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Circadian rhythms in RA
  1. M Cutolo,
  2. B Seriolo,
  3. C Craviotto,
  4. C Pizzorni,
  5. A Sulli
  1. Research Laboratory and Division of Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto XV,6 16132 Genova, Italy Correspondence to: Professor M Cutolo;

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    Possible roles of cortisol and melatonin

    It is well known that some clinical signs and symptoms of rheumatoid arthritis (RA) vary within a day and between days, and the morning stiffness seen in patients with RA has become one of the diagnostic criteria of the disease (fig 1).1

    Figure 1

    Clinical signs and symptoms of articular inflammation in patients with RA change consistently as a function of the hours of the day: pain and joint stiffness are greater after waking up in the morning than in the afternoon or evening.

    Among the clinical signs of joint inflammation in patients with RA, the intensity of pain changes consistently as a function of the hours of the day: pain is greater after waking up in the morning than in the afternoon or evening.2 In patients with RA circadian variations are also found in joint swelling and finger size and these symptoms are in phase with the circadian rhythm of pain. The RA rhythms differ in phase by about 12 hours from the circadian changes of left and right hand grip strength: a greater grip strength is seen when joint circumferences and the subjective ratings of stiffness and pain are least and vice versa.3

    “Clinical signs and symptoms in RA depend on the time of day”

    Therefore, clinical signs and symptoms in RA show a rhythm that seems driven by a biological clock.

    Biological rhythms in experimental inflammation

    Biological rhythms have been seen in different models of inflammation, and maximal inflammation occurred during the activity period of the animals—that is, between midnight and 8 00 am.4

    Biological rhythms with a periodicity longer than 24 hours have also been detected, and a circaseptan rhythm (almost seven days) of paw oedema, over a period of 30 days, was observed, with peak of inflammation every 6–7 days.5 Furthermore, …

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