Drug-Induced Lupus Erythematosus

  • Jack Uetrecht


Systemic Lupus Erythematosus Aromatic Amine Reactive Metabolite Acetylator Phenotype Autoimmune Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams LE, Hess EV (1991) Drug-related lupus. Drug Safety 6:431–449PubMedGoogle Scholar
  2. Alarcon-Segovia D, Fishbein E, Reyes PA, Dies H, Shwadsky S (1972) Antinuclear antibodies in patients on anticonvulsant therapy. Clin Exp Immunol 12:39–47PubMedGoogle Scholar
  3. Alloway JA, Salata MP (1995) Quinidine-induced rheumatic syndromes. Semin Arthritis Rheum 24:315–322CrossRefPubMedGoogle Scholar
  4. Amrhein JA, Kenny FM, Ross D (1970) Granulocytopenia, lupus-like syndrome, and other complications of propylthiouracil therapy. J Pediatr 76:54–63PubMedGoogle Scholar
  5. Aucoin DP, Peterson ME, Hurvitz AI, Drayer DE, Lahita RG, Quimby FW, Reidenberg MM (1985) Propylthiouracil-induced immune-mediated disease in the cat. J Pharmacol Exp Ther 234:13–18PubMedGoogle Scholar
  6. Aucoin DP, Rubin RL, Peterson ME, Reidenberg MM, Drayer DE, Hurvitz AI, Lahita RG (1988) Dose-dependent induction of anti-native DNA antibodies in cats by propylthiouracil. Arthritis Rheum 31:688–692PubMedGoogle Scholar
  7. Batchelor JR, Welsh KI, Tinoco RM, Dollery CT, Hughes GR, Bernstein R, Ryan P, Naish PF, Aber GM, Bing RF, Russel GI (1980) Hydralazine-induced systemic lupus erythematosus: influence of HLA-DR and sex on susceptibility. Lancet 1:1107–1109CrossRefPubMedGoogle Scholar
  8. Beernink DH, Miller JJ (1973) Anticonvulsant-induced antinuclear antibodies and lupus-like disease in children. J Pediatr 82:113–117PubMedGoogle Scholar
  9. Blomgren SE, Condemi JJ, Vaughn JH (1972) Procainamide-induced lupus erythematosus: clinical and laboratory observations. Am J Med 52:338–348CrossRefPubMedGoogle Scholar
  10. Booth RJ, Wilson JD, Bullock JY (1982) β-Adrenergic-receptor blockers and antinuclear antibodies in hypertension. Clin Pharmacol Ther 31:555–558PubMedGoogle Scholar
  11. Brand C, Davidson A, Littlejohn G, Ryan P (1984) Hydralazine-induced lupus: no association with HLA-DR4. Lancet 1:462CrossRefGoogle Scholar
  12. Burlingame RW, Rubin RL (1991) Drug-induced anti-histone autoantibodies display two patterns of reactivity with substructures of chromatin. J Clin Invest 88:680–690PubMedGoogle Scholar
  13. Cameron HA, Ramsay LE (1984) The lupus syndrome induced by hydralazine: a common complication with low dose therapy. Br Med J 289:410–412Google Scholar
  14. Canoso R, Lewis M, Yunis E (1982) Association of HLA-Bw44 with chlorpromazine-induced autoantibodies. Clin Immunol Immunopathol 25:278–282PubMedGoogle Scholar
  15. CAST (1989) Preliminary report: Effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med 321:406–412Google Scholar
  16. Charles PJ, Smeenk RJ, De Jong J, Feldmann M, Maini RN (2000) Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, A monoclonal antibody to tumor necrosis factor alpha: findings in open-label and randomized placebo-controlled trials. Arthritis Rheum 43:2383–2390CrossRefPubMedGoogle Scholar
  17. Chin G, Kong N, Lee B, Rose I (1991) Penicillamine induced lupus-like syndrome in a patient with classical rheumatoid arthritis. J Rheumatol 18:947–948PubMedGoogle Scholar
  18. Christie DJ, Mullen PC, Aster RH (1985) Fab-mediated binding of drug-dependent antibodies to platelets in quinidine-and quinine-induced thrombocytopenia. J Clin Invest 75:310–314PubMedGoogle Scholar
  19. Cornacchia E, Golbus J, Maybaum J, Strahler J, Hanash S, Richardson B (1988) Hydralazine and procainamide inhibit T cell DNA methylation and induce autoreactivity. J Immunol 140:2197–2200PubMedGoogle Scholar
  20. Derksen R, Kater L (1985) Lupus anticoagulant: revival of an old phenomenon. Clin Exp Rheumatol 3:349–357PubMedGoogle Scholar
  21. Donker AJ, Venuto RC, Vladutiu AO, Brentjens JR, Andres GA (1984) Effects of prolonged administration of D-penicillamine or captopril in various strains of rats. Clin Immunol Immunopath 30:142–155CrossRefGoogle Scholar
  22. Dubois EL, Wallace DJ (1987) Drugs that exacerbate and induce systemic lupus erythematosus In: Wallace DJ, Dubois EL (eds) Dubois’ Lupus Erythematosus. Lea & Febiger, Philadelphia, pp 450–469Google Scholar
  23. Dubois EL, Tallman E, Wonka RA (1972) Chlorpromazine-induced systemic lupus erythematosus: case report and review of the literature. J Am Med Assoc 221:595–596CrossRefGoogle Scholar
  24. Dubroff LM, Reid R Jr, Papalian M (1981) Molecular models for hydralazine-related systemic lupus erythematosus. Arthritis Rheum 24:1082–1085PubMedGoogle Scholar
  25. Dunphy J, Oliver M, Rands AL, Lovell CR, McHugh NJ (2000) Antineutrophil cytoplasmic antibodies and HLA class II alleles in minocycline-induced lupus-like syndrome. Br J Dermatol 142:461–467CrossRefPubMedGoogle Scholar
  26. Falk RJ, Terrell RS, Charles LA, Jennette JC (1990) Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci USA 87:4115–4119PubMedGoogle Scholar
  27. Fritzler MJ, Tan EM (1978) Antibodies to histones in drug-induced and idiopathic lupus erythematosus. J Clin Invest 62:560–567PubMedGoogle Scholar
  28. Fukuyama S, Kajiwara E, Suzuki N, Miyazaki N, Sadoshima S, Onoyama K (2000) Systemic lupus erythematosus after alpha-interferon therapy for chronic hepatitis C: a case report and review of the literature. Am J Gastroenterol 95:310–312PubMedGoogle Scholar
  29. Ghate J, Turner M, Rudek M, Figg W, Dahut W, Dyer V, Pluda J, Reed E (2001) Drug-induced lupus associated with COL-3: report of 3 cases. Arch Dermatol 137:471–474PubMedGoogle Scholar
  30. Gleichmann E, Pals WT, Rolink AG, Radaszkiewicz T, Gleichmann H (1984) Graft-versus-host reactions: clues to the etiopathology of a spectrum of immunological diseases. Immunol Today 5:324–332CrossRefGoogle Scholar
  31. Gleichmann H (1982) Systemic lupus erythematosus triggered by diphenylhydantoin. Arthritis Rheum 25:1387–1388Google Scholar
  32. Graninger WB, Hassfeld W, Pesau BB, Machold KP, Zielinski CC, Smolen JS (1991) Induction of systemic lupus erythematosus by interferon-gamma in a patient with rheumatoid arthritis. J Rheumatol 18:1621–1622PubMedGoogle Scholar
  33. Griem P, Wulferink M, Sachs B, Gonzalez JB, Gleichmann E (1998) Allergic and autoimmune reactions to xenobiotics: how do they arise? Immunol Today 19:133–141CrossRefPubMedGoogle Scholar
  34. Gunnarsson I, Kanerud L, Pettersson E, Lundberg I, Lindblad S, Ringertz B (1997) Predisposing factors in sulphasalazine-induced systemic lupus erythematosus. Br J Rheumatol 36:1089–1094PubMedGoogle Scholar
  35. Hahn BH, Sharp GC, Irvin WS, Kantor OS, Gardner CA, Bagby MK, Perry HM Jr, Osterland CK (1972) Immune responses to hydralazine and nuclear antigens in hydralazine-induced lupus erythematosus. Ann Intern Med 76:365–374PubMedGoogle Scholar
  36. Harkcom TM, Conn DL, Holley KE (1978) D-Penicillamine and lupus erythematosus-like syndrome. Ann Intern Med 89:1012Google Scholar
  37. Henningsen NC, Cederberg A, Hanson A, Johansson BW (1975) Effects of long-term treatment with procaine amide. Acta Med Scand 198:475–482PubMedGoogle Scholar
  38. Hieronymus T, Grotsch P, Blank N, Grunke M, Capraru D, Geiler T, Winkler S, Kalden JR, Lorenz HM (2000) Chlorpromazine induces apoptosis in activated human lymphoblasts: a mechanism supporting the induction of drug-induced lupus erythematosus? Arthritis Rheum 43:1994–2004PubMedGoogle Scholar
  39. Hoffman BJ (1945) Sensitivity to sulfadiazine resembling acute lupus erythematosus. Arch Dermatol Syph 51:190–192Google Scholar
  40. Hofstra A, Uetrecht JP (1993) Metabolism of hydralazine to a reactive intermediate by the oxidizing system of activated leukocytes. Chem Biol Interact 89:183–196CrossRefPubMedGoogle Scholar
  41. Jaffe IA (1981) Induction of auto-immune syndromes by penicillamine therapy in rheumatoid arthritis and other diseases. Springer Semin Immunopathol 4:193–207CrossRefPubMedGoogle Scholar
  42. Jain KK (1991) Systemic lupus erythematosus (SLE)-like syndromes associated with carbamazepine therapy. Drug Saf 6:350–360PubMedGoogle Scholar
  43. Ju C, Uetrecht JP (1999) Detection of 2-hydroxyiminostilbene in the urine of patients taking carbamazepine and its oxidation to a reactive iminoquinone intermediate. J Pharmacol Exp Ther 288:51–56PubMedGoogle Scholar
  44. Kalyanaraman B, Sohnle PG (1985) Generation of free radical intermediates from foreign compounds by neutrophil-derived oxidants. J Clin Invest 75:1618–1622PubMedGoogle Scholar
  45. Kammuller ME, Bloksma N, Seinen W (1988) Chemical-induced autoimmune reactions and Spanish toxic oil syndrome. Focus on hydantoins and related compounds. J Toxicol Clin Toxicol 26:157–174PubMedGoogle Scholar
  46. Khan MF, Kaphalia BS, Prabhakar BS, Kanz MF, Ansari GA (1995) Trichloroethene-induced autoimmune response in female MRL +/+ mice. Toxicol Appl Pharmacol 134:155–160CrossRefPubMedGoogle Scholar
  47. Kilburn KH, Warshaw RH (1992) Prevalence of symptoms of systemic lupus erythematosus (SLE) and of fluorescent antinuclear antibodies associated with chronic exposure to trichloroethylene and other chemicals in well water. Environ Res 57:1–9CrossRefPubMedGoogle Scholar
  48. Knezevic W, Mastaglia FL, Quintner J, Zilko PJ (1984) Guillain-Barré syndrome and pemphigus foliaceus associated with D-penicillamine therapy. Aust NZ J Med 14:50–52Google Scholar
  49. Kretz-Rommel A, Duncan SR, Rubin RL (1997) Autoimmunity caused by disruption of central T cell tolerance. A murine model of drug-induced lupus. J Clin Invest 99:1888–1896PubMedGoogle Scholar
  50. Kretz-Rommel A, Rubin RL (1999) Persistence of autoreactive T cell drive is required to elicit antichromatin antibodies in a murine model of drug-induced lupus. J Immunol 162:813–820PubMedGoogle Scholar
  51. Laversuch CJ, Collins DA, Charles PJ, Bourke BE (1995) Sulphasalazine-induced autoimmune abnormalities in patients with rheumatic disease. Br J Rheumatol 34:435–439PubMedGoogle Scholar
  52. Lawson TM, Amos N, Bulgen D, Williams BD (2001) Minocycline-induced lupus: clinical features and response to rechallenge. Rheumatology (Oxford) 40:329–335CrossRefPubMedGoogle Scholar
  53. Lee SL, Chase PH (1975) Drug-induced systemic lupus erythematosus: a critical review. Semin Arthritis Rheum 5:83–103CrossRefPubMedGoogle Scholar
  54. Lessard E, Fortin A, Belanger PM, Beaune P, Hamelin BA, Turgeon J (1997) Role of CYP2D6 in the N-hydroxylation of procainamide. Pharmacogenetics 7:381–390PubMedGoogle Scholar
  55. Machold KP, Smolen JS (1990) Interferon-gamma induced exacerbation of systemic lupus erythematosus. J Rheumatol 17:831–832PubMedGoogle Scholar
  56. Mackie BS, Mackie LE (1999) The PABA story. Australas J Dermatol 40:51–53CrossRefPubMedGoogle Scholar
  57. Maddrey WC, Boitnott JK (1973) Isoniazid hepatitis. Ann Intern Med 79:1–12PubMedGoogle Scholar
  58. Malinow MR, Bardana EJ, Pirofsky B, Craig S, McLaughlin P (1982) Systemic lupus erythematosus-like syndrome in monkeys fed alfalfa sprouts: role of a nonprotein amino acid. Science 216:415–417PubMedGoogle Scholar
  59. Markham A, Lamb HM (2000) Infliximab: a review of its use in the management of rheumatoid arthritis. Drugs 59:1341–1359PubMedGoogle Scholar
  60. Matsuura T, Shimizu Y, Fujimoto H, Miyazaki T, Kano S (1992)Minocycline-related lupus. Lancet 340:1553CrossRefPubMedGoogle Scholar
  61. Nassberger L, Sjoholm AG, Jonsson H, Sturfelt G, Akesson A (1990) Autoantibodies against neutrophil cytoplasm components in systemic lupus erythematosus and in hydralazine-induced lupus. Clin Exp Immunol 81:380–383PubMedGoogle Scholar
  62. Perry HM (1973) Late toxicity to hydralazine resembling systemic lupus erythematosus or rheumatoid arthritis. Am J Med 54:58–72CrossRefPubMedGoogle Scholar
  63. Perry HM, Tan EM, Cordody S, Sahamato A (1970) Relationship of acetyl transferase activity to antinuclear antibodies and toxic symptoms on hypertensive patients treated with hydralazine. J Lab Clin Med 76:114–125PubMedGoogle Scholar
  64. Portanova JP, Arndt RE, Tan EM, Kotzin BL (1987) Anti-histone antibodies in idiopathic and drug-induced lupus recognize distinct intrahistone regions. J Immunol 138:446–451PubMedGoogle Scholar
  65. Price EJ, Venables PJ (1995) Drug-induced lupus. Drug Saf 12:283–290PubMedGoogle Scholar
  66. Raftery EB, Denman AM (1973) Systemic lupus erythematosus syndrome induced by practolol. Br Med J 2:452–455PubMedGoogle Scholar
  67. Reidenberg MM (1983) Aromatic amines and the pathogenesis of lupus erythematosus. Am J Med 75:1037–1042CrossRefPubMedGoogle Scholar
  68. Reidenberg MM, Durant PJ, Harris RA, De Boccardo G, Lahita R, Stenzel KH (1983) Lupus erythematosus-like disease due to hydrazine. Am J Med 75:365–370CrossRefPubMedGoogle Scholar
  69. Reza MJ, Dornfeld L, Goldberg LS (1975) Hydralazine therapy in hypertensive patients with idiopathic systemic lupus erythematosus. Arthritis Rheum 18:335–338PubMedGoogle Scholar
  70. Rich MW (1996) Drug-induced lupus: the list of culprits grows. Postgrad Med 100:299–308PubMedGoogle Scholar
  71. Richardson B, Scheinbart L, Strahler J, Gross L, Hanash S, Johnson M (1990) Evidence for impaired T cell methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 33:1665–1673PubMedGoogle Scholar
  72. Ronnblom LE, Alm GV, Oberg KE (1990) Possible induction of systemic lupus erythematosus by interferon-alpha treatment in a patient with a malignant carcinoid tumour. J Intern Med 227:207–210PubMedGoogle Scholar
  73. Rothfield NF, Bierer WF, Garfield JW (1978) Isoniazid induction of antinuclear antibodies: a prospective study. Ann Intern Med 88:650–652PubMedGoogle Scholar
  74. Rutgeerts P, D’Haens G, Targan S, Vasiliaskas E, Hanauer SB, Present DH, Mayer L, Van Hogezand RA, Braakman T, DeWoody KL, Schaible TF, Van Deventer SJ (1999) Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn’s disease. Gastroenterology 117:761–769PubMedGoogle Scholar
  75. Schaffer JV, Davidson DM, McNiff JM, Bolognia JL (2001) Perinuclear antineutrophilic cytoplasmic antibody-positive cutaneous polyarteritis nodosa associated with minocycline therapy for acne vulgaris. J Am Acad Dermatol 44:198–206CrossRefPubMedGoogle Scholar
  76. Schilling PJ, Kurzrock R, Kantarjian H, Gutterman JU, Talpaz M (1991) Development of systemic lupus erythematosus after interferon therapy for chronic myelogenous leukemia. Cancer 68:1536–1537PubMedGoogle Scholar
  77. Shapiro KS, Pinn VW, Harrington JT, Levey AS (1984) Immune complex glomerulnephritis in hydralazine-induced SLE. Am J Kidney Dis 3:270–274PubMedGoogle Scholar
  78. Shapiro LE, Knowles SR, Shear NH (1997) Comparative safety of tetracycline, minocycline, and doxycycline. Arch Dermatol 133:1224–1230PubMedGoogle Scholar
  79. Shapiro LE, Uetrecht J, Shear NH (2001) Minocycline, perinuclear antineutrophilic cytoplasmic antibody, and pigment: the biochemical basis. J Am Acad Dermatol 45:787–789PubMedGoogle Scholar
  80. Shear NH, Spielberg SP (1988) Anticonvulsant hypersensitivity syndrome. J Clin Invest 82:1826–1832PubMedGoogle Scholar
  81. Sim E, Law SA (1985) Hydralazine binds covalently to complement component C4: different reactivity of C4A and C4B gene products. FEBS 184:323–327Google Scholar
  82. Sim E, Stanley L, Gill EW, Jones A (1988) Metabolites of procainamide and practolol inhibit complement components C3 and C4. Biochem J 251:323–326PubMedGoogle Scholar
  83. Spielberg SP, Gordon GB, Blake DA, Mellits ED, Bross DS (1981) Anticonvulsant toxicity in vitro: possible role of arene oxides. J Pharmacol Exp Ther 217:386–389PubMedGoogle Scholar
  84. Stec GP, Lertora JJL, Atkinson AJ, Nevin MJ, Kushner W, Jones C, Schmid FR, Askenazi J (1979) Remission of procainamide-induced lupus erythematosus with N-acetylprocainamide therapy. Ann Intern Med 90:799–801PubMedGoogle Scholar
  85. Steinberg AD, Gourley MF, Klinman DM, Tsokos GC, Scott DE, Krieg AM (1991) NIH conference. Systemic lupus erythematosus. Ann Intern Med 115:548–559PubMedGoogle Scholar
  86. Tournade H, Pelletier L, Pasquier R, Vial M, Mandet C, Druet P (1990) D-Penicillamine-induced autoimmunity in Brown-Norway rats: similarities with HgCl2-Induced autoimmunity. J Immunol 144:2985–2991PubMedGoogle Scholar
  87. Uetrecht JP (1988) Mechanism of drug-induced lupus. Chem Res Toxicol 1:133–143PubMedGoogle Scholar
  88. Uetrecht JP (1996) Drug-induced lupus: possible mechanisms and their implications for prediction of which new drugs may induce lupus. Expert Opinion on Invest Drugs 5:851–860Google Scholar
  89. Uetrecht JP, Woosley RL (1981) Acetylator phenotype and lupus erythematosus. Clin Pharmacokin 6:118–134Google Scholar
  90. Waldhauser L, Uetrecht J (1991) Oxidation of propylthiouracil to reactive metabolites by activated neutrophils: implications for agranulocytosis. Drug Metab Dispos 19:354–359PubMedGoogle Scholar
  91. Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S (1992) Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356:314–317CrossRefPubMedGoogle Scholar
  92. Wilson JD, Bullock JY, Sutherland DC, Main C, O’Brien KP (1978) Antinuclear antibodies in patients receiving non-practolol beta-blockers. Br Med J 1:14–16PubMedGoogle Scholar
  93. Woosley RL, Drayer DE, Reidenberg MM, Nies AS, Carr K, Oates JA (1978) Effect of acetylator phenotype on the rate at which procainamide induces antinuclear antibodies and the lupus syndrome. N Engl J Med 298:1157–1159PubMedGoogle Scholar
  94. Yung RL, Richardson BC (1994) Drug-induced lupus. Rheum Dis Clin North Am 20:61–86PubMedGoogle Scholar
  95. Zarrabi MH, Zucker S, Miller F, Derman RM, Romano GS, Hartnett JA, Varma AO (1979) Imunologic and coagulation disorders in chlorpromazine-treated patients. Ann Intern Med 91:194–199.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 2005

Authors and Affiliations

  • Jack Uetrecht

There are no affiliations available

Personalised recommendations