Toxicity of longterm low dose D-penicillamine therapy in rheumatoid arthritis. Cooperative Systematic Studies of Rheumatic Disease Group.

After a controlled, double blind multicenter trial of D-penicillamine in the treatment of rheumatoid arthritis, 148 patients were followed for an additional year in an open label trial. Complications of longterm D-penicillamine included rash, gastrointestinal manifestations, proteinuria, bone marrow depression, myasthenia gravis, myositis, acute febrile reaction and pemphigus foliaceus. With the exception of one patient with myasthenia gravis, all adverse reactions resolved after withdrawal of D-penicillamine. While the complications of D-penicillamine therapy are usually dose related, these reactions can occur at any time and at any dose. Continued and frequent longterm monitoring of D-penicillamine therapy is required.