Gold therapy

If a response occurs, treatment intervals may be lengthened to every two weeks, then three weeks, and then monthly. Patients who respond usually remain at least on monthly therapy. Discontinuation of gold therapy maintenance may result in recurrence of arthritic symptoms, which may not remit even with reinstitution of gold therapy. Auranofin (22), adrninistered in 3-mg amounts twice daily or 6 mg once daily, should be continued for at least six months, assuming a favorable response. 

Penicillamine (29) can be effective in patients with refractory RA and may delay progression of erosions, but adverse effects limit its useflilness. The most common adverse side effects for penicillamine are similar to those of parenteral gold therapy, ie, pmritic rash, protein uria, leukopenia, and thrombocytopenia. Decreased or altered taste sensation is a relatively common adverse effect for penicillamine. A monthly blood count, platelet count, and urinalysis are recommended, and also hepatic and renal function should be periodically monitored. Penicillamine is teratogenic and should not be used during pregnancy. 

Clinical trials for r-IEN-y in RA indicated that the dmg is well tolerated (52). Consistent improvement in tender and swollen joint scores was observed, but a large number of patients were needed in the trial to show statistical significance for r-IEN-y treatment. In certain individuals, responses were remarkable. An additive effect between r-IEN-y and penicillamine was detected. Efficacy was lower when r-IEN-y was combined with gold therapy. Research is continuing. 

Gold suppresses or prevents but, but does not cure, arthritis and synovitis. The therapeutic effects from gold compounds occur slowly. Early improvement is often limited to reduction in morning stiffness. The full effects of gold therapy are not known for 6 to 8 weeks or in some cases after 6 months of therapy. 

Tolerance to gold usually decreases with age. The older adult must be carefully monitored when receiving gold therapy. 

Gold compounds are given cautiousty to older adults Tolerance for gold therapy decreases with advancing age. 

Penicillamine Gold therapy, antimalarial or cytotoxic drugs, oxyphenbutazone or phenylbutazone A Do not use these drugs in patients who are concurrently receiving penicillamine. These drugs are associated with similar serious hematologic and renal reactions. 

Many drugs, especially quinidine and heparin, induce antibodies leading to thrombocytopenia. In most cases the antibodies are drug-dependent however, there are many examples in which the antibodies are autoimmune in nature [42], even for drugs, such as quinidine that are classically associated with drug-dependent antibodies [43], Gold therapy, in particular, is associated with autoimmune-thrombocytopenia [44],... 

A common metabolite found in the urine and plasma of patients treated with gold drugs is [Au(CN)2], an ion which readily enters cells and can inhibit the oxidative burst of white blood cells. It may therefore be an active metabolite of gold drugs. It also exhibits anticancer and anti-HIV activity. The high Au contents of red blood cells of smokers receiving gold therapy has been attributed to the inhalation of HCN in smoke (420). 

As with many metals, gold can damage the kidney. Lesions of the mouth and skin are seen following gold therapy to treat arthritis. 

Toxic manifestations of gold therapy are most common after a minimal total amount (200-300 mg) of gold has been administered. Serious reactions necessitating discontinuance of therapy or antidotal therapy are encountered in perhaps 5% of the patients. 

Both oral and parenteral gold therapy frequently produces dermatitis, usually preceded and accompanied by pruritus. Stomatitis may accompany dermatitis, which may be preceded by a metallic taste in the mouth of the patient. Blue or gray skin discoloration can arise from gold deposition in that tissue, and photosensitivity may also occur. Unlike parenteral gold compounds, au-ranofin does not accumulate appreciably in the skin. Auranofin, but not the parenteral gold preparations, most frequently causes diarrhea (about 50%), abdominal pain, nausea, and anorexia. 

Mild proteinuria is fairly common and does not always require discontinuance of therapy however, severe proteinuria may indicate a toxic nephritis. The proteinuria is usually reversible when gold administration is stopped. Hepatotoxicity has also been reported. Fatahties from gold therapy have been reported, usually a consequence of a blood dyscrasia. The most common hematological abnormality is eosinophilia. Serious blood dyscrasias, such as thrombocytopenia, agranulocytosis, and hypoplastic or aplastic anemia, are rare. 

Bone marrow aplasia, history of gold-induced pathologies, including blood dyscra-sias, exfoliative dermatitis, necrotizing enterocolitis, and pulmonary fibrosis, serious adverse effects with previous gold therapy, severe blood dyscrasias... 

Several reviews on gold therapy have appeared recently, with an emphasis on metabolism by Shaw,19 on ligand exchange reactions by Sadler and coworkers,20 on EXAFS and XANES studies by Elder et al.,21 and on studies of gold thiolate complexes in vivo and in vitro by Brown and Smith.22... 

Forrestier, in the 1940s, believed the copper-containing compounds Cupralene (sodium 3-(allylcuprothiouredo)-l-benzoate) and Dicuprene (bis[8-hydroxyquinolinedi(diethylammonium sulfonate)]Cu(II)) to be superior to gold therapy.24... 

Adverse Side Effects. Adverse effects are relatively common with gold therapy, with approximately one third of patients experiencing some form of toxic effect.84 The primary side effects caused by gold compounds are gastrointestinal distress (diarrhea, indigestion), irritation of the oral mucosa, and rashes and... 

Penicillamine (Cuprimine), a derivative of penicillin, is officially classified as a chelating agent that is often used in the treatment of heavy metal intoxication (e.g., lead poisoning). In addition, this drug has been used in patients with severe rheumatoid arthritis, and seems to be as effective as other DMARDs such as methotrexate, sulfasalazine, and gold therapy.68 98 Penicillamine, however, tends to be substantially more toxic than other DMARDs, and is therefore used rarely in the treatment of specific patients with rheumatoid arthritis.68... 

Because ocular chrysiasis does not lead to visual impairment, inflammation, or corneal endothelial changes, gold therapy does not need to be reduced or discontinued. This benign process requires only routine follow-up.The deposits often disappear within 3 to 6 months after cessation of therapy occasionally, they are found years after therapy has been discontinued. 

Haemochromatosis leads to an increase in the density of the liver parenchyma, which correlates with the accumulation of iron. CT scans reveal a remarkably dense and bright liver parenchyma with density values of up to +140 HU (so-called white liver). The deposition of 1 g iron results in a rise in density of 1 HU. (20) CT densitometry clearly facilitates effective control of therapeutic success in this storage disease. It is not possible, however, to differentiate pronounced secondary haemo-siderosis. Hyperdense values are also found in longterm gold therapy, in glycogen thesaurismosis and M. Wilson, or in chronic arsenic poisoning. 

Liver injury is an extremely rare complication of gold therapy (SEDA-14, 189) (48). The underlying mechanisms are probably complex and certainly variable. Overdosage can cause centrilobular necrosis and bile... 

There are various contraindications to gold therapy (83) active hepatic disease, impaired renal function, colitis, patients with a history of hematological disorders, and patients who have recently had radiotherapy (because of the depressant action of radiotherapy on hemopoietic tissue). 

Rau R. Hepatotoxicity of gold compounds. In Schattenkirchner M, Muller W, editors. Modem Aspects of Gold Therapy. Rheumatology, an Annual Review. Basel-New York Karger, 1983 8 188. 

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