, et al.: A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981, 30:239–245.PubMedCrossRefGoogle Scholar
  22. 22.
    Kramer MS, Leventhal JM, Hutchinson TA, Feinstein AR: An algorithm for the operational assessment of adverse drug reactions. I. Background, description, and instructions for use. JAMA 1979, 242:623–632.PubMedCrossRefGoogle Scholar
  23. 23.
    Haverkos HV, Amsel Z, Drotman P: Adverse virus-drug interactions. Rev Infect Dis 1991, 13:697–704.PubMedGoogle Scholar
  24. 24.
    Cars O, Molstad S, Melander A: Variation in antibiotic use in the European Union. Lancet 2001, 357:1851–1853.PubMedCrossRefGoogle Scholar
  25. 25.
    McCaig L, Hughes JM: Trends in antimicrobial drug prescribing among office-based physicians in the United States. JAMA 1995, 273:214–219.PubMedCrossRefGoogle Scholar
  26. 26.
    Guillemot D, Maison P, Carbon C, et al.: Trends in antimicrobial drug use in the community-France, 1981–1992. J Infect Dis 1998, 177:492–497.PubMedCrossRefGoogle Scholar
  27. 27.
    Blanca M, Mayorga C, Torres MJ, et al.: Side chain specific reactions to beta-lactams: fourteen years later. Clin Exp Allergy 2002, 32:192–197.PubMedCrossRefGoogle Scholar
  28. 28.
    Torres MJ, Romano A, Mayorga C, et al.: Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing. Allergy 2001, 56:850–856.PubMedCrossRefGoogle Scholar
  29. 29.
    Chandra RK, Joglekar SA, Tomas E: Penicillin allergy: antipenicillin IgE antibodies and immediate hypersensitivity skin reactions employing major and minor determinants of penicillin. Arch Dis Child 1980, 55:857–860.PubMedGoogle Scholar
  30. 30.
    Blanca M, Torres MJ, García JJ, et al.: Natural evolution of skin test sensitivity in patients allergic to beta-lactam antibiotics. J Allergy Clin Immunol 1999, 103:918–924.PubMedCrossRefGoogle Scholar
  31. 31.
    Redmond AP, Levine BB: Delayed skin reactions to benzylpenicillin in man. Int Arch Allergy 1968, 33:193–206.PubMedGoogle Scholar
  32. 32.
    Aihara M, Ikezawa Z: Evaluation of the skin test reactions with delayed type rash induced by penicillins and cephalosporins. J Dermatol 1987, 14:440–448.PubMedGoogle Scholar
  33. 33.
    Romano A, Di Fonso M, Papa G, et al.: Evaluation of adverse cutaneous reactions to aminopenicillins with emphasis on those manifested by maculopapular rashes. Allergy 1995, 50:113–118.PubMedCrossRefGoogle Scholar
  34. 34.
    Romano A, Quaratino D, Di Fonso M, et al.: A diagnostic protocol for evaluating nonimmediate reactions to aminopenicillins. J Allergy Clin Immunol 1999, 103:1186–1190.PubMedCrossRefGoogle Scholar
  35. 35.
    Romano A, Viola M, Mondino C, et al.: Diagnosing nonimmediate reactions to penicillins by in vivo tests. Int Arch Allergy Immunol 2002, 129:169–174.PubMedCrossRefGoogle Scholar
  36. 36.
    Torres MJ, Sánchez-Sabate E, Álvarez J, et al.: Skin test evaluation in nonimmediate allergic reactions to penicillins. Allergy 2004, 59:219–224.PubMedCrossRefGoogle Scholar
  37. 37.
    Lebel B, Messaad D, Kvedariene V, et al.: Cysteinyl-leukotriene release test (CAST) in the diagnosis of immediate drug reactions. Allergy 2001, 56:688–692.PubMedCrossRefGoogle Scholar
  38. 38.
    Pichler WJ, Tilch J: The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy 2004, 59:809–820.PubMedCrossRefGoogle Scholar
  39. 39.
    Green GR, Rosenblum AH, Sweet LC: Evaluation of penicillin hypersensitivity: value of clinical history and skin testing with penicilloyl-polylysine and penicillin G. A comparative prospective study of the penicillin study group of the American Academy of Allergy. J Allergy Clin Immunol 1977, 60:339–345.PubMedCrossRefGoogle Scholar
  40. 40.
    Mendelson LM, Ressler C, Rosen JP, Selcow JE: Routine elective penicillin allergy skin testing in children and adolescents: study of sensitization. J Allergy Clin Immunol 1984, 73:76–81.PubMedCrossRefGoogle Scholar
  41. 41.
    Parker PJ, Parrinello JT, Condemi JJ, Rosenfeld S: Penicillin resensitization among hospitalized patients. J Allergy Clin Immunol 1991, 88:213–217.PubMedCrossRefGoogle Scholar
  42. 42.
    López-Serrano MC, Caballero MT, Barranco P, Martínez-Alzamora F: Booster responses in the study of allergic reactions to beta-lactam antibiotics. J Invest Allergol Clin Immunol 1996, 6:30–35.Google Scholar
  43. 43.
    Pichichero ME, Pichichero DM: Diagnosis of penicillin, amoxicillin, and cephalosporin allergy: reliability of examination assessed by skin testing and oral challenge. J Pediatr 1998, 132:137–43.PubMedCrossRefGoogle Scholar
  44. 44.
    Romano A, Guéant-Rodriguez RM, Viola M, et al.: Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins. Ann Intern Med 2004, 141:16–22.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2005

Authors and Affiliations

  • Pascal Demoly
    • 1
  • Antonino Romano
    • 1
  1. 1.Exploration des Allergies, Maladies Respiratoires, INSERM U454-IFR3, Hôpital Arnaud de VilleneuveUniversity Hospital of MontpellierMontpellier Cedex 5France

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