Rheumatoid arthritis, treatment with gold compounds

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. 

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. 

Chrysotherapy was not readily accepted in the United States As late as 1934, Cecil reported that drugs played a relatively minor role in treatment of rheumatoid arthritis and that his experience with gold compounds had never shown striking results (19) ... 

The two best-known therapies involving kinetically inert coordination compounds are chrysotherapy (treatment of rheumatoid arthritis with gold compounds) and the relatively new treatment of certain cancers with platinum compounds. 

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. 

Specific criteria for the diagnosis of rheumatoid arthritis in adults are listed in Table 16-1. In addition to the adult form of this disease, there is also a form of arthritis that occurs in children known commonly as juvenile rheumatoid arthritis, or by the more recent term juvenile idiopathic arthritis (JIA). Juvenile arthritis differs from the adult form of this disease—the age of onset (younger than 16 years) and other criteria help to differentiate these two types of rheumatoid joint disease.69,109 Drug treatment of adult and juvenile rheumatoid arthritis is fairly similar, however, with the exception that children may not respond as well to certain medications (e.g., hydroxychloroquine, gold compounds, penicillamine) compared to adults.79 80 Consequently, in this chapter most of the discussion of the management of rheumatoid arthritis is directed toward the adult form. 

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. ... 

---