Rheumatoid arthritis (RA) is a multisystem disease with a complex immunologic pathophysiology. Likewise, sleep disorders can involve a complicated interplay between the neurologic pathways, immune system, and respiratory system. Recent studies have shown an elevated prevalence of sleep abnormalities in connective tissue disorders compared to the general population. Restless legs syndrome (RLS) may be present in up to 30% of RA patients. These findings may be related to cytokine release and other immunomodulatory responses. TNF-α levels relate to sleep physiology and anti-TNF-α therapy may improve sleep patterns. Most of the patients with this disorder can distinguish their RLS sensations from their arthritic symptoms. RLS is a common comorbidity seen with RA, and prompt recognition and treatment can improve patient quality of life. 1. Introduction Restless legs syndrome (RLS), also called Willis-Ekbom’s disease, is a common clinical syndrome which consists of an uncomfortable sensation in one’s legs and an irresistible desire to move them usually occurring in the evening. This disorder has been underrecognized and misunderstood by many health care providers as well as the general public. While the original description of RLS was first reported by Dr. Karl Ekbom in 1945, this entity was mainly ignored by clinicians and researchers until the late 1980s [1]. Due to the lack of clear criteria, the International Restless Legs Syndrome Study Group (IRLSSG) was formed and developed clinical criteria in 1995 [2]. Subsequently, the IRLSSG has released revised guidelines to help in the clinical diagnosis and epidemiologic research of RLS [3]. This has helped to both significantly raise awareness of this disorder as well as to further basic scientific and clinical research into RLS. 2. RLS Diagnosis and Background The Willis-Ekbom (RLS) Foundation describes this disease as a disruptive neurologic disorder that seriously affects 2-3% of the population and may affect up to 10% of the U.S. population [4]. Patients will describe an uncomfortable itching or “creepy-crawling” sensation on the legs in the evenings, and this may impact negatively on sleep and quality of life. The 2003 IRLSSG criteria originally listed four essential criteria to clinically diagnose RLS with a 2011 revision adding a fifth criteria. 2011 Revised IRLSSG Diagnostic Criteria(1)An urge to move the legs usually but not always accompanied by or felt to be caused by uncomfortable or unpleasant sensations in the legs.(2)The urge to move the legs and any accompanying unpleasant sensations begin or
References
[1]
A. S. Walters and W. Hening, “Clinical presentation and neuropharmacology of restless legs syndrome,” Clinical Neuropharmacology, vol. 10, no. 3, pp. 225–237, 1987.
[2]
M. S. Aldrich, R. Allen, S. Ancoli-Isreal et al., “Toward a better definition of the Restless Legs Syndrome,” Movement Disorders, vol. 10, no. 5, pp. 634–642, 1995.
[3]
R. P. Allen, D. Picchietti, W. A. Hening et al., “Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health,” Sleep Medicine, vol. 4, no. 2, pp. 101–119, 2003.
[4]
Restless Legs Foundation, February 2013, http://www.rls.org/.
[5]
J. Montplaisir, S. Boucher, G. Poirier, G. Lavigne, O. Lapierre, and P. Lespérance, “Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria,” Movement Disorders, vol. 12, no. 1, pp. 61–65, 1997.
[6]
W. A. Hening, R. P. Allen, M. Washburn, S. R. Lesage, and C. J. Earley, “The four diagnostic criteria for Restless Legs Syndrome are unable to exclude confounding conditions (“mimics”),” Sleep Medicine, vol. 10, no. 9, pp. 976–981, 2009.
[7]
R. P. Allen, B. J. Burchell, B. MacDonald, W. A. Hening, and C. J. Earley, “Validation of the self-completed Cambridge-Hopkins questionnaire (CH-RLSq) for ascertainment of restless legs syndrome (RLS) in a population survey,” Sleep Medicine, vol. 10, no. 10, pp. 1097–1100, 2009.
[8]
K. Berger, J. Luedemann, C. Trenkwalder, U. John, and C. Kessler, “Sex and the risk of restless legs syndrome in the general population,” Archives of Internal Medicine, vol. 164, no. 2, pp. 196–202, 2004.
[9]
B. Phillips, T. Young, L. Finn, K. Asher, W. A. Hening, and C. Purvis, “Epidemiology of restless legs symptoms in adults,” Archives of Internal Medicine, vol. 160, no. 14, pp. 2137–2141, 2000.
[10]
B. Benediktsdottir, C. Janson, E. Lindberg et al., “Prevalence of restless legs syndrome among adults in Iceland and Sweden: lung function, comorbidity, ferritin, biomarkers and quality of life,” Sleep Medicine, vol. 11, no. 10, pp. 1043–1048, 2010.
[11]
F. Tison, A. Crochard, D. Léger, S. Bouée, E. Lainey, and A. El Hasnaoui, “Epidemiology of restless legs syndrome in French adults—a nationwide survey: The INSTANT Study,” Neurology, vol. 65, no. 2, pp. 239–246, 2005.
[12]
R. P. Allen, A. S. Walters, J. Montplaisir et al., “Restless legs syndrome prevalence and impact: REST general population study,” Archives of Internal Medicine, vol. 165, no. 11, pp. 1286–1292, 2005.
[13]
N.-H. Chen, L.-P. Chuang, C.-T. Yang et al., “The prevalence of restless legs syndrome in Taiwanese adults,” Psychiatry and Clinical Neurosciences, vol. 64, no. 2, pp. 170–178, 2010.
[14]
G. Merlino, M. Valente, A. Serafini, and G. L. Gigli, “Restless legs syndrome: diagnosis, epidemiology, classification and consequences,” Neurological Sciences, vol. 28, no. 1, pp. S37–S46, 2007.
[15]
J. R. Connor, P. J. Boyer, S. L. Menzies et al., “Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome,” Neurology, vol. 61, no. 3, pp. 304–309, 2003.
[16]
M. Michaud, J.-P. Soucy, A. Chabli, G. Lavigne, and J. Montplaisir, “SPECT imaging of striatal pre- and postsynaptic dopaminergic status in restless legs syndrome with periodic leg movements in sleep,” Journal of Neurology, vol. 249, no. 2, pp. 164–170, 2002.
[17]
C. J. Earley, H. Kuwabara, D. F. Wong et al., “The dopamine transporter is decreased in the striatum of subjects with restless legs syndrome,” Sleep, vol. 34, no. 3, pp. 341–347, 2011.
[18]
H. Stefansson, D. B. Rye, A. Hicks, et al., “A genetic risk factor for periodic limb movements in sleep,” The New England Journal of Medicine, vol. 357, no. 7, pp. 639–647, 2007.
[19]
V. C. Abad, P. S. A. Sarinas, and C. Guilleminault, “Sleep and rheumatologic disorders,” Sleep Medicine Reviews, vol. 12, no. 3, pp. 211–228, 2008.
[20]
H. Moldofsky, “Rheumatic manifestations of sleep disorders,” Current Opinion in Rheumatology, vol. 22, no. 1, pp. 59–63, 2010.
[21]
S. R. Reading, C. S. Crowson, R. J. Rodeheffer, P. D. Fitz-Gibbon, H. Maradit-Kremers, and S. E. Gabriel, “Do rheumatoid arthritis patients have a higher risk for sleep apnea?” Journal of Rheumatology, vol. 36, no. 9, pp. 1869–1872, 2009.
[22]
B. J. Bloom, J. A. Owens, M. McGuinn, C. Nobile, L. Schaeffer, and A. J. Alario, “Sleep and its relationship to pain, dysfunction, and disease activity in juvenile rheumatoid arthritis,” Journal of Rheumatology, vol. 29, no. 1, pp. 169–173, 2002.
[23]
R. M. Taylor-Gjevre, J. A. Gjevre, R. Skomro, and B. Nair, “Restless legs syndrome in a rheumatoid arthritis patient cohort,” Journal of Clinical Rheumatology, vol. 15, no. 1, pp. 12–15, 2009.
[24]
G. Reynolds, D. R. Blake, H. S. Pall, and A. Williams, “Restless leg syndrome and rheumatoid arthritis,” British Medical Journal, vol. 292, no. 6521, pp. 659–660, 1986.
[25]
C. Auger, J. Montplaisir, and P. Duquette, “Increased frequency of restless legs syndrome in a French-Canadian population with multiple sclerosis,” Neurology, vol. 65, no. 10, pp. 1652–1653, 2005.
[26]
N. Hassan, C. A. Pineau, A. E. Clarke, E. Vinet, R. Ng, and S. Bernatsky, “Systemic lupus and risk of restless legs syndrome,” Journal of Rheumatology, vol. 38, no. 5, pp. 874–876, 2011.
[27]
F. Kapsimalis, G. Richardson, M. R. Opp, and M. Kryger, “Cytokines and normal sleep,” Current Opinion in Pulmonary Medicine, vol. 11, no. 6, pp. 481–484, 2005.
[28]
D. Lorton, C. L. Lubahn, C. Estus et al., “Bidirectional communication between the brain and the immune system: implications for physiological sleep and disorders with disrupted sleep,” NeuroImmunoModulation, vol. 13, no. 5-6, pp. 357–374, 2007.
[29]
J. M. Krueger, J. Fang, P. Taishi, Z. Chen, T. Kushikata, and J. Gardi, “Sleep—a physiologic role for IL-1β and TNF-αa,” Annals of the New York Academy of Sciences, vol. 856, pp. 148–159, 1998.
[30]
I. B. McInnes and G. Schert, “Cytokines in the pathogenesis of rheumatoid arthritis,” Nature Reviews Immunology, vol. 7, pp. 429–442, 2007.
[31]
C. Zamarrón, F. Maceiras, A. Mera, and J. J. Gómez-Reino, “Effect of the first infliximab infusion on sleep and alertness in patients with active rheumatoid arthritis,” Annals of the Rheumatic Diseases, vol. 63, no. 1, pp. 88–90, 2004.
[32]
R. M. Taylor-Gjevre, J. A. Gjevre, B. V. Nair, R. P. Skomro, and H. J. Lim, “Improved sleep efficiency after anti-tumor necrosis factor α therapy in rheumatoid arthritis patients,” Therapeutic Advances in Musculoskeletal Disease, vol. 3, no. 5, pp. 227–233, 2011.
[33]
F. Wolfe and K. Michaud, “Fatigue, rheumatoid arthritis, and anti-tumor necrosis factor therapy: an investigation in 24,831 patients,” Journal of Rheumatology, vol. 31, no. 11, pp. 2115–2120, 2004.
[34]
S. Yount, M. V. Sorensen, D. Cella, N. Sengupta, J. Grober, and E. K. Chartash, “Adalimumab plus methotrexate or standard therapy is more effective than methotrexate or standard therapies alone in the treatment of fatigue in patients with active, inadequately treated rheumatoid arthritis,” Clinical and Experimental Rheumatology, vol. 25, no. 6, pp. 838–846, 2007.
[35]
G. Wells, T. Li, L. Maxwell, R. Maclean, and P. Tugwell, “Responsiveness of patient reported outcomes including fatigue, sleep quality, activity limitation, and quality of life following treatment with abatacept for rheumatoid arthritis,” Annals of the Rheumatic Diseases, vol. 67, no. 2, pp. 260–265, 2008.
[36]
S. Van Santen, E. C. Van Dongen-Lases, F. De Vegt et al., “Hepcidin and hemoglobin content parameters in the diagnosis of iron deficiency in rheumatoid arthritis patients with anemia,” Arthritis and Rheumatism, vol. 63, no. 12, pp. 3672–3680, 2011.
[37]
J. Wang, B. O'Reilly, R. Venkataraman, V. Mysliwiec, and A. Mysliwiec, “Efficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: a randomized, double-blind, placebo-controlled study,” Sleep Medicine, vol. 10, no. 9, pp. 973–975, 2009.
[38]
L. M. Trotti, S. Bhadriraju, and L. A. Becker, “Iron for restless legs syndrome,” Cochrane Database of Systematic Reviews, no. 5, Article ID CD007834, 2009.
[39]
A. Hassan, J. H. Bower, N. Kumar et al., “Dopamine agonist-triggered pathological behaviors: surveillance in the PD clinic reveals high frequencies,” Parkinsonism and Related Disorders, vol. 17, no. 4, pp. 260–264, 2011.
[40]
M. M. Mokhles, G. Trifiro, J. P. Dieleman, et al., “The risk of new onset heart failure associated with dopamine agonist use in Parkinson’s disease,” Pharmacological Research, vol. 65, no. 3, pp. 358–364, 2012.
