Rheumatoid arthritis, gold effect

There are two classes of drugs, gold compounds and antimalarials which, whilst they have been shown to possess certain experimental anti-inflammatory activities, seem, on the basis of their clinical effects, to have a delayed action against rheumatoid arthritis. Their effect appears to be more selective than that of the salicylates and other drugs previously discussed. Indeed, in view of their favourable influence on the sheep-cell agglutination titre (SCAT), they may even modify the disease process itself. Control of the disease, however, is usually incomplete and their ultimate effect is doubtful . 

The extraction of gold by leaching is described in the previous section. Gold is used extensively in the manufacture of jewelry. Interestingly, Au(I) compounds are very effective in the treatment of rheumatoid arthritis, and there is recent evidence that certain go Id-containing compounds have anticancer properties. 

Two forms of gold provide medical treatments. The radioactive isotope Au-198, with a short half-life of 2.7 days, is used to treat cancer and is produced by subjecting pure gold to neutrons within a nuclear reactor. A gold salt, a solution called sodium thiosulfate (AuNa O Cl ), is injected as an internal treatment for rheumatoid arthritis. However, since gold and some of its compounds are toxic when ingested, this treatment may cause complications such as skin rashes and kidney failure. It is a less popular treatment, particularly with the development of newer and more effective medications. 

Penicillamine is an analog of cysteine. Only the d-isomer is used. In patients with progressive rheumatoid arthritis which is refractory to treatment with gold compounds it may retard progression of articular cartilage and bone destruction. For these effects to become apparent a latency period of 3 4 month often is needed. Its mechanism is unknown but it supposedly interferes with the synthesis of DNA, collagen and mucopolysaccharides. 

Sulfasalazine (Azulfidine) is approved for the treatment of rheumatoid arthritis and ulcerative colitis. It is also used to treat ankylosing spondylitis and Crohn s disease. Comparisons of sulfasalazine with other DMARDs suggest that it is more effective than hydroxychloroquine, azathioprine, and oral gold compounds. It is at least as effective as intramuscular gold and penicillamine. It has a greater degree of toxicity than hydroxychloroquine but less than gold compounds and penicillamine. After 5 years, approximately 75% of patients have discontinued sulfasalazine therapy, primarily because of a lack of efficacy as opposed to intolerable side effects. 

Mecfianism of Action Gold compounds that alter cellular mechanisms, collagen biosynthesis, enzyme systems, and immune responses. Therapeutic Effect Suppress synovitis in the active stage of rheumatoid arthritis. 

Gold sodium thiomalate provides a stimulus for liver, kidney and possibly other cells to change the body distribution of zinc and copper. Proteins such as metalloproteins, superoxide dismutase and metallothioneins19 help the cell carry out this task. These essential metals are important in the physiological processes relevant to rheumatoid arthritis, and thus it also appears possible that the gold complexes may mediate their antiarthritic activity through an effect on the metabolism of zinc and copper. 

Methotrexate (Folex, Rheumatrex) is an antimetabolite used frequently in the treatment of cancer (see Chapter 36). There is considerable evidence that this drug is also one of the most effective DMARDs.15 76 Methotrexate has been shown to slow the effects of rheumatoid arthritis as evidenced by decreased synovitis, decreased bone erosion, and less narrowing of the joint space.37 The therapeutic effects of methotrexate have also been reported to be equal to, or better than, other DMARDs such as oral gold or azathioprine, and methotrexate may offer an advantage in terms of a rapid onset.68,90 Hence, methotrexate s popularity as a DMARD has increased during the past few years, and this drug is often the first DMARD used to treat rheumatoid arthritis in both adults and children.76... 

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... 

The disease-modifying agents used in rheumatoid arthritis are associated with a number of side effects that could influence rehabilitation. Some of these drugs, such as the gold compounds and methotrexate, may cause headache and nausea, which may be bothersome during the therapy session. Joint pain and swelling may also occur with drugs such as methotrexate and peni-... 

Gold is effective for active rheumatoid arthritis and has been shown to slow radiologic progression of the disease. It has also been used in Sjogren s syndrome and juvenile rheumatoid arthritis, while use in psoriatic arthritis is controversial. In Japan, gold is used to treat asthma. The oral form of gold is effective in rheumatoid arthritis, but it appears less effective than the intramuscular formulation and is generally felt to have only modest effects. 

Chrysiasis, or gold deposition in various tissues of the body, can occur in the conjunctiva after gold injection for rheumatoid arthritis and appears as irregular brownish deposits in the cornea and superficial layers of the conjunctiva. No deposits are found in the skin of the lid. Conjunctival changes associated with gold treatment are generally benign. Discontinuation of therapy usually eliminates these effects. 

Thiomalate (salt of ester of the malic acid) also has been used very successfully to treat severe cases of rheumatoid arthritis. A complete cure or a significant improvement has been noted in approximately 50% of patients using this treatment modality, with 40% of patients exhibiting side effects. Thiomalate is also toxic and possesses cumulative action. Minimal concentrations of the gold compounds reach many cells and remain in the body for years. ... 

In rheumatoid arthritis the most commonly used gold salts are sodium aurothiomalate and aurothioglucose (3). There is some reason to believe that adverse effects are less frequent with the suspensions (of aurothioglucose or aurothiosulfate) than with the more rapidly absorbed solution (of sodium gold thiomalate) (SEDA-16, 233) (4). 

Gold-induced lung toxicity is an infrequent adverse effect in patients with rheumatoid arthritis and psoriatic arthritis. There are three types interstitial pneumonitis, bronchiolitis obliterans with organizing pneumonia, and bronchiolitis obliterans the first is the most frequent. There have been two reports of gold-induced lung toxicity in psoriatic arthritis (16). 

In one series of some 5500 patients with juvenile rheumatoid arthritis, 105 were found to have developed secondary amyloidosis 37 of the latter had been receiving sodium aurothiomalate. In 12 of these children the time between withdrawal of gold (because of adverse effects) and the finding of amyloid A was less than six months (SEDA-21,237). 

Hill C, Pile K, Henderson D, Kirkham B. Nenrological side effects in two patients receiving gold injections for rheumatoid arthritis. Br J Rheumatol 1995 34(10) 989-90. 

Furst DE. Mechanism of action, pharmacology, chnical efficacy and side effects of auranofin. An orally administered organic gold compound for the treatment of rheumatoid arthritis. Pharmacotherapy 1983 3(5) 284-98. 

Hakala M, van Assendeht AH, 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(3) 177-82. 

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