Gold salts have been used in the treatment of patients with rheumatoid arthritis since 1927 [1]. After a controlled study, the Empire Rheumatism Council [2], confirmed the effectiveness of gold salts for the treatment of rheumatoid arthritis. Even today, chrysotherapy has remained one of the major therapeutic modalities in the second line treatment of progressive rheumatoid arthritis. Gold salts are also used in the treatment of pemphigus vulgaris [3] and bronchial asthma [4]. Before the introduction of an orally administered gold compound, auranofin (triethylphosphine gold tetra-acetyl glycopyranoside), to clinical use [5-7], parenterally administered gold salts, such as sodium aurothiomalate and gold thioglucose comprised chrysotherapy. The frequency and severity of the side effects for patients treated with parenteral gold versus those given oral gold preparations are significantly different [8-10]. With introduction of newer parental DMARDs, toxicity has been reduced using combination therapy [10a, 10b].
Chapter PDF
Similar content being viewed by others
Keywords
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.
References
Lande K. Die gunstige Beeinflussung schleichender Dauerinfekte durch Solganal. Munchen Med Wochenshr 1927; 74: 1132-1134.
The Research Sub-Committee of the Empire Rheumatism Council. Gold therapy in rheumatoid arthritis. Final report of a multi-center controlled trial. Ann Rheum Dis 1961; 20: 315-333.
Penneys NS, Eaglestein WH, Frost P. Management of pemphigus with gold compounds. Arch Dermatol 1976; 112: 185-187.
Muranaka M, Miyamoto T, Shida T, Kabe J, Makino S, Okumura H, Takeda K, Suzuki S, Horiuchi Y. Gold salt in the treatment of bronchial asthma - a double blind study. Ann Allergu 1978; 40: 132-137.
Finkelstein AE, Walz DT, Batista V, Mizrazi M, Roisman F, Misher A. Auranofin - new oral gold compound for treatment of rheu-matoid arthritis. Ann Rheum Dis 1976; 35: 251-257.
Berglof FE, Berglof K, Walz DT. Auranofin: an oral chrysotherapeutic agent for the treatment of rheumatoid arthritis. J Rheumatol 1978; 5: 68-74.
Weisman MH, Hannifin DH. Management of rheumatoid arthritis with oral gold. Arthritis Rheum 1979; 22: 922-925.
Davis P, Menard H, Thompson J, Harth M, Beaudet F. One-year comparative study of gold sodium thiomalate and auranofin in the treatment of rheumatoid arthritis. J Rheumatol 1985; 12: 60-67.
Ward JR, Williams HJ, Egger MJ, Reading JC, Boyce E, Altz-Smith M, Samuelson CO, Willkens RF, Solsky MA, Hayes SP, Blocka KL, Weinstein A, Meenan RF, Guttadauria M, Kaplan SB, Klippel J. Comparison of auranofin, gold sodium thiomalate and placebo in the treatment of rheumatoid arthritis: A controlled clinical trial. Arthritis Rheum 1983; 26: 1303-1315.
Heuer MA, Pietrusko RG, Morris RW, Scheffler BJ. An analysis of worldwide safety experience with auranofin. J Rheumatol 1985; 12: 695-699.
O’Dell JR, Petersen K, Leff R, Palmer W, Schned E, Blakely K, Haire C, Fernandez A. Etanercept in combination with sulfasalaazine, hydroxychloroquine, or gold in the treatment of rheumatoid arthritis. J Rheumatol 2006;33:213-218.
Rau R, Schleusser B, Herborn G, Karger T. Longterm combination therapy of refractory and destructive rheumatoid arthritis with methotrexate (MTX) and intramuscular gold or other disease modifying antirheumatic drugs compare to MTX monotherapy. J Rheumatol 1998;25:1485-1492.
Hartfall SJ, Garland HG, Goldie W. Gold treatment of arthritis. A review of 900 cases. Lancet 1937; 9: 838-842.
Gibbons RB. Complication of chrysotherapy. A review of recent studies. Arch Intern Med 1979; 139: 343-346.
Penneys NS, Ackerman AB, Gottlieb NL. Gold dermatitis. Arch Dermatol 1979; 109: 372-376.
Benson WG, Moore N, Tugwell P, D, Souza M, Singal DP. HLA antigens and toxic reactions to sodium aurothiomalate in patients with rheumatoid arthritis. J Rheumatol 1984; 11: 358-361.
Adachi JD, Bensen WG, Singal DP, Powers PJ. Gold-induced thrombocytopenia: platelet associated IgG and HLA typing in three patients. J Rheumatol 1984; 11: 355-357.
Gottlieb NL, Gray RG. Diagnosis and management of adverse reaction from gold compounds. J Analytic Toxicol 1978; 2: 173.
Baldwin JL, Storb R, Thomas ED, Mannik M. Bone marrow transplantation in patients with gold-induced marrow aplasia. Arthritis Rheum 1977; 20: 1043-1048.
Gibson J, McGirr EE, York J, Kronenberg H. Aplastic anemia in association with gold therapy for rheumatoid arthritis. Aust NZ J Med 1983; 13: 130-135.
Winterbauer RH, Wilske KR, Wheelis RF. Diffuse pulmonary injury associated with gold treatment. N Engl J Med 1976; 294: 919-921.
Partanen J, van Assendelft AHW, Koskimies S, Forsberg S, Hakala M, Ilonen J. Patients with rheumatoid arthritis and fold-induced pneumonitis express two high-risk major histocompatibility complex patterns. Chest 1987; 92: 277-281.
Fam AG, Paton TW, Shamess CJ, Lewis AJ. Fulminant colitis complicating gold therapy. J Rheumatol 1980; 7: 479-485.
Silverberg DS, Kidd EG, Shnitka TK, Ulan RA. Gold nephropathy. A clinical and pathological study. Arthritis Rheum 1970; 13: 812-825.
Kean WF, Anastassiades TP. Long-term chrysotherapy. Incidence of toxicity and efficacy during sequential time periods. Arthritis Rheum 1979; 22: 495-501.
Katz WA, Blodgett RC Jr, Pietrusko RG. Proteinuria in gold treated rheumatoid arthritis. Ann Intern Med 1984; 101: 176-179.
Brock H, Han MT. Gold nephrosis. N Engl J Med 1966; 274: 210-211.
Furst DE, Levine S, Srinivasan R, Metzger L, Bangert R, Paulus E. A double-blind trial of high versus conventional dosages of gold salts for rheumatoid arthritis. Arthritis Rheum 1977; 20: 1473-1480.
Gran JT, Husby G, Thorsby E. HLA DR antigens and gold toxicity. Ann Rheum Dis 1983; 42: 63-66.
Bensen WG, Moore N, Tugwell P, D Souza M, Singal DP. HLA antigens and toxic reactions to sodium aurothiomalate in patients with rheumatoid arthritis. J Rheumatol 1984; 11: 358-361.
Barger BO, Acton RT, Koopman WJ, Alarcon GS. DR antigens and gold toxicity in white rheumatoid patients. Arthritis Rheum 1984; 27: 601-605.
Hakala M, van Assendelef AHW, Ilonen J, Jalava S, Tiilikainen A. Association of different HLA antigens with various toxic effects of gold salts in rheumatoid arthritis. Ann Rheum Dis 1986; 45: 177-182.
Vaamaonde CA, Hunt FR. The nephritic syndrome as a complication of gold therapy. Arthritis Rheum 1970; 13: 826-834.
Francis KL, Jenis EH, Jensen GE, Calcagno PL. God-associated nephropathy. Arch Pathol Lab Med 1984; 108: 234-238.
Hall CL, Fothergill NJ, Blackwell MM, Harrison PR, MacKenzie JC, Maclver AG. The natural course of gold nephropathy: long term study of 21 patients. Br Med J 1987; 295: 745-748.
Tornroth T, Skrifvars B. Gold nephropathy. Prototype of membranous glomerulonephritis. Am J Med 1974; 75: 573-590
Hall CL. Gold nephropathy. Nephron 1988;50:265-272.
Hall CL, The natural course of gold and penicillamine nephropathy. A longterm study of 54 patients. Adv. Exp Med Biol 1989;252:247-256/
Klinkhoff AV, Teufel A. Reinstitution of gold after gold induced proteinuria. J Rheumatol 1997;24:1277-1279.
Lee JC, Dushinkin M, Eyring EJ, Engleman EP, Hopper JR. Renal lesions associated with gold therapy. Light and electron microscopic studies. Arthritis Rheum 1965; 8: 1-13.
Mattson JC. Glomerular diseases as a complication of gold therapy. Lab Invest 1974; 30: 383.
Katz A, Little AH. Gold nephropathy. An immunopathologic study. Arch Pathol 1973; 96: 133-136.
Watanabe I, Whitter FC, Moore J, Cuppage FE. Gold nephropathy. Ultrastructural fluorescent and microanalytic study of two human cases. Arch Path Lab Med 1976; 100: 632-635.
Davies DJ, Dowling J, Xipell JM. Gold nephropathy. Pathology 1977; 9: 281-288.
Skrifvars BV, Tornroth TS, Tallqvist GN. Gold-induced immune complex nephritis in seronegative rheumatoid arthritis. Ann Rheum Dis 1977; 36: 549-556.
Wolters J, Frederik P, van Rie H, Zeppenfeldt E. Minimal change nephropathy during gold treatment. A case with unusual his- topathological and immunopathological features. Netherland J Med 1987; 31: 234-240.
Skirfvars B, Tornroth T, Flalck HM. Granulomatous glomerulonephritis in a patient with rheumatoid arthritis treated with gold salts. Scand J Rheumatol 1979; 8: 234-240.
Cramer CR, Hagler HK, Silva FG, Eigenbrodt EH, Meltzer JI, Pirani CL. Chronic interstitial nephritis associated with gold nephropathy. Arch Path Lab Med 1983; 107: 258-263.
Tubbs RR, Valenzuela R, McGorman LJ, Pohl MA, Barenberg S. Gold nephropathy. New Eng J Med 1977; 296: 1413-1414.
Yarom R, Stein H, Peter PD, Slavin S, Hall TA. Nephrotoxic effect of parenteral and intraarticular gold. Ultrastructural and electron microprobe examination of clinical and experimental materials. Arthritis Rheum 1975; 99: 36-43.
Iesato K, Mori Y, Ueda S, Wakashin Y, Wakashin M, Matsui N, Inoue S, Okuda K. Renal tubular dysfunction as a complication of gold therapy in patients with rheumatoid arthritis. Clin Nephrol 1982; 17: 46-52.
Ueda S, Wakashin M, Wakashin Y, Yoshida H, Iesato K, Mori T, Mori Y, Akikusa B, Okuda K. Experimental gold nephropathy in guinea pigs: Detection of autoantibodies to renal tubular antigens. Kidney Int 1986; 29: 539-548.
Nagi AH, Alexander F, Barabas AZ. Gold nephropathy in rats. Light and electron microscopic studies. Exp Molec Path 1971; 15:354-362.
Eiseman JL, Ribas JL, Knight E, Alvares AP. Acute nephropathy induced by gold sodium thiomalate: Alterations in renal heme metabolism and morphology. Toxicol Appl Pharmacol 1987; 91: 193-203.
Bretza J, Wells I, Novey HS. Association of IgE antibodies to sodium aurothiomalate and adverse reactions to chrysotherapy for rheumatoid arthritis. Am J Med 1983; 74: 945-950.
Davis P, Ezeoke A, Munro J, Hobbs JR, Hughes GRV. Immunological studies on the mechanism of gold hypersensitivity reactions. Br Med J 1973; 3: 676-678.
Denman EJ, Denman AM. The lymphocyte transformation test and gold hypersensitivity. Ann Rheum Dis 1968; 27: 582-588.
Derot M, Kahn J, Mazalton A, Peyrafort J. Fatal anuric nephritis with associated chrysocyanosis following gold therapy. Bull Soc Med Hop Paris 1954; 70: 234-239.
Palosuo T, Provast TT, Milgrom F. Gold nephropathy. Serologic data suggesting an immune complex disease. Clin Exp Immunol 1976; 25: 311-318.
Skirfvars B. Hypothesis for the pathogenesis of sodium aurothiomalate induced immune complex nephritis. Scand J Rheumatol 1979; 8: 113-118.
Jessop JD, Vernon-Roberts B, Harris J. Effects of gold salts and prednisolone on inflammatory cells. I. Phagocytic activity of macrophages and polymorphs in inflammatory exudates studied by a ‘skin-window’ technique in rheumatoid and control patients. Ann Rheum Dis 1973; 32: 294-300.
Vernon-Roberts B, Jessop JD, Dore J. Effects of gold salts and prednisolone on inflammatory cells. II. Suppression of inflammation and phagocytosis in the rat. Ann Rheum Dis 1973; 32: 301-307.
Panush RS. Effects of certain antirheumatic drugs on normal human peripheral blood lymphocytes. Inhibition of mitogen- and antigen- stimulated incorporation of tritiated thymidine. Arthritis Rheum 1976; 19: 907-917.
Harth M, Stiller CR, Sinclair C, Evans J, McGirr D, Zuberi R. Effects of a gold salt on lymphocyte responses. Clin Exp Immunol 1977; 27: 357-364.
Measel W. Effects of gold on the immune response of mice. Infect Immunity 1975; 11: 350-354.
Ueda S, Wakashin M, Wakashin Y, Yoshida H, Azemoto R, Iesato K, Mori T, Mori Y, Ogawa M, Okuda K. Autoimmune interstitial nephritis in inbred mice. Analysis of mouse tubular basement membrane antigen and genetic control of immune response to it. Am J Pathol 1988; 132: 304-318.
Ueda S, Wakashin Y, Yoshida H, Mori T, Mori Y, Azemoto R, Ogawa M, Kato I, Wakashin M. Gold nephropathy - effect of gold on immune response to renal tubular basement membrane (TBM) antigen in mice. In: Nephrotoxicity. In vitro to in vivo, animals to man. Bach BH, Lock EA, editors. Plenum, New York 1989; p. 139-145.
Lorber A, Kunishima D, Simon T. Selective inhibition of T suppressor lymphocytes during chrysotherapy [Abstract]. Clin Pharmacol Ther 1983; 303: 300-302.
Newton O, Swinburn WR, Swinson DR. Proteinuria with gold nephropathy: When should gold be permanently stopped? Br J Rheumatol 1983; 22: 11-17.
Howard-Lock HE, Lock CJL, Mewa A, Kean WF. D-penicillamine; Chemistry and clinical use in rheumatic disease. Sem Arthritis Rheum 1986; 15: 261-281.
Manthorpe R, Bendixen G. Auranofin in rheumatoid arthritis: Use in patients with side-effect or lack of effect to gold sodium thiomalate or gold thioglucose and/or D-penicillamine. Scand J Rheumatol 1988; 17: 401-405.
Panayi GS, Wooley P, Batchelor JR. Genetic basis of R.A. HLA antigen, disease manifestations and toxic reactions to drugs. Br Med J 1978; 11: 1326-1328.
Wooly PH, Griffen J, Panayi GS, Batchelor JR, Welsh KI, Gibson TJ. HLA-DR antigens and toxic reaction to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis. N Engl J Med 1980; 303: 300-302.
Bardin T, Legrand L, Naveau B, Marcelli-Barge A, Debeyre N, Lathrop GM, Poirier JC, Schmid M, Ryckewaert A, Dryll A. HLA antigens and seronegative rheumatoid arthritis. Ann Rheum Dis 1985; 44: 50-53.
Dequeker J, Van Wanghe P, Verdickt W. A systematic survey of HLA-A, B, C, and D antigens and drug toxicity in rheumatoid arthritis. J Rheumatol 1984; 11: 282-286.
Ford PM. HLA antigens and drug toxicity in rheumatoid arthritis. J Rheumatol 1984; 11: 269-261.
Van Riel PL, Van de Putte LB, Gribnau FW, de Waal RM. Serum IgA and gold induced toxic effects in patients with rheumatoid arthritis. Arch Intern Med 1984; 144: 1401-1403.
Ostuni PA, Simioni M, Marson P, Travaglia P, Volante D, Gambari PF. Serum IgA and gold toxicity in rheumatoid arthritis: lack of predicting value. Clin Exp Rheumatol 1986; 4: 359-362.
Ayesh R, Mitchell SC, Waring RH, Withrington RH, Seifert MH, Smith RL. Sodium aurothiomalate toxicity and sulphoxidation capacity in rheumatoid arthritis patients. Br J Rheumatol 1987; 26: 197-201.
Shah P, Griffith SM, Shadforth MF, Fisher J, Dawes PT, Poulton KV, Thomson W, Ollier WE, Mattey DL. Can gold ltherapy be used more safely in rheumatoid arthritis? Adverse drug reactions are more likely in patients with nodular disease, independent of HLA-DR3 status. J Rheumatol 2004;31:1903-1905.
Pissuwan D, Vlaenzuela SM, Cortie MB. Therapeutic possibilities of plasmonicall heated gold nanoparticles. Trends in Biotech. 2006;24:62-67
Zharov VP, Galitovskaya EN, Johnson C, Kelly T. Synergistic enhancement of selective nanophotothermolysis with gold nanoclusters: Potential for cancer therapy. Lasers in Surg Med. 2005;37:219-226.
Blodgett RC Jr, Heuer MA, Pietrusko RG. Auranofin: a unique oral chrysotherapeutic agent. Semin Arthritis Rheum 1984; 13:255-273.
Bandilla K, Gross D, Gross W, Herrlinger J-D, Kriegel W, Muller W, Siegmeth W, Tausch G, Thumb N, Wagenhauser J. Oral gold therapy with auranofin (SK&F39162). J Rheumatol 1982; 9 (Suppl 8): 154-159.
Katz W, Alexander S, Bland J, Blechman W, Bluhm GB, Bonebrake Ra, Falbo A, Greenwald RA, Hartman S, Hobbs T, Indenbaum S, Lergier JE, Lanier BG, Lightfoot RW, Phelps P, Sheon RP, Torretti D, Wenger ME, Wilske K. The efficacy and safety of auranofin compared to placebo in rheumatoid arthritis. J Rheumatol 1982; 9 (Suppl 8): 173-178.
Wenger ME, Alexander S, Bland JH, Blechman WJ. Auranofin versus placebo in the treatment of rheumatoid arthritis. Am J Med 1983; 75: 123-127.
Menard HA, Beaudet F, Davis O, Harth M, Percy JS, Russell AS, Thompson M. Gold therapy in rheumatoid arthritis. Interim report of the Canadian multicentre prospective trial comparing sodium aurothiomalate and auranofin. J Rheumatol 1982; 9: 179-183.
Felix-Davies DD, Stewart AM, Wilkinson BR, Bateman JR, Delamere JP. A 12-month comparative trial of auranofin and D-penicil-lamine in rheumatoid arthritis. Am J Med 1983; 75(6A): 138-141.
Manthrope R, Horbov S, Sylvest J, Vinterberg H. Auranofin versus penicillamine in rheumatoid arthritis. One-year results from a prospective clinical investigation. Scand J Rheumatol 1986; 15: 13-22.
Hochberg MC. Auranofin or D-penicillamine in the treatment of rheumatoid arthritis. Ann Intern Med 1986; 105: 528-535.
Revach M, Freed RL, Ehrlich GE. Reversible proteinuria as a complication of oral gold therapy [Letter]. Arthritis Rheum 1979; 22: 1417-1418.
Plaza JJ, Herrero G, Barat A, Loutaif JJ, Hernando L, Vallado P, Oliva H. Membranous glomerulonephritis as a complication of oral gold therapy [Letter]. Ann Intern Med 1982; 97: 563-564.
Gottlieb NL. Comparative pharmacokinetics of parenteral and oral gold compounds. J Rheumatol 1982; 9 (Suppl 8): 99-109.
Blocka K. Auranofin versus injectable gold: Comparison of pharmacokinetic properties. Am J Med 1983; 75(6A): 114-122.
Abraham EP, Chain E, Baker W, Robinson R. Penicillamine, a characteristic degradiation product of penicillin. Nature 1943; 151: 107.
Walshe JM: Penicillamine. A new oral therapy for Wilson’s disease. Am J Med 1956; 2: 487-495.
Drawhall JC, Scowen EF, Watts RWE. Effects of penicillamine on cystinuria. Br Med J 1963; 1: 588-590.
Jaffe IA. Intra-articular dissociation of the rheumatoid factor. J Lab Clin Med 1962; 60: 409-421.
Jaffe IA. The effect of penicillamine in the laboratory parameters in rheumatoid arthritis. Arthritis Rheum 1965; 8: 1064-1078.
Multicenter trial group. Controlled trial of D-penicillamine in severe rheumatoid arthritis. Lancet 1973; 1: 275-280.
Steen VD, Medsger TA, Rodnan GP. D-penicillamine therapy in progressive systemic sclerosis (scleroderma). A retrospective analysis. Ann Intern Med 1982; 97: 652-659.
Jain S, Scherer PJ, Samourian S. A controlled trial of D-penicillamine therapy in primary biliary cirrhosis. Lancet 1977; 1: 831-834.
Goldberg Am Smith JA, Lochhead AC. Treatment of lead poisoning with oral penicillamine. Br Med J 1963; 1: 1270-1275.
Freeman HC, Huq F, Stevens GN: Metal binding by D-penicillamine: Crystal structure of D-penicillamine cadmium (II) hydrate. J Chem Soc Chem Commun 1976; 90-91.
Tamir M, Boustein B, Behar M, Chwat M. Mercury poisoning from an unsuspected source. Br J Ind Med 1968; 21: 299-303.
Deutsch MF, Morton JI. Dissociation of human serum macroglobulins. Science 1957; 125: 600-601.
Kean WF, Dwosh JL, Anastassiades TP, Ford PM, Kelly HG. The toxicity pattern of D-penicillamine therapy. A guide to the use in RA. Arthritis Rheum 1980; 23: 158-165.
Stein HB, Patterson AC, Offer RC, Atkins CJ, Teufel A, Robinson HS. Adverse effects of D-penicillamine in rheumatoid arthritis. Ann Intern Med 1980; 92: 24-29.
Kean WF, Lock CJL, Howard-Lock HE, Buchanan WW. Prior gold therapy does not influence the adverse effects of D-penicillamine in rheumatoid arthritis. Arthritis Rheum 1982; 25: 917-922.
Wollheim FA, Lindstrom CG. Liver abnormalities in penicillamine treated patients with rheumatoid arthritis. Scand J Rheumatol 1979; 28 (Suppl):100-107.
Barzilai D, Dickstein G, Enat R, Bassan H, Lichtig C, Gellei B. Cholestatic jaundice caused by D-penicillamine. Ann Rheum Dis 1978; 37: 98-100.
Multz CV. Cholestatic hepatitis caused by penicillamine. JAMA 1981; 246: 674-675.
Hickling P, Fuller J. Penicillamine causing acute colitis. Br Med J 1979; 2: 367.
Crawhall JC. Proteinuria in D-penicillamine-treated rheumatoid arthritis. J Rheumatol 1981; 8: 161-163.
Davison AM, Day AT, Golding JR, Thomson D. Effect of penicillamine on the kidney. Proc R Soc Med 1977; 70: 109-113.
Barraclough D, Cunningham TJ, Muirden KD. Microscopic haematuria in patients with rheumatoid arthritis on D-penicillamine. Aust NZ J Med 1981; 11: 706-708.
Singh G, Fries JF, Williams CA, Zatarain E, Spitz P, Bloch DA. Toxicity profiles of disease modifying antirheumatic drugs in rheu-matoid arthritis. J Rheumatol 1991;18: 188-194.
Weiss AS, Markenson JA, Weiss MS, Kammerer WH. Toxicity of D-penicillamine in rheumatoid arthritis. A report of 63 patients including two with aplastic anemia and one with the nephritic syndrome. Am J Med 1978; 64: 114-120.
Chalmers A, Thompson D, Stein HE, Reid G, Patterson HC. Systemic Lupus Erythematosus during penicillamine therapy for rheumatoid arthritis. Ann Intern Med 1982; 97: 659-663.
Walshe JM. Penicillamine and the SLE syndrome. J Rheumatol 1981; 8 (Suppl 7): 155-160.
Sternlieb I, Bennet B, Scheinberg IH. D-penicillamine induced Goodpasture’s syndrome in Wilson’s disease. Ann Intern Med 1975; 82: 673.
Gibson T, Barry HC, Ogg C. Goodpastures’ syndrome and D-penicillamine. Ann Intern Med 1976; 84: 100.
Gavaghan TE, McNaught PJ, Ralston M, Hayes JM. Penicillamine-induced ‘Goodpasture’s syndrome’; successful treatment of a fulminant case. Aust NZ J Med 1981; 11: 261-265.
Jaffe IA. The treatment of rheumatoid arthritis and necrotizing vasculitis with penicillamine. Arthritis Rheum 1970; 13: 436-443.
Banfi G, Imbasciati E, Guerra L, Mihatsch MJ, Ponticelli C. Extracapillary glomerulonephritis with necrotizing vasculitis in D-peni-cillamine treated patients with rheumatoid arthritis. Nephron 1983; 33: 56-60.
Torres CF, Griggs RC, Baum J, Penn AS. Penicillamine induced myasthenia gravis in progressive sclerosis. Arthritis Rheum 1980; 23: 505-508.
Dawkins RL, Garlepp MJ, McDonald BL, Williamson J. Myasthenia gravis and D-penicillamine. J Rheumatol 1981; 8 (Suppl 7): 169-174.
Vincent A, Newsom-Davis J. Acetylcholine receptor antibody characteristic in myasthenia gravis. Patients with penicillamine-induced myasthenia or idiopathic myasthenia of recent onset. Clin Exp Immunol 1982; 49: 266-272.
Bever CT, Chang HW, Penn AS, Jaffe IA, Bock E. Penicillamine induced myasthenia gravis. Effects of penicillamine on acetylcholine receptor. Neurology 1982; 32: 1077-1082.
Bocanegra T, Espinoza LR, Vassey FB, Germain BF. Myasthenia gravis in penicillamine treatment of RA. JAMA 1980; 244: 1822-1823.
Cucher BG, Goldman AL. D-penicillamine induced polymyositis in RA. Ann Intern Med 1976; 85: 615-618.
Schreider PL, Peters HA, Dahl DS. Polymyositis and penicillamine. Arch Neurol 1972; 27: 456-457.
Wojnarowska F. Dermatomyositis induced by penicillamine. J R Soc Med 1980; 73: 884.
Halverson PB, Kozin F, Bernhard GC, Goldman AL. Toxicity of penicillamine. A serious limitation to therapy in rheumatoid arthritis. JAMA 1978; 240: 1870-1871.
Steen VD, Blair S, Medsger TA. The toxicity of D-penicillamine in systemic sclerosis. Ann Intern Med 1986; 104: 699-705.
Moens HJB, Ament BJW, Feltkamp BW, Korst JK. Longterm followup of treatment with D-penicillamine to rheumatoid arthritis: effectivity and toxicity in relation to HLA antigens. J Rheumatol 1987; 14: 1115-1119.
Shiokawa Y, Horiuchi Y, Honma M, Kageyama T, Okada T, Azuma T. Clinical evaluation of D-penicillamine by multicentric double blind comparative study in chronic rheumatoid arthritis. Arthritis Rheum 1977; 20: 1464-1472.
Stockman A, Zilko PJ, Major GAC, Tait BD, Property DN, Mathews JD, Hannah MC, McCluskey J, Muirden KD. Genetic markers in rheumatoid arthritis-Relationship of toxicity from D-penicillamine. J Rheumatol 1986; 13: 269-273.
Hill HFH, Hill AGS, Day AT, Brown RM, Golding JR, Lyle WH. Maintenance dose of penicillamine in rheumatoid arthritis: A com-parison between standard and a response-related flexible regimen. Ann Rheum Dis 1979; 38: 429-433.
Williams HJ, Ward JR, Reading JC, Egger MJ, Grandone JT, Samuelson CO, Furst DE, Sullivan JM, Watson MA, Guttadauria M, Cathcart ES, Kaplan SB, Halla JT, Weinstein A, Plotz PH. Low dose D-penicillamine treatment of R.A. A controlled double blind clinical trial. Arthritis Rheum 1983; 26: 581-592.
Hill H, Hill A, Davison M. Resumption of treatment with penicillamine after proteinuria. Ann Rheum Dis 1979; 38: 229-231.
Billingsley LM, Stevens MB. The relationship between D-penicillamine-induced proteinuria and prior gold nephropathy. Johns Hopkins Med J 1981; 148: 64-67.
Halla JT, Cassidy J, Hardin JG. Sequential gold and penicillamine therapy in rheumatoid arthritis. Am J Med 1982; 72: 423-426.
Ross JH, McGinty F, Brewer DG. Penicillamine nephropathy. Nephron 1980; 26: 184-186.
Dische FE, Swinson DR, Hamilton EBD, Parsons V. Immunopathology of penicillamine-induced glomerular disease. J Rheumatol 1976; 3: 145-154.
Halla JT, Cassidy J, Hardin JG. Sequential gold and penicillamine therapy in rheumatoid arthritis. Am J Med 1982; 72: 423-426.
Bacon PA, Tribe CR, MacKenzie JC, Jones JV, Cumming RH, Amer B. Penicillamine nephropathy in rheumatoid arthritis. Q J Med 1976; 45: 661-684.
Jaffe IA, Treser G, Suzuki Y, Ehrenreich T. Nephropathy induced by D-penicillamine. Ann Intern Med 1968; 69: 549-556.
Swinson DR, Hamilton EBD, Dische FE. Penicillamine nephropathy [letter]. Ann Rheum Dis 1975; 34: 544.
Neild GH, Gartner HV, Bohle A. Penicillamine induced membranous nephritis. Scand J Rheumatol 1979; 28: 79-90.
Sellars L, Siamopoulos K, Wilkinson R, Leohapand T, Morley AR. Renal biopsy appearances in rheumatoid disease. Clin Nephrol 1983; 20: 114-120.
Herve JP, Leguy P, Cledes J, Leroy JP. Nephrotic syndrome with minimal glomerular lesions during treatment with D-penicillamine. Nouv Press Med 1980; 9: 2847.
Kitazawa K, Ohseto Y, Kawazumi H, Saito K, Shibata T, Uchida J, Yonekura M, Schiwachi S, Ito S, Sugisaki T. D-penicillamine induced lipoid nephrosis in a patient with scleroderma. Ryumachi 1982; 22: 397-403.
Hayslett JP, Bensch KG, Kashgarian MZ, Rosenberg LE. Focal glomerulitis due to penicillamine. Lab Invest 1968; 19; 376-381.
Rehan A, Johnson K. IgM Nephropathy associated with penicillamine. Am J Nephrol 1986; 6: 71-74.
Liao K, Huang CC, Ho HH, Wu CH, Hsueh S. IgM nephropathy after D-penicillamine therapy: Report of a case. J Formosan Med Assoc 1987; 86: 906-909.
Hall CL. Jawad S, Harrison PR, MacKenzie JC, Bacon PA, Klouda PT, Maclver AG. Natural course of penicillamine nephropathy: A long-term study of 33 patients. Br Med J 1988; 296: 1083-1086.
Jaffe IA. D-penicillamine. Bull Rheum Dis 1977-8; 28: 948-952.
Jaffe IA. Penicillamine in rheumatoid disease with particular reference to the rheumatic factor. Postgrad Med J 1968 (suppl): 34-40.
Swainson CP, Thompson D, Short AIK, Winney RJ. Plasma exchange in the successful treatment of drug-induced renal disease. Nephron 1982; 30: 244-249.
Peces R, Rivera JR, Arboleya LR, Lopez-Larrea C, Alvarez J. Goodpasture’s syndrome in a patient receiving penicillamine and carbimazole. Nephron 1985; 45: 316-320.
Matloff DS, Kaplan MM. D-penicillamine-induced Goodpasture’s-like syndrome in primary biliary cirrhosis: successful treatment with plasmapheresis and immunosuppressives. Gastroenterology 1980; 78: 1046-1049.
Devogelaer J-P, Pirson Y, Vandenbroucke J-M, Cosyns J-P, Brichard S, Deuxchaisnes CN. D-penicillamine induced crescentic glomerulonephritis: Report and review of the literature. J Rheumatol 1987; 14: 1036-1041.
Derk CT & Jimenez SA. Goodpasture-like syndrome induced by d-penicillamine in a patient with systemic sclerosis: Report and review of the literature. J. Rheumatol 2003;30:1616-1620.
Bienaime G, Clerbaux G, Plaisier E, Mougenot B. Ronco P, Rougier JP. D-penicillamine-induced ANCA-associated crescentic glomerulonephritis in Wilson disease. Am J Kid Dis 2007;50:821-825.
Falck HM, Tornooth T, Kock B, Wegelius O. Fatal renal vasculitis with minimal change glomerulonephritis complicating treatment with penicillamine. Acta Med Scand 1979; 205: 133-138.
Ntoso KA, Tomaszewski JE, Jimenez SA, Neilson DG. Penicillamine-induced rapidly progressive glomerulonephritis in patients with progressive systemic sclerosis: Successful treatment of two patients and review of the literature. Am J Kidney Dis 1986; 8: 159-163.
Camus J-P, Homberg JC, Crouzet J, Mery C, Delrieu F, Massias P, Abuaf N. Autoantibody formation in D-penicillamine treated rheumatoid arthritis. J Rheumatol 1981; 7 (suppl): 80-83.
Mohammed I, Barraclough D, Holborrow EJ, Ansell BM. Effect of D-penicillamine therapy on circulating immune complexes in rheumatoid arthritis. Ann Rheum Dis 1976; 35: 458-462.
Aarden LA. Pathogencity of immune complexes. In: Non-articular forms of rheumatoid arthritis. Feltkamp TEW, editor. Stafleu’s Scientific Publishing Co, Leyden 1977; 15.
Kirby JD, Dieppe PA, Huskisson EC, Smith B. D-penicillamine and immune complex deposition. Ann Rheum Dis 1979; 38: 344-346.
Nagata N, Hurtenbach U, Gleichmann E. Specific sensitization of Lyt-1+2-stereoisomer. J Immunol 1986; 136: 136-142.
Doyle MK and Cuellar ML. Drug-induced vasculitis. Expert Opin Drug Saf. 2003;2:401-409.
Emery P, Panayi GS, Huston G, Welsh KI, Mitchell SC, Shah RR, Idle JR, Smith RL, Waring RH. E-penicillamine induced toxicity in rheumatoid arthritis: the role of sulphoxidation status and HLA-DR3. J Rheumatol 1984; 11: 626-632.
Speerstra F, Reekers P, van de Putte LBA, Vandenbroucke JP, Rasker JJ, de Rooij DJRAM. HLA-DR antigens and proteinuria induced by aurothioglucose and D-penicillamine in patients with rheumatoid arthritis. J Rheumatol 1983; 10: 948-953.
Moutsopoulos HM, Skopouli FN, Sarras AK, Tsampoulas C, Mavridis AK, Constantopoulos SH, Maddison PJ. Anti-Ro(SSA) positive rheumatoid arthritis: a clinicoserological group of patients with high incidence of D-penicillamine side effects. Ann Rheum Dis 1985; 44: 215-219.
Moutsopoulos HM, Giotaki H, Maddison PJ, Mavridis AK, Drosos AA, Skopouli FN. Antibodies to cellular antigens in Greek patients with autoimmune diseases: anti-Ro(SSA) antibody a possible marker of D-penicillamine intolerance. Ann Rheum Dis 1984; 43: 285-287.
Dodd MJ, Griffiths ID, Thomson M. Adverse reaction to D-penicillamine after gold toxicity. Br Med J 1980; 26: 1498-1500.
Webley M, Coomes EN. Is penicillamine therapy in RA. influenced by previous gold ? Br Med J 1978; 2: 91.
Klouda PT, Manos J, Acheson EJ, Dyer PA, Goldby FS, Harris R, Lawler W, Mallick NP, Williams G. Strong association between idiopathic membranous nephropathy and HLA-DRW3. Lancet 1979; 2: 770-771.
Swiss Federal Commission for the rheumatic diseases, Subcommission for Research. HLA-DR antigens in rheumatoid arthritis -A Swiss collaborative study; final report. Rheumatol Int 1986; 6: 89-92.
Schiff MH and Whelton A. Renal toxicity associated with disease-modifying antirheumatic drugs used for the treatment of rheumatoid arthritis. Semin Arthritis Rheum 2000; 30:196-208.
Rundles RW, Wyngaarden JB, Hitchings GH, Elison B, Silberman HR. Effects of a xanthine oxidase inhibitor on thiopurine me-tabolism, hyperuricemia, and gout. Trans Assoc Am Physicians 1963; 76: 126-140.
Rundles RW, Metz EN, Silberman HR. Allopurinol in the treatment of gout. Ann Intern Med 1966; 64: 229-258.
Auerbach R, Orentrich N. Alopecia and ichthyosis secondary to allopurinol. Arch Dermatol 1968; 98: 104.
Boston Collaborative Drug Surveillance Program. Allopurinol and cytotoxic drugs. JAMA 1974; 227: 1036-1040.
Pinnas G. Possible association between macular lesions and allopurinol. Arch Ophthalmol 1968; 79: 786-787.
Korting HC, Lesch R. Acute cholangitis after allopurinol treatment. Lancet 1978; 1: 275-276.
Boyer TD, Sun N, Reynolds TB. Allopurinol-hypersensitivity. Vasculitis and liver damage. West J Med 1977; 126: 143-147.
Raper R, Barnes P, Ibels L, Lunzer M, Lauer C. Fulminant hepatic failure due to allopurinol. Aust NZ J Med 1984; 14: 63-65.
Bailey RR, Neale TJ, Lynn KL. Allopurinol-associated arteritis. Lancet 1976; 2: 907.
Greene ML, Fujimoto WY, Seegmiller JE. Urinary xanthine stones, a rare complication of allopurinol therapy. N Eng J Med 1969; 280: 426-427.
LaRosa C, McMullen L, Bakdash S, Ellis D, Krishnamurti L, Wu HY, Mortiz ML. Acute renal failure from xanthine nephropathy during management of acute leukemia. Pediatr Nephrol 2007;22:132-135
Rebentisch G, Stolz s, Muche J. Xanthinuria with xantine lithiasis in a patient with Lesch-Nyhan syndrome under allopurinol therapy. Aktuelle Urol. 2004;215-221.
Jarzobski J, Ferry J, Womboldt D, Fitch DM, Egan JD: Vasculitis with allopurinol therapy. Am Heart J 1970; 79: 116-121.
Kantor GC. Toxic epidermal necrolysis, azotemia, and death after allopurinol therapy. JAMA 1970; 212: 478-479.
Mills RM. Severe hypersensitivity reactions associated with allopurinol. JAMA 1971; 216: 799-802.
Young JC, Boswell RB, Niles AS: Severe allopurinol hypersensitivity. Arch Intern Med 1974; 134: 553-558.
Gelbart DC, Weinstein AB, Fajardo CF. Allopurinol-induced interstitial nephritis. Ann Intern Med 1977; 86: 196-198.
Lupton GP, Odom RB. The allopurinol hypersensitivity syndrome. J Am Acad Dermatol 1979; 1(4): 365-374.
Grussendorf M, Andrassy K, Waldherr R, Ritz E. Systemic hypersensitivity to allopurinol with acute interstitial nephritis. Am J Nephrol 1981; 1: 195-109.
Singer JZ, Wallace SL. The allopurinol hypersensitivity syndrome. Unnecessary morbidity and mortality. Arthritis Rheum 1986; 29: 82-87.
Tausche AK, Aringer M, Schroeder HE, Bornstein SR, Wunderlich C, Wozel G. The janus faces of allopurinol - Allopurinol Hyper-sensitivity Syndrome. Am J Med. 2008;121:e3-e4.
Petersel D, Schlesinger N. Treatment of acute gout in hospitalized patients. J. Rheumatol 2007;34:1566-1568.
Raebel MA, McClure DL, Simon SR, Chan KA, Feldstein AC. Gunter MJ, Lafata JE, Harrold L, Nelson WW, Platt R. Frequency of serum creatinine monitoring during allopurinol therapy in ambulatory patients. Ann Pharmacother 2006;40:386-391.
McMenamie RA, Davies LM, Crasswell OW. Drug induced interstitial nephritis, hepatitis and exfoliative dermatitis. Aust NZ J Med 1976; 6: 583-587.
McKendrick MW, Geddes AM. Allopurinol hypersensitivity. Br J Med 1979; i: 988.
Boyer TD, Sun N, Reynolds TB. Allopurinol-hypersensitivity. Vasculitis and liver damage. West J Med 1977; 126: 143-147.
Morel D, Cuez S, Merville P, Deminiere C, Tamisier JM, Potaux L. Recurrent renal failure associated with hypersensitivity to al-lopurinol. Nephrol Dial Transplant 1999;14:780-781.
Emmerson BT, Hazelton RA, Frazer IH. Some adverse reactions to allopurinol may be mediated by lymphocyte reactivity to oxypurinol. Arthritis Rheum 1988; 31: 436-440.
Elion GB, Kovensky A, Hitchings GH. Metabolic studies of allopurinol, an inhibitory of xanthine oxidase. Biochem Pharmacol 1965; 15: 863-880.
Elion GB, Yu TF, Gutman AB, Hitchings GH. Renal clearance of oxypurinol, the chief metabolite of allopurinol. Am J Med 1968; 45: 69-77.
Hande KR, Noone RM, Stone WJ. Severe allopurinol toxicity. Description and guidelines for prevention in patients with renal insufficiency. Am J Med 1984; 76: 47-56.
Simmonds HA, Cameron JS, Morris GS, Davies PM. Allopurinol in renal failure and the tumor lysis syndrome. Clin Chim Acta 1986; 31: 189-195.
Puig JP, Casas EA, Ramos TH, Michan AA, Mateos FA. Plasma oxypurinol concentration in a patient with allopurinol hypersensitiv-ity. J Rheumatol 1989; 16: 842-844.
Suzuki Y, Inagi R, Aono T, Yamanishi K, Shihara T. Human herpesvirus 6 infrction a risk factor for the development of severe drug-induced hypersensitivity syndrome. Arch Dermatol 1998; 134: 1108-1112.
Tiu RV, Mountantonakis SE, Dunbar AJ, Schreiber MJ Jr. Tumor lysis syndrome. Semin Thromb Hemost. 2007;33:397-407.
Becker MA, Schumacher R Jr., Wortmann RL, MacDonald PA, Eustace D, Palo WA, Streit J, Joseph-Ridge N. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Eng J Med 2005;353:2450-2461.
Gelber AC. Febuxostat versus allopurinol for gout. N Engl J Med 2006;354:1532-1533.
Stamp L, Searle M, O’Donnell J, Chapman P. Gout in solid organ transplantation; A challenging clinical problem. Drugs 2005;65:2593-2611.
Sood AR, Burry LD, Cheng DKF. Clarifying the role of rasburicase in tumor lysis syndrome. Pharmacother 2007;27:11-=121.
Bessmertny O, Robitaille LM, Cairo MS. Rasburicase: a new approach for preventing and/or treating tumor lysis syndrome. Cur-rent Pharmaceutical Design. 2005;11:4177-4185.
Ronco C, Inguaggiato P, Bordoni V, DeCal M, Bonello M, Andrikos E, Assuman Y, Rattanarat R, Bellomo R. Rasburicase therapy in acute hyperuricemia and renal dysfunction. Contrib Nephrol 2005;147:115-123.
Suh WM, Wainberg ZA, deVos S, Cohen AH, Kurtz I, Nguyen MK. Acute lymphoblastic leukemia presenting as acute renal failure. Naature Clin Pract. Nephrology 2007;3:106-110.
DeAngelis S, Noce A, DiRenzo L, Cianci R, Naticchia A, Giarrizzo GR, Giordano F, Tozzo C, Splendiani G, DeLorenzo A. Is rasburicase an effective alternative to allopurinol for the management of hyperuricemia in renal failure patients/ A double -blind randomized study. Euro Rev Med Pharmacol Sci. 2007;11:179-184.
Kelley WN. Gout and related disorders of purine metabolism. In: Textbook of Rheumatology (1st edition). Kelly WN, Harris Jr ED, Sledge CB, editors. WB Saunders, Philadelphia 1981; p. 1397-1437.
Fam AG. Gout in the elderly. Drug & Aging. 1999;13:229-243.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Ueda, S., Porter, G.A. (2008). Gold salts, D-penicillamine and allopurinol. In: De Broe, M.E., Porter, G.A., Bennett, W.M., Deray, G. (eds) Clinical Nephrotoxins. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-84843-3_19
Download citation
DOI: https://doi.org/10.1007/978-0-387-84843-3_19
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-84842-6
Online ISBN: 978-0-387-84843-3
eBook Packages: MedicineMedicine (R0)