Sjögren Sendromu Tanılı Hastalarda Kronik Yorgunluğun Uyku Durumu ve Melatonin Düzeyi ile İlişkisi

Year 2025, Volume: 22 Issue: 1, 141 - 146, 26.03.2025

Oğur Karhan , Ali Berkant Avcı , İkbal Özen Kucukcetin , V Yazisiz

https://doi.org/10.35440/hutfd.1631258

Abstract

Amaç: Primer Sjögren sendromu (pSS), sistemik bir otoimmün hastalıktır ve hastaların çoğu yorgunluk ve uykusuzluk yaşamaktadır. Melatonin, uyku kalitesini ve süresini iyileştirmenin yanı sıra birçok farklı işlevi olan bir hormondur. Bu çalışmanın amacı, yorgunluk ve uykusuzluk arasındaki ilişkiyi ve melatonin seviyelerinin yorgunluk ve uykusuzluk ile olan bağlantısını pSS hastalarında araştırmaktır.
Materyal ve Metod: Bu kesitsel kohort çalışmasına 116 hasta ve 27 sağlıklı kontrol dahil edilmiştir. Epworth Uykululuk Ölçeği (ESS), Yorgunluk Şiddeti Ölçeği (FSS) ve SF-36 anketleri hastalardan elde edilmiştir. Hastaların serum melatonin seviyeleri ELISA yöntemiyle ölçülmüştür.
Bulgular: pSS hastaları kontrol grubuna kıyasla daha fazla yorgunluk göstermiştir. Ayrıca, gündüz aşırı uykululuğu olan hastalar, olmayanlara göre daha yüksek yorgunluk seviyelerine sahipti. Yorgunluğu olan hastalarda medyan melatonin seviyesi 239 ng/L (189-460) iken, yorgunluğu olmayan hastalarda 266 ng/L (219-552) olarak ölçülmüştür (p=0.11). Gündüz aşırı uykululuğu olan ve olmayan hastaların mela-tonin seviyeleri benzer bulunmuştur. Sağlıklı bireylerde medyan melatonin seviyesi 429 ng/L (268-774) iken, pSS hastalarında 254 ng/L (197-491) olarak ölçülmüştür (p=0.0098). SF-36 ile ölçülen yaşam kali-tesi, yorgunluğu olan hastalarda tüm alt gruplarda yorgunluğu olmayanlara kıyasla anlamlı derecede daha kötüydü. Melatonin seviyeleri ile SF-36’nın alt parametreleri arasında bir korelasyon bulunmamış-tır.
Sonuç: Yorgunluk, hem yaşam kalitesi hem de uyku hali üzerinde olumsuz etkiye sahiptir. Gündüz uykululuğu yaşayan hastalar daha düşük yaşam kalitesine sahiptir. pSS hastalarında sabah erken saatler-de ölçülen serum melatonin seviyeleri daha düşük bulunmuştur. Yorgunluğu olan ve olmayan hastalar arasında serum melatonin seviyeleri açısından anlamlı bir fark saptanmamıştır. Ayrıca, serum melatonin seviyeleri ile yaşam kalitesi arasında bir korelasyon bulunmamıştır.

Keywords

Sjögren sendromu, Yorgunluk, Uykululuk, Melatonin, Yaşam kalitesi

The Relationship Between Chronic Fatigue, Sleep quality, and Melatonin Levels in Sjogren's Syndrome

Abstract

Background: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease and majority of pa-tients have fatigue and insomnia. Melatonin has many functions in addition to improving sleep quality and duration.The aim of this study was to explore the relationship between fatigue and insomnia, and the association of melatonin levels with fatigue and insomnia in patients with pSS.
Materials and Methods: This cross-sectional cohort study included 116 patients and 27 healthy con-trols. Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS) and SF-36 questionnaires were ob-tained from patients. Melatonin was measured by ELISA from the patients' serum.
Results: Patients with pSS exhibited greater fatigue compared to the control group, additionally, pa-tients with somnolence exhibited higher levels of fatigue compared to those without somnolence. The median melatonin level was 239 ng/L (189-460) in patients with fatigue and 266 ng/L (219-552) in patients without fatigue (p=0.11). Patients with and without daytime sleepiness had similar melatonin levels, too. The median melatonin level was 429 ng/L (268-774) in healthy controls compared to 254 ng/L (197-491) in patients with PSS (p=0.0098) The quality of life, as measured by the SF-36, was signif-icantly worse in patients with fatigue across all subgroups compared to those without fatigue. There was no correlation between melatonin levels and the subparameters of the SF-36.
Conclusions: Fatigue had a negative impact on both quality of life and sleepiness. Those who experi-enced sleepiness had a poorer quality of life. Early morning serum melatonin levels were lower in PSS patients. There was no significant difference in mean serum melatonin levels between patients with and without fatigue. No correlation was found between serum melatonin levels and quality of life.

Keywords

Sjogren, Fatigue, Sleepiness, Melatonin, Quality of life

References

• 1. Stefanski AL, Tomiak C, Pleyer U, Dietrich T, Burmester GR, Dörner T. The Diagnosis and Treatment of Sjögren's Syn-drome. Dtsch Arztebl Int. 2017;114(20):354-61.
• 2. Mæland E, Miyamoto ST, Hammenfors D, Valim V, Jonsson MV. Understanding Fatigue in Sjögren's Syndrome: Outcome Measures, Biomarkers and Possible Interventions. Front Im-munol. 2021;12:703079.
• 3. Lewis I, Hackett KL, Ng WF, Ellis J, Newton JL. A two-phase cohort study of the sleep phenotype within primary Sjögren's syndrome and its clinical correlates. Clin Exp Rheumatol. 2019;37 Suppl 118(3):78-82.
• 4. Goulabchand R, Castille E, Navucet S, Etchecopar-Etchart D, Matos A, Maria A, et al. The interplay between cognition, depression, anxiety, and sleep in primary Sjogren's syndrome patients. Sci Rep. 2022;12(1):13176.
• 5. Dardin LP, Garcia ABA, Gazoni FM, Santos FCD, Mello MT, Trevisani VFM. Correlation of sleep quality with fatigue and disease activity among patients with primary Sjögren's syn-drome: a cross-sectional study. Sao Paulo Med J. 2020;138(2):146-51.
• 6. Belenguer R, Ramos-Casals M, Brito-Zerón P, del Pino J, Sentís J, Aguiló S, et al. Influence of clinical and immunolog-ical parameters on the health-related quality of life of pa-tients with primary Sjögren's syndrome. Clin Exp Rheumatol. 2005;23(3):351-6.
• 7. Dias LH, Miyamoto ST, Giovelli RA, de Magalhães CIM, Valim V. Pain and fatigue are predictors of quality of life in primary Sjögren's syndrome. Adv Rheumatol. 2021;61(1):28.
• 8. Hartkamp A, Geenen R, Bijl M, Kruize AA, Godaert GL, Derksen RH. Serum cytokine levels related to multiple di-mensions of fatigue in patients with primary Sjogren's syn-drome. Ann Rheum Dis. 2004;63(10):1335-7.
• 9. Davies K, Mirza K, Tarn J, Howard-Tripp N, Bowman SJ, Lendrem D, et al. Fatigue in primary Sjögren's syndrome (pSS) is associated with lower levels of proinflammatory cy-tokines: a validation study. Rheumatol Int. 2019;39(11):1867-73.
• 10. Miglianico L, Cornec D, Devauchelle-Pensec V, Berrouiguet S, Walter M, Stéphan F. Inflammatory biomarkers associated with depression, anxiety, and/or fatigue in primary Sjögren's syndrome–a systematic review. The European Journal of Psy-chiatry. 2022;36(3):143-51.
• 11. Liu Y, Tan YQ, Zhou G. Melatonin: a potential therapeutic approach for the management of primary Sjögren's syn-drome. Immunol Res. 2023;71(3):373-87.
• 12. Liu Y, Weng X, Wei M, Yu S, Ding Y, Cheng B. Melatonin regulates the immune response and improves Sjögren's syn-drome-like symptoms in NOD/Ltj Mice. Biochem Pharmacol. 2022;201:115073.
• 13. Liu Y, Wang F, Cheng B, Zhou G. Melatonin improves salivary gland damage and hypofunction in pSS by inhibiting IL-6/STAT3 signaling through its receptor-dependent manner. Mol Immunol. 2024;169:10-27.
• 14. Rasheed AB, Daoud MS, Gorial FI. Diagnostic utility of serum melatonin levels in systemic lupus erythematosus: a case-control study. Reumatismo. 2017;69(4):170-4.
• 15. Liu Y, Chen XQ, Wang F, Cheng B, Zhou G. Melatonin relieves Th17/CD4(-)CD8(-) T cells inflammatory responses via nuclear-receptor dependent manner in peripheral blood of primary Sjögren's syndrome. Int Immunopharmacol. 2022;109:108778.
• 16. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540-5.
• 17. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fa-tigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46(10):1121-3.
• 18. Saris-Baglama RN, Dewey CJ, Chisholm GB, Plumb E, King J, Kosinski M, et al. QualityMetric health outcomes™ scoring software 4.0: installation guide. Lincoln (RI): QualityMetric Incorporated. 2010.
• 19. Hackett KL, Gotts ZM, Ellis J, Deary V, Rapley T, Ng WF, et al. An investigation into the prevalence of sleep disturbances in primary Sjögren's syndrome: a systematic review of the liter-ature. Rheumatology (Oxford). 2017;56(4):570-80.
• 20. Gudbjörnsson B, Broman JE, Hetta J, Hällgren R. Sleep dis-turbances in patients with primary Sjögren's syndrome. Br J Rheumatol. 1993;32(12):1072-6.
• 21. Xie Z, Chen F, Li WA, Geng X, Li C, Meng X, et al. A review of sleep disorders and melatonin. Neurol Res. 2017;39(6):559-65.
• 22. de Carvalho JF, Skare TL. Melatonin supplementation im-proves rheumatological disease activity: A systematic review. Clin Nutr ESPEN. 2023;55:414-9.
• 23. Uysal HA, Tıftıkcıoğlu BI, Öcek L, Zorlu Y. Serum Levels of Melatonin and Sleep Evaluation Scales in the Diagnosis of Sleep Disorders in Patients with Idiopathic Parkinson's Dis-ease. Noro Psikiyatr Ars. 2019;56(4):264-8.
• 24. Tcholakov B, Qasim H. The Relationship Between Sjogren's Syndrome and Sleep Disturbance: A Case Report. Cureus. 2022;14(10):e30321.
• 25. Ng WF, Bowman SJ. Primary Sjogren's syndrome: too dry and too tired. Rheumatology (Oxford). 2010;49(5):844-53.
• 26. Korszun A, Sackett-Lundeen L, Papadopoulos E, Brucksch C, Masterson L, Engelberg NC, et al. Melatonin levels in women with fibromyalgia and chronic fatigue syndrome. J Rheu-matol. 1999;26(12):2675-80.
• 27. Ibn Yacoub Y, Rostom S, Laatiris A, Hajjaj-Hassouni N. Primary Sjögren's syndrome in Moroccan patients: characteristics, fa-tigue and quality of life. Rheumatol Int. 2012;32(9):2637-43.
• 28. Priori R, Minniti A, Antonazzo B, Fusconi M, Valesini G, Curcio G. Sleep quality in patients with primary Sjögren's syndrome. Clin Exp Rheumatol. 2016;34(3):373-9.
• 29. Cui Y, Li J, Li L, Zhao Q, Chen S, Xia L, et al. Prevalence, correlates, and impact of sleep disturbance in Chinese pa-tients with primary Sjögren's syndrome. Int J Rheum Dis. 2020;23(3):367-73.
• 30. Castaño MY, Garrido M, Rodríguez AB, Gómez M. Melatonin Improves Mood Status and Quality of Life and Decreases Cor-tisol Levels in Fibromyalgia. Biol Res Nurs. 2019;21(1):22-9.
• 31. Fan R, Bu X, Yang S, Tan Y, Wang T, Chen H, et al. Effect of melatonin on quality of life and symptoms in patients with cancer: a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2022;12(9):e060912.