Effects of Sleep Pathophysiology on Rheumatoid Arthritis

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  • Impact of Sleep Deprivation on Patients With Rheumatoid Arthritis

    Impact of Sleep Deprivation on Patients With Rheumatoid Arthritis

    The impact of sleep deprivation as a health hazard is well recognized. Sleep is considered an important predictor of immunity. There is increasing evidence that sleep deprivation may in fact be a driver for the development or progression of inflammatory joint diseases, including rheumatoid arthritis (RA).

  • There is emerging evidence that circadian rhythm, which determines the timing of sleep in a 24-hour rhythm in accordance with the external light-dark cycle, is a strong regulator of immunologic processes.Circadian oscillation of components of the immune system has been shown to be an integral regulator and may have an impact on disease onset and response to therapies.

    The Impacts of Circadian Rhythm on RA Disease Onset

    There is emerging evidence that circadian rhythm, which determines the timing of sleep in a 24-hour rhythm in accordance with the external light-dark cycle, is a strong regulator of immunologic processes.Circadian oscillation of components of the immune system has been shown to be an integral regulator and may have an impact on disease onset and response to therapies.

  • Controlled experimental studies on the effects of acute sleep loss in human subjects have shown that mediators of inflammation are altered by sleep deprivation. There is evidence that impaired functioning of regulatory T cells is involved.

    Effects of Acute Sleep Loss on Inflammation

    Controlled experimental studies on the effects of acute sleep loss in human subjects have shown that mediators of inflammation are altered by sleep deprivation. There is evidence that impaired functioning of regulatory T cells is involved.

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  • In addition to optimizing relief of the core symptoms of RA, chronotherapy might also relieve important comorbid conditions such as depression and sleep disturbances. It has been argued that increased relief of pain and stiffness, resulting from improved treatment efficacy with chronotherapy, might also alleviate the psychological impact of RA that manifests as depression and anxiety.

    Addressing Comorbid Conditions in Patients with RA

    In addition to optimizing relief of the core symptoms of RA, chronotherapy might also relieve important comorbid conditions such as depression and sleep disturbances. It has been argued that increased relief of pain and stiffness, resulting from improved treatment efficacy with chronotherapy, might also alleviate the psychological impact of RA that manifests as depression and anxiety.

  • Although the pathophysiologic mechanisms are largely unknown, the link between sleep deprivation and RA is thought to involve the breakdown of immunologic self-tolerance, thereby driving development of autoimmune diseases.

    Pathophysiologic Link Between Sleep Deprivation and RA

    Although the pathophysiologic mechanisms are largely unknown, the link between sleep deprivation and RA is thought to involve the breakdown of immunologic self-tolerance, thereby driving development of autoimmune diseases.

  • The most compelling evidence for successful RA chronotherapy is with glucocorticoids. The coordination of glucocorticoid administration with the nocturnal rise in blood IL-6 concentrations results in substantially reduced morning stiffness and pain, compared with the same dose taken in the morning. Modified-release prednisone enables bedtime administration with release of glucocorticoids at the optimal time for suppression of proinflammatory cytokines.

    Glucocorticoid Chronotherapy

    The most compelling evidence for successful RA chronotherapy is with glucocorticoids. The coordination of glucocorticoid administration with the nocturnal rise in blood IL-6 concentrations results in substantially reduced morning stiffness and pain, compared with the same dose taken in the morning. Modified-release prednisone enables bedtime administration with release of glucocorticoids at the optimal time for suppression of proinflammatory cytokines.

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  • Sleep deprivation has also been shown to increase levels of several proinflammatory cytokines, including interleukin (IL)-1, IL-1β, IL-6, IL-17, and tumor necrosis factor-alpha (TNF-α), all of which are known to be associated with several autoimmune diseases, including RA.

    Sleep Deprivation and Increases in Proinflammatory Cytokines

    Sleep deprivation has also been shown to increase levels of several proinflammatory cytokines, including interleukin (IL)-1, IL-1β, IL-6, IL-17, and tumor necrosis factor-alpha (TNF-α), all of which are known to be associated with several autoimmune diseases, including RA.

  • Chronotherapeutic tailoring of RA treatment with nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, or glucocorticoids to suppress proinflammatory peripheral mediators might therefore have the additional benefit of reducing symptoms by reducing neuroimmune periphery-to-brain signaling.

    Chronotherapeutic Tailoring of RA Treatment

    Chronotherapeutic tailoring of RA treatment with nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, or glucocorticoids to suppress proinflammatory peripheral mediators might therefore have the additional benefit of reducing symptoms by reducing neuroimmune periphery-to-brain signaling.

  • The prevalence of sleep disorders in those with RA is high, and clinicians should consider evaluating this important problem to improve not only quality of life for patients but also to influence disease outcome by improving sleep quality.

    Summary and Clinical Applicability

    The prevalence of sleep disorders in those with RA is high, and clinicians should consider evaluating this important problem to improve not only quality of life for patients but also to influence disease outcome by improving sleep quality.

Sleep deprivation is common in those with rheumatoid arthritis (RA) and is associated with poor health outcomes. It may also be a driver for RA disease processes. Chronotherapy that targets the nocturnal rise in inflammatory mediators in the blood of patients with RA may have an important complementary role in RA treatment to improve both radiographic progression of disease and patient-reported outcomes, including fatigue and depression.

The prevalence of sleep disorders in those with RA is high, and clinicians should consider evaluating this important problem to improve not only quality of life for patients but also to influence disease outcome by improving sleep quality.

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References

1. Buttgereit F, Smolen JS, Coogan AN, Cajochen C. Clocking in: chronobiology in rheumatoid arthritis. Nat Rev Rheumatol. 2015;11(6):349-356.

2. Gibbs JE, Ray DW. The role of the circadian clock in rheumatoid arthritis. Arthritis Res Ther. 2013;15(1):205.

3. Hegarty RS, Treharne GJ, Stebbings S, Conner TS. Fatigue and mood among people with arthritis: carry-over across the day. Health Psychol. 2016 Feb 11. [Epub ahead of print]

4. Hsiao YH, Chen YT, Tseng CM, et al. Sleep disorders and increased risk of autoimmune diseases in individuals without sleep apnea. Sleep. 2015;38(4):581-586.

5. Katz P, Margaretten M, Trupin L, Schmajuk G, Yazdany J, Yelin E. Role of sleep disturbance, depression, obesity, and physical inactivity in fatigue in rheumatoid arthritis. Arthritis Care Res (Hoboken). 2016;68(1):81-90

6. Purabdollah M, Lakdizaji S, Rahmani A, Hajalilu M, Ansarin K. Relationship between sleep disorders, pain and quality of life in patients with rheumatoid arthritis. J Caring Sci. 2015;4(3):233-241.

7. Sangle SR, Tench CM, D’Cruz DP. Autoimmune rheumatic disease and sleep: a review. Curr Opin Pulm Med. 2015;21(6):553-556.

8. Sariyildiz MA, Batmaz I, Bozkurt M, et al. Sleep quality in rheumatoid arthritis: relationship between the disease severity, depression, functional status and the quality of life. J Clin Med Res. 2014;6(1):44-52.

9. Westhovens R, Van der Elst K, Matthys A, Tran M, Gilloteau I. Sleep problems in patients with rheumatoid arthritis. J Rheumatol. 2014;41(1):31-40.

10. Xu Y, Zhang L, Huang A, Zhao Y, Liu Y. An investigation of sleep disturbance and related factors in rheumatoid arthritis patients [in Chinese]. Zhonghua Nei Ke Za Zhi. 2015;54(11):927-930.

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