Gold toxicity: chemical, structural, biological and clinical experimental issues

Abstract

Gold compounds have been used in the treatment of rheumatoid arthritis since 1929 [1]. but to date the mechanisms of efficacy and toxicity have not been established. Forestier’s original study of 15 patients treated with gold thiopropanol sodium sulphonate identified adverse effects in 11 patients, 3 of whom were stated to have serious side-effects [1]. Today, the incidence of gold therapy associated toxicity is in the order of 30–50% with approximately 10% of patients experiencing a significantly severe problem which requires withdrawal from therapy [2]. However, clinical interpretation of severity varies, and author bias is a major factor in identification of frequency of adverse reactions. An experienced clinician may continue gold treatment even after the development of a mild skin rash or small degree of proteinuria whereas the inexperienced clinician may immediately discontinue therapy. In a clinical trial such outcomes will be recorded differently. Of equal importance to the problem of interpretation, is the fact that the pharmacodynamics of gold compounds are poorly understood. Several factors contribute to this problem: the nature of gold chemistry, the structural formulation of the compounds and the biological activity of gold and the ligands. The following review of the literature outlines some of the basic science experimental issues we have encountered in the study of gold toxicity and outlines our clinical research experience with adverse reactions to gold complexes.