Drug Safety

, Volume 12, Issue 4, pp 283–290 | Cite as

Drug-Induced Lupus

  • Elizabeth J. Price
  • Patrick J. W. Venables
Review Article Pharmacoepidemiology

Summary

Drug-induced lupus is a syndrome resembling mild systemic lupus erythematosus which can complicate treatment with certain apparently unrelated therapies. The most common individual agents are procainamide and hydralazine. Drugs less frequently associated with the disease are chlorpromazine, isoniazid, methyldopa, penicillamine, quinidine and sulfasalazine. Whole drug groups have also been implicated, such as the anticonvulsants, β-blockers, sulfonamides and some of the newer ‘biological’ agents.

The syndrome is characterised by arthralgia, myalgia, pleurisy, rashes and fever in association with antinuclear antibodies in the serum. More serious features of idiopathic lupus such as nephritis and cerebral disease are rare in drug-induced disease. The pathogenesis is unknown but in some cases is thought to be due to interactions between the drug and DNA or histones, rendering them immunogenic. For the biological agents, including interferons and antibodies to tumour necrosis factor-α, it has been suggested that it is due to disruption of the cytokine network.

Although extremely rare, recognition of drug-induced lupus is important because it reverts within a few weeks of stopping the drug. It is possible that understanding its pathogenesis may shed light on its more serious relative, systemic lupus erythematosus.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Tan EM, Cohen ES, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–7PubMedCrossRefGoogle Scholar
  2. 2.
    Hoffman BJ. Sensitivity of sulfadiazine resembling acute disseminated lupus erythematosus. Arch Dermatol Syph 1945; 51: 190–2CrossRefGoogle Scholar
  3. 3.
    Gold S. Role of sulphonamides and penicillin in the pathogenesis of systemic lupus erythematosus. Lancet 1951; 1: 268–72PubMedCrossRefGoogle Scholar
  4. 4.
    Morrow JD, Schroeder HA, Perry HM. Studies on the control of hypertension by Hyphex: II. Toxic reactions and side effects. Circulation 1953; 8: 829–39PubMedCrossRefGoogle Scholar
  5. 5.
    Lindqvist T. Lupus erythematosus disseminatus after administration of mesantoin. Report of two cases. Acta Med Scand 1957; 158: 131–8PubMedCrossRefGoogle Scholar
  6. 6.
    Benton JW, Tynes B, Register HB. Systemic lupus erythematosus occurring during anticonvulsant drug therapy. JAMA 1962; 180: 115CrossRefGoogle Scholar
  7. 7.
    Ladd AT. Procainamide-induced lupus erythematosus. N Engl J Med 1962; 267: 1357–8PubMedCrossRefGoogle Scholar
  8. 8.
    Cannat A, Seligmann M. Possible induction of antinuclear antibodies by isoniazid. Lancet 1966; 1: 185–7PubMedCrossRefGoogle Scholar
  9. 9.
    Yung RL, Richardson BC. Drug-induced lupus. Rheum Dis Clin North Am 1994; 20(1): 61–86PubMedGoogle Scholar
  10. 10.
    Blomgren SE, Condemi JJ, Vaughan JH. Procainamide-induced lupus erythematosus. Clinical and laboratory observations. Am J Med 1972; 52: 338–48PubMedCrossRefGoogle Scholar
  11. 11.
    Mansilla-Tinoco R, Harland SJ, Ran PJ. Hydralazine, antinuclear antibodies and the lupus syndrome. BMJ 1982; 284: 936–9PubMedCrossRefGoogle Scholar
  12. 12.
    Vivino FB, Schumacher HR. Synovial fluid characteristics and the lupus erythematosus cell phenomenon in drug-induced lupus. Finding in three patients and review of the literature. Arthritis Rheum 1989; 32: 560–8PubMedCrossRefGoogle Scholar
  13. 13.
    Utsinger PD, Zvaifler NJ, Bluestein HG. Hypocomplementemia in procainamide-associated systemic lupus erythematosus. Ann Intern Med 1976; 84: 293PubMedGoogle Scholar
  14. 14.
    Alarcon-Segovia D, Kraus A. Drug-related lupus syndromes and their relationship to spontaneously occurring systemic lupus erythematosus [review]. Baillieres Clin Rheumatol 1991; 5(1): 1–12PubMedCrossRefGoogle Scholar
  15. 15.
    Cush JJ, Goldings EA. Drug-induced lupus: clinical spectrum and pathogenesis. Am J Med Sci 1985; 290: 36–45PubMedCrossRefGoogle Scholar
  16. 16.
    Alarcon-Segovia D, Wakim KG, Worthington JW. Clinical and experimental studies on the hydralazine syndrome and its relationship to systemic lupus erythematosus. Medicine 1967; 46: 1–33PubMedCrossRefGoogle Scholar
  17. 17.
    Cameron HA, Ramsay LE. The lupus syndrome induced by hydralazine: a common complication with low dose treatment. BMJ 1984; 289: 410–2PubMedCrossRefGoogle Scholar
  18. 18.
    Hess EV, Mongey AB. Drug-related lupus. Bull Rheum Dis 1991; 40(4): 1–8PubMedGoogle Scholar
  19. 19.
    Sinclair AJ, Warrington SJ. Severe renal failure in hydralazine-induced lupus. Hum Toxicol 1981; 1: 65–9PubMedCrossRefGoogle Scholar
  20. 20.
    Grossman J, Callerame ML, Condemi JJ. Skin immunofluorescence studies on lupus erythematosus and other antinuclear-antibody-positive diseases. Ann Intern Med 1974; 76: 365–74Google Scholar
  21. 21.
    Ahmad S. Procainamide and peripheral neuropathy. South Med J 1981; 74: 509–10PubMedCrossRefGoogle Scholar
  22. 22.
    Chong WK, Dewhurst AG, Dathan JR. Acute laryngeal stridor with respiratory arrest in drug-induced systemic lupus erythematosus. BMJ 1988; 297: 660–1PubMedCrossRefGoogle Scholar
  23. 23.
    Ihle BU, Whitworth JA, Dowling JP. Hydralazine and lupus nephritis. Clin Nephrol 1984; 22: 230–8PubMedGoogle Scholar
  24. 24.
    Doherty M, Maddison PJ, Grey RH. Hydralazine induced lupus syndrome with eye disease. Br Med J Clin Res Ed 1985; 290: 675PubMedCrossRefGoogle Scholar
  25. 25.
    Nichols CJ, Mieler WF. Severe retinal vaso-occlusive disease secondary to procainamide-induced lupus. Ophthalmology 1989; 96: 1535–40PubMedGoogle Scholar
  26. 26.
    Jackson C, Phillips PE. Procainamide-induced lupus with vasculitis. Clin Exp Rheumatol 1986; 4: 290–2PubMedGoogle Scholar
  27. 27.
    Martinez-Vea A, Ferrer I, Carcia C. Systemic vasculitis resembling polyarteritis nodosa in the lupus-like syndrome induced by hydralazine. Am J Nephrol 1987; 7: 71–3PubMedCrossRefGoogle Scholar
  28. 28.
    Drory VE, Korczyn AD. Hypersensitivity vasculitis and systemic lupus erythematosus induced by anticonvulsants. Clin Neuropharmacol 1993; 16(1): 19–29PubMedCrossRefGoogle Scholar
  29. 29.
    Hughes GRV, Pynes RI, Gharavi A, et al. The heterogeneity of serological findings and predisposing host factors in drug-induced lupus erythematosus. Arthritis Rheum 1987; 24(8): 1070–3CrossRefGoogle Scholar
  30. 30.
    Gioud M, Kaci MA, Monier JC. Histone antibodies in systemic lupus erythematosus. A possible diagnostic tool. Arthritis Rheum 1982; 25: 407–13PubMedCrossRefGoogle Scholar
  31. 31.
    Burlingame RW, Rubin RL. Drug-induced anti-histone antibodies display two patterns of reactivity with substructures of chromatin. J Clin Invest 1991; 88: 680–90PubMedCrossRefGoogle Scholar
  32. 32.
    Portanova JP, Arndt RE, Tan EM, et al. Anti-histone antibodies in idiopathic and drug-induced lupus recognise distinct intrahistone regions. J Immunol 1987; 138: 446–51PubMedGoogle Scholar
  33. 33.
    McNeil HP, Chesterman CN, Krilis SA. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 1991; 49: 193–280PubMedCrossRefGoogle Scholar
  34. 34.
    Zarrabi M, Zucker S, Miller F. Immunological and coagulation disorders in chlorpromazine treated patients. Ann Intern Med 1979; 91: 194–9PubMedGoogle Scholar
  35. 35.
    Derksen RHWM, Kater L. Lupus anticoagulant: Revival of an old phenomenon. Clin Exp Rheumatol 1985; 3: 349–57PubMedGoogle Scholar
  36. 36.
    Canoso RT, de Oliveira RM. Chlorpromazine-induced lupus anticardiolipin antibodies and lupus anticoagulant: absence of thrombosis. Am J Haematol 1988; 27: 272–5CrossRefGoogle Scholar
  37. 37.
    Rogers HJ, Spector RG, Trounce JR. A textbook of clinical pharmacology. London: Hodder & Stoughton Educational, 1981: 396–432Google Scholar
  38. 38.
    Mongey AB, Donovan-Brand R, Thomas TJ, et al. Serological evaluation of patients receiving procainamide. Arthritis Rheum 1992; 35(2): 219–23PubMedCrossRefGoogle Scholar
  39. 39.
    Sturman SG, Kumararatne D, Beevers DG. Fatal hydralazine induced systemic lupus erythematosus. Lancet 1988; 2: 1304PubMedCrossRefGoogle Scholar
  40. 40.
    Alarcon-Segovia D. Acute immunologic hydralazine reaction. Clinical and serological changes after hydralazine administration to a patient with circulating antinuclear antibodies. Rev Invest Clin 1972; 24: 167–74PubMedGoogle Scholar
  41. 41.
    Butikofer P, Lin ZW, Kuypers FA. Chlorpromazine inhibits vesiculation, alters phosphoinositide turnover and changes deformability of ATP-depleted RBCs. Blood 1989; 73: 1699–704PubMedGoogle Scholar
  42. 42.
    Steen VD, Ramse-Goldman R. Phenothiazine-induced systemic lupus erythematosus with superior vena cava syndrome: case report and review of the literature. Arthritis Rheum 1988; 31: 923–6PubMedCrossRefGoogle Scholar
  43. 43.
    Kendall MJ, Hawkins CF. Quinidine-induced systemic lupus erythematosus. Postgrad Med J 1970; 46: 729–31PubMedCrossRefGoogle Scholar
  44. 44.
    West SG, McMahon M, Portanova JP. Quinidine-induced lupus erythematosus. Ann Intern Med 1981; 100: 840–2Google Scholar
  45. 45.
    Cohen MG, Kevat S, Prowse MV, et al. Two distinct quinidine-induced rheumatic syndromes. Ann Intern Med 1988; 108: 369–71PubMedGoogle Scholar
  46. 46.
    Ronnblom LE, Alm GV, Oberg KE. Autoimmunity after alpha-interferon therapy for malignant carcinoid tumours. Ann Intern Med 1991; 115: 178–83PubMedGoogle Scholar
  47. 47.
    Machold KP, Smolen JS. Interferon-gamma induced exacerbation of systemic lupus erythematosus. J Rheumatol 1990; 17: 831–2PubMedGoogle Scholar
  48. 48.
    Graninger WB, Hassfeld W, Pesau BB, et al. Induction of systemic lupus erythematosus by interferon-gamma in a patient with rheumatoid arthritis. J Rheumatol 1991; 18(10): 1621–2PubMedGoogle Scholar
  49. 49.
    Maini RN, Elliot MJ, Charles PJ, et al. Immunological intervention reveals reciprocal roles for TNFα and IL-10 in rheumatoid arthritis and SLE. Springer Semin Immunopathol. In pressGoogle Scholar
  50. 50.
    Mills JA. Systemic lupus erythematosus. N Engl J Med 1994; 330(26): 1871–9PubMedCrossRefGoogle Scholar
  51. 51.
    Arnett FC. Genetic aspects of human lupus. Clin Immunol Immunopathol 1992; 63: 4–6PubMedCrossRefGoogle Scholar
  52. 52.
    Speirs C, Fielder AH, Chapel H, et al. Complement system protein C4 and susceptibility to hydralazine-induced systemic lupus erythematosus. Lancet 1989; 1: 922–4PubMedCrossRefGoogle Scholar
  53. 53.
    Gatenby PA. The role of complement in the aetiopathogenesis of systemic lupus erythematosus. Autoimmunity 1991; 11: 61–6PubMedCrossRefGoogle Scholar
  54. 54.
    Thomas TJ, Messner RP. Effects of lupus-inducing drugs on the B to Z transition of synthetic DNA. Arthritis Rheum 1986; 29(5): 638–45PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • Elizabeth J. Price
    • 1
  • Patrick J. W. Venables
    • 1
  1. 1.Matilda and Terence Kennedy Institute of RheumatologyHammersmith LondonEngland

Personalised recommendations