Penicillamine in rheumatoid arthritis. Connective tissue changes and alterations in serum copper and phase reactants in relation to clinical improvement.

Thirteen patients, aged 27 to 70 years, with definite or classical rheumatoid arthritis were treated with penicillamine for six months. Skin biopsies and blood samples were compared with a clinical evaluation before and after therapy. The analyses of the skin included determinations of total collagen, thermal reaction of collagen, salt soluble collagen, in vitro uptake of 14C-proline and synthesis of 14C-hydroxyproline, as well as determinations of nucleic acids and proteoglycans. Serum concentrations of acute phase reactants, immunoglobulins, complement C3 and C4, rheumatoid factor, and iron, copper, and zinc were also determined. A positive correlation was found between clinical improvement and a fall in the number of granulocytes, a decrease in the concentration of acute phase reactants and serum copper, and an increase in salt soluble collagen of the skin. The total skin collagen decreased during treatment with penicillamine. The changes in skin collagen may reflect a generalized effect of penicillamine on collagen. These alterations may be part of an anti-inflammatory action of penicillamine.