Skip to main content
SpringerLink
Log in

Drug-Related Lupus

Incidence, Mechanisms and Clinical Implications

  • Review Article
  • Drug Safety Concepts
  • Published:
Drug Safety Aims and scope Submit manuscript

Summary

Adverse side effects to drugs and chemicals in which immune mechanisms may be responsible have been described in drug-related lupus (DRL). The spectrum of drugs that may elicit DRL includes such classes as the hydrazines, arylamines, and chemicals that can be metabolised to amines. The 2 major pathways of metabolism — acetylation and N-hydroxylation — are described in detail.

The events leading to autoantibody production are not well understood; however, specific consideration of the genetic makeup of patients who are candidates for treatment with these drugs may help identify those at risk of developing DRL.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adams LE, Carter JM, Hess EV. Induction of hapten-specific antibody to procainamide (PA) metabolites in Lewis Rats. Abstract 90-1. 7th International Congress of Immunology, Berlin, 30 July–5 August, 1989

  • Adams LE, Roberts SM, Carter JM, Wheeler JF, et al. Effects of procainamide hydroxylamine on generation of reactive oxygen species by macrophages and production of cytokines. International Journal of Immunopharmacology 12: 809–819, 1990

    PubMed  CAS  Google Scholar 

  • Adams LE, Sanders CE, Budinsky RA, Donovan-Brand RJ, Hess EV. Immunomodulatory effects of procainamide metabolites: their implications in drug-related lupus. Journal of Laboratory and Clinical Medicine 113: 482–492, 1989

    PubMed  CAS  Google Scholar 

  • Alarcon-Segovia D. Drug-induced antinuclear antibodies and lupus syndrome. Drugs 12: 69–77, 1976

    PubMed  CAS  Google Scholar 

  • Alarcon-Segovia D. Drug-induced lupus syndrome. Mayo Clinic Proceedings 44: 664–681, 1969

    PubMed  CAS  Google Scholar 

  • Alarcon-Segovia D, Wakim KG, Worthington JW, Ward LE. Clinical and experimental studies on the hydralazine syndrome and its relationship to systemic lupus erythematosus. Medicine 46: 1–33, 1967

    PubMed  CAS  Google Scholar 

  • Allan IM, Lunec J, Salmon M, Bacon PA. Selective lymphocyte killing by lack of reactive oxygen species (ROS). Agents and Actions 19: 351–352, 1986

    PubMed  CAS  Google Scholar 

  • Allison AC. Unresponsiveness to self-antigen. Lancet 2: 1401–1403, 1971

    PubMed  CAS  Google Scholar 

  • Alvan G. Individual differences in the disposition of drugs metabolised in the body. Clinical Pharmacokinetics 3: 155–175, 1978

    PubMed  CAS  Google Scholar 

  • Alvan G, von Bahr C, Seidman P, et al. High plasma concentrations of β-receptor blocking drugs and deficient debrisoquine hydroxylation. Lancet 1: 333, 1982

    PubMed  CAS  Google Scholar 

  • Andersson M, Hanson A, England G, et al. Inhibition of complement components C3 and C4 by cadralazine and its active metabolites. European Journal of Clinical Pharmacology 40: 261–265, 1991

    PubMed  CAS  Google Scholar 

  • Babbitt BP, Allen PM, Matsueda G, et al. Binding of immunogenic peptides to la histocompatibility molecules. Nature 317: 359–361, 1985

    PubMed  CAS  Google Scholar 

  • Batchelor JR, Fielder AHL, Walport MJ, et al. Family study of the major histocompatibility complex in HLA-DR3 negative patients with SLE. Clinical and Experimental Immunology 70: 364–371, 1987

    PubMed  CAS  Google Scholar 

  • Batchelor JR, Welsh Kl, Tinoco RM, Dollery CT, Hughes GRV, et al. Hydralazine-induced systemic lupus erythematosus: influence of HLA-DR and sex on susceptibility. Lancet 1: 1107–1109, 1980

    PubMed  CAS  Google Scholar 

  • Beernink DH, Miller JJ. Anticonvulsant-induced antinuclear antibodies and lupus-like disease in children. Pediatric Pharmacology 88: 113–117, 1973

    Google Scholar 

  • Bigazzi PE. Autoimmunity induced by chemicals. Clinical Toxicology 26: 125–156, 1988

    PubMed  CAS  Google Scholar 

  • Bluestein HG, Redelman D, Zvaifler NJ. Procainamide lymphocyte reactions: a possible explanation for drug induced autoimmunity. Arthritis and Rheumatism 24: 1019–1023, 1981

    PubMed  CAS  Google Scholar 

  • Boobis AR, Davies DS. Human cytochromes P-450. Xenobiotica 14: 151–185, 1984

    PubMed  CAS  Google Scholar 

  • Brand C, Davison A, Littlejohn G, Ryan P. Hydralazine-induced lupus: no association with HLA-DR4. Lancet 2: 462, 1984

    Google Scholar 

  • Budinsky RA, Roberts SM, Coast EA, Adams L, Hess EV. The formation of procainamide hydroxylamine by rat and human liver microsomes. Drug Metabolites and Disposition 15: 37–43, 1987

    CAS  Google Scholar 

  • Burlingame RW, Rubin RL. Anti-histone antibody induction by drugs implicates autoimmunization with nucleohistone. Abstract A63. Arthritis and Rheumatism 32: 4S, 1989

    Google Scholar 

  • Camus JP, Homberg JC, Crouzet J, et al. Autoantibody formation in D-penicillinamine treated rheumatoid arthritis. Journal of Rheumatology 8 (Suppl. 7): 80–83, 1981

    Google Scholar 

  • Canoso RT, de Oliveira RM. Chlorpromazine induced anticardiolipin antibodies and lupus anticoagulant in the absence of thrombosis. American Journal of Hematology 27: 272–275, 1988

    PubMed  CAS  Google Scholar 

  • Canoso RP, Lewis ME, Yunis EJ. Association of HLA BW44 with chlorpromazine induced autoantibodies. Clinical Immunology and Immunopathology 25: 278–282, 1982

    PubMed  CAS  Google Scholar 

  • Cohen MG, Kevat S, Prowse MV, et al. Two distinct quinidine-induced rheumatic syndromes. Annals of Internal Medicine 108: 369–371, 1988

    PubMed  CAS  Google Scholar 

  • Coleman JW, Yeung JHK, Roberts DH, et al. Drug specific antibodies in patients receiving captopril. British Journal of Clinical Pharmacology 22: 161–165, 1986

    PubMed  CAS  Google Scholar 

  • Cornacchia E, Golbus J, Maybalm J, Strahler J, Hanash S, et al. Hydralazine and procainamide inhibit T-cell DNA methylation and induce autoreactivity. Journal of Immunology 140: 2197–2200, 1988

    CAS  Google Scholar 

  • Craft JE, Radding JA, Harding MA, Bernstein RM, Hardin JA. Autoantigenic histone epitopes: a comparison between procainamide- and hydralazine-induced lupus. Arthritis and Rheumatism 30: 689–694, 1987

    PubMed  CAS  Google Scholar 

  • Cush JJ, Goldings EA. Southwestern Internal Medicine Conference: drug-induced lupus. Clinical spectrum and pathogenesis. American Journal of Medical Sciences 290: 36–46, 1985

    CAS  Google Scholar 

  • Dayer P, Courvoisier F, Balant L, et al. Beta-blockers and drug oxidation status. Lancet 1: 508–509, 1985

    Google Scholar 

  • Drayer DE, Lorenzi B, Lahita RG, et al. Microsomal hydroxylation as measured by pentobarbital elimination in patients with systemic lupus erythematosus. Clinical Pharmacology and Therapeutics 32: 195–200, 1982

    PubMed  CAS  Google Scholar 

  • Drayer DE, Reidenberg MM. Clinical consequences of polymorphic acetylation of basic drugs. Clinical Pharmacology and Therapeutics 22: 251–258, 1977

    PubMed  CAS  Google Scholar 

  • Dubois EL, Wallace DJ. Drugs that exacerbate and induce systemic lupus erythematosus. In Wallace et al. (Eds) Dubois’ lupus erythematosus, 3rd ed, pp. 450–453, Lea and Febiger, Philadelphia, 1987

    Google Scholar 

  • Edwards CRW, Padfield PL. Angiotensin-converting enzyme inhibitors: past, present, and bright future. Lancet 1: 30–34, 1985

    PubMed  CAS  Google Scholar 

  • Emery P, Panayi GS, Husten G, et al. D-penicillamine induced toxicity in rheumatoid arthritis: the role of sulphoxidation status and HLA-DR3. Journal of Rheumatology 11: 626–632, 1984

    PubMed  CAS  Google Scholar 

  • Epstein A, Barland P. The diagnostic value of antihistone antibodies in drug-induced lupus erythematosus. Arthritis and Rheumatism 28: 158–162, 1985

    PubMed  CAS  Google Scholar 

  • Evans DAP, White TA. Human acetylation polymorphism. Journal of Laboratory and Clinical Medicine 63: 394–403, 1964

    PubMed  CAS  Google Scholar 

  • Facchini V, Timbrell JA. Future evidence for an acetylator phenotype difference in the metabolism of hydralazine in man. British Journal of Clinical Pharmacology 11: 345–351, 1981

    PubMed  CAS  Google Scholar 

  • Fielder AHL, Walport MJ, Batchelor JR, et al. Family study of the major histocompatibility complex in patients with SLE. Importance of null alleles of C4A and C4B in determining susceptibility. British Medical Journal 286: 425–428, 1983

    PubMed  CAS  Google Scholar 

  • Foad B, Litwin A, Zimmer H, et al. Acetylator phenotype in systemic lupus erythematosus. Arthritis and Rheumatism 20: 815–818, 1977

    PubMed  CAS  Google Scholar 

  • Forrester J, Golbus J, Brede D, Hudson J, Richardson B. B cell activation in patients with active procainamide-induced lupus. Journal of Rheumatology 15: 1384–1388, 1988

    PubMed  CAS  Google Scholar 

  • Freeman RW, Woosley RL, Oats JH, Harbison RD. Evidence for the biotransformation of procainamide to a reactive metabolite. Toxicology and Applied Pharmacology 50: 9–16, 1979

    PubMed  CAS  Google Scholar 

  • Fronek Z, Timmerman LA, McDevitt. A rare HLA-DQB allele sequenced from patients with systemic lupus erythematosus. Human Immunology 30: 77–84, 1991

    PubMed  CAS  Google Scholar 

  • Gastineau DA, Holcomb GR. Lupus anticoagulant in drug-induced systemic lupus erythematosus (SLE). Archives of Internal Medicine 145: 1926–1927, 1985

    PubMed  CAS  Google Scholar 

  • Gelber R, Peters JH, Gordon GR, et al. The polymorphic acetylation of dapsone in man. Clinical Pharmacology and Therapeutics 12: 225–238, 1971

    PubMed  CAS  Google Scholar 

  • Gleichmann E, Pals ST, Rolink AG, et al. Graft-versus-host reactions. Clues to the etiopathology of a spectrum of immunological diseases. Immunology Today 5: 324–332, 1984

    Google Scholar 

  • Goldberg MJ, Hsain M, Wajszczuk WJ, Rubenfire M. Procainamide-induced lupus erythematosus pericarditis encountered during coronary bypass surgery. American Journal of Medicine 69: 159–162, 1980

    PubMed  CAS  Google Scholar 

  • Goldstein R, Sengar DPS. Comparative study of HLA association and C4A gene detection in French-Canadian and non-French-Canadian Caucasians with systemic lupus erythematosus (SLE.). Fifteenth Annual Meeting of American Society for Histocompatibility and Immunogenetics, Toronto, September 17–21, 1989

  • Goter Robinson CJ, Abraham AA, Balazs T. Induction of antinuclear antibodies in mercuric chloride in mice. Clinical and Experimental Immunology 58: 300–306, 1984

    Google Scholar 

  • Grant DM, Morike K, Eichelbaum M. Acetylation pharmacogenetics: the slow acetylator phenotype is caused by decreased or absent arylamine N-acetyl-transferase in human liver. Journal of Clinical Investigation 85: 968–972, 1990

    PubMed  CAS  Google Scholar 

  • Guengerich FP, Distlerath LM, Reilly PEB, et al. Human-liver cytochromes P-450 involved in polymorphisms of drug oxidation. Xenobiotica 16: 367–378, 1986

    PubMed  CAS  Google Scholar 

  • Hahn B, Sharp GC, Irvin WS, et al. Immune responses to hydralazine and nuclear antigens in hydralazine-induced lupus erythematosus. Annals of Internal Medicine 76: 365–374, 1972

    PubMed  CAS  Google Scholar 

  • Henningsen NC, Cederberg A, Hanson A, Johansson BW. Effects of long-term treatment with procainamide. Acta Medica Scandinavica 198: 475–482, 1975

    PubMed  CAS  Google Scholar 

  • Hess EV. Symposium on Drug-Related Systemic Lupus. Arthritis and Rheumatism 24: 979–1111, 1981

    Google Scholar 

  • Hess EV. Drug related lupus: the same or different? In Lahita (Ed.) Systemic lupus erythematosus, pp. 869–879, John Wiley & Sons, New York, 1987

    Google Scholar 

  • Hess EV. Drug-related lupus (Ed). New England Journal of Medicine 318: 1460–1462; 1988

    PubMed  CAS  Google Scholar 

  • Hess EV, Knapp D. The immune system and aging: a case of the cart before the horse? Journal of Chronic Diseases 31: 647–649, 19

  • Hess EV, Litwin A. Drug-related rheumatic diseases: basic mechanisms. In Gupta et al. (Eds) Immunology of rheumatic diseases, pp. 651–668, Plenum Publishing Corporation, New York, 1985

    Google Scholar 

  • Hoffman BJ. Sensitivity of sulfadiazine resembling acute disseminated lupus erythematosus. Archives Dermatologic Symposium 51: 190–192, 1945

    Google Scholar 

  • Hoorntje SJ, Kallenberg CGM, Weening JJ, et al. Immune-complex glomerulopathy in patients treated with captopril. Lancet 1: 1212–1214, 1980

    PubMed  CAS  Google Scholar 

  • Holers VM, Kotzin BL. Human peripheral blood monocytes display surface antigens recognised by monoclonal antinuclear antibodies. Journal of Clinical Investigation 76: 991–998, 1985

    PubMed  CAS  Google Scholar 

  • Hughes GRV, Pynes RI, Gharavi A, Ryan PFJ, Sewell J, et al. The heterogeneity of serologic findings and predisposing host factors in drug-induced lupus erythematosus. Arthritis and Rheumatism 24: 1070–1073, 1987

    Google Scholar 

  • Kalow W. Ethnic differences in drug metabolism. Clinical Pharmacokinetics 7: 373–400, 1982

    PubMed  CAS  Google Scholar 

  • Kammuller ME, Bloksam J, Seinen W. Chemical-induced autoimmune reactions and Spanish toxic oil syndrome. Focus on hydantoins and related compounds. Clinical Toxicology 26: 157–174, 1988

    PubMed  CAS  Google Scholar 

  • Kaplan A, Zakher F, Sabin S, Drug-induced lupus erythematosus with in vitrolupus erythematosus cells in pleural fluid. Chest 73: 873–876, 1978

    Google Scholar 

  • Kim SY, Benowitz NL. Poisoning due to class IA antiarrhythmic drugs: quinidine, procainamide and disopyramide. Drug Safety 5: 393–420, 1990

    PubMed  CAS  Google Scholar 

  • Kirtland HH, Mohler DN, Horowitz DA. Methyldopa inhibition of suppressor-lymphocyte function: a proposed cause of autoimmune hemolytic anemia. New England Journal of Medicine 302: 825–832, 1980

    PubMed  CAS  Google Scholar 

  • Klajman A, Camin-Belsky N, Kimichi A, Ben-Efraim S. Occurrence, immunoglobulin pattern and specificity of antinuclear antibodies in sera of procainamide treated patients. Clinical and Experimental Immunology 7: 641–649, 1970

    PubMed  CAS  Google Scholar 

  • Kupfer A, Preisig R. Pharmacogenetics of mephenytoin: a new drug hydroxylation polymorphism in man. European Journal of Clinical Pharmacology 26: 753–759, 1984

    PubMed  CAS  Google Scholar 

  • Ladd AT. Procainamide-induced lupus erythematosus. New England Journal of Medicine 267: 1357–1358, 1962

    PubMed  CAS  Google Scholar 

  • Lafer EM, Valler PC, Moller A, Nordheim A, Schur PH, et al. Z-DNA-specific antibodies in human systemic lupus erythematosus. Journal of Clinical Investigation 71: 314–321, 1983

    PubMed  CAS  Google Scholar 

  • Lambert C, Maggs JL, Park BK, et al. Formation of chemically reactive drug metabolites by activated human polymorphonuclear leukocytes. British Journal of Clinical Pharmacology 25: 143P-144P, 1988

    Google Scholar 

  • Lee SL, Chase PH. Drug-induced systemic lupus erythematosus: a critical review. Seminars in Arthritis and Rheumatism 5: 83–103, 1975

    PubMed  CAS  Google Scholar 

  • Lennard MS, Silas JH, Freestone S, et al. Oxidative phenotype — a major determinant of metoprolol metabolism and response. New England Journal of Medicine 307: 1558–1560, 1982

    PubMed  CAS  Google Scholar 

  • Lerner RA, Dixon FJ, Crocker BP, et al. The possible role of occovirus in the etiology and pathogenesis of murine lupus. Advances in Bioscience 12: 356–365, 1974

    Google Scholar 

  • Litwin A, Adams LE, Zimmer H, Foad B, Loggie JH, et al. Prospective study of immunologic effects of hydralazine in hypertensive patients. Clinical Pharmacology and Therapeutics 24: 447–456, 1981

    Google Scholar 

  • Litwin A, Adams LE, Zimmer H, Hess EV. Immunologic effects of hydralazine in hypertensive patients. Arthritis and Rheumatism 24: 1074–1078, 1981

    PubMed  CAS  Google Scholar 

  • Lou YC. Differences in drug metabolism polymorphism between Orientals and Caucasians. Drug Metabolism Reviews 22: 451–475, 1990

    PubMed  CAS  Google Scholar 

  • Lunde PKM, Frislid K, Hansteen V. Disease and acetylation polymorphism. Clinical Pharmacokinetics 2: 132–197, 1977

    Google Scholar 

  • Mackay IR. Autoimmunity in relation to lupus erythematosus. In Wallace et al. (Eds) DuBois’ lupus erythematosus, 3rd ed., pp. 44–62, Lea and Febiger, Philadelphia, 1987

    Google Scholar 

  • Makinodan T, Geokas MC, Lakatta EG. The aging process. Annals of Internal Medicine 113: 455–466, 1990

    PubMed  Google Scholar 

  • Malinow MR, Bardana EJ, Pirofsky B, et al. Systemic lupus erythematosus-like syndrome in monkeys fed alfalfa sprouts: role of a non-protein amino acid. Science 216: 415–417, 1982

    PubMed  CAS  Google Scholar 

  • McDermott M, McDevitt HO. The immunogenetics of rheumatic disease. Bulletin of Rheumatic Diseases 38: 1–10, 1988

    CAS  Google Scholar 

  • Miller KB, Salem D. Immune regulatory abnormalities produced by procainamide. American Journal of Medicine 73: 487–492, 1982

    PubMed  CAS  Google Scholar 

  • Mitchell JA, Batchelor JR, Chapel H, Speirs CN, Sim E. Erythrocyte complement receptor type I (CRI) expression and circulating immune complex (CIC) levels in hydralazine-induced SLE. Clinical and Experimental Immunology 68: 446–456, 1987

    PubMed  CAS  Google Scholar 

  • Mitchell JA, Gillam EMJ, Stanley LA. Immunotoxic side-effects of drug therapy. Drug Safety 5: 168–178, 1990

    PubMed  CAS  Google Scholar 

  • Mitchell JR, Thorgeirsson UP, Black M, et al. Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydrazine metabolites. Clinical Pharmacology and Therapeutics 18: 70–79, 1975

    PubMed  CAS  Google Scholar 

  • Mongey A-B, Donovan-Brand RJ, Thomas TJ, et al. Serological evaluation of patients receiving procainamide. Arthritis and Rheumatism, in press, 1991

  • Mongey A-B, Hess EV. Drug-related lupus. Current Opinion in Rheumatology 1: 353–359, 1989

    PubMed  CAS  Google Scholar 

  • Mongey A-B, Hess EV. Antinuclear antibodies and disease specificity. Advances in Internal Medicine 36: 151–169, 1991

    PubMed  CAS  Google Scholar 

  • Morrow JD, Schroeder HA, Perry Jr HM. Studies on the control of hypertension by hyphex: II. Toxic reactions and side effects. Circulation 8: 829–839, 1953

    PubMed  CAS  Google Scholar 

  • Nebert DW. Clinical pharmacology: possible clinical importance of genetic differences in drug metabolism. British Medical Journal 283: 567–541, 1981

    Google Scholar 

  • Ochi T, Goldings EA, Lipsky PE, Ziff M. Immunomodulatory effect of procainamide in man. Journal of Clinical Investigation 71: 36–45, 1983

    PubMed  CAS  Google Scholar 

  • Ohsawa M, Takahashi K, Otsuka F. Induction of antinuclear antibodies in mice orally exposed to cadmium at low concentrations. Clinical and Experimental Immunology 73: 98–102, 1988

    PubMed  CAS  Google Scholar 

  • Pålsson L, Weiner L, England G, Henning M. Cadralazine challenge in patients with previous hydralazine-induced lupus: a 6-month study. Clinical Pharmacology and Therapeutics 46: 177–181, 1991

    Google Scholar 

  • Park BK, Kitteringham NR. Drug protein conjugation and its immunological consequences. Drug Metabolism Reviews 22: 87–144, 1990

    PubMed  CAS  Google Scholar 

  • Pavlidakey GP, Hashimoto K, Heller GL, Daneshvar S. Chlorpromazine-induced lupus-like disease. Case report and review of the literature. American Journal of Academic Dermatology 13: 109–115, 1985

    CAS  Google Scholar 

  • Pereyo N. Tartrazine, hydrazine amino compounds and systemic lupus erythematosus. Science-Ciencia 14: 31–34, 1987

    Google Scholar 

  • Perry Jr HJ, Tan EM, Carmody S, Sakamoto A. Relationship of acetyl transferase activity to antinuclear antibodies and toxic symptoms in hypertensive patients treated with hydralazine. Journal of Laboratory and Clinical Medicine 76: 114–125, 1970

    PubMed  Google Scholar 

  • Peters JH, Levy L. Dapsone acetylation in man: another example of polymorphic acetylation. Annals of the New York Academy of Sciences 179: 660–666, 1971

    PubMed  CAS  Google Scholar 

  • Phair JP, Kauffman CA, Bjornson A, Gallagher J, Adams LE, et al. Host defenses in the aged: evaluation of competence of the inflammatory and immune responses. Journal of Infectious Disease 138: 67–73, 1978

    CAS  Google Scholar 

  • Portanova JP, Arndt RE, Tan EM, Kotzin BL. Antihistone antibodies in idiopathic and drug-induced lupus recognize distinct intrahistone regions. Journal of Immunology 138: 446–451, 1987

    CAS  Google Scholar 

  • Portanova JP, Claman HN, Kotzin BL. Autoimmunization in murine graft vs host disease: 1. Selective production of antibodies to histones and DNA. Journal of Immunology 135: 3850–3856, 1985

    CAS  Google Scholar 

  • Price-Evans DA. N-acetyltransferase. Pharmacology and Therapeutics 42: 157–234, 1989

    Google Scholar 

  • Price Evans DA, Manley KA, McKusick VA. Genetic control of isoniazid metabolism in man. British Medical Journal 2: 485–491, 1960

    Google Scholar 

  • Price Evans DA, White TA. Human acetylation polymorphism. Journal of Laboratory and Clinical Medicine 63: 364–403,1964

    Google Scholar 

  • Quismorio FP, Bjarnason DF, Kiely WF, DuBois EL, Friou GJ. Antinuclear antibodies in chronic psychotic patients treated with chlorpromazine. American Journal of Psychiatry 132: 1204–1206, 1975

    PubMed  CAS  Google Scholar 

  • Reidenberg MM. Aromatic amines and the pathogenesis of lupus erythematosus. American Journal of Medicine 75: 1037–1042, 1983

    PubMed  CAS  Google Scholar 

  • Reidenberg MM. The chemical induction of systemic lupus erythematosus and lupus-like illnesses. Arthritis and Rheumatism 24: 1004–1008, 1981

    PubMed  CAS  Google Scholar 

  • Reidenberg MM, Chase DB, Drayer DE, et al. Development of antinuclear antibody in patients treated with high doses of captopril. Arthritis and Rheumatism 27: 579–581, 1984

    PubMed  CAS  Google Scholar 

  • Reidenberg MM, Drayer D, Demario AL, et al. Hydralazine elimination in man. Clinical Pharmacology and Therapeutics 14: 970–977, 1973

    PubMed  CAS  Google Scholar 

  • Reidenberg MM, Drayer DE, Levy M, et al. Polymorphic acetylation of procainamide in man. Clinical Pharmacology and Therapeutics 17: 722–730, 1975

    PubMed  CAS  Google Scholar 

  • Reidenberg MM, Levy M, Drayer DE, et al. Acetylator phenotype in idiopathic systemic lupus erythematosus. Arthritis and Rheumatism 25: 569–573, 1980

    Google Scholar 

  • Reidenberg MM, Martin JH. The acetylator phenotype of patients with systemic lupus erythematosus. Drug Metabolism and Disposition 2: 71–73, 1974

    PubMed  CAS  Google Scholar 

  • Roberts DL, Marks R. Skin reactions to carbamazepine. Archives of Dermatology 117: 273–275, 1983

    Google Scholar 

  • Roberts SM, Adams LE, Donovan-Brand RJ, Budinsky RA, Skoulis NP, et al. Procainamide hydroxylamine lymphocyte toxicity: I. Evidence for participation by hemoglobin. International Journal of Immunopharmacology 12: 1–9, 1989

    Google Scholar 

  • Roberts SM, Budinsky RA, Adams LE, Litwin A, Hess EV. Procainamide acetylation in strains of rat and mouse. Drug Metabolism and Disposition 13: 517–519, 1985

    PubMed  CAS  Google Scholar 

  • Rubin RL. Autoimmune reaction induced by procainamide and hydralazine. In Kamuller et al. (Eds) Autoimmunity and toxicology, pp. 119–150, Elsevier, Amsterdam, 1989

    Google Scholar 

  • Rubin RL. Drug-induced lupus. Clinical Aspects of Autoimmunity 2: 16–29, 1988

    Google Scholar 

  • Rubin RL, Uetrecht JP, Jones JE. Cytotoxicity of oxidative metabolites of procainamide. Journal of Pharmacology and Experimental Therapy 242: 833–841, 1987

    CAS  Google Scholar 

  • Russell GI Bing RF, Jones JAG, Thursont H, Swales JD. Hydralazine sensitivity: clinical features, autoantibody changes and HLA-DR phenotype. Quarterly Journal of Medicine, New Series 65: 845–852, 1987

    CAS  Google Scholar 

  • Schroder H, Campbell DTS. Absorption metabolism and excretion of salicylazosulphapyridine in man. Clinical Pharmacology and Therapeutics 13: 539–551, 1972

    PubMed  CAS  Google Scholar 

  • Schur PH, Marcus-Bagley D, Awdeh Z, Yunis EJ, Alper CA. The effect of ethnicity on major histocompatibility complex complement allotypes and extended haplotypes in patients with systemic lupus erythematosus. Arthritis and Rheumatism 33: 985–992, 1990

    PubMed  CAS  Google Scholar 

  • Shah RR, Oates NS, Idle JR, et al. Impaired oxidation of debrisoquine in patients with perhexiline neuropathy. British Medical Journal 284: 295–299, 1982

    PubMed  CAS  Google Scholar 

  • Shapiro KS, Pinn VW, Harrington JT, Levey AS. Immune complex glomerulo-nephritis in hydralazine-induced SLE. American Journal of Kidney Disorders 3: 270–271, 1984

    CAS  Google Scholar 

  • Shear NH, Spielberg SP, Grant DW, et al. Differences in metabolism of sulfonamides predisposing to idiosyncratic toxicity. Annals of Internal Medicine 105: 179–184, 1986

    PubMed  CAS  Google Scholar 

  • Sieber C, Grimm E, Follath F. Captopril and systemic lupus erythematosus syndrome. British Medical Journal 301: 669, 1990

    PubMed  CAS  Google Scholar 

  • Silas JH, McGourty JC, Lennard MS, et al. Polymorphic metabolism of metoprolol: clinical studies. European Journal of Clinical Pharmacology 28: 85–88, 1985

    PubMed  CAS  Google Scholar 

  • Sim E, Dodds AW, Goldin A. Inhibition of the covalent binding reaction of complement component C4 by penicillamine, an anti-rheumatic agent. Biochemical Journal 259: 415–419, 1989

    PubMed  CAS  Google Scholar 

  • Sim E, Gill EW. Drugs that induce systemic lupus erythematosus inhibit complement component C4. Lancet 2: 422–424, 1984

    PubMed  CAS  Google Scholar 

  • Sim E, Stanley L, Gill EW, Jones A. Metabolites of procainamide and practolol inhibit complement components of C3 and C4. Biochemistry Journal 251: 323–326. 1988

    CAS  Google Scholar 

  • Singsen BH, Fishman L, Hanson V. Antinuclear antibodies and lupus-like syndromes in children receiving anticonvulsants. Pediatrics 57: 529–534, 1976

    PubMed  CAS  Google Scholar 

  • Solinger AM. Drug-related lupus: clinical and etiologic considerations. Rheumatic Disease Clinics of North America 14: 187–202, 1988

    PubMed  CAS  Google Scholar 

  • Sonnhag C, Karlsson E, Hed J. Procainamide-induced lupus erythematosus-like syndrome in relation to acetylator phenotype and plasma levels of procainamide. Acta Medica Scandinavica 206: 245–251, 1979

    PubMed  CAS  Google Scholar 

  • Speirs C, Fielder AHL, Chapel H, Davey NJ, Batchelor JR. Complement system protein C4 and susceptibility to hydralazine-induced systemic lupus erythematosus. Lancet 1: 922–924, 1989

    PubMed  CAS  Google Scholar 

  • Spencer-Green G, Kelley L, Adams LE, Donovan-Brand R, Hess EV. Polynucleotide antibodies in connective tissue disease: viral markers or disease mediators? Journal of Laboratory and Clinical Medicine 107: 159–165, 19

  • Streeter AJ, Timbrell JA. Studies on the in vivometabolism of hydralazine in the rat. Drug Metabolism and Disposition 11: 184–189, 1983

    PubMed  CAS  Google Scholar 

  • Svejgaard A, Platz P, Ryder LP. HLA and disease, 1982— a survey. Immunological Reviews 70: 193–218, 1983

    PubMed  CAS  Google Scholar 

  • Tabuenca JM. Toxic-allergic syndrome caused by ingestion of rapeseed oil denatured with aniline. Lancet 2: 567–568, 1981

    PubMed  CAS  Google Scholar 

  • Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, et al. The 1982revised criteria for the classification of systemic lupus erythematosus. Arthritis and Rheumatism 25: 1271–1277, 1982

    PubMed  CAS  Google Scholar 

  • Teoh PC, Chan HL. Lupus-scleroderma syndrome induced by ethosuximide. Archives of Diseases in Childhood 50: 658–661, 1975

    CAS  Google Scholar 

  • Thomas TJ, Messner RP. Effects of lupus-inducing drugs on the B to Z transition of synthetic DNA. Arthritis and Rheumatism 29: 638–645, 1986

    PubMed  CAS  Google Scholar 

  • Totoritis MC, Rubin RL. Drug-induced lupus. Genetic, clinical and laboratory features. Postgraduate Medicine 78: 149–161, 1985

    PubMed  CAS  Google Scholar 

  • Totoritis MC, Tan EM, McNally EM, Rubin RL. Association of antibody to histone complex H2A-H2B with symptomatic procainamide-induced lupus. New England Journal of Medicine 318: 1431–1436, 1988

    PubMed  CAS  Google Scholar 

  • Tsankov NK, Lazarova AZ, Vasileva SG, et al. Lupus erythematosus-like eruption due to D-penicillamine in progressie systemic sclerosis. International Journal of Dermatology 29: 571–574, 1990

    PubMed  CAS  Google Scholar 

  • Uetrecht JP. Mechanism of drug-induced lupus. Chemical Research Toxicology 1: 133–143, 1988

    CAS  Google Scholar 

  • Uetrecht JP. Reactivity and possible significance of hydroxylamine and nitroso metabolites of procainamide. Journal of Pharmacology and Experimental Therapeutics 232: 420–425, 1985

    PubMed  CAS  Google Scholar 

  • Uetrecht JP, Sweetman BJ, Woosley RL, Oates JA. Metabolism of procainamide to a hydroxylamine by rat and human hepatic microsomes. Drug Metabolism and Disposition 12: 77–81, 1984

    PubMed  CAS  Google Scholar 

  • Uetrecht JP, Woosley RL. Acetylator phenotype and lupus erythematosus. Clinical Pharmacokinetics 6: 118–134, 1981

    PubMed  CAS  Google Scholar 

  • Uetrecht J, Zahid N, Rubin R. Metabolism of procainamide to a hydroxylamine by human neutrophils and mononuclear leukocytes. Chemical Research and Toxicology 1: 74–78, 1988

    CAS  Google Scholar 

  • Varga J, Heiman-Patterson TD, Emery DR, et al. Clinical spectrum of systemic manifestations of the eosinophilia-myalgia syndrome. Seminars in Arthritis and Rheumatism 19: 313–328, 1990

    PubMed  CAS  Google Scholar 

  • Vesell ES. Why individuals vary in their response to drugs. Trends in Pharmacological Science 1: 349–351, 1980

    CAS  Google Scholar 

  • Walport MJ, Black CN, Batchelor JR. The immunogenetics of SLE. In Hughes (Ed.) Clinics in rheumatic diseases, pp. 3–21, WB Saunders, London, 1982

    Google Scholar 

  • Weber WW. Acetylation of drugs. In Fishman (Ed.) Metabolic conjugation and metabolic hydrolysis, Vol. 3, pp. 249–296, Academic Press, New York, 1973

    Google Scholar 

  • Weber WW, Glowinski IB. Acetylation. In Jokoby (Ed.) Enzymatic mechanism of detoxication, Vol. 2, pp. 169–196, Academic Press, New York, 1980

    Google Scholar 

  • Weber WE, Hein DW. N-acetylation pharmacogenetics. Pharmacological Reviews 37: 25–79, 1985

    PubMed  CAS  Google Scholar 

  • Weigle WO. Immunological unresponsiveness. Advances in Immunology 16: 61–122, 1973

    PubMed  CAS  Google Scholar 

  • Weinstein A. Drug-induced systemic lupus erythematosus. Progress in Clinical Immunology 4: 1–21, 1980

    PubMed  CAS  Google Scholar 

  • Welch TR, Beischel LS, Balakrishnan K, et al. Major histocompatibility complex extended haplotypes in systemic lupus erythematosus. Disease Markers 6: 247–255, 1988

    PubMed  CAS  Google Scholar 

  • West SG, McMahon M, Portanova JP. Quinidine-induced lupus erythematosus. Annals of Internal Medicine 100: 840–842, 1984

    PubMed  CAS  Google Scholar 

  • Wheeler JF, Adams LE, Mongey A-B, Roberts SM, et al. Determination of metabolically derived nitro-procainamide in the urine of procainamide-dosed humans and rats by liquid chromatography with electrochemical detection. Drug Metabolism and Disposition 19: 691–695, 1991

    PubMed  CAS  Google Scholar 

  • Wheeler JF, Lunte CE, Heineman WR,Adams LE, Hess EV. Electrochemical determination of N-oxidized procainamide metabolites and functional assessment of effects on murine cells in vitro.Proceedings of the Society for Experimental Biology and Medicine 188: 381–386, 1988

    PubMed  CAS  Google Scholar 

  • Wheeler JF, Lunte CE, Zimmer H, Heineman WR. Electrochemical investigations of immunologically reactive procainamide metabolites. Journal of Pharmaceutical and Biomedical Analysis 8: 143–150, 1990

    PubMed  CAS  Google Scholar 

  • Whiteside T, Mulhern L, Buckingham R, Luksock J. Procainamide induced lupus (PLE) is associated with an increased frequency of HLA DR 6Y. Abstract. Arthritis and Rheumatism 25: S41, 1982

    Google Scholar 

  • Woosley RL, Drayer DE, Reidenberg MD, Nies AS, Carr K, et al. Effect of acetylator phenotype on the rate at which procainamide induces antinuclear antibodies and the lupus syndrome. New England Journal of Medicine 298: 1157–1179, 1978

    PubMed  CAS  Google Scholar 

  • Yamauchi Y, Litwin A, Adams LE, Zimmer H, Hess EV. Induction of antibodies to nuclear antigens in rabbits by immunization with hydralazine-human serum albumin conjugates. Journal of Clinical Investigation 56: 958–969, 1975

    PubMed  CAS  Google Scholar 

  • Yeung JHK, Coleman JW, Park BK. Drug protein conjugates: IX. Immunogenicity of captopril-protein conjugates. Biochemical Pharmacology 34: 4005–4013, 1985

    PubMed  CAS  Google Scholar 

  • Yu C-L, Ziff M. Effects of long term procainamide therapy on immunoglobulin synthesis. Arthritis and Rheumatism 28: 276–284, 1985

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Immunology, Department of Internal Medicine, University of Cincinnati Medical Center, 231 Bethesda Ave., M.L. 564, Cincinnati, Ohio, 45267, USA

    Louis E. Adams &  Evelyn V. Hess (Director)

Authors
  1. Louis E. Adams
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evelyn V. Hess
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adams, L.E., Hess, E.V. Drug-Related Lupus. Drug-Safety 6, 431–449 (1991). https://doi.org/10.2165/00002018-199106060-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199106060-00004

Keywords

Search

Navigation