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Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis
  1. Andrea W M Evers1,
  2. Elisabeth W M Verhoeven2,
  3. Henriët van Middendorp1,
  4. Fred C G J Sweep3,
  5. Floris W Kraaimaat1,
  6. A Rogier T Donders4,
  7. Agnes E Eijsbouts5,
  8. Antoinette I M van Laarhoven1,
  9. Sabine J M de Brouwer1,
  10. Lieke Wirken1,
  11. Timothy R D J Radstake6,
  12. Piet L C M van Riel7
  1. 1Department of Medical Psychology, Radboud University Nijmegen Medical Centre 840, Nijmegen, The Netherlands
  2. 2Dr. Leo Kannerhuis, Nijmegen, The Netherlands
  3. 3Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  4. 4Department for Health Evidence, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  5. 5Department of Rheumatology, St Maartenskliniek, Nijmegen, The Netherlands
  6. 6Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, The Netherlands
  7. 7Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  1. Correspondence to Professor A W M Evers, Department of Medical Psychology, Radboud University Nijmegen Medical Centre 840, PO Box 9101, Nijmegen 6500 HB, The Netherlands; a.evers{at}


Objectives Both stressors and stress vulnerability factors together with immune and hypothalamus–pituitary–adrenal (HPA) axis activity components have been considered to contribute to disease fluctuations of chronic inflammatory diseases, such as rheumatoid arthritis (RA). The aim of the present study was to investigate whether daily stressors and worrying as stress vulnerability factor as well as immune and HPA axis activity markers predict short-term disease activity and symptom fluctuations in patients with RA.

Methods In a prospective design, daily stressors, worrying, HPA axis (cortisol) and immune system (interleukin (IL)-1β, IL-6, IL-8, interferon (IFN)-γ, tumour necrosis factor α) markers, clinical and self-reported disease activity (disease activity score in 28 joints, RA disease activity index), and physical symptoms of pain and fatigue were monitored monthly during 6 months in 80 RA patients.

Results Multilevel modelling indicated that daily stressors predicted increased fatigue in the next month and that worrying predicted increased self-reported disease activity, swollen joint count and pain in the next month. In addition, specific cytokines of IL-1β and IFN-γ predicted increased fatigue 1 month later. Overall, relationships remained relatively unchanged after controlling for medication use, disease duration and demographic variables. No evidence was found for immune and HPA axis activity markers as mediators of the stress–disease relationship.

Conclusions Daily stressors and the stress-vulnerability factor worrying predict indicators of the short-term course of RA disease activity and fatigue and pain, while specific cytokines predict short-term fluctuations of fatigue. These stress-related variables and immune markers seem to affect different aspects of disease activity or symptom fluctuations independently in RA.

  • Psychology
  • Rheumatoid Arthritis
  • Disease Activity

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