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Peripheral and Central Mechanisms of Fatigue in Inflammatory and Noninflammatory Rheumatic Diseases

  • RHEUMATIC MANIFESTATIONS OF OTHER DISEASES (R STAUD, SECTION EDITOR)
  • Published:
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Abstract

Fatigue is a common symptom in a large number of medical and psychological disorders, including many rheumatologic illnesses. A frequent question for health care providers is related to whether reported fatigue is “in the mind” or “in the body”—that is, central or peripheral. If fatigue occurs at rest without any exertion, this suggests psychological or central origins. If patients relate their fatigue mostly to physical activities, including exercise, their symptoms can be considered peripheral. However, most syndromes of fatigue seem to depend on both peripheral and central mechanisms. Sometimes, muscle biopsy with histochemistry may be necessary for the appropriate tissue diagnosis, whereas serological tests generally provide little reliable information about the origin of muscle fatigue. Muscle function and peripheral fatigue can be quantified by contractile force and action potential measurements, whereas validated questionnaires are frequently used for assessment of mental fatigue. Fatigue is a hallmark of many rheumatologic conditions, including fibromyalgia, myalgic encephalitis/chronic fatigue syndrome, rheumatoid arthritis, systemic lupus, Sjogren’s syndrome, and ankylosing spondylitis. Whereas many studies have focused on disease activity as a correlate to these patients’ fatigue, it has become apparent that other factors, including negative affect and pain, are some of the most powerful predictors for fatigue. Conversely, sleep problems, including insomnia, seem to be less important for fatigue. There are several effective treatment strategies available for fatigued patients with rheumatologic disorders, including pharmacological and nonpharmacological therapies.

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References

Papers of particular interest, published recently, have been highlighted as: •Of importance •• Of major importance

  1. Pawlikowska T, Chalder T, Hirsch SR, Wallace P, Wright DJ, Wessely SC. Population based study of fatigue and psychological distress. BMJ. 1994;308:763–6.

    PubMed  CAS  Google Scholar 

  2. Chen MK. The epidemiology of self-perceived fatigue among adults. Prev Med. 1986;15:74–81.

    PubMed  CAS  Google Scholar 

  3. Chaudhuri A, Behan PO. Fatigue in neurological disorders. Lancet. 2004;363:978–88.

    PubMed  Google Scholar 

  4. Chaudhuri A, Behan PO. Fatigue and basal ganglia. J Neurol Sci. 2000;179:34–42.

    PubMed  CAS  Google Scholar 

  5. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International chronic fatigue syndrome study group. Ann Intern Med. 1994;121:953–9.

    PubMed  CAS  Google Scholar 

  6. Kuratsune H, Yamaguti K, Takahashi M, Misaki H, Tagawa S, Kitani T. Acylcarnitine deficiency in chronic fatigue syndrome. Clin Infect Dis. 1994;18 Suppl 1:S62–7.

    PubMed  Google Scholar 

  7. Narita M, Nishigami N, Narita N, et al. Association between serotonin transporter gene polymorphism and chronic fatigue syndrome. Biochem Biophys Res Commun. 2003;311:264–6.

    PubMed  CAS  Google Scholar 

  8. Tanaka S, Kuratsune H, Hidaka Y, et al. Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome. Int J Mol Med. 2003;12:225–30.

    PubMed  CAS  Google Scholar 

  9. Buchwald D, Pearlman T, Umali J, Schmaling K, Katon W. Functional status in patients with chronic fatigue syndrome, other fatiguing illnesses, and healthy individuals. Am J Med. 1996;101:364–70.

    PubMed  CAS  Google Scholar 

  10. Hurwitz BE, Coryell VT, Parker M, et al. Chronic: fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function. Clin Sci. 2010;118:125–35.

    Google Scholar 

  11. Lavergne MR, Cole DC, Kerr K, Marshall LM. Functional impairment in chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivity. Can Fam Physician. 2010;56:e57–65.

    PubMed  Google Scholar 

  12. Jason LA, Richman JA, Rademaker AW, et al. A community-based study of chronic fatigue syndrome. Arch Intern Med. 1999;159:2129–37.

    PubMed  CAS  Google Scholar 

  13. Jason LA, Porter N, Hunnell J, Rademaker A, Richman JA. CFS prevalence and risk factors over time. J Health Psychol. 2011;16:445–56.

    PubMed  Google Scholar 

  14. Komaroff AL, Fagioli LR, Doolittle TH, et al. Health status in patients with chronic fatigue syndrome and in general population and disease comparison groups. Am J Med. 1996;101:281–90.

    PubMed  CAS  Google Scholar 

  15. Cairns R, Hotopf M. A systematic review describing the prognosis of chronic fatigue syndrome. Occup Med-Oxf. 2005;55:20–31.

    PubMed  CAS  Google Scholar 

  16. Jason LA, Taylor RR, Kennedy CL. Chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivities in a community-based sample of persons with chronic fatigue syndrome-like symptoms. Psychosom Med. 2000;62:655–63.

    PubMed  CAS  Google Scholar 

  17. Aaron LA, Burke MM, Buchwald D. Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch Intern Med. 2000;160:221–7.

    PubMed  CAS  Google Scholar 

  18. Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res. 2010;62:600–10.

    Google Scholar 

  19. White KP, Speechley M, Harth M, Ostbye T. Co-existence of chronic fatigue syndrome with fibromyalgia syndrome in the general population. A controlled study. Scand J Rheumatol. 2000;29:44–51.

    PubMed  CAS  Google Scholar 

  20. Hudson JI, Goldenberg DL, Pope Jr HG, Keck Jr PE, Schlesinger L. Comorbidity of fibromyalgia with medical and psychiatric disorders. Am J Med. 1992;92:363–7.

    PubMed  CAS  Google Scholar 

  21. Goldenberg DL, Simms RW, Geiger A, Komaroff AL. High frequency of fibromyalgia in patients with chronic fatigue seen in a primary care practice. Arthritis Rheum. 1990;33:381–7.

    PubMed  CAS  Google Scholar 

  22. Lombardi VC, Ruscetti FW, Das GJ, et al. Detection of an Infectious Retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science. 2009;326:585–9.

    PubMed  CAS  Google Scholar 

  23. Light AR, Lee S. Spinal cord physiology of nociception. In: Bushnell MC, Basbaum AI, editors. Pain. San Diego: Academic Press; 2008. p. 311–30.

    Google Scholar 

  24. Light AR, Hughen RW, Zhang J, Rainier J, Liu Z, Lee J. Dorsal root ganglion neurons innervating skeletal muscle respond to physiological combinations of protons, ATP, and lactate mediated by ASIC, P2X, and TRPV1. J Neurophysiol. 2008;100:1184–201.

    PubMed  CAS  Google Scholar 

  25. Light AR, Vierck CJ, Light KC. Myalgia and Fatigue. In: Kruger L, Light AR, editors. Translational pain research: From mouse to man. Boca Raton: CRC Press; 2010. p. 150–72.

    Google Scholar 

  26. Ream E, Richardson A. Fatigue: a concept analysis. Int J Nurs Stud. 1996;33:519–29.

    PubMed  CAS  Google Scholar 

  27. Ream E, Richardson A. Fatigue in patients with cancer and chronic obstructive airways disease: a phenomenological enquiry. Int J Nurs Stud. 1997;34:44–53.

    PubMed  CAS  Google Scholar 

  28. Tiesinga LJ, Dassen TW, Halfens RJ. Fatigue: a summary of the definitions, dimensions, and indicators. Nurs Diagn. 1996;7:51–62.

    PubMed  CAS  Google Scholar 

  29. Witte KK, Clark AL. Why does chronic heart failure cause breathlessness and fatigue? Prog Cardiovasc Dis. 2007;49:366–84.

    PubMed  Google Scholar 

  30. Pollard LC, Choy EH, Gonzalez J, Khoshaba B, Scott DL. Fatigue in rheumatoid arthritis reflects pain, not disease activity. Rheumatology. 2006;45:885–9.

    PubMed  CAS  Google Scholar 

  31. Atzeni F, Cazzola M, Benucci M, Di Franco M, Salaffi F, Sarzi-Puttini P. Chronic widespread pain in the spectrum of rheumatological diseases. Best Pract Res Clin Rheumatol. 2011;25:165–71.

    PubMed  Google Scholar 

  32. Piepoli M, Clark AL, Volterrani M, Adamopoulos S, Sleight P, Coats AJ. Contribution of muscle afferents to the hemodynamic, autonomic, and ventilatory responses to exercise in patients with chronic heart failure: effects of physical training. Circulation. 1996;93:940–52.

    PubMed  CAS  Google Scholar 

  33. Lipkin DP, Canepa-Anson R, Stephens MR, Poole-Wilson PA. Factors determining symptoms in heart failure: comparison of fast and slow exercise tests. Br Heart J. 1986;55:439–45.

    PubMed  CAS  Google Scholar 

  34. Adamopoulos S, Coats AJ, Brunotte F, et al. Physical training improves skeletal muscle metabolism in patients with chronic heart failure. J Am Coll Cardiol. 1993;21:1101–6.

    PubMed  CAS  Google Scholar 

  35. Light KC, Bragdon EE, Grewen KM, Brownley KA, Girdler SS, Maixner W. Adrenergic Dysregulation and Pain With and Without Acute Beta-Blockade in Women With Fibromyalgia and Temporomandibular Disorder. J Pain. 2009;10:542–52.

    PubMed  CAS  Google Scholar 

  36. Wyller VB, Saul JP, Walloe L, Thaulow E. Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome. Eur J Appl Physiol. 2008;102:623–32.

    PubMed  Google Scholar 

  37. Kaye DM, Lambert GW, Lefkovits J, Morris M, Jennings G, Esler MD. Neurochemical evidence of cardiac sympathetic activation and increased central nervous system norepinephrine turnover in severe congestive heart failure. J Am Coll Cardiol. 1994;23:570–8.

    PubMed  CAS  Google Scholar 

  38. Hasking GJ, Esler MD, Jennings GL, Burton D, Johns JA, Korner PI. Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation. 1986;73:615–21.

    PubMed  CAS  Google Scholar 

  39. Notarius CF, Ando S, Rongen GA, Floras JS. Resting muscle sympathetic nerve activity and peak oxygen uptake in heart failure and normal subjects. Eur Heart J. 1999;20:880–7.

    PubMed  CAS  Google Scholar 

  40. Francis GS, Cohn JN, Johnson G, Rector TS, Goldman S, Simon A. Plasma norepinephrine, plasma renin activity, and congestive heart failure. Relations to survival and the effects of therapy in V-HeFT II. The V-HeFT VA Cooperative Studies Group. Circulation. 1993;87:VI40–8.

    PubMed  CAS  Google Scholar 

  41. Notarius CF, Atchison DJ, Floras JS. Impact of heart failure and exercise capacity on sympathetic response to handgrip exercise. Am J Physiol Heart Circ Physiol. 2001;280:H969–76.

    PubMed  CAS  Google Scholar 

  42. Cordero DL, Sisto SA, Tapp WN, LaManca JJ, Pareja JG, Natelson BH. Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome. Clin Auton Res. 1996;6:329–33.

    PubMed  CAS  Google Scholar 

  43. Bearn J, Wessely S. Neurobiological aspects of the chronic fatigue syndrome. Eur J Clin Invest. 1994;24:79–90.

    PubMed  CAS  Google Scholar 

  44. Freeman R, Komaroff AL. Does the chronic fatigue syndrome involve the autonomic nervous system? Am J Med. 1997;102:357–64.

    PubMed  CAS  Google Scholar 

  45. Lucini D, Covacci G, Milani R, Mela GS, Malliani A, Pagani M. A controlled study of the effects of mental relaxation on autonomic excitatory responses in healthy subjects. Psychosom Med. 1997;59:541–52.

    PubMed  CAS  Google Scholar 

  46. Montague TJ, Marrie TJ, Klassen GA, Bewick DJ, Horacek BM. Cardiac function at rest and with exercise in the chronic fatigue syndrome. Chest. 1989;95:779–84.

    PubMed  CAS  Google Scholar 

  47. Fischler B, Dendale P, Michiels V, Cluydts R, Kaufman L, De MK. Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatization and psychopathology. J Psychosom Res. 1997;42:369–78.

    PubMed  CAS  Google Scholar 

  48. Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation. 1991;84:482–92.

    PubMed  CAS  Google Scholar 

  49. Pagani M, Lucini D, Mela GS, Langewitz W, Malliani A. Sympathetic overactivity in subjects complaining of unexplained fatigue. Clin Sci (Lond). 1994;87:655–61.

    CAS  Google Scholar 

  50. Maloney EM, Gurbaxani BM, Jones JF, Coelho LD, Pennachin C, Goertzel BN. Chronic fatigue syndrome and high allostatic load. Pharmacogenomics. 2006;7:467–73.

    PubMed  Google Scholar 

  51. Wang HJ, Li YL, Gao L, Zucker IH, Wang W. Alteration in skeletal muscle afferents in rats with chronic heart failure. J Physiol. 2010;588:5033–47.

    PubMed  CAS  Google Scholar 

  52. Scott AC, Wensel R, Davos CH, et al. Chemical mediators of the muscle ergoreflex in chronic heart failure: a putative role for prostaglandins in reflex ventilatory control. Circulation. 2002;106:214–20.

    PubMed  CAS  Google Scholar 

  53. Meeus M, Nijs J. Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clin Rheumatol. 2007;26:465–73.

    PubMed  Google Scholar 

  54. Buchwald D. Fibromyalgia and chronic fatigue syndrome: similarities and differences. Rheum Dis Clin North Am. 1996;22:219–43.

    PubMed  CAS  Google Scholar 

  55. Woolf CJ. Central sensitization: Implications for the diagnosis and treatment of pain. Pain. 2011;152:S2–S15.

    PubMed  Google Scholar 

  56. Staud R, Nagel S, Robinson ME, Price DD. Enhanced central pain processing of fibromyalgia patients is maintained by muscle afferent input: a randomized, double-blind, placebo controlled trial. Pain. 2009;145:96–104.

    PubMed  Google Scholar 

  57. Affaitati G, Costantini R, Fabrizio A, Lapenna D, Tafuri E, Giamberardino MA. Effects of treatment of peripheral pain generators in fibromyalgia patients. Eur J Pain. 2011;15:61–9.

    PubMed  Google Scholar 

  58. Alonso-Blanco C, Fernandez-de-las-Penas C, Morales-Cabezas M, Zarco-Moreno P, Ge HY, Florez-Garcia M. Multiple active myofascial trigger points reproduce the overall spontaneous pain pattern in women with fibromyalgia and are related to widespread mechanical hypersensitivity. Clin J Pain. 2011;27:405–13.

    PubMed  Google Scholar 

  59. Zhou QQ, Verne GN. New insights into visceral hypersensitivity-clinical implications in IBS. Nature Rev Gastroenterol Hepatol. 2011;8:349–55.

    Google Scholar 

  60. Kosek E, Ordeberg G. Abnormalities of somatosensory perception in patients with painful osteoarthritis normalize following successful treatment. Eur J Pain. 2000;4:229–38.

    PubMed  CAS  Google Scholar 

  61. Vierck Jr CJ. Mechanisms underlying development of spatially distributed chronic pain (fibromyalgia). Pain. 2006;124:242–63.

    PubMed  Google Scholar 

  62. Meeus M, Roussel NA, Truijen S, Nijs J. Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain an experimental study. J Rehabil Med. 2010;42:884–90.

    PubMed  Google Scholar 

  63. •• Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10:895–926. Excellent review of mechanisms of dorsal horn neuronal plasticity related to pain.

    PubMed  Google Scholar 

  64. • Geisser ME, Glass JM, Ralcevska LD, et al. A psychophysical study of auditory and pressure sensitivity in patients with fibromyalgia and healthy controls. J Pain. 2008;9:417–22. Hypersensitivity of FM patients is not limited to nociception but also includes sound.

    PubMed  Google Scholar 

  65. Wilbarger JL, Cook DB. Multisensory hypersensitivity in women with fibromyalgia: implications for well being and intervention. Arch Phys Med Rehabil. 2011;92:653–6.

    PubMed  Google Scholar 

  66. van der Linden D, Frese M, Meijman TF. Mental fatigue and the control of cognitive processes: effects on perseveration and planning. Acta Psychol (Amst). 2003;113:45–65.

    Google Scholar 

  67. van der Linden D, Eling P. Mental fatigue disturbs local processing more than global processing. Psychol Res. 2006;70:395–402.

    PubMed  Google Scholar 

  68. Lange G, Steffener J, Cook DB, et al. Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory. NeuroImage. 2005;26:513–24.

    PubMed  CAS  Google Scholar 

  69. Caseras X, Mataix-Cols D, Giampietro V, et al. Probing the working memory system in chronic fatigue syndrome: a functional magnetic resonance imaging study using the n-back task. Psychosom Med. 2006;68:947–55.

    PubMed  Google Scholar 

  70. Schmaling KB, Lewis DH, Fiedelak JI, Mahurin R, Buchwald DS. Single-photon emission computerized tomography and neurocognitive function in patients with chronic fatigue syndrome. Psychosom Med. 2003;65:129–36.

    PubMed  Google Scholar 

  71. Adams RD, Victor M, Ropper AH. Fatigue, asthenia, anxiety, and depressive reactions. In: Adams RD, Victor M, Ropper AH, editors. Principles of neurology. New York: McGraw-Hill; 1997. p. 497–507.

    Google Scholar 

  72. Appenzeller S, Rondina JM, Li LM, Costallat LT, Cendes F. Cerebral and corpus callosum atrophy in systemic lupus erythematosus. Arthritis Rheum. 2005;52:2783–9.

    PubMed  Google Scholar 

  73. Appenzeller S, Bonilha L, Rio PA, Min LL, Costallat LT, Cendes F. Longitudinal analysis of gray and white matter loss in patients with systemic lupus erythematosus. NeuroImage. 2007;34:694–701.

    PubMed  Google Scholar 

  74. Jung RE, Segall JM, Grazioplene RG, Qualls C, Sibbitt WL, Roldan CA. Cortical thickness and subcortical gray matter reductions in neuropsychiatric systemic lupus erythematosus. PLoS One. 2010;5:e9302.

    PubMed  Google Scholar 

  75. • Wartolowska K, Hough MG, Jenkinson M, Andersson J, Wordsworth BP, Tracey I. Structural changes of the brain in rheumatoid arthritis. Arthritis Rheum. 2012;64:371–9. RA patients show atrophy of basal ganglia on MRI.

    PubMed  Google Scholar 

  76. Carr A, Hewlett S, Hughes R, et al. Rheumatology outcomes: The patient's perspective. J Rheumatol. 2003;30:880–3.

    PubMed  Google Scholar 

  77. Ahlmen M, Nordenskiold U, Archenholtz B, et al. Rheumatology outcomes: the patient's perspective. A multicentre focus group interview study of Swedish rheumatoid arthritis patients. Rheumatology (Oxford). 2005;44:105–10.

    CAS  Google Scholar 

  78. Huyser BA, Parker JC, Thoreson R, Smarr KL, Johnson JC, Hoffman R. Predictors of subjective fatigue among individuals with rheumatoid arthritis. Arthritis Rheum. 1998;41:2230–7.

    PubMed  CAS  Google Scholar 

  79. Riemsma RP, Rasker JJ, Taal E, Griep EN, Wouters JM, Wiegman O. Fatigue in rheumatoid arthritis: the role of self-efficacy and problematic social support. Br J Rheumatol. 1998;37:1042–6.

    PubMed  CAS  Google Scholar 

  80. Rupp I, Boshuizen HC, Jacobi CE, Dinant HJ, van den Bos GA. Impact of fatigue on health-related quality of life in rheumatoid arthritis. Arthritis Rheum. 2004;51:578–85.

    PubMed  Google Scholar 

  81. Tack BB. Fatigue in rheumatoid arthritis. Conditions, strategies, and consequences. Arthritis Care Res. 1990;3:65–70.

    PubMed  CAS  Google Scholar 

  82. Fifield J, Tennen H, Reisine S, McQuillan J. Depression and the long-term risk of pain, fatigue, and disability in patients with rheumatoid arthritis. Arthritis Rheum. 1998;41:1851–7.

    PubMed  CAS  Google Scholar 

  83. Fifield J, McQuillan J, Tennen H, et al. History of affective disorder and the temporal trajectory of fatigue in rheumatoid arthritis. Ann Behav Med. 2001;23:34–41.

    PubMed  CAS  Google Scholar 

  84. Jump RL, Fifield J, Tennen H, Reisine S, Giuliano AJ. History of affective disorder and the experience of fatigue in rheumatoid arthritis. Arthritis Rheum. 2004;51:239–45.

    PubMed  Google Scholar 

  85. Crosby LJ. Factors which contribute to fatigue associated with rheumatoid arthritis. J Adv Nurs. 1991;16:974–81.

    PubMed  CAS  Google Scholar 

  86. Belza BL, Henke CJ, Yelin EH, Epstein WV, Gilliss CL. Correlates of fatigue in older adults with rheumatoid arthritis. Nurs Res. 1993;42:93–9.

    PubMed  CAS  Google Scholar 

  87. Belza BL. Comparison of self-reported fatigue in rheumatoid arthritis and controls. J Rheumatol. 1995;22:639–43.

    PubMed  CAS  Google Scholar 

  88. Pinals RS, Masi AT, Larsen RA. Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum. 1981;24:1308–15.

    PubMed  CAS  Google Scholar 

  89. Wolfe F, Hawley DJ, Wilson K. The prevalence and meaning of fatigue in rheumatic disease. J Rheumatol. 1996;23:1407–17.

    PubMed  CAS  Google Scholar 

  90. Pollard LC, Choy EH, Gonzalez J, Khoshaba B, Scott DL. Fatigue in rheumatoid arthritis reflects pain, not disease activity. Rheumatology. 2006;45:885–9.

    PubMed  CAS  Google Scholar 

  91. Weinblatt ME, Keystone EC, Furst DE, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003;48:35–45.

    PubMed  CAS  Google Scholar 

  92. Strand V, Scott DL, Emery P, et al. Physical function and health related quality of life: analysis of 2-year data from randomized, controlled studies of leflunomide, sulfasalazine, or methotrexate in patients with active rheumatoid arthritis. J Rheumatol. 2005;32:590–601.

    PubMed  CAS  Google Scholar 

  93. Bates DW, Schmitt W, Buchwald D, et al. Prevalence of fatigue and chronic fatigue syndrome in a primary care practice. Arch Intern Med. 1993;153:2759–65.

    PubMed  CAS  Google Scholar 

  94. McCarty DJ. Differential diagnosis of the rheumatic diseases: Analysis of signs and symptoms. In: Koopman WJ, Moreland LW, editors. Arthritis and allied conditions. 15th ed. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 781–809.

    Google Scholar 

  95. Felson DT, Smolen JS, Wells G, et al. American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis. 2011;70:404–13.

    PubMed  Google Scholar 

  96. Tassiulas IO, Boumpas DT. Clinical features and treatment of systemic lupus erythematosus. In: Firestein GS, Budd RC, Harris ED, McInnes IB, Ruddy S, Sergent JS, editors. Kelley's textbook of rheumatology. 8th ed. Philadelphia: W.B. Saunders Company; 2008. p. 1263–300.

    Google Scholar 

  97. Liang MH, Rogers M, Larson M, et al. The psychosocial impact of systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 1984;27:13–9.

    PubMed  CAS  Google Scholar 

  98. Krupp LB, LaRocca NG, Muir J, Steinberg AD. A study of fatigue in systemic lupus erythematosus. J Rheumatol. 1990;17:1450–2.

    PubMed  CAS  Google Scholar 

  99. Middleton GD, McFarlin JE, Lipsky PE. The prevalence and clinical impact of fibromyalgia in systemic lupus erythematosus. Arthritis Rheum. 1994;37:1181–8.

    PubMed  CAS  Google Scholar 

  100. Gladman DD, Urowitz MB, Gough J, MacKinnon A. Fibromyalgia is a major contributor to quality of life in lupus. J Rheumatol. 1997;24:2145–8.

    PubMed  CAS  Google Scholar 

  101. Bruce IN, Mak VC, Hallett DC, Gladman DD, Urowitz MB. Factors associated with fatigue in patients with systemic lupus erythematosus. Ann Rheum Dis. 1999;58:379–81.

    PubMed  CAS  Google Scholar 

  102. Liang MH, Socher SA, Larson MG, Schur PH. Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum. 1989;32:1107–18.

    PubMed  CAS  Google Scholar 

  103. Zonana-Nacach A, Roseman JM, McGwin G, et al. Systemic lupus erythematosus in three ethnic groups. VI: factors associated with fatigue within 5 years of criteria diagnosis. Lupus. 2000;9:101–9.

    PubMed  CAS  Google Scholar 

  104. Wysenbeek AJ, Leibovici L, Weinberger A, Guedj D. Fatigue in systemic lupus erythematosus. Prevalence and relation to disease expression. Br J Rheumatol. 1993;32:633–5.

    PubMed  CAS  Google Scholar 

  105. McKinley PS, Ouellette SC, Winkel GH. The contributions of disease activity, sleep patterns, and depression to fatigue in systemic lupus erythematosus. A proposed model. Arthritis Rheum. 1995;38:826–34.

    PubMed  CAS  Google Scholar 

  106. Tench C, Bentley D, Vleck V, McCurdie I, White P, D'Cruz D. Aerobic fitness, fatigue, and physical disability in systemic lupus erythematosus. J Rheumatol. 2002;29:474–81.

    PubMed  Google Scholar 

  107. Wang B, Gladman DD, Urowitz MB. Fatigue in lupus is not correlated with disease activity. J Rheumatol. 1998;25:892–5.

    PubMed  CAS  Google Scholar 

  108. Tench CM, McCurdie I, White PD, D'Cruz DP. The prevalence and associations of fatigue in systemic lupus erythematosus. Rheumatology. 2000;39:1249–54.

    PubMed  CAS  Google Scholar 

  109. Anon. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999;42:599–608.

    Google Scholar 

  110. Petri M, Naqibuddin M, Carson KA, et al. Depression and cognitive impairment in newly diagnosed systemic lupus erythematosus. J Rheumatol. 2010;37:2032–8.

    PubMed  Google Scholar 

  111. Mariette X, Gottenberg JE. Pathogenesis of Sjogren's syndrome and therapeutic consequences. Curr Opin Rheumatol. 2010;22:471–7.

    PubMed  CAS  Google Scholar 

  112. Sutcliffe N, Stoll T, Pyke S, Isenberg DA. Functional disability and end organ damage in patients with systemic lupus erythematosus (SLE), SLE and Sjogren's syndrome (SS), and primary SS. J Rheumatol. 1998;25:63–8.

    PubMed  CAS  Google Scholar 

  113. Fox RI. Sjogren's syndrome. Lancet. 2005;366:321–31.

    PubMed  CAS  Google Scholar 

  114. Barendregt PJ, Visser MR, Smets EM, et al. Fatigue in primary Sjogren's syndrome. Ann Rheum Dis. 1998;57:291–5.

    PubMed  CAS  Google Scholar 

  115. Bonafede RP, Downey DC, Bennett RM. An association of fibromyalgia with primary Sjogren's syndrome: a prospective study of 72 patients. J Rheumatol. 1995;22:133–6.

    PubMed  CAS  Google Scholar 

  116. Gudbjornsson B, Broman JE, Hetta J, Hallgren R. Sleep disturbances in patients with primary Sjogren's syndrome. Br J Rheumatol. 1993;32:1072–6.

    PubMed  CAS  Google Scholar 

  117. Dagfinrud H, Vollestad NK, Loge JH, Kvien TK, Mengshoel AM. Fatigue in patients with ankylosing spondylitis: a comparison with the general population and associations with clinical and self-reported measures. Arthritis Rheum. 2005;53:5–11.

    PubMed  Google Scholar 

  118. Jones SD, Koh WH, Steiner A, Garrett SL, Calin A. Fatigue in ankylosing spondylitis: its prevalence and relationship to disease activity, sleep, and other factors. J Rheumatol. 1996;23:487–90.

    PubMed  CAS  Google Scholar 

  119. van Tubergen A, Coenen J, Landewe R, et al. Assessment of fatigue in patients with ankylosing spondylitis: a psychometric analysis. Arthritis Rheum. 2002;47:8–16.

    PubMed  Google Scholar 

  120. Dernis-Labous E, Messow M, Dougados M. Assessment of fatigue in the management of patients with ankylosing spondylitis. Rheumatol (Oxf). 2003;42:1523–8.

    CAS  Google Scholar 

  121. Mengshoel AM, Forre O, Komnaes HB. Muscle strength and aerobic capacity in primary fibromyalgia. Clin Exp Rheumatol. 1990;8:475–9.

    PubMed  CAS  Google Scholar 

  122. Moldofsky H, Scarisbrick P, England R, Smythe H. Musculosketal symptoms and non-REM sleep disturbance in patients with "fibrositis syndrome" and healthy subjects. Psychosom Med. 1975;37:341–51.

    PubMed  CAS  Google Scholar 

  123. Calin A, Edmunds L, Kennedy LG. Fatigue in ankylosing spondylitis–why is it ignored? J Rheumatol. 1993;20:991–5.

    PubMed  CAS  Google Scholar 

  124. Mahowald MW, Mahowald ML, Bundlie SR, Ytterberg SR. Sleep fragmentation in rheumatoid arthritis. Arthritis Rheum. 1989;32:974–83.

    PubMed  CAS  Google Scholar 

  125. Lavie P, Epstein R, Tzischinsky O, et al. Actigraphic measurements of sleep in rheumatoid arthritis: comparison of patients with low back pain and healthy controls. J Rheumatol. 1992;19:362–5.

    PubMed  CAS  Google Scholar 

  126. Uveges JM, Parker JC, Smarr KL, et al. Psychological symptoms in primary fibromyalgia syndrome: relationship to pain, life stress, and sleep disturbance. Arthritis Rheum. 1990;33:1279–83.

    PubMed  CAS  Google Scholar 

  127. Taylor HG, Wardle T, Beswick EJ, Dawes PT. The relationship of clinical and laboratory measurements to radiological change in ankylosing spondylitis. Br J Rheumatol. 1991;30:330–5.

    PubMed  CAS  Google Scholar 

  128. Nicassio PM, Wallston KA. Longitudinal relationships among pain, sleep problems, and depression in rheumatoid arthritis. J Abnorm Psychol. 1992;101:514–20.

    PubMed  CAS  Google Scholar 

  129. Mengshoel AM, Forre O. Pain and fatigue in patients with rheumatic disorders. Clin Rheumatol. 1993;12:515–21.

    PubMed  CAS  Google Scholar 

  130. Friend R, Bennett RM. Distinguishing fibromyalgia from rheumatoid arthritis and systemic lupus in clinical questionnaires: an analysis of the revised Fibromyalgia Impact Questionnaire (FIQR) and its variant, the Symptom Impact Questionnaire (SIQR), along with pain locations. Arthritis Res Ther. 2011;13:R58.

    PubMed  Google Scholar 

  131. Bennett RM, Jones J, Turk DC, Russell IJ, Matallana L. An internet survey of 2,596 people with fibromyalgia. BMC Musculoskelet Disord. 2007;8:1–11.

    Google Scholar 

  132. Mease PJ, Clauw DJ, Gendreau RM, et al. The efficacy and safety of milnacipran for treatment of fibromyalgia. A randomized, double-blind, placebo-controlled trial. J Rheumatol. 2009;36:398–409.

    PubMed  CAS  Google Scholar 

  133. Hauser W, Bernardy K, Uceyler N, Sommer C. Treatment of fibromyalgia syndrome with gabapentin and pregabalin - A meta-analysis of randomized controlled trials. Pain. 2009;145:69–81.

    PubMed  Google Scholar 

  134. Spaeth M, Bennett RM, Benson BA, Wang YG, Lai CL, Choy EH. Sodium oxybate therapy provides multidimensional improvement in fibromyalgia: results of an international phase 3 trial. Ann Rheum Dis. 2012;71:935–42.

    PubMed  CAS  Google Scholar 

  135. Hartkamp A, Geenen R, Godaert GL, Bijl M, Bijlsma JW, Derksen RH. Effects of dehydroepiandrosterone on fatigue and well-being in women with quiescent systemic lupus erythematosus: a randomised controlled trial. Ann Rheum Dis. 2010;69:1144–7.

    PubMed  CAS  Google Scholar 

  136. Hartkamp A, Geenen R, Godaert GL, et al. Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjogren syndrome: a randomised controlled trial. Ann Rheum Dis. 2008;67:91–7.

    PubMed  CAS  Google Scholar 

  137. Scalapino KJ, Davis Jr JC. The treatment of ankylosing spondylitis. Clin Exp Med. 2003;2:159–65.

    PubMed  CAS  Google Scholar 

  138. • Inman RD, Davis Jr JC, Heijde D, et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 2008;58:3402–12. Golimumab improved sleep and reduced fatigue of AS patients.

    PubMed  CAS  Google Scholar 

  139. Deodhar A, Braun J, Inman RD, et al. Golimumab reduces sleep disturbance in patients with active ankylosing spondylitis: results from a randomized, placebo-controlled trial. Arthritis Care Res (Hoboken ). 2010;62:1266–71.

    Google Scholar 

  140. Oldfield V, Felson DT. Exercise therapy and orthotic devices in rheumatoid arthritis: evidence-based review. Curr Opin Rheumatol. 2008;20:353–9.

    PubMed  Google Scholar 

  141. Robb-Nicholson LC, Daltroy L, Eaton H, et al. Effects of aerobic conditioning in lupus fatigue: a pilot study. Br J Rheumatol. 1989;28:500–5.

    PubMed  CAS  Google Scholar 

  142. Ramsey-Goldman R, Schilling EM, Dunlop D, et al. A pilot study on the effects of exercise in patients with systemic lupus erythematosus. Arthritis Care Res. 2000;13:262–9.

    PubMed  CAS  Google Scholar 

  143. Daltroy LH, Robb-Nicholson C, Iversen MD, Wright EA, Liang MH. Effectiveness of minimally supervised home aerobic training in patients with systemic rheumatic disease. Br J Rheumatol. 1995;34:1064–9.

    PubMed  CAS  Google Scholar 

  144. Carvalho MR, Sato EI, Tebexreni AS, Heidecher RT, Schenkman S, Neto TL. Effects of supervised cardiovascular training program on exercise tolerance, aerobic capacity, and quality of life in patients with systemic lupus erythematosus. Arthritis Rheum. 2005;53:838–44.

    PubMed  Google Scholar 

  145. Tench CM, McCarthy J, McCurdie I, White PD, D'Cruz DP. Fatigue in systemic lupus erythematosus: a randomized controlled trial of exercise. Rheumatology. 2003;42:1050–4.

    PubMed  CAS  Google Scholar 

  146. Hauser W, Klose P, Langhorst J, et al. Efficacy of different types of aerobic exercise in fibromyalgia syndrome: a systematic review and meta-analysis of randomised controlled trials. Arthritis Res Ther. 2010;12:R79.

    PubMed  Google Scholar 

  147. Etnier JL, Karper WB, Gapin JI, Barella LA, Chang YK, Murphy KJ. Exercise, fibromyalgia, and fibrofog: a pilot study. J Phys Act Heal. 2009;6:239–46.

    Google Scholar 

  148. Gordon BA, Knapman LM, Lubitz L. Graduated exercise training and progressive resistance training in adolescents with chronic fatigue syndrome: a randomized controlled pilot study. Clin Rehabil. 2010;24:1072–9.

    PubMed  Google Scholar 

  149. • van Hoogmoed D, Fransen J, Bleijenberg G, van Riel P. Physical and psychosocial correlates of severe fatigue in rheumatoid arthritis. Rheumatol (Oxf). 2010;49:1294–302. A large number of RA patients (42 %) have similar fatigue levels than patients with ME/CFS.

    Google Scholar 

  150. Jump RL, Robinson ME, Armstrong AE, Barnes EV, Kilbourn KM, Richards HB. Fatigue in systemic lupus erythematosus: contributions of disease activity, pain, depression, and perceived social support. J Rheumatol. 2005;32:1699–705.

    PubMed  Google Scholar 

  151. Da Costa D, Dritsa M, Bernatsky S, et al. Dimensions of fatigue in systemic lupus erythematosus: relationship to disease status and behavioral and psychosocial factors. J Rheumatol. 2006;33:1282–8.

    PubMed  Google Scholar 

  152. Omdal R, Waterloo K, Koldingsnes W, Husby G, Mellgren SI. Fatigue in patients with systemic lupus erythematosus: the psychosocial aspects. J Rheumatol. 2003;30:283–7.

    PubMed  Google Scholar 

  153. Seawell AH, Danoff-Burg S. Psychosocial research on systemic lupus erythematosus: a literature review. Lupus. 2004;13:891–9.

    PubMed  CAS  Google Scholar 

  154. Karlson EW, Liang MH, Eaton H, et al. A randomized clinical trial of a psychoeducational intervention to improve outcomes in systemic lupus erythematosus. Arthritis Rheum. 2004;50:1832–41.

    PubMed  Google Scholar 

  155. Austin JS, Maisiak RS, Macrina DM, Heck LW. Health outcome improvements in patients with systemic lupus erythematosus using two telephone counseling interventions. Arthritis Care Res. 1996;9:391–9.

    PubMed  CAS  Google Scholar 

  156. Sohng KY. Effects of a self-management course for patients with systemic lupus erythematosus. J Adv Nurs. 2003;42:479–86.

    PubMed  Google Scholar 

  157. Greco CM, Rudy TE, Manzi S. Effects of a stress-reduction program on psychological function, pain, and physical function of systemic lupus erythematosus patients: a randomized controlled trial. Arthritis Rheum -Arthritis Care Res. 2004;51:625–34.

    Google Scholar 

  158. Bernardy K, Fuber N, Kollner V, Hauser W. Efficacy of cognitive-behavioral therapies in fibromyalgia syndrome - a systematic review and metaanalysis of randomized controlled trials. J Rheumatol. 2010;37:1991–2005.

    PubMed  Google Scholar 

  159. Price JR, Mitchell E, Tidy E, Hunot V. Cognitive behaviour therapy for chronic fatigue syndrome in adults. Cochrane Database of Systematic Reviews 2009; 1.

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Dr. Staud has received grant support from Forest Laboratories and Pfizer.

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    Roland Staud

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Staud, R. Peripheral and Central Mechanisms of Fatigue in Inflammatory and Noninflammatory Rheumatic Diseases. Curr Rheumatol Rep 14, 539–548 (2012). https://doi.org/10.1007/s11926-012-0277-z

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