Does sulphoxidation state predict gold toxicity in rheumatoid arthritis?

Gold (sodium aurothiomalate) is commonly used as a disease modifying agent in rheumatoid arthritis. Its use is, however, limited by occurrence of toxic reactions, which may develop in up to 45% of patients.' The mechanism of toxicity is not clear, although a genetic basis for haematological and renal toxicity has been shown.2 Penicillamine and captopril are also effective disease modifying drugs and share a similar toxicity profile to sodium aurothiomalate.3 All three drugs have in common a sulphydryl group: their toxicity and efficacy may be due to parent sulphydryl groups or a toxic metabolite of oxidation of sulphur. The oxidation of some sulphydryl groups is thought to be mediated by a hepatic flavoprotein oxidase.4 The ability of this or an associated enzyme system to handle sulphydryl groups seems to correlate with ability to oxidise sulphur, as measured by the ratio of free sulphides to sulphoxides after a fixed oral dose of carbocisteine (another drug containing sulphur); this ratio is the sulphoxidation index. Patients with rheumatoid arthritis with a poor sulphoxidation state are more susceptible to penicillamine toxicity5; we assessed whether they are also more susceptible to sodium aurothiomalate toxicity.