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Acetylator Phenotype and Lupus Erythematosus

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Summary

There are several known therapeutic implications of acetylator phenotype; among them, the association of a higher incidence of procainamide- and hydralazine-induced lupus in slow acetylators. Presumably, this is because acetylation of the aromatic amine or hydrazine functional group leads to a non-toxic product. Several other drugs which have been implicated in drug-induced lupus also contain an aromatic amine or hydrazine group.

The clinical and laboratory characteristics of drug-induced and idiopathic lupus are similar but the degree to which the pathophysiological mechanisms are related, if at all, is unknown.

There is also evidence reported for an association between the slow acetylator phenotype and idiopathic lupus. If true, this relationship should provoke some new experimental approaches to investigation into the mechanism of idiopathic lupus.

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References

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

    Article  PubMed  Google Scholar 

  • Alarcón-Segovia, D.; Fishbein, E. and Alcala, H.: Isoniazid acetylation rate and development of antinuclear antibodies upon isoniazid treatment. Arthritis and Rheumatism 14(6): 748–752 (1971).

    Article  PubMed  Google Scholar 

  • Alarcón-Segovia, D.; Worthington, J.W.; Ward, L.E. and Wakim, K.G.: Lupus diathesis and the hydralazine syndrome. New England Journal of Medicine 272: 462–466 (1965).

    Article  PubMed  Google Scholar 

  • Alexander, S.: Lupus erythematosus in two patients after griseofulvin treatment of Trichopyton rubrum infection. British Journal of Dermatology 74: 72–74 (1962).

    Article  PubMed  CAS  Google Scholar 

  • Amrhein, J.A.; Kenny, F.M. and Ross, D.: Granulocytopenia, lupus-like syndrome, and other complications of Propylthiouracil therapy. Journal of Pediatrics 76(1): 54–63 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Anderson, B. and Stillman, M.T.: False-positive FTA-ABS in hydralazine-induced lupus. Journal of the American Medical Association 239: 1392–1393 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Ansell, J.; Tiarks, C. and Sternthal, E.: Procainamide-induced systemic lupus erythematosus with lupus-like coagulation inhibitor. Blood 52: 177 (Suppl. 1) [1978].

    Google Scholar 

  • Armstrong, A.R. and Peart, H.E.: Comparison between the behavior of Eskimos and non-Eskimos to the administration of isoniazid. American Review of Respiratory Diseases 81: 588–594 (1960).

    CAS  Google Scholar 

  • Ashford, R.; Staughton, R. and Brighton, W.D.: Cutaneous vasculitis due to acebutolol. Lancet 2: 462 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Batchelor, J.R.; Welsh, K.I.; Tinoco, R.M.; Dollery, C.T.; Hughes, G.R.V.; Bernstein, R.; Ryan, P.; Naish, P.F.; Aber, G.M.; Bing, R.F. and Russell, G.I.: Hydralazine-induced systemic lupus erythematosus: influence of HLA-DR and sex susceptibility. Lancet 1(8178): 1107–1109 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Becker, M.; Klajman, A.; Moalem, T.; Yaretzky, A. and Ben-Efraim, S.: Circulating immune complexes in sera from patients receiving procainamide. Clinical Immunology and Immunopathology 12: 220–227 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Beernink, D.H. and Miller, J.J.: Anticonvulsant-induced antinuclear antibodies and lupus-like disease in children. Pediatric Pharmacology and Therapeutics 82(1): 113–117 (1973).

    CAS  Google Scholar 

  • Bell, W.R.; Boss, G.R. and Wolfson, J.S.: Circulating anticoagulant in the procainamide-induced lupus syndrome. Archives of Internal Medicine 137: 1471–1473 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Bensaid, J.; Aldigier, J. and Gualde, N.: Systemic lupus erythematosus syndrome induced by Pindolol. British Medical Journal 1: 1603–1604 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Bing, R.F.; Russell, G.I.; Thurston, H. and Swales, J.O.: Hydrallazine in hypertension: Is there a safe dose? British Medical Journal 281: 353–354 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Black, M.; Rabin, L. and Schatz, N.: Nitrofurantoin-induced chronic active hepatitis. Annals of Internal Medicine 92: 62–64 (1980).

    PubMed  CAS  Google Scholar 

  • Blomgren, S.E.; Condemi, J.J.; Bignall, M.C. and Vaughan, J.H.: Antinuclear antibody induced by procainamide. New England Journal of Medicine 281(2): 64–66 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Blomgren, S.E.; Condemi, J.J. and Vaughan, J.H.: Procainamideinduced lupus erythematosus. American Journal of Medicine 52: 338–348 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Blomgren, S.E. and Vaughan, J.H.: The immunogenicity of photo-oxidized DNA and of the photoproduct of DNA and procainamide hydrochloride. Arthritis and Rheumatism 11: 470 (1968).

    Google Scholar 

  • Bluestein, H.G.; Weisman, M.H.; Zraifler, N.J. and Shapiro, R.F.: Lymphocyte alteration by procainamide: relation to drug-induced lupus erythematosus syndrome. Lancet 2: 816–819 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Booth, R.J.; Bullock, J.Y. and Wilson, J.D.: Antinuclear antibodies in patients on acebutolol. British Journal of Clinical Pharmacology 9: 515–517 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Brown, P.; Baddeley, H.; Read, A.E.; Davies, J.D. and McGarry, J.: Sclerosing peritonitis, an unusual reaction to a betaadrenergic-blocking drug (practolol). Lancet 2: 1477–1481 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Burrows, A.W.; Hockaday, T.D.R.; Mann, J.I. and Taylor, J.G.: Diabetic dimorphism according to acetylator status. British Medical Journal 1: 208–210 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Buxman, M.M.: The role of enzymatic coupling of drugs to proteins in induction of drug specific antibodies. Journal of Investigative Dermatology 73: 256–258 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Campbell, W.; Tilstone, W.J.; Lawson, D.H.; Hutton, I. and Lawrie, T.D.V.: Acetylator phenotype and the clinical pharmacology of slow-release procainamide. British Journal of Clinical Pharmacology 3: 1023–1026 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Carr, K.; Oates, J.A.; Nies, A.S. and Woosley, R.L.: Simultaneous analysis of dapsone and monoacetyldapsone employing high performance liquid chromatography: a rapid method for determination of acetylator phenotype. British Journal of Clinical Pharmacology 6: 421–427 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Chan, W.: Less common side effects of methyldopa. Medical Journal of Australia 2: 14–15 (1977).

    PubMed  CAS  Google Scholar 

  • Chapron, D.J.; Kramer, P.A. and Mercik, S.A.: Kinetic discrimination of three sulfamethazine acetylation phenotypes. Clinical Pharmacology and Therapeutics 27(1): 104–113 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Cody, R.J. Jr; Calabrese, L.H.; Clough, J.D.; Tarazi, R.C. and Bravo, E.L.: Development of antinuclear antibodies during acebutolol therapy. Clinical Pharmacology and Therapeutics 25(6): 800–805 (1979).

    PubMed  Google Scholar 

  • Condemi, J.J.: SLE: Idiopathic or drug-induced? Geriatrics 35: 81–88 (1980).

    PubMed  CAS  Google Scholar 

  • Davies, D.M.; Beedie M.A. and Rawlins, M.D.: Antinuclear antibodies during procainamide treatment and drug acetylation. British Medical Journal 3: 682–683 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Drayer, D.E.; Lowenthal, D.T.; Woosley, R.L.; Nies, A.S.; Schwartz, A. and Reidenberg, M.M.: Cumulation of N-acetylprocainamide, an active metabolite of procainamide, in patients with impaired renal function. Clinical Pharmacology and Therapeutics 22(1): 63–69 (1977).

    PubMed  CAS  Google Scholar 

  • Drayer, D.E.; Strong, J.M.; Jones, B.; Sandier, A. and Reidenberg, M.M.: In vitro acetylation of drugs by human blood cells. Drug Metabolism and Disposition 2(6): 499–505 (1974).

    PubMed  CAS  Google Scholar 

  • Dubois, E.L.: Lupus Erythematosus. pp.385–397 (University of Southern California Press, Los Angeles 1974).

    Google Scholar 

  • Dubois, E.L.; Tallman, E. and Wonka, R.A.: Chlorpromazine-induced systemic lupus erythematosus. Journal of the American Medical Association 221: 595–596 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Dubroff, L.M. and Reid, R.J. Jr.: Hydralazine-pyrimidine interactions may explain hydralazine-induced lupus erythematosus. Science 208: 404–406 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Durant, P.J. and Harris, R.A.: Hydralazine and lupus. New England Journal of Medicine 303: 584–585 (1980).

    PubMed  CAS  Google Scholar 

  • Eidus, L.; Glatthaar, E.; Hodgkin, M.M.; Nel, E.E. and Kleeberg, H.H.: Phenotyping of South African black tuberculosis patients for inactivation of isoniazid. Research Communications in Chemical Pathology and Pharmacology 23(2): 243–256 (1979).

    PubMed  CAS  Google Scholar 

  • Eliastam, M. and Holmes, A.W.: Hepatitis, arthritis and lupus cell phenomena caused by methyldopa. Digestive Diseases 16(11): 1014–1018 (1971).

    Article  CAS  Google Scholar 

  • Ellard, G.A.: Variations between individuals and populations in the acetylation of isoniazid and its significance for treatment of pulmonary tuberculosis. Clinical Pharmacology and Therapeutics 19: 610–625 (1976).

    PubMed  CAS  Google Scholar 

  • Evans, D.A.P.: Genetic variations in acetylation of isoniazid and other drugs. Annals of New York Academy of Sciences 151(2): 723–733 (1968).

    Article  CAS  Google Scholar 

  • Evans, D.A.P.: An improved and simplified method of detecting the acetylator phenotype. Journal of Medical Genetics 6: 405–407 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Evans, D.A.P.; Manley, K.A. and McKusick, V.A.: Genetic control of isoniazid metabolism in man. British Medical Journal 2: 485–491 (1960).

    Article  PubMed  CAS  Google Scholar 

  • Evans, D.A.P. and White, T.A.: Human acetylation polymorphism. Journal of Laboratory and Clinical Medicine 63: 394–403 (1964).

    PubMed  CAS  Google Scholar 

  • Fishbein, E. and Alarcon-Segovia, D.: Slow acetylation phenotype in systemic lupus erythematosus. Arthritis and Rheumatism 22: 95–96 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Foad, B.; Litwin, A.; Zimmer, H. and Hess, E.V.: Acetylator phenotype in systemic lupus erythematosus. Arthritis and Rheumatism 20(3): 815–818 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Foucar, E.; Erickson, D.G. and Tung, K.S.K.: Glomerulonephritis in procainamide-induced lupus erythematosus: report of a case and review of the literature. Journal of Clinical Laboratory Immunology 2: 79–84 (1979).

    PubMed  CAS  Google Scholar 

  • Freeman, R.W.; Woosley, R.L.; Oates, J.A. and Harbison, R.D.: Evidence for the biotransformation of procainamide to a reactive metabolite. Toxicology and Applied Pharmacology 50: 9–16 (1979a).

    Article  PubMed  CAS  Google Scholar 

  • Freeman, R.W.; Woosley, R.L.; Uetrecht, J.P.; Oates, J.A. and Harbison, R.D.: In vitro and in vivo covalent binding of procainamide to hepatic protein in mice. Pharmacologist 21(3): 221 (1979b).

    Google Scholar 

  • Fries, J.F. and Holman, H.R.: Systemic lupus erythematosus: A clinical analysis: in Smith (Ed) Major Problems in Internal Medicine. Vol. 6, pp.134–139 (W.B. Saunders Co., Philadelphia 1975).

    Google Scholar 

  • Frislid, K.; Berg, M.; Hansteen, V. and Lunde, P.K.M.: Comparison of the acetylation of procainamide and sulfadimidine in man. European Journal of Clinical Pharmacology 9: 433–438 (1976).

    Article  CAS  Google Scholar 

  • Fritzler, M.J. and Tan, E.M.: Antibodies to histones in drug-induced and idiopathic lupus erythematosus. Journal of Clinical Investigation 62(3): 560–567 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Gelber, R.; Peters, J.H.; Gordon, G.R.; Glazko, A.J. and Levy, L.: The polymorphic acetylation of dapsone in man. Clinical Pharmacology and Therapeutics 12: 225–238 (1971).

    PubMed  CAS  Google Scholar 

  • Gold, E.F.; Ben-Efraim, S.; Faivisewitz, A.; Steiner, Z. and Klajman, A.: Experimental studies on the mechanism of induction of anti-nuclear antibodies by procainamide. Clinical Immunology and Immunopathology 7: 176–186 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Goldberg, L.S. and Bluestone, R.: Studies on serologic abnormalities induced by L-dopa. Vox Sanguinis 24: 171–174 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Grayson, M.F.; Martin, V.M. and Markham, R.L.: Antinative DNA antibodies as a reaction to pyrazole drugs. Annals of the Rheumatic Diseases 34: 373–375 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Griffiths, I.D. and Kane, S.P.: Sulphasalazine-induced lupus syndrome in ulcerative colitis. British Medical Journal 2: 1188–1189 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Griffiths, I.D. and Richardson, J.: Lupus-type illness associated with labetalol. British Medical Journal 2: 496–497 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Hahn, B.H.; Sharp, G.C.; Irvin, W.S.; Kantor, O.S.; Gardner, C.A.; Bagby, M.K.; Perry, H.M., Jr and Osterland, C.K.: Immune responses to hydralazine and nuclear antigens in hydralazine-induced lupus erythematosus. Annals of Internal Medicine 76: 365–374 (1972).

    PubMed  CAS  Google Scholar 

  • Handley, A.J.: Thrombocytopenia and LE cells after oxyphenbutazone. Lancet 1: 245 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Hanngren, A.; Borga, O. and Sjoqvist, F.: Inactivation of isoniazid (INH) in Swedish tuberculous patients before and during treatment with para-aminosalicylic acid (PAS). Scandinavian Journal of Respiratory Diseases 51: 61–69 (1970).

    PubMed  CAS  Google Scholar 

  • Harkcom, T.M.; Conn, D.L. and Holley, K.E.: D-Penicillamine and lupus erythematosus like syndrome. Annals of Internal Medicine 89(6): 1012 (1978).

    PubMed  CAS  Google Scholar 

  • Harland, S.J.; Facchini, V. and Timbrell, J.A.: Hydrallazine-induced lupus erythematosus-like syndrome in a patient of the rapid acetylator phenotype. British Medical Journal 281: 273–274 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Harrison, T.; Sisca, T.S. and Wood, W.H.: Propranolol-induced lupus syndrome?. Postgraduate Medicine 59(1): 241–244 (1976).

    PubMed  CAS  Google Scholar 

  • Hashem, N.; Khalifa, S. and Nour, A.: The frequency of isoniazid acetylase enzyme deficiency among Egyptians. American Journal of Physical Anthropology 31: 97–102 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Hearse, D.J. and Weber, W.W.: Tissue distribution, characterization and significance of mammalian N-acetyltransferase. Biochemical Journal 132: 519–526 (1973).

    PubMed  CAS  Google Scholar 

  • Henningsen, N.C.; Cederberg, A.; Hanson, A. and Johansson, B.W.: Effects of long-term treatment with procainamide. Acta Medica Scandinavica 198: 475–482 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Heykants, J.; Pardoel, L. and Janssen, P.A.J.: On the distribution and metabolism of Azaperone (R1929) in the rat and pig. Arzneimittel-Forschung 21: 982–984 (1971).

    PubMed  CAS  Google Scholar 

  • James, O.F.W.: Drug metabolism in the elderly. Age and Ageing 7 (Supplement): 81–85 (1978).

    Article  Google Scholar 

  • Jaup, B.H.: Salazosulfapyridine-induced lupus erythematosus syndrome in ulcerative colitis. Deutsche Medizinische Wochen-schrift 103(30): 1211–1213 (1978).

    Article  CAS  Google Scholar 

  • Jessamine, A.G.; Hamilton, E.J. and Eidus, L.: A clinical study of isoniazid inactivation. Canadian Medical Association Journal 89: 1214–1217 (1963).

    PubMed  CAS  Google Scholar 

  • Johansson, E.A.; Mustakallio, K.K.; Mattila, M.M. and Tiilikainen, A.: Cutaneous reactions to drugs, acetylation phenotype and HLA antigens in patients with and without systemic lupus erythematosus (SLE). Annals of Clinical Research 8: 126–128 (1976).

    PubMed  CAS  Google Scholar 

  • Kendall, M.J. and Hawkins, C.F.: Quinidine-induced systemic lupus erythematosus. Postgraduate Medical Journal 46: 729–731 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Kosowsky, B.D.; Taylor, J.; Lown, B. and Ritchie, R.F.: Longterm use of procainamide following acutc rnyocardial infarction. Circulation 47: 1204–1210 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Krakauer, R.S.; Strober, W.; Rippeon, D.L. and Waldmann, T.A.: Prevention of autoimmunity in experimental lupus erythematosus by soluble immune response suppressor. Science 196: 56–59 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Lahita, R.; Kluger, J.; Drayer, D.E.; Koffler, D. and Reidenberg, M.M.: Antibodies to nuclear antigens in patients treated with procainamide or acetylprocainamide. New England Journal of Medicine 301(25): 1382–1385 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Larsson, R.; Karlsson, E. and Molin, L.: Spontaneous systemic lupus erythematosus and acetylator phenotype. Acta Medica Scandinavica 201: 223–226 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Lawson, D.H.; Henry, D.A.; Lowe, J.; Reavey, P.; Rennie, J.A.N. and Solomon, A.: Acetylator phenotype in spontaneous SLE and rheumatoid arthritis. Annals of the Rheumatic Diseases 38: 171–173 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Lee, S.L. and Chase, P.H.: Drug-induced systemic lupus erythematosus: a critical review. Seminars in Arthritis and Rheumatism 5(1): 83–103 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Levo, Y.; Pick, A.I.; Avidor, I. and Ben-Bassat, M.: Clinicopathological study of a patient with procainamide-induced systemic lupus erythematosus. Annals of the Rheumatic Diseases 35: 181–185 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Link, F. and Müller-Fassbender, H.: Medikamentös induzierter Lupus erythematodes. Munchener Medizinische Wochenschrift 122: 1099–1100 (1980).

    PubMed  CAS  Google Scholar 

  • Lorand, L.; Campbell, L.K. and Robertson, J.B.: Enzymatic coupling of isoniazid to proteins. Biochemistry 11: 434–438 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Lunde, P.K.M.; Frislid, K. and Hansteen, V.: Disease and acetylation polymorphism. Clinical Pharmacokinetics 2: 182–197 (1977).

    Article  PubMed  CAS  Google Scholar 

  • McQueen, E.G.: Pharmacological basis of adverse drug reactions. Genetically determined reactions; in Avery (Ed) Drug Treatment, 2nd ed, pp.218–225 (ADIS Press, Sydney and New York; Churchill Livingstone, Edinburgh 1980).

    Google Scholar 

  • Maher, J.R.; Whitney, J.M.; Chambers, J.S. and Stanonis, D.J.: The quantitative determination of isoniazid and paraaminosalicylic acid in body fluids. American Review of Tuberculosis 76: 852–861 (1957).

    PubMed  CAS  Google Scholar 

  • Marshall, A.J.; McGraw, M.E. and Barritt, D.W.: Positive antinuclear factor tests with prazosin. British Medical Journal 1: 165–166 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Massarotti, G. and Passaleva, A.: Lupus-like autoimmune syndrome after levodopa and benserazide. British Medical Journal 2: 553 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Mattila, M.J. and Tiitinen, H.: The rate of isoniazid inactivation in Finnish diabetic and non-diabetic patients. Annales Medicinae Internae Fenniae 45: 423–427 (1967).

    CAS  Google Scholar 

  • Milner, G.R.; Holt, P.J.L.; Bottomley, J. and Maciver, J.E.: Practolol therapy associated with a systemic lupus erythematosuslike syndrome and an inhibitor to factor XIII. Journal of Clinical Pathology 30: 770–773 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Mitchell, R.S.; Bell, J.C. and Riemensneider, D.K.: Further observations with isoniazid inactivation tests. Veterans Administration 19th Conference of Chemotherapy of Tuberculosis. p.62 (Ed. by VA Department of Medicine and Surgery Central Office, Washington, DC 1960).

    Google Scholar 

  • Molin, L.; Larsson, R. and Karlsson, E.: Evaluation of the sulfpyridine acetylator phenotyping test in healthy subjects and in patients with cardiac and renal diseases. Acta Medica Scandinavica 1: 217–222 (1977).

    Google Scholar 

  • Morris, R.J.; Freed, C.R. and Kohler, P.F.: Drug acetylation phenotype unrelated to development of spontaneous systemic lupus erythematosus. Arthritis and Rheumatism 22(7): 777–780 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Oka, M. and Seppällä, O.: Acetylation phenotype in rheumatoid arthritis. Scandinavian Journal of Rheumatology 7: 29–30 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Olsen, H. and Mørland, J.: Ethanol-induced increase in drug acetylation in man and isolated rat liver cells. British Medical Journal 2: 1260–1262 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Perry, H.M. Jr: Late toxicity to hydralazine resembling systemic lupus erythematosus or rheumatoid arthritis. American Journal of Medicine 54: 58–71 (1973).

    Article  PubMed  Google Scholar 

  • Perry, H.M. Jr; Chaplin, H. Jr; Carmody, S.; Haynes, C. and Frei, G: Immunologic findings in patients receiving methyldopa: a prospective study. Journal of Laboratory Medicine 78(6): 905–917 (1971).

    Google Scholar 

  • Perry, H.M. Jr; Tan, E.M.; Cordody, S. and Sahamato, A. Relationship of acetyl transferase activity to antinuclear antibodies and toxic symptoms on hypertensive patients treated with hydralazine. Journal of Laboratory and Clinical Medicine 76: 114–125 (1970).

    PubMed  Google Scholar 

  • Pugh, S.; Pelton, B.; Raftery, E.B. and Denman, A.M.: Abnormal lymphocyte function is secondary to drug induced autoimmunity. Annals of the Rheumatic Diseases 35: 344–348 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Raftery, E.B. and Denman, A.M.: Systemic lupus erythematosus syndrome induced by practolol. British Medical Journal 2: 452–455 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Rao, K.V.R.M.; Diaz, R. and Quigley, T.J.: Procainamide-induced systemic lupus erythematosus with hypocomplementemia. Journal of the American Geriatrics Society 25(5): 230–231 (1977).

    PubMed  CAS  Google Scholar 

  • Reidenberg, M.M.; Drayer, D.E.; Levy, M. and Warner, H.: Polymorphic acetylation of procainamide in man. Clinical Pharmacology and Therapeutics 17: 722–730 (1975).

    PubMed  CAS  Google Scholar 

  • Reidenberg, M.M.; Kostenbauder, H. and Adams, W.P.: Rate of drug metabolism in obese volunteers before and during starvation and in azotemic patients. Metabolism 18: 209–213 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Reidenberg, M.M.; Levy, M.; Drayer, D.E.; Zylber-Katz, E. and Robbins, W.C.: Acetylator phenotype in idiopathic systemic lupus erythematosus. Arthritis and Rheumatism 23(5): 569–573 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Reidenberg, M.M. and Martin, J.H.: The acetylator phenotype of patients with systemic lupus erythematosus. Drug Metabolism and Disposition 2(1): 71–73 (1974).

    PubMed  CAS  Google Scholar 

  • Reynolds, T.B.; Peters, R.L. and Yamada, S.: Chronic active and lupoid hepatitis caused by a laxative, oxyphenisatin. New England Journal of Medicine 285(15): 813–820 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Reza, M.J.; Dornfeld, L. and Goldberg, L.S.: Hydralazine therapy in hypertensive patients with idiopathic systemic lupus erythematosus. Arthritis and Rheumatism 18(4): 335–338 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Roden, D.M.; Reele, S.B.; Higgins, S.B.; Smith, R.; Oates, J.A. and Woosley, R.L.: Antiarrhythmic efficacy, pharmacokinetics and safety of N-acetylprocainamide in man. American Journal of Cardiology 46: 463 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Rothfield, N.F.; Bierer, W.F. and Garfield, J.W.: Isoniazid induction of antinuclear antibodies. Annals of Internal Medicine 88: 650–652 (1978).

    PubMed  CAS  Google Scholar 

  • Schneck, D.W.; Sprouse, J.S.; Hayes, A.H. and ShirolT, R.A.: The effect of hydralazine and other drugs on the kinetics of procainamide acetylation by rat liver and kidney N-acetyltransferase. Journal of Pharmacology and Experimental Therapeutics 204(1): 212–218 (1978).

    PubMed  CAS  Google Scholar 

  • Schneck, D.W.; Sprouse, J.S.; Shiroff, R.A.; Vary, J.E.; DeWitt, F.O. and Hayes, AH.: Effect of co-administration of procainamide and isoniazid on each other’s acetylation pathway. Pharmacology 18: 34–41 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Selroos, O. and Edgren, J.: Lupus-like syndrome associated with pulmonary reaction to nitrofurantoin. Acta Medica Scandinavica 197: 125–129 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Sharp, J.R.; Ishak, K.G. and Zimmerman, H.J.: Chronic active hepatitis and severe hepatic necrosis associated with nitrofurantoin. Annals of Internal Medicine 92: 14–19 (1980).

    PubMed  CAS  Google Scholar 

  • Simpson, P.B. and Oppenheim, R.C.: Phospholipid monolayers and systemic lupus erythematosus. New Zealand Medical Journal 86: 19–20 (1977).

    PubMed  CAS  Google Scholar 

  • Singsen, B.H.; Fishman, L. and Hanson, V.: Antinuclear antibodies and lupus-like syndromes in children receiving anticonvulsants. Pediatrics 57(4): 529–534 (1976).

    PubMed  CAS  Google Scholar 

  • Sprouse, J.S.; Schneck, D.W. and Hayes, A.H.: The effect of isoniazid and other drugs on the acetylation of procainamide in the intact rat. Journal of Pharmacology and Experimental Therapeutics 207(3): 698–704 (1978).

    PubMed  CAS  Google Scholar 

  • Sunahara, S.; Urano, M. and Ogawa, M.: Genetical and geographic studies on isoniazid inactivation. Science 134: 1530–1531 (1961).

    Article  PubMed  CAS  Google Scholar 

  • Swartz, C.: Lupus-like reaction to phenelzine. Journal of the American Medical Association 239(25): 2693 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Tan, E.M.: Drug-induced autoimmune disease. Federation Proceedings 33(8): 1894–1897 (1974).

    PubMed  CAS  Google Scholar 

  • Testa, B. and Jenner, P.: Drug Metabolism, pp.180–186 (Marcel Dekker, Inc., New York 1976).

    Google Scholar 

  • Tiitinen, H.: Isoniazid and ethionamide serum levels and inactivation in Finnish subjects. Scandinavian Journal of Respiratory Diseases 50: 110–124 (1969).

    PubMed  CAS  Google Scholar 

  • Utsinger, P.D.; Zvaifier, N.J. and Bluestein, H.G.: Hypocomplementemia in procainamide-associated systemic lupus erythematosus. Annals of Internal Medicine 84: 293 (1976).

    PubMed  CAS  Google Scholar 

  • Vansant, J.; Woosley, R.L.; John, J.T. and Sergent, J.S.: Normal distribution of acetylation phenotypes in systemic lupus erythematosus. Arthritis and Rheumatism 21(2): 192–195 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Weber, W.W.: Acetylation of Drugs: in Fishman (Ed) Metabolic Conjugation and Metabolic Hydrolysis, pp. 249–296 (Academic Press, New York 1973).

    Google Scholar 

  • Weber, W.W. and Glowinski, I.B.: Acetylation: in Jakoby (Ed) Enzymatic Basis for Detoxification (Academic Press, New York, In Press 1979).

    Google Scholar 

  • Weber, W.W. and Hein, D.W.: Clinical pharmacokinetics of isoniazid. Clinical Pharmacokinetics 4: 401–422 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Weber, W.W.; Hein, D.W.; Hirata, M. and Patterson, E.: Genetics of drug acetylation: Molecular nature of the INH acetylation polymorphism: in Aitio (Ed) Conjugation Reactions in Drug Biotransformation, pp. 145–153 (Eisevier/North-Holland Biomedical Press, Amsterdam 1978).

    Google Scholar 

  • Weber, W.W.; Radtke, H.E. and Tannen, R.H.: Extra-hepatic N-acetyltransferases and N-deacetylasis: in Gram (Ed) Extrahepatic Metabolism of Drugs and Other Foreign Compounds (Spectrum Publications, Jamaica, New York, In Press 1980).

    Google Scholar 

  • Weinstein, J.: Hypocomplementemia in hydralazine-associated systemic lupus erythematosus. American Journal of Medicine 65: 553–556 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Whittle, T.S. and Ainsworth, S.K.: Procainamide-induced systemic lupus erythematosus. Archives of Pathology and Laboratory Medicine 100: 469–474 (1976).

    PubMed  Google Scholar 

  • Wilson, J.D.: Antinuclear antibodies and cardiovascular drugs. Drugs 19: 292–305 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Winfield, J.B. and Davis, J.S.: Anti-DNA antibody in procainamide-induced lupus erythematosus. Arthritis and Rheumatism 17(2): 97–110 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Woosley, R.L.; Drayer, D.E.; Reidenberg, M.M.; Nies, A.S.; Carr, K. and Oates, J.A.; Effect of acetylator phenotype on the rate at which procainamide induces antinuclear antibodies and the lupus syndrome. New England Journal of Medicine 298: 1157–1159 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Wright, P.: Untoward effects associated with practolol administration: oculomucocutaneous syndrome. British Medical Journal 1: 595–598 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Yudis, M. and Meehan, J.J.: Quinidine-induced lupus nephritis. Journal of the American Medical Association 235(18): 2000 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Zarrabi, M.H.; Zucher, S.; Miller, F.; Derman, R.M.; Romano, G.S.; Hartnett, J.A. and Varma, A.O.: Immunologic and coagulation disorders in chlorpromazine-treated patients. Annals of Internal Medicine 91: 194–199 (1979).

    PubMed  CAS  Google Scholar 

  • Zech, P.; Colon, S.; Labecuw, M.; Bernheim, J. and Blanc-Brunat, N.: Nephrotic syndrome in procainamide-induced lupus nephritis. Clinical Nephrology 11(4): 218–221 (1979).

    PubMed  CAS  Google Scholar 

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  1. Division of Clinical Pharmacology, Departments of Pharmacology and Medicine, School of Medicine Vanderbilt University, Nashville, Tennessee, 37232, USA

    Jack P. Uetrecht &  Raymond L. Woosley

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  1. Jack P. Uetrecht
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Uetrecht, J.P., Woosley, R.L. Acetylator Phenotype and Lupus Erythematosus. Clin Pharmacokinet 6, 118–134 (1981). https://doi.org/10.2165/00003088-198106020-00003

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