Drug-Induced Autoimmunity

  • Martine Szyper-Kravitz
  • Yehuda Shoenfeld


Drug-induced autoimmunity encompasses a wide range of serological and clinical manifestations that develop after exposure to a drug. The classical and most studied example is drug-induced lupus (DIL). Although autoimmunity secondary to drugs has been recognized for more than 50 years, the introduction of new drugs has extended the spectrum and severity of clinical manifestations. Several drugs are associated with the induction of antinuclear and anti-DNA antibodies, but clinical lupus is rare, and a number of drugs are associated with antineutrophilic cytoplasmic antibody (ANCA)-positive vasculitis. The diagnosis of these conditions is not simple and requires careful elimination of other possible conditions. Although rare cases of life-threatening autoimmune conditions have been described, the majority of cases are mild and resolve after the offending drug is discontinued.


Drug-induced idiosyncratic reactions drug-induced lupus 


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  1. 1.
    Yung RL, Richardson BC. Drug-induced lupus. Rheum Dis Clin North Am 1994; 20: 61–86.PubMedGoogle Scholar
  2. 2.
    Vial T, Nicolas B, Descortes J. Drug-induced autoimmunity: Experience of the French Pharmacovigilance system. Toxicology 1997; 119: 23–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Price EJ, Venables PJW. Drug-induced lupus. Drug Saf 1995; 1: 283–90.CrossRefGoogle Scholar
  4. 4.
    Kretz-Rommel A, Rubin RL. Disruption of positive selection of thymocytes causes autoimmunity. Nat Med 2000; 6: 298–305.CrossRefPubMedGoogle Scholar
  5. 5.
    Bucy RP, Xu XY, Li J, Huang GO. Cyclosporine A-induced autoimmune disease in mice. J Immunol 1993; 151: 1039–50.PubMedGoogle Scholar
  6. 6.
    Oelke K, Lu O, Richardson D, Wu A, Deng C, Hanash S, Richardson B. Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors. Arthritis Rheum 2004; 50: 1850–60.CrossRefPubMedGoogle Scholar
  7. 7.
    Pichler WJ. Drug-induced autoimmunity. Curr Opin Allergy Clin Immunol 2003; 3: 249–53.CrossRefPubMedGoogle Scholar
  8. 8.
    Rao T, Richardson B. Environmentally induced autoimmune diseases: Potential mechanisms. Environ Health Perspect 1999; 107(Suppl. 5): 737–42.CrossRefPubMedGoogle Scholar
  9. 9.
    Uetrecht JP. Idiosyncratic drug-reactions: Current understanding. Annu Rev Pharmacol Toxicol 2007; 47: 13–39.CrossRefGoogle Scholar
  10. 10.
    Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol 1994; 12: 991–1045.PubMedGoogle Scholar
  11. 11.
    Rubin RL. Drug-induced lupus. Toxicology 2005; 209: 135–47.CrossRefPubMedGoogle Scholar
  12. 12.
    Yung R, Richardson B. Drug-induced rheumatic syndromes. Bull Rheum Dis 2002; 51. 1–6.Google Scholar
  13. 13.
    Elkayam O, Yaron M, Caspi D. Minocycline-induced autoimmune syndromes: An overview. Semin Arthritis Rheum 1999; 28: 392–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Aloush V, Litinsky I, Caspi D, Elkayam O. Propylthiouracil-induced autoimmune syndromes: Two distinct clinical presentations with different course and management. Semin Arthritis Rheum 2006; 36: 4–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Masi A, Hamilos DL. Leukotriene antagonists: Bystanders or causes of Churg-Strauss syndrome. Semin Arthritis Rheum 2002; 31: 211–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Oppenheim Y, Ban Y, Tomer Y. Interferon induced autoimmune thyroid disease (AITD): A model for human autoimmunity. Autoimmun Rev 2004; 3: 388–93.CrossRefPubMedGoogle Scholar
  17. 17.
    De Bandt M, Sibilia J, Le Loët X, Prouzeau S, Fautrel B, Marcelli C, Boucquillard E, Siame JL, Mariette X. Systemic lupus erythematosus induced by anti-tumour necrosis factor alpha therapy: A French national survey. Arthritis Res Ther 2005; 7: R545–51.CrossRefPubMedGoogle Scholar
  18. 18.
    De Rycke L, Kruithof E, Van Damme N, Hoffman IE, Van den Bossche N, Van den Bosch F, Veys EM, De Keyser F. Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy. Arthritis Rheum 2003; 48: 1015–23.CrossRefPubMedGoogle Scholar
  19. 19.
    Ioannou Y, Isenberg DA. Review: Current evidence for the induction of autoimmune rheumatic manifestations by cytokine therapy. Arthritis Rheum 2000; 43: 1431–41.CrossRefPubMedGoogle Scholar
  20. 20.
    Centocor, Inc. Remicade (infliximab). Data on file. Malvern, PA, USA: Centocor, Inc.Google Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Martine Szyper-Kravitz
    • 1
  • Yehuda Shoenfeld
    • 2
    • 3
  1. 1.Center for Autoimmune Diseases and, Department of Medicine B, Chaim Sheba Medical Center Tel-Hashomer, Sackler Faculty of MedicineTel Aviv UniversityIsrael
  2. 2.Department of Medicine B, Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, And Sackler Faculty of MedicineTel Aviv UniversityIsrael
  3. 3.Incumbent of the Laura Schwartz Kipp Chair, for Research of Autoimmune DiseasesTel Aviv UniversityIsrael

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