Penicillamine in rheumatoid arthritis. A problem of toxicity

Penicillamine has proved an effective second line agent in rheumatoid arthritis. Its use, however, is limited by its toxicity. Long term studies show that only between 30 and 40% of patients started on penicillamine are still taking the drug at 2 years. Toxicity is the chief reason for stopping treatment, the commonest adverse effects requiring cessation of therapy being proteinuria (10 to 13%), skin rashes (5 to 9%), gastrointestinal events (5%) and thrombocytopenia or leucopenia (2 to 5%). A number of autoimmune syndromes may rarely be induced by penicillamine. HLA-B8, Dr3 positive individuals and poor sulfoxidisers are at increased risk of developing toxicity. Meticulous supervision of penicillamine therapy is required to minimise toxicity.