C-reactive protein (CRP) levels were measured in 105 patients with rheumatoid arthritis (RA) during treatment with slow-acting anti-rheumatoid drugs D-penicillamine, alclofenac, hydroxychloroquine, gold, sulphasalazine and azathioprine. A control group treated with aspirin alone was also included. Patients were assessed clinically (pain score, articular index and summated change score) and in terms of acute-phase reactants (CRP, haptoglobin, fibrinogen, ESR and plasma viscosity) at eight separate clinic visits during the 6-month treatment period. The estimation of CRP was found to be more useful than haptoglobin, fibrinogen or ESR as an index of disease activity.

Most arthritic conditions are characterized by chronic inflammation, resulting in secondary changes in serum biochemistry. In an attempt to profile different mechanisms of inflammation which might account for the clinical diversity of rheumatic diseases, we have measured C-reactive protein (CRP), plasma viscosity, serum histidine and total serum sulphydryl in 259 patients with rheumatoid arthritis (RA), 84 with ankylosing spondylitis (AS), 76 with osteoarthritis, 69 with psoriatic arthritis, 34 with systemic lupus erythematosus (SLE), 36 with Reiter's syndrome and 121 normal controls. The most extreme abnormalities were seen in rheumatoid arthritis and the least in osteoarthritis. The seronegative spondarthritides and SLE occupied a midway position, emphasizing a correlation between biochemical abnormality and severity of inflammation. A low serum histidine characterized both RA and SLE. The former was more likely to be associated with a raised CRP. Plasma viscosity was characteristically raised in psoriatic arthritis and CRP in AS.

Diphosphonates reduce the rate of bone turnover. They have additional pharmacological properties improving adjuvant arthritis in rats and lowering ESR in this condition. We have evaluated etidronate disodium, a diphosphonate commonly prescribed in the United Kingdom for Paget's disease in patients with rheumatoid arthritis. Apart from an early improvement in articular index, perhaps reflecting anti-inflammatory activity, no significant change occurred in clinical variables or in laboratory indices of 'secondline' action at a dose of 5 mg/kg/day.

The serum and synovial fluid (SF) histidine, sulphydryl, and protein concentrations were compared in simultaneous samples from 84 patients with rheumatoid arthritis (RA) and a control group comprising 29 patients with osteoarthritis (OA). The SF levels of histidine were higher than the serum levels in the RA patients but significantly lower than corresponding results in patients with OA (P less than 0.001). The latter had levels of serum and SF histidine which were equivalent and within the normal range. Greater quantities of protein were found in the SF of the patients with RA compared with the OA group. The serum and SF sulphydryl concentrations expressed as mumol/g protein were low but in equilibrium in patients with RA. However the SF sulphydryl (mumol/g protein) was depressed relative to serum levels in patients with OA.

HertsSUMMARY To investigate the cause of low serum histidine in rheumatoid arthritis (RA) single oral and intravenous doses of L-histidine were administered to patients with active RA, and to an equal number of age and sex matched control subjects. In the first study 13 patients and their controls received a 100 mg kg-1 dose of L-histidine as an aqueous slurry. Significant differences were seen in body weight, predose baseline serum histidine concentration, Cmax, t,½, and area under curve, AUCOo In a second study six patients and six controls each received a 50 mg kg-1 dose of L-histidine both orally and intravenously on two separate occasions. The patients with RA had a lower baseline serum histidine concentration, a lower volume of distribution, and a shorter plasma half life than the controls, but these differences were not statistically significant. No difference was seen in bioavailability or clearance. Low serum histidine in RA is unlikely to be due to malabsorption from the gut, uptake by abnormal gut flora, or increased metabolism.