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Are patients with systemic lupus erythematosus at increased risk for Fibromyalgia?

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Abstract

Widespread chronic pain, fatigue, and distress do not represent risk factors for future systemic lupus erythematosus (SLE) or other autoimmune syndromes. On the other hand, SLE seems to be a significant risk factor for fibromyalgia (FM). Up to 47% of SLE patients fulfill FM criteria. SLE patients with concomitant FM are often highly symptomatic and dysfunctional. The presence of FM symptoms in SLE patients, however, does not predict more extensive organ involvement or lupus activity. The high concordance of SLE with FM suggests common mechanisms related to pain and distress in both patient groups. Recent research suggests involvement of N-methyl-D-aspartate (NMDA) and neurokinin receptor systems. Thus, autoimmune activity against these receptor systems in SLE patients could result in pain, cognitive defects, and chronic pain states including FM. Conversely, treatment of SLE-FM patients with inhibitors of NMDA or neurokinin receptors may prevent or alleviate cognitive abnormalities and chronic pain, as well as FM.

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References and Recommended Reading

  1. Gowers WR: Lumbago—its lessons and analogues. Br Med J 1904, 1:117–121.

    Article  Google Scholar 

  2. 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, 37:341–351.

    PubMed  CAS  Google Scholar 

  3. Smythe HA, Moldofsky H: Two contributions to understanding of the "fibrositis" syndrome. Bull Rheum Dis 1977, 28:928–931.

    PubMed  Google Scholar 

  4. Wolfe F, Smythe HA, Yunus MB, et al.: The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990, 33:160–172.

    Article  PubMed  CAS  Google Scholar 

  5. Wolfe F, Ross K, Anderson J, et al.: The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 1995, 38:19–28.

    Article  PubMed  CAS  Google Scholar 

  6. Staud R, Rodriguez ME: Mechanisms of disease: Pain in fibromyalgia syndrome. Nat Clin Pract Rheumatol 2006, 2:90–98. Fibromyalgia pain is consistently felt in deep tissues including ligaments, joints, and muscles. Increasing evidence points toward these tissues as relevant contributors of nociceptive input that might initiate and/or maintain central sensitization.

    Article  PubMed  Google Scholar 

  7. Hudson JI, Arnold LM, Keck PE: Family study of fibromyalgia and affective spectrum disorder. Biol Psychiatry 2004, 56:884–891.

    Article  PubMed  Google Scholar 

  8. White KP, Speechley M, Harth M, Ostbye T: Fibromyalgia in rheumatology practice: a survey of Canadian rheumatologists. J Rheumatol 1995, 22:722–726.

    PubMed  CAS  Google Scholar 

  9. Goldenberg DL: Office management of fibromyalgia. Rheum Dis Clin North Am 2002, 28:437–446.

    Article  PubMed  Google Scholar 

  10. Yunus MB, Holt GS, Masi AT, Aldag JC: Fibromyalgia syndrome among the elderly. Comparison with younger patients. J Am Geriatr Soc 1988, 36:987–995.

    PubMed  CAS  Google Scholar 

  11. Naranjo A, Ojeda S, Francisco F, et al.: Fibromyalgia in patients with rheumatoid arthritis is associated with higher scores of disability. Ann Rheum Dis 2002, 61:660–661.

    Article  PubMed  CAS  Google Scholar 

  12. Middleton GD, McFarlin JE, Lipsky PE: The prevalence and clinical impact of fibromyalgia in systemic lupus erythematosus. Arthritis Rheum 1994, 37:1181–1188.

    Article  PubMed  CAS  Google Scholar 

  13. Grafe A, Wollina U, Tebbe B, et al.: Fibromyalgia in lupus erythematosus. Acta Derm Venereol 1999, 79:62–64.

    Article  PubMed  CAS  Google Scholar 

  14. Bennett RM: Fibromyalgia and the disability dilemma. A new era in understanding a complex, multidimensional pain syndrome. Arthritis Rheum 1996, 39:1627–1634.

    Article  PubMed  CAS  Google Scholar 

  15. Dinerman H, Goldenberg DL, Felson DT: A prospective evaluation of 118 patients with the fibromyalgia syndrome: prevalence of Raynaud’s phenomenon, sicca symptoms, ANA, low complement, and Ig deposition at the dermalepidermal junction. J.Rheumatol 1986, 13:368–373.

    PubMed  CAS  Google Scholar 

  16. Da Costa D, Bernatsky S, Dritsa M, et al.: Determinants of sleep quality in women with systemic lupus erythematosus. Arthritis Rheum 2005, 53:272–278.

    Article  Google Scholar 

  17. Akkasilpa S, Goldman D, Magder LS, Petri M: Number of fibromyalgia tender points is associated with health status in patients with systemic lupus erythematosus. J Rheumatol 2005, 32:48–50. FM was present in 5% and FM/FM-like manifestations in 13% of SLE patients. No difference was noted between those with and without FM with respect to gender, education level, income below poverty level, disease activity, or damage.

    PubMed  Google Scholar 

  18. Friedman AW, Tewi MB, Ahn C, et al.: Systemic lupus erythematosus in three ethnic groups: XV. Prevalence and correlates of fibromyalgia. Lupus 2003, 12:274–279. FM manifestations correlate best with ethnicity, concomitant anxiety, or affective disorder, and to a lesser extent with poorer self-reported physical functioning. African-American ethnicity is negatively associated with the FM manifestations. Clinical measures of disease activity, disease damage, specific organ dysfunction, sociodemographic factors, and serologic features of SLE patients were not correlated with FM.

    Article  PubMed  CAS  Google Scholar 

  19. 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, 33:1282–1288. Similar to FM, fatigue in SLE is multidimensional, with physical and mental aspects likely having different etiologies. A detailed assessment of fatigue in SLE is necessary to optimize interventions aimed at alleviating fatigue.

    Google Scholar 

  20. Wysenbeek AJ, Leibovici L, Amit M, Weinberger A: Disease patterns of patients with systemic lupus erythematosus as shown by application of factor analysis. J Rheumatol 1992, 19:1096–1099.

    PubMed  CAS  Google Scholar 

  21. Wallace DJ, Schwartz E, Chin-Lin H, Peter JB: The "rule out lupus" rheumatology consultation: clinical outcomes and perspectives. J Clin Rheumatol 1995, 1:158–164.

    Article  PubMed  CAS  Google Scholar 

  22. Morand EF, Miller MH, Whittingham S, Littlejohn GO: Fibromyalgia syndrome and disease activity in systemic lupus erythematosus. Lupus 1994, 3:187–191.

    PubMed  CAS  Google Scholar 

  23. Calvo-Alen J, Bastian HM, Straaton KV, et al.: Identi- fication of patient subsets among those presumptively diagnosed with, referred, and/or followed up for systemic lupus erythematosus at a large tertiary care center. Arthritis Rheum 1995, 38:1475–1484.

    Article  PubMed  CAS  Google Scholar 

  24. Tang S, Calkins H, Petri M: Neurally mediated hypotension in systemic lupus erythematosus patients with fibromyalgia. Rheumatology 2004, 43:609–614. FM is a major determinant of poor health status in SLE. Similar to FM, SLE has not only been shown to be associated with neurally mediated hypotension but also has a high prevalence rate (58%).

    Article  PubMed  CAS  Google Scholar 

  25. Middleton GD, McFarlin JE, Lipsky PE: The prevalence and clinical impact of fibromyalgia in systemic lupus erythematosus. Arthritis Rheum 1994, 37:1181–1188.

    Article  PubMed  CAS  Google Scholar 

  26. Buskila D, Press J, Abu-Shakra M: Fibromyalgia in systemic lupus erythematosus: prevalence and clinical implications. Clin Rev Allergy Immunol 2003, 25:25–28.

    Article  PubMed  Google Scholar 

  27. Weir PT, Harlan GA, Nkoy FL: The incidence of fibromyalgia and its associated comorbidities: a population-based retrospective cohort study based on international classi fication of diseases, 9th revision codes. J Clin Rheumatol 2006, 12:124–128. Large epidemiologic study of FM patients. Female patients were more likely to be diagnosed with FM than males (2:1), and there were strong associations for comorbid conditions including SLE.

    Article  PubMed  Google Scholar 

  28. Taylor J, Skan J, Erb N, et al.: Lupus patients with fatigue—is there a link with fibromyalgia syndrome? Rheumatology (Oxford) 2000, 39:620–623.

    Article  CAS  Google Scholar 

  29. Lopez-Osa A, Jimenez-Alonso J, Garcia-Sanchez A, et al.: Fibromyalgia in Spanish patients with systemic lupus erythematosus. Lupus 1999, 8:332–333.

    Article  PubMed  CAS  Google Scholar 

  30. Valencia-Flores M, Cardiel MH, Santiago V, et al.: Prevalence and factors associated with fibromyalgia in Mexican patients with systemic lupus erythematosus. Lupus 2004, 13:4–10.

    Article  PubMed  CAS  Google Scholar 

  31. Handa R, Aggarwal P, Wali JP, et al.: Fibromyalgia in Indian patients with SLE. Lupus 1998, 7:475–478.

    Article  PubMed  CAS  Google Scholar 

  32. Wolfe F, Cathey MA, Kleinheksel SM: Fibrositis (fibromyalgia) in rheumatoid arthritis. J Rheumatol 1984, 11:814–818.

    PubMed  CAS  Google Scholar 

  33. Wolfe F, Michaud K: Severe rheumatoid arthritis (RA), worse outcomes, comorbid illness, and sociodemographic disadvantage characterize RA patients with fibromyalgia. J Rheumatol 2004, 31:695–700. Similar to SLE, FM exists in a substantial number of patients with RA (17.1%). Contrary to SLE, however, RA patients with FM have more severe RA by subjective and objective measures, greater medical costs, worse outcomes, more comorbidities, sociodemographic disadvantage, and substantially lower quality of life.

    PubMed  Google Scholar 

  34. Ostuni P, Botsios C, Sfriso P, et al.: Fibromyalgia in Italian patients with primary Sjogren’s syndrome. Joint Bone Spine 2002, 69:51–57.

    Article  PubMed  Google Scholar 

  35. Bennett RM: Confounding features of the fibromyalgia syndrome: a current perspective of differential diagnosis. J Rheumatol 1989, 16:58–61.

    Google Scholar 

  36. Al Allaf AW, Ottewell L, Pullar T: The prevalence and significance of positive antinuclear antibodies in patients with fibromyalgia syndrome: 2—4 years’ follow-up. Clin Rheumatol 2002, 21:472–477.

    Article  Google Scholar 

  37. Yunus MB, Hussey FX, Aldag JC: Antinuclear antibodies and connective tissue disease features in fibromyalgia syndrome: a controlled study. J Rheumatol 1993, 20:1557–1560.

    PubMed  CAS  Google Scholar 

  38. Reilly PA, Littlejohn GO: Peripheral arthralgic presentation of fibrositis/fibromyalgia syndrome. J Rheumatol 1992, 19:281–283.

    PubMed  CAS  Google Scholar 

  39. Yunus MB, Berg BC, Masi AT: Multiphase skeletal scintigraphy in primary fibromyalgia syndrome: a blinded study. J Rheumatol 1989, 16:1466–1468.

    PubMed  CAS  Google Scholar 

  40. Bennett RM, Clark SR, Campbell SM, et al.: Symptoms of Raynaud’s syndrome in patients with fibromyalgia. A study utilizing the Nielsen test, digital photoplethysmography, and measurements of platelet alpha 2-adrenergic receptors. Arthritis Rheum 1991, 34:264–269.

    Article  PubMed  CAS  Google Scholar 

  41. Caro XJ: Immunofluorescent studies of skin in primary fibrositis syndrome. Am J Med 1986, 81:43–49.

    Article  PubMed  CAS  Google Scholar 

  42. Caro XJ, Wolfe F, Johnston WH, Smith AL: A controlled and blinded study of immunoreactant deposition at the dermal-epidermal junction of patients with primary fibrositis syndrome. J Rheumatol 1986, 13:1086–1092.

    PubMed  CAS  Google Scholar 

  43. Carlomagno S, Migliaresi S, Ambrosone L, et al.: Cognitive impairment in systemic lupus erythematosus: a follow-up study. J Neurol 2000, 247:273–279.

    Article  PubMed  CAS  Google Scholar 

  44. Jump RL, Robinson ME, Armstrong AE, et al.: Fatigue in systemic lupus erythematosus: Contributions of disease activity, pain, depression, and perceived social support. J Rheumatol 2005, 32:1699–1705. This study emphasizes the importance of depression, pain, and perceived social support in predicting somatic symptoms in SLE patients. However, disease activity was not correlated with fatigue in SLE.

    PubMed  Google Scholar 

  45. Suhr JA: Neuropsychological impairment in fibromyalgia— Relation to depression, fatigue, and pain. J Psychosom Res 2003, 55:321–329.

    Article  PubMed  Google Scholar 

  46. Park DC, Glass JM, Minear M, Crofford LJ: Cognitive function in fibromyalgia patients. Arthritis Rheum 2001, 44:2125–2133.

    Article  PubMed  CAS  Google Scholar 

  47. Forslid J, Heigl Z, Jonsson J, Scheynius A: The prevalence of antinuclear antibodies in healthy young persons and adults, comparing rat liver tissue sections with HEp-2 cells as antigen substrate. Clin Exp Rheumatol 1994, 12:137–141.

    PubMed  CAS  Google Scholar 

  48. Kennedy M, Felson DT: A prospective long-term study of fibromyalgia syndrome. Arthritis Rheum 1996, 39:682–685.

    Article  PubMed  CAS  Google Scholar 

  49. Bengtsson A, Backman E, Lindblom B, Skogh T: Long-term follow-up of fibromyalgia patients: clinical symptoms, muscular function, laboratory tests—an eight year comparison study. J Musculoskel Pain 1994, 2:67–80.

    Article  Google Scholar 

  50. Burckhardt CS, Clark SR, Bennett RM: Fibromyalgia and quality of life: a comparative analysis. J Rheumatol 1993, 20:475–479.

    PubMed  CAS  Google Scholar 

  51. Staud R: The neurobiology of chronic musculoskeletal pain (including chronic regional pain). In Fibromyalgia and Other Central Pain Syndromes. Edited by Wallace DJ, Clauw DJ. Philadelphia: Lippincott William & Wilkins; 2005:45–62.

    Google Scholar 

  52. Manfredini D, Tognini F, Montagnani G, et al.: Comparison of masticatory dysfunction in temporomandibular disorders and fibromyalgia. Minerva Stomatol 2004, 53:641–650.

    PubMed  CAS  Google Scholar 

  53. Sollecito TP, Stoopler ET, DeRossi SS, Silverton S: Temporomandibular disorders and fibromyalgia: comorbid conditions? Gen Dent 2003, 51:184–187.

    PubMed  Google Scholar 

  54. Rhodus NL, Friction J, Carlson P, Messner R: Oral symptoms associated with fibromyalgia syndrome. J Rheumatol 2003, 30:1841–1845.

    PubMed  Google Scholar 

  55. Wallace DJ: Genitourinary manifestations of fibrositis: an increased association with the female urethral syndrome. J Rheumatol 1990, 17:238–239.

    PubMed  CAS  Google Scholar 

  56. Henriksson CM: Longterm effects of fibromyalgia on everyday life. A study of 56 patients. Scand J Rheumatol 1994, 23:36–41.

    PubMed  CAS  Google Scholar 

  57. Waylonis GW, Ronan PG, Gordon C: A profile of fibromyalgia in occupational environments. Am J Phys Med Rehabil 1994, 73:112–115.

    Article  PubMed  CAS  Google Scholar 

  58. Gupta A, Silman AJ: Psychological stress and fibromyalgia: a review of the evidence suggesting a neuroendocrine link. Arthritis Res Ther 2004, 6:98–106.

    Article  PubMed  CAS  Google Scholar 

  59. Mufson M, Regestein QR: The spectrum of fibromyalgia disorders. Arthritis Rheum 1993, 36:647–650.

    Article  PubMed  CAS  Google Scholar 

  60. Croft P, Schollum J, Silman A: Population study of tender point counts and pain as evidence of fibromyalgia. BMJ 1994, 309:696–699.

    PubMed  CAS  Google Scholar 

  61. White KP, Speechley M, Harth M, Ostbye T: The London Fibromyalgia Epidemiology Study: Direct health care costs of fibromyalgia syndrome in London, Canada. J Rheumatol 1999, 26:885–889.

    PubMed  CAS  Google Scholar 

  62. Desmeules JA, Cedraschi C, Rapiti E, et al.: Neurophysiologic evidence for a central sensitization in patients with fibromyalgia. Arthritis Rheum 2003, 48:1420–1429.

    Article  PubMed  CAS  Google Scholar 

  63. Kotzin BL, West SG: Systemic lupus erythematosus. In Clinical Immunology: Principles and Practice, 2nd edition. Edited by Rich RR, Fleisher TA, Shearer WT, et al. London: Mosby; 2001:1–24.

    Google Scholar 

  64. DeGiorgio LA, Konstantinov KN, Lee SC, et al.: A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med 2001, 7:1189–1193.

    Article  PubMed  CAS  Google Scholar 

  65. Diamond B, Volpe B: On the track of neuropsychiatric lupus. Arthritis Rheum 2003, 48:2710–2712.

    Article  PubMed  Google Scholar 

  66. Kowal C, DeGiorgio LA, Nakaoka T, et al.: Cognition and immunity; antibody impairs memory. Immunity 2004, 21:179–188.

    Article  PubMed  CAS  Google Scholar 

  67. Diamond B, Kowal C, Huerta PT, et al.: Immunity and acquired alterations in cognition and emotion: lessons from SLE. In Advances in Immunology. Edited by Alt F. New York:Academic Press; 2006:289–320. Recently, brain-reactive antibodies have been demonstrated in the serum of patients with numerous neurologic diseases, including SLE. In general, the contribution these antibodies make to neuronal dysfunction has not been determined. Serum antibodies to the N-methyl-D-aspartate receptor occur frequently in patients with SLE and can cause alterations in cognition and behavior following a breach in the blood-brain barrier.

    Google Scholar 

  68. Emori A, Matsushima E, Aihara O, et al.: Cognitive dysfunction in systemic lupus erythematosus. Psychiatry and Clinical Neurosciences 2005, 59:584–589.

    Article  PubMed  Google Scholar 

  69. McLaurin EY, Holliday SL, Williams P, Brey RL: Predictors of cognitive dysfunction in patients with systemic lupus erythematosus. Neurology 2005, 64:297–303.

    PubMed  CAS  Google Scholar 

  70. Yoshio T, Hirata D, Onda K, et al.: Antiribosomal P protein antibodies in cerebrospinal fluid are associated with neuropsychiatric systemic lupus erythematosus. J Rheumatol 2005, 32:34–39.

    PubMed  CAS  Google Scholar 

  71. Navarrete MG, Brey RL: Neuropsychiatric systemic lupus erythematosus. Curr Treat Options Neurol 2000, 2:473–485.

    PubMed  Google Scholar 

  72. Huerta PT, Kowal C, DeGiorgio LA, et al.: Immunity and behavior: antibodies alter emotion. Proc Natl Acad Sci USA 2006, 103:678–683.

    Article  PubMed  CAS  Google Scholar 

  73. Coderre TJ, Katz J, Vaccarino AL, Melzack R: Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain 1993, 52:259–285.

    Article  PubMed  CAS  Google Scholar 

  74. Woolf CJ: Windup and central sensitization are not equivalent. Pain 1996, 66:105–108.

    Article  PubMed  CAS  Google Scholar 

  75. Mendell LM, Wall PD: Responses of single dorsal cord cells to peripheral cutaneous unmyelinated fibres. Nature 1965, 206:97–99.

    Article  PubMed  CAS  Google Scholar 

  76. Dickenson AH, Sullivan AF: NMDA receptors and central hyperalgesic states. Pain 1991, 46:344–346.

    Article  PubMed  CAS  Google Scholar 

  77. Dougherty PM, Willis WD: Enhancement of spinothalamic neuron responses to chemical and mechanical stimuli following combined micro-iontophoretic application of Nmethyl- D-aspartic acid and substance P. Pain 1991, 47:85–93.

    Article  PubMed  CAS  Google Scholar 

  78. Russell IJ, Orr MD, Littman B, et al.: Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum 1994, 37:1593–1601.

    Article  PubMed  CAS  Google Scholar 

  79. Vaeroy H, Helle R, Forre O, et al.: Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis. Pain 1988, 32:21–26.

    Article  PubMed  CAS  Google Scholar 

  80. Petzke F, Clauw DJ, Wolf JM, Gracely RH: Pressure pain in fibromyalgia and healthy control: Functional MRI of subjective pain experience versus objective stimulus intensity. Arthritis Rheum 2000, 43:S400.

    Article  Google Scholar 

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Staud, R. Are patients with systemic lupus erythematosus at increased risk for Fibromyalgia?. Curr Rheumatol Rep 8, 430–435 (2006). https://doi.org/10.1007/s11926-006-0037-z

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