Evaluation of patients diagnosed with primary Sjogren’s syndrome with and without pulmonary involvement

Zehra Ozsoy; Tuğçe Şahin Ozdemırel; Kerem  Ensarıoğlu; Hakan  Erturk; Zeynep  Ozturk; Hasret  Yıldırım; Esma Sevil  Akkurt; Esin  Beyan; Umut  Kalyoncu; Berna Akıncı  Ozyurek

doi:10.36141/svdld.v42i3.17364

Evaluation of patients diagnosed with primary Sjogren’s syndrome with and without pulmonary involvement

Authors

Zehra Ozsoy Division of Rheumatology, Department of Internal Medicine, Ankara Atatürk Sanatorium Training and Research Hospital, University of Health Sciences, Ankara, Turkey
Tuğçe Şahin Ozdemırel Department of Pulmonology, Ankara Atatürk Sanatorium Training and Research Hospital, University of Health Sciences, Ankara, Turkey
Kerem Ensarıoğlu Department of Pulmonology, Ankara Atatürk Sanatorium Training and Research Hospital, University of Health Sciences, Ankara, Turkey
Hakan Erturk Department of Radiology, Ankara Atatürk Sanatorium Training and Research Hospital, University of Health Sciences, Ankara, Turkey
Zeynep Ozturk Division of Rheumatology, Department of Internal Medicine, Ankara Atatürk Sanatorium Training and Research Hospital, University of Health Sciences, Ankara, Turkey
Hasret Yıldırım Department of Pulmonology, Ankara Atatürk Sanatorium Training and Research Hospital, University of Health Sciences, Ankara, Turkey
Esma Sevil Akkurt Department of Pulmonology, Ankara Atatürk Sanatorium Training and Research Hospital, University of Health Sciences, Ankara, Turkey
Esin Beyan Department of Internal Medicine, Ankara Atatürk Sanatorium Training and Research Hospital, University of Health Sciences, Ankara, Turkey
Umut Kalyoncu Division of Rheumatology, Department of Internal Medicine, Hacettepe University Faculty of Medicine, University of Health Sciences, Ankara, Turkey
Berna Akıncı Ozyurek Department of Pulmonology, Ankara Atatürk Sanatorium Training and Research Hospital, University of Health Sciences, Ankara, Turkey

Keywords:

Sjögren’s Syndrome, pulmonary involvement, interstitial lung disease, antifibrotic therapies

Abstract

Background and aim: Interstitial lung disease (ILD) is the most severe pulmonary complicationin Primary Sjögren’s Syndrome (pSS). We aimed to evaluate and compare the pulmonary involvement patterns, respiratory parameters, clinical, radiological, pathological, and laboratory features, disease activity scores, treatment choices, and the relationships between these findings at diagnosis in pSS patients with and without pulmonary involvement.

Methods: Patients at Ankara Ataturk Sanatorium Training and Research Hospital were included in the analysis. Patients with ILD who met the classification criteria were included as the study group. Patients who met the SS classification criteria but had no findings in the lungs were included as the control group.

Results: The median disease duration of ILD patients included in the study was 9.98 months. In pSS patients, patients with ILD had demographic (older age, male gender, more frequent smoking), symptomatology (frequent dry eyes), auto-antibody positivity (more frequent antinuclear antibodies (ANA), anti-Sjögren’s Syndrome-related antigen A (SS-A), anti-Sjögren’s Syndrome-related antigen B (SS-B)), higher disease activity and more frequent immunosuppressive use. When patients with pSS and ILD were compared according to high resolution computed tomography (HRCT) uptake pattern as nonspecific interstitial pneumonia (NSIP) (fibrotic or not) and unclassified, there were more male gender, lower forced vital capacity (FVC) values, and more frequent immunosuppressive and anti-fibrotic use in the NSIP group. When patients with ILD were classified according to gender, males had more smoking, SSB positivity, fibrotic NSIP, and lower FVC and diffusing lung capacity for carbon monoxide (DLCO) values.

Conclusion: A multidisciplinary approach involving pulmonologists, radiologists, and rheumatologists who are experts in ILD is important to increase diagnostic reliability. Pulmonary involvement in pSS is an important cause of morbidity and mortality and should be managed more carefully in male patients.

References

1. Fox RI. Sjögren’s syndrome. Lancet. 2005;366(9482):321-31.

2. Sandhya P, Janardana R, Sudarsanam T, Mahasampath G, Prakash JAJ, Danda D. Determinants of diagnosis and disease course in primary Sjögren’s syndrome: Results from datamining of electronic health records. Int J Rheum Dis. 2019;22(9):1768-74.

3. Parambil JG, Myers JL, Lindell RM, Matteson EL, Ryu JH. Interstitial lung disease in primary Sjögren syndrome. Chest. 2006;130(5):1489-95.

4. He C, Chen Z, Liu S, Chen H, Zhang F. Prevalence and risk factors of interstitial lung disease in patients with primary Sjögren’s syndrome: A systematic review and metaanalysis. Int J Rheum Dis. 2020;23:1009-18.

5. Sambataro G, Ferro F, Orlandi M, et al. Clinical, morphological features and prognostic factors associated with interstitial lung disease in primary Sjögren’s syndrome: a systematic review from the Italian Society of Rheumatology. Autoimmun Rev. 2020;19:102447.

6. Wells AU, Denton CP. Interstitial lung disease in connective tissue disease—Mechanisms and management. Nat Rev Rheumatol. 2014;10:728-39.

7. Flament T, Bigot A, Chaigne B, Henique H, Diot E, Marchand-Adam S. Pulmonary manifestations of Sjögren’s syndrome. Eur Respir Rev. 2016;25:110-23.

8. Palm O, Garen T, Berge Enger T, et al. Clinical pulmonary involvement in primary Sjögren’s syndrome: Prevalence, quality of life and mortality—A retrospective study based on registry data. Rheumatology. 2013;52:173-9.

9. Berardicurti O, Marino A, Genovali I, et al. Interstitial lung disease and pulmonary damage in primary Sjögren’s syndrome: A systematic review and meta- analysis. J Clin Med. 2023;12:2586. doi:10.3390/jcm12072586.

10. Seror R, Bowman SJ, Brito-Zeron P, et al. EULAR Sjögren’s syndrome disease activity index [ESSDAI]: A user guide. RMD Open. 2015;1:e000022.

11. Nannini C, Jebakumar AJ, Crowson CS, Ryu JH, Matteson EL. Primary Sjögren’s syndrome 1976–2005 and associated interstitial lung disease: A population-based study of incidence and mortality. BMJ Open. 2013;3:e003569.

12. Zhang T, Yuan F, Xu L, Sun W, Liu L, Xue J. Characteristics of patients with primary Sjögren’s syndrome associated interstitial lung disease and relevant features of disease progression. Clin Rheumatol. 2020;39:1561-8.

13. Chatzis L, Pezoulas VC, Ferro F, et al. Sjögren’s syndrome: The clinical spectrum of male patients. J Clin Med. 2020;9:2620.

14. Brandt JE, Priori R, Valesini G, Fairweather D. Sex differences in Sjögren’s syndrome: A comprehensive review of immune mechanisms. Biol Sex Differ. 2015;6:19.

15. Brennan M, Fox P. Sex differences in primary Sjögren’s syndrome. J Rheumatol. 1999;26:2373-6.

16. Diaz-Lopez C, Geli C, Corominas H, et al. Are there clinical or serological differences between male and female patients with primary Sjögren’s syndrome? J Rheumatol. 2004;31:1352-5.

17. Sepúlveda JIR, Kvarnström M, Eriksson P, et al. Long-term follow-up in primary Sjögren’s syndrome reveals differences in clinical presentation between female and male patients. Biol Sex Differ. 2017;8:25.

18. Manikuppam P, Padiyar S, Yadav B, Nair AA, Mane M, Mathew J. Clinical characteristics and outcomes of interstitial lung disease in primary Sjögren’s syndrome: A retrospective cohort study. Mediterr J Rheumatol. 2024;35(1):108-14.

19. Li X, Xu B, Ma Y, et al. Clinical and laboratory profiles of primary Sjögren’s syndrome in a Chinese population: A retrospective analysis of 315 patients. Int J Rheum Dis. 2015;18:439-46.

20. La Rocca G, Ferro F, Sambataro G, et al. Interstitial lung disease phenotypes and predictive risk factors in primary Sjögren’s syndrome. J Clin Med. 2024;13:4963.

21. Koh JH, Park Y, Lee J, et al. Long-term outcome of interstitial lung disease in patients with primary Sjögren's syndrome: A retrospective observational study. Korean J Intern Med. 2024.

22. Yang Z, Zhao H, Shan L, Wang D. Clinical features and risk factors for primary Sjögren’s syndrome combined with interstitial lung disease: A retrospective study. Acta Biochim Pol. 2024;71:12461.

23. Konak HE, Atalar E, Hezer H, et al. Interstitial lung disease in primary Sjögren’s syndrome: Risk factors for occurrence and radiographic progression. Sarcoidosis Vasc Diffuse Lung Dis. 2024;41(3):E2024035.

24. Roca F, Dominique S, Schmidt J, Smail A, Duhaut P, Levesque H, Marie I. Interstitial lung disease in primary Sjögren’s syndrome. Autoimmun Rev. 2017;16:48-54.

25. Wang Y, Hou Z, Qiu M, Ye Q. Risk factors for primary Sjögren syndrome-associated interstitial lung disease. J Thorac Dis. 2018;10:2108-17.

26. Gao H, Zhang XW, He, et al. Prevalence, risk factors, and prognosis of interstitial lung disease in a large cohort of Chinese primary Sjögren syndrome patients: A case-control study. Medicine (Baltimore). 2018;97:e11003.

27. Buvry C, Cassagnes L, Tekath M, et al. Anti-Ro52 antibodies are a risk factor for interstitial lung disease in primary Sjögren syndrome. Respir Med. 2020;163:105895.

28. Dong X, Gao YL, Lu Y, Zheng Y. Characteristics of primary Sjögren’s syndrome-related lymphocytic interstitial pneumonia. Clin Rheumatol. 2021;40:601-12. doi:10.1007/s10067-020-05236-8.

29. Sambataro G, Libra A, Spicuzza L, et al. Clinical presentation of connective tissue disease patients with and without interstitial lung disease: A retrospective study. Respiration. 2023;102:405-15. doi:10.1159/000530785.

30. Enomoto Y, Takemura T, Hagiwara E, et al. Prognostic factors in interstitial lung disease associated with primary Sjögren’s syndrome: A retrospective analysis of 33 pathologically proven cases. PLoS One. 2013;8:e73774.

31. Ito I, Nagai S, Kitaichi M, et al. Pulmonary manifestations of primary Sjögren’s syndrome: A clinical, radiologic, and pathologic study. Am J Respir Crit Care Med. 2005;171:632-8.

32. Desai SR, Veeraraghavan S, Hansell DM, et al. CT features of lung disease in patients with systemic sclerosis: Comparison with idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Radiology. 2004;232:560-7.

33. Travis WD, Costabel U, Hansell DM, et al. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188:733-48.

34. Fischer A, Strek ME, Cottin V, et al. Proceedings of the American College of Rheumatology/Association of Physicians of Great Britain and Ireland connective tissue disease-associated interstitial lung disease summit: A multidisciplinary approach to address challenges and opportunities. Arthritis Rheumatol. 2019;71:182-95.

35. Lohrmann C, Uhl M, Warnatz K, et al. High-resolution CT imaging of the lung for patients with primary Sjögren’s syndrome. Eur J Radiol. 2004;52:137-43.

36. Ciancio N, Pavone M, Torrisi SE, et al. Contribution of pulmonary function tests (PFTs) to the diagnosis and follow-up of connective tissue diseases. Multidiscip Respir Med. 2019;14:17.

37. Vacchi C, Sebastiani M, Cassone G, et al. Therapeutic options for the treatment of interstitial lung disease related to connective tissue diseases: A narrative review. J Clin Med. 2020;9:407.

38. Lee AS, Scofield RH, Hammitt KM, et al. Consensus guidelines for evaluation and management of pulmonary disease in Sjögren’s. Chest. 2021;159:683-98.

39. Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381:1718-27.

40. Huang H, Xie W, Geng Y, Fan Y, Zhang Z. Mortality in patients with primary Sjögren’s syndrome: A systematic review and meta-analysis. Rheumatology. 2021;60:4029-38.