Time of day of prednisolone administration in rheumatoid arthritis.

Twelve patients with rheumatoid arthritis took low dosage prednisolone, mean 5.6 mg daily, at either 0800 h, 1300 h or 2300 h in a double-blind within-patient controlled trial. Each patient was studied on each of the 3 regimens to assess control of symptoms and side effects and also to examine circadian rhythms in signs and symptoms. For several days during each drug regimen patients collected urine at each micturition and self-assessed their signs and symptoms. Circadian rhythms of finger joint swelling and of grip strength were determined, and were similar on all regimens, with morning peaks of symptoms and signs. Subjective and objective assessments showed no differences in effectiveness between the 3 times of administration of prednisolone. Urinary excretion patterns were similar to those observed in untreated people. The quantity and circadian pattern of 11-hydroxycorticosteroids excreted were similar to those in healthy patients, providing no evidence of adrenal cortical suppression at the dose levels studied, even when this dose was taken in the evening. A single morning dose of prednisolone appears in many patients to be as effective as a single evening dose or divided doses. It is therefore reasonable to initiate therapy with a morning-only regimen, because adrenopituitary suppression should be minimised.

Spontaneous rupture of the Achilles tendon in a patient with gout.

A 49-year-old man with long-standing gout suffered a spontaneous rupture of the Achilles tendon. Surgical repair was performed, and gouty tophi were found in the severed end of the tendon. The possible causes of this spontaneous rupture are discussed.

Circadian variations in the signs and symptoms of rheumatoid arthritis and in the therapeutic effectiveness of flurbiprofen at different times of day.

1 Seventeen patients with rheumatoid arthritis were studied in a double-blind crossover trial contrasting three different times of administration of twice-daily flurbiprofen. 2 Twelve of these patients were also studied when taking the same dose of flurbiprofen as a split dose four times a day. 3 Symptoms and signs of the disease were self-assessed throughout the day for several days on each regimen and the information was analysed for rhythmicity. 4 Twice a day flurbiprofen may be more effective than four times daily flurbiprofen, and the regimen without an evening dose was the least effective of three twice-daily treatments tested. 5 Circadian rhythms of grip strength and finger joint size were demonstrated, and were similar on all treatment regimens. 6 These rhythms have a similar pattern to those detected during studies of immune responses, and it is suggested that morning stiffness in rheumatoid arthritis is not only the result of nocturnal inactivity, and may respond to appropriately timed medication given to decrease inflammation or to suppress other aspects of the immune response.