Phenytoin in rheumatoid arthritis

SIR, We were interested to read the comparative study of phenytoin and gold in rheumatoid arthritis (RA) by Richards et al,' prompted by the work of Macfarlane et al, who had shown improvements in clinical and laboratory tests and suggested that phenytoin may, therefore, have properties of a second line drug.2 Richards et al found phenytoin to have significant beneficial effects on haemoglobin and the erythrocyte sedimentation rate but on only one of four clinical measurements. We have also studied phenytoin in RA,3 but without knowledge of other work in progress. Our interest was stimulated by several properties of phenytoin, including inhibition of collagenase and stimulation of collagen synthesis4 5; there appeared to be possible implications with respect to prevention and reversal of rheumatoid bone loss. In an open study with follow up after drug withdrawal we found significant improvements in clinical measurements over 32 weeks; serum C reactive protein, plasma viscosity, and haemoglobin also improved, but changes were not significant. Three independent studies have, therefore, shown slightly divergent although positive results with phenytoin in RA. Richards et al commented that phenytoin may be unique among second line drugs in having a greater effect on laboratory than on clinical tests, though Macfarlane et al and we showed significant clinical improvement, albeit in open studies. Confirmation of a positive effect of phenytoin on the erythrocyte sedimentation rate is, however, of particular interest because its control within the normal range may reduce the rate of bone erosion.6 7 The most appropriate assessment of phenytoin in RA may be by its long term effects on bone assessed radiographically and to our knowledge this has not been examined. Although 'phenytoin is unlikely to become a first choice second line agent',' it should not now be dismissed.