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Autonomic dysfunction in primary Sjogren's syndrome: a prospective cohort analysis of 154 Korean patients

  • Koh, Jung Hee (Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Kwok, Seung-Ki (Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Lee, Jennifer (Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Park, Sung-Hwan (Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
  • Received : 2015.07.13
  • Accepted : 2015.08.10
  • Published : 2017.01.01

Abstract

Background/Aims: To determine the prevalence of autonomic dysfunction among Korean patients with primary Sjogren's syndrome (pSS) and its associations with the clinical features of pSS. Methods: We analyzed 154 participants from the Korean Initiative of primary Sjogren's Syndrome (KISS) as a prospective pSS cohort and 154 age- and sex-matched healthy controls. A standardized 5-minute, supine, resting heart rate variability (HRV) test was performed, and autonomic dysfunction was defined as standard deviation of normal-to-normal RR intervals (SDNN) < 30 ms in patients < 50 years old and SDNN < 20 ms in patients ${\geq}50$ years old. The associations between autonomic dysfunction and various clinical features of pSS were analyzed. Results: The overall autonomic activity in patients with pSS was significantly lower than that in controls. Autonomic dysfunction with the HRV test was observed in 35.7% of the KISS participants and was associated with a higher European League Against Rheumatism Sjogren's Syndrome Patient Reported Index fatigue score (p = 0.024). Raynaud's phenomenon was a more frequent clinical presentation in pSS patients with autonomic dysfunction than in those without autonomic dysfunction (29.4% and 14.4%, respectively; p = 0.048). Decreased parasympathetic activity was observed in 41.6% of pSS patients. No differences were found in the oral and ocular signs of pSS according to the decreased parasympathetic activity. Conclusions: In Korean patients with pSS, decreased and imbalanced autonomic activity is prevalent and is associated with fatigue. However, an association between autonomic dysfunction and glandular manifestations was not detected.

Keywords

Acknowledgement

Supported by : Ministry of Health and Welfare

References

  1. Fox RI. Sjogren's syndrome. Lancet 2005;366:321-331. https://doi.org/10.1016/S0140-6736(05)66990-5
  2. Voulgarelis M, Tzioufas AG, Moutsopoulos HM. Mortality in Sjogren's syndrome. Clin Exp Rheumatol 2008;26(5 Suppl 51):S66-S71.
  3. Hernandez-Molina G, Michel-Peregrina M, Bermudez-Bermejo P, Sanchez-Guerrero J. Early and late extraglandular manifestations in primary Sjogren's syndrome. Clin Exp Rheumatol 2012;30:455.
  4. Barendregt PJ, van den Bent MJ, van Raaij-van den Aarssen VJ, et al. Involvement of the peripheral nervous system in primary Sjogren's syndrome. Ann Rheum Dis 2001;60:876-881.
  5. Andonopoulos AP, Lagos G, Drosos AA, Moutsopoulos HM. The spectrum of neurological involvement in Sjogren's syndrome. Br J Rheumatol 1990;29:21-23. https://doi.org/10.1093/rheumatology/29.1.21
  6. Mandl T, Wollmer P, Manthorpe R, Jacobsson LT. Autonomic and orthostatic dysfunction in primary Sjogren's syndrome. J Rheumatol 2007;34:1869-1874.
  7. Ng WF, Stangroom AJ, Davidson A, Wilton K, Mitchell S, Newton JL. Primary Sjogrens syndrome is associated with impaired autonomic response to orthostasis and sympathetic failure. QJM 2012;105:1191-1199. https://doi.org/10.1093/qjmed/hcs172
  8. Mandl T, Hammar O, Theander E, Wollmer P, Ohlsson B. Autonomic nervous dysfunction development in patients with primary Sjogren's syndrome: a follow-up study. Rheumatology (Oxford) 2010;49:1101-1106. https://doi.org/10.1093/rheumatology/keq042
  9. Humphreys-Beher MG, Brayer J, Yamachika S, Peck AB, Jonsson R. An alternative perspective to the immune response in autoimmune exocrinopathy: induction of functional quiescence rather than destructive autoaggression. Scand J Immunol 1999;49:7-10. https://doi.org/10.1046/j.1365-3083.1999.00490.x
  10. Newton JL, Frith J, Powell D, et al. Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjogren's syndrome. Ann Rheum Dis 2012;71:1973-1979. https://doi.org/10.1136/annrheumdis-2011-201009
  11. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation 1996;93:1043-1065. https://doi.org/10.1161/01.CIR.93.5.1043
  12. Vitali C, Bombardieri S, Jonsson R, et al. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002;61:554-558. https://doi.org/10.1136/ard.61.6.554
  13. Shiboski SC, Shiboski CH, Criswell L, et al. American College of Rheumatology classification criteria for Sjogren's syndrome: a data-driven, expert consensus approach in the Sjogren's International Collaborative Clinical Alliance cohort. Arthritis Care Res (Hoboken) 2012;64:475-487. https://doi.org/10.1002/acr.21591
  14. Martinez-Martinez LA, Mora T, Vargas A, Fuentes-Iniestra M, Martinez-Lavin M. Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis: a review of case-control studies. J Clin Rheumatol 2014;20:146-150. https://doi.org/10.1097/RHU.0000000000000089
  15. Bonnemeier H, Richardt G, Potratz J, et al. Circadian profile of cardiac autonomic nervous modulation in healthy subjects: differing effects of aging and gender on heart rate variability. J Cardiovasc Electrophysiol 2003;14:791-799. https://doi.org/10.1046/j.1540-8167.2003.03078.x
  16. Park SB, Lee BC, Jeong KS. Standardized tests of heart rate variability for autonomic function tests in healthy Koreans. Int J Neurosci 2007;117:1707-1717. https://doi.org/10.1080/00207450601050097
  17. Voss A, Heitmann A, Schroeder R, Peters A, Perz S. Shortterm heart rate variability: age dependence in healthy subjects. Physiol Meas 2012;33:1289-1311. https://doi.org/10.1088/0967-3334/33/8/1289
  18. Seror R, Ravaud P, Bowman SJ, et al. EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome. Ann Rheum Dis 2010;69:1103-1109. https://doi.org/10.1136/ard.2009.110619
  19. Seror R, Ravaud P, Mariette X, et al. EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjogren's syndrome. Ann Rheum Dis 2011;70:968-972. https://doi.org/10.1136/ard.2010.143743
  20. Thomson WM, Chalmers JM, Spencer AJ, Williams SM. The xerostomia inventory: a multi-item approach to measuring dry mouth. Community Dent Health 1999;16:12-17.
  21. Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the ocular surface disease index. Arch Ophthalmol 2000;118:615-621. https://doi.org/10.1001/archopht.118.5.615
  22. Kovacs L, Paprika D, Takacs R, et al. Cardiovascular autonomic dysfunction in primary Sjogren's syndrome. Rheumatology (Oxford) 2004;43:95-99. https://doi.org/10.1093/rheumatology/keg468
  23. Niemela RK, Hakala M, Huikuri HV, Airaksinen KE. Comprehensive study of autonomic function in a population with primary Sjogren's syndrome: no evidence of autonomic involvement. J Rheumatol 2003;30:74-79.
  24. Kleiger RE, Bigger JT, Bosner MS, et al. Stability over time of variables measuring heart rate variability in normal subjects. Am J Cardiol 1991;68:626-630. https://doi.org/10.1016/0002-9149(91)90355-O
  25. Wulsin LR, Horn PS, Perry JL, Massaro JM, D'Agostino RB. Autonomic imbalance as a predictor of metabolic risks, cardiovascular disease, diabetes, and mortality. J Clin Endocrinol Metab 2015;100:2443-2448. https://doi.org/10.1210/jc.2015-1748
  26. Sajadieh A, Nielsen OW, Rasmussen V, Hein HO, Hansen JF. C-reactive protein, heart rate variability and prognosis in community subjects with no apparent heart disease. J Intern Med 2006;260:377-387. https://doi.org/10.1111/j.1365-2796.2006.01701.x
  27. Tsuji H, Larson MG, Venditti FJ Jr, et al. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation 1996;94:2850-2855. https://doi.org/10.1161/01.CIR.94.11.2850
  28. Gravani F, Papadaki I, Antypa E, et al. Subclinical atherosclerosis and impaired bone health in patients with primary Sjogren's syndrome: prevalence, clinical and laboratory associations. Arthritis Res Ther 2015;17:99. https://doi.org/10.1186/s13075-015-0613-6
  29. Bartoloni E, Baldini C, Schillaci G, et al. Cardiovascular disease risk burden in primary Sjogren's syndrome: results of a population-based multicentre cohort study. J Intern Med 2015;278:185-192. https://doi.org/10.1111/joim.12346
  30. Konttinen YT, Sorsa T, Hukkanen M, et al. Topology of innervation of labial salivary glands by protein gene product 9.5 and synaptophysin immunoreactive nerves in patients with Sjogren's syndrome. J Rheumatol 1992;19:30-37.
  31. Bacman S, Berra A, Sterin-Borda L, Borda E. Muscarinic acetylcholine receptor antibodies as a new marker of dry eye Sjogren syndrome. Invest Ophthalmol Vis Sci 2001;42:321-327.
  32. Bacman S, Sterin-Borda L, Camusso JJ, Arana R, Hubscher O, Borda E. Circulating antibodies against rat parotid gland M3 muscarinic receptors in primary Sjogren's syndrome. Clin Exp Immunol 1996;104:454-459. https://doi.org/10.1046/j.1365-2249.1996.42748.x
  33. Imrich R, Alevizos I, Bebris L, et al. Predominant glandular cholinergic dysautonomia in patients with primary Sjogren's syndrome. Arthritis Rheumatol 2015;67:1345-1352.
  34. Tumiati B, Perazzoli F, Negro A, Pantaleoni M, Regolisti G. Heart rate variability in patients with Sjogren's syndrome. Clin Rheumatol 2000;19:477-480. https://doi.org/10.1007/PL00011180
  35. Segal B, Thomas W, Rogers T, et al. Prevalence, severity, and predictors of fatigue in subjects with primary Sjogren's syndrome. Arthritis Rheum 2008;59:1780-1787. https://doi.org/10.1002/art.24311
  36. Barendregt PJ, Visser MR, Smets EM, et al. Fatigue in primary Sjogren's syndrome. Ann Rheum Dis 1998;57:291-295. https://doi.org/10.1136/ard.57.5.291
  37. Meeus M, Goubert D, De Backer F, et al. Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review. Semin Arthritis Rheum 2013;43:279-287. https://doi.org/10.1016/j.semarthrit.2013.03.004
  38. Nunan D, Sandercock GR, Brodie DA. A quantitative systematic review of normal values for short-term heart rate variability in healthy adults. Pacing Clin Electrophysiol 2010;33:1407-1417. https://doi.org/10.1111/j.1540-8159.2010.02841.x

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