Major side effects of gold therapy
- Alice Klinkhoff, MD
Alice Klinkhoff, MD
- Clinical Associate Professor
- University of British Columbia
- Section Editor
- Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
- Section Editor — Rheumatoid Arthritis
- Emeritus Professor of Rheumatology, Imperial College London
- Visiting Professor, Oxford University
Gold is used in the treatment of rheumatoid arthritis (RA) and has also been used for the treatment of other rheumatic and autoimmune diseases, including psoriatic arthritis and pemphigus vulgaris. Its use is limited by a high incidence of side effects, a requirement for close clinical and laboratory monitoring, and the need for gold sodium thiomalate (GST), the more efficacious form of gold, to be administered by periodic intramuscular injection.
Gold is used in a highly selected patient population, given the many treatment options for RA. Patients are typically referred for gold therapy because of one of the following: concerns regarding immunosuppression, coexisting chronic infection, contraindications to other therapies or the failure of such therapies, unavailability of other medications due to excessive cost for the patient or health care system, and pregnancy planning in selected women in whom treatment options may be limited .
The major side effects of gold therapy and their management will be reviewed here. The use of gold compounds for the treatment of rheumatic disease and the pulmonary adverse effects of gold therapy are discussed in detail elsewhere. (See "Use of gold compounds in rheumatic diseases" and "Drug-induced lung disease in rheumatoid arthritis", section on 'Gold'.)
OVERVIEW OF GOLD TOXICITY
Side effects occur in approximately 30 percent of patients treated with parenteral gold compounds, and are the most common reason for discontinuing gold therapy (table 1) [2-4]. The following major points should be noted:
●The most common side effects are pruritus, dermatitis, stomatitis, and proteinuria (see 'Mucocutaneous effects' below and 'Proteinuria and membranous glomerulonephritis' below). These toxicities typically present within the first six months of therapy, and occur more frequently in patients treated with gold sodium thiomalate (GST), the parenterally administered preparation, compared with auranofin, which is taken orally. Loose, soft stools are a common side effect of auranofin, and watery diarrhea may occur in up to 5 percent of patients on this drug [4,5].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Cheung JM, Scarsbrook D, Klinkhoff AV. Characterization of patients with arthritis referred for gold therapy in the era of biologics. J Rheumatol 2012; 39:716.
- Gordon DA, Klinkhoff AV. Second line agents: Sulfasalzine, antimalarials, gold and penicillamine. In: Kelley's Textbook of Rheumatology, 7th ed, Ruddy S, Harris ED, Sledge CB (Eds), WB Saunders, Philadelphia 2005. p.877.
- van Jaarsveld CH, Jahangier ZN, Jacobs JW, et al. Toxicity of anti-rheumatic drugs in a randomized clinical trial of early rheumatoid arthritis. Rheumatology (Oxford) 2000; 39:1374.
- Kean WF, Kean IR. Clinical pharmacology of gold. Inflammopharmacology 2008; 16:112.
- Abruzzo JL. Auranofin: a new drug for rheumatoid arthritis. Ann Intern Med 1986; 105:274.
- Ho M, Pullar T. Vasomotor reactions with gold. Br J Rheumatol 1997; 36:154.
- Healey LA, Backes MB. Nitritoid reactions and angiotensin-converting-enzyme inhibitors. N Engl J Med 1989; 321:763.
- Nixon J, Pande I. Gold, nitritoid reactions and angiotensin-converting enzyme inhibitors. Rheumatology (Oxford) 2006; 45:118.
- Arthur AB, Klinkhoff A, Teufel A. Nitritoid reactions: case reports, review, and recommendations for management. J Rheumatol 2001; 28:2209.
- Van Gaalen FA, Allaart CF. Parenteral gold, antimalarials, and sulfasalazine. In: Rheumatology, Fifth edition, Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH (Eds), Mosby/Elsevier, Philadelphia 2011. p.505-507.
- Penneys NS. Gold therapy: dermatologic uses and toxicities. J Am Acad Dermatol 1979; 1:315.
- Jones G, Brooks PM. Injectable gold compounds: an overview. Br J Rheumatol 1996; 35:1154.
- Klinkhoff AV, Teufel A. How low can you go? Use of very low dosage of gold in patients with mucocutaneous reactions. J Rheumatol 1995; 22:1657.
- Lehman AJ, Esdaile JM, Klinkhoff AV, et al. A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study. Arthritis Rheum 2005; 52:1360.
- Leonard PA, Moatamed F, Ward JR, et al. Chrysiasis: the role of sun exposure in dermal hyperpigmentation secondary to gold therapy. J Rheumatol 1986; 13:58.
- Almoallim H, Klinkhoff AV, Arthur AB, et al. Laser induced chrysiasis: disfiguring hyperpigmentation following Q-switched laser therapy in a woman previously treated with gold. J Rheumatol 2006; 33:620.
- Sakkas LI, Chikanza IC, Vaughan RW, et al. Gold induced nephropathy in rheumatoid arthritis and HLA class II genes. Ann Rheum Dis 1993; 52:300.
- Hall CL, Fothergill NJ, Blackwell MM, et al. The natural course of gold nephropathy: long term study of 21 patients. Br Med J (Clin Res Ed) 1987; 295:745.
- Klinkhoff AV, Teufel A. Reinstitution of gold after gold induced proteinuria. J Rheumatol 1997; 24:1277.
- Silverberg DS, Kidd EG, Shnitka TK, Ulan RA. Gold nephropathy. A clinical and pathologic study. Arthritis Rheum 1970; 13:812.
- Leonard PA, Bienz SR, Clegg DO, Ward JR. Hematuria in patients with rheumatoid arthritis receiving gold and D-penicillamine. J Rheumatol 1987; 14:55.
- Adachi JD, Bensen WG, Kassam Y, et al. Gold induced thrombocytopenia: 12 cases and a review of the literature. Semin Arthritis Rheum 1987; 16:287.
- von dem Borne AE, Pegels JG, van der Stadt RJ, et al. Thrombocytopenia associated with gold therapy: a drug-induced autoimmune disease? Br J Haematol 1986; 63:509.
- Aaron S, Davis P, Percy J. Neutropenia occurring during the course of chrysotherapy: a review of 25 cases. J Rheumatol 1985; 12:897.
- Yan A, Davis P. Gold induced marrow suppression: a review of 10 cases. J Rheumatol 1990; 17:47.
- Kay AG. Myelotoxicity of gold. Br Med J 1976; 1:1266.
- Gordon DA, Hyland RH, Broder I. Rheumatoid arthritis. In: The Lung in Rheumatic Diseases, Cannon GW, Zimmerman GA (Eds), Marcel Dekker, New York 1990. p.229.
- Tomioka R, King TE Jr. Gold-induced pulmonary disease: clinical features, outcome, and differentiation from rheumatoid lung disease. Am J Respir Crit Care Med 1997; 155:1011.
- Winterbauer RH, Wilske KR, Wheelis RF. Diffuse pulmonary injury associated with gold treatment. N Engl J Med 1976; 294:919.
- Fam AG, Paton TW, Shamess CJ, Lewis AJ. Fulminant colitis complicating gold therapy. J Rheumatol 1980; 7:479.
- Stein HB, Urowitz MB. Gold-induced enterocolitis. Case report and literature review. J Rheumatol 1976; 3:21.
- Kaplinsky N, Pras M, Frankl O. Case reports. Severe enterocolitis complicating chrysotherapy. Ann Rheum Dis 1973; 32:574.
- Ward JR, Williams HJ, Egger MJ, et al. Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum 1983; 26:1303.
- Favreau M, Tannenbaum H, Lough J. Hepatic toxicity associated with gold therapy. Ann Intern Med 1977; 87:717.
- Fam AG, Gordon DA, Sarkozi J, et al. Neurologic complications associated with gold therapy for rheumatoid arthritis. J Rheumatol 1984; 11:700.
- Almarzouqi M, Scarsbrook D, Klinkhoff A. Gold therapy in women planning pregnancy: outcomes in one center. J Rheumatol 2007; 34:1827.
- Tarp U, Graudal H. A followup study of children exposed to gold compounds in utero. Arthritis Rheum 1985; 28:235.
- OVERVIEW OF GOLD TOXICITY
- POSTINJECTION VASOMOTOR/NITRITOID REACTIONS
- ADVERSE EFFECTS OF CHRONIC THERAPY
- Mucocutaneous effects
- Proteinuria and membranous glomerulonephritis
- Hematologic toxicity
- - Thrombocytopenia
- - Neutropenia and aplastic anemia
- Interstitial pneumonitis
- Diarrhea and enterocolitis
- Other side effects
- MONITORING FOR TOXICITY
- MANAGEMENT OF GOLD TOXICITY
- SUMMARY AND RECOMMENDATIONS