Clinical response in relation to dose of penicillamine in the treatment of rheumatoid arthritis.

Large differences exist in the maintenance doses of penicillamine that clinicians regard as effective and safe in rheumatoid arthritis. From a study of the results of several clinical trials and surveys it is evident that, while some of the differences of regimen result from true individual variation in the response of patients to particular doses, others derive from the variety of criteria of efficacy and toxicity used by different clinicians. No regimen has proved clinically curative or has consistently halted radiographic deterioration. In most surveys regardless of dose at least one-third of the patients stop treatment because of toxicity or inefficacy. Placebo-controlled trials have been of short (less than 1 year) duration and longer term surveys have not included a placebo group so that the therapeutic contribution of penicillamine therapy in the long-term treatment of the generality of rheumatoid patients cannot be estimated accurately. Good control of the disease has been recorded in numbers of patients for five years or more at different doses of penicillamine, most clinicians being prepared to raise or lower doses according to response. Under the prevailing circumstances it may be impossible to complete an adequately controlled long term dose/response study of penicillamine in rheumatoid arthritis.

Penicillamine in metal poisoning.

Penicillamine is used to treat heavy metal poisonings because it forms complexes in vitro with several toxic metals, including lead, cadmium, mercury, and gold. Urinary excretion of lead is immediately, markedly increased by penicillamine, but this is not true for the urinary excretion of cadmium, mercury, and gold. There is evidence that cadmium is shifted from 1 binding site to another in vivo; this may also be true of mercury and gold. Whether the effects of such possible shifts are beneficial or adverse is unknown.

Maintenance dose of penicillamine in rheumatoid arthritis: a comparison between a standard and a response-related flexible regimen.

There is much individual variation in the response of rheumatoid arthritis (RA) to penicillamine, some patients deriving benefit from very small doses. A dose of 750 mg daily is widely regarded as standard, and, while their RA commonly responds, many patients discontinue treatment because of adverse reactions to penicillamine. A more flexible prescribing policy might be more successful in the long term and was tested in 1 group of 20 patients, another receiving a 'standard' regimen, each beginning treatment at a low dose level. Of those who were given increases of dose only if response was poor 17 completed 1 year of treatment on an average maintenance dose of 308 mg daily, but only 11 of the other group on an average dose 613 mg daily. Proteinuria, which was found only in the latter group accounted for 6 withdrawals, all at doses of 625 mg daily or above. The reduction in rheumatoid activity appeared to be of about the same degree among the members of both groups who completed 12 months of treatment. Penicillamine should be given initially in a low dose and this should be raised only if there is lack of response after at least 4 weeks.

Dimethylformamide and alcohol intolerance.

Facial flushing and other symptoms were reported by 19 of a group of 102 men who worked with dimethylformamide (DMF). Twenty-six of the 34 episodes occurred after the workers had consumed alcoholic drinks. The metabolite N-methylformamide (MF) was detected in the urine on 45 occasions, the highest recorded concentration being 77 microliter/litre. The highest recorded concentration of DMF in air was 200 ppm. The DMF-ethanol reaction is possibly attributable to the inhibition of acetaldehyde metabolism, probably by MF.

Haemodialysis and copper fever.

A syndrome of headache, chills, sweating, nausea, and exhaustion during and after haemodialysis is described and likened to metal fume fever. A patient has been cured of this syndrome following removal of copper-containing parts from the water-path of her home dialysis system.