Onset and progression factors for Systemic Sclerosis-associated interstitial lung disease: Data from a North African cohort

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Published Sep 13, 2026
https://doi.org/10.62438/tunismed.v104i08.6411
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Vol. 104 No. 08 (2026): Tunis Med Aug 2026

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Houssem Abida
Internal medicine department, Mongi Slim University Hospital, Tunis, Faculty of Medicine of Tunis, University of Tunis El Manar, 1068, Tunis, Tunisia
Zeineb Meddeb
Internal medicine department, Mongi Slim University Hospital, Tunis, Faculty of Medicine of Tunis, Laboratory of Genetics, Immunology, and Human Pathology, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia
Meriem Affes
Radiology department, Abderrahmen Mami University Hospital, Tunis, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
Saoussen Hantous
Radiology department, Abderrahmen Mami University Hospital, Tunis, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
Siwar Sbaihi
Radiology department, Mohamed Taher Maamouri University Hospital, Nabeul, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
Sana Toujani
Internal medicine department, Mongi Slim University Hospital, Tunis, Faculty of Medicine of Tunis, University of Tunis El Manar, 1068, Tunis, Tunisia
Cherifa Abdelkefi
Internal medicine department, Mongi Slim University Hospital, Tunis, Faculty of Medicine of Tunis, University of Tunis El Manar, 1068, Tunis, Tunisia
Mariem Jebri
Internal medicine department, Charles Nicolle University Hospital,Tunis, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
Henda Neji
Radiology department, Abderrahmen Mami University Hospital, Tunis, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
Kamel Bouslama
Internal medicine department, Mongi Slim University Hospital, Tunis, Faculty of Medicine of Tunis, University of Tunis El Manar, 1068, Tunis, Tunisia
Lamia Ben Hassine
Internal medicine department, Charles Nicolle University Hospital,Tunis, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
Saloua B’chir Hamzaoui
Internal medicine department, Mongi Slim University Hospital, Tunis, Faculty of Medicine of Tunis, University of Tunis El Manar, 1068, Tunis, Tunisia
Amira Elouni
Internal medicine department, Mongi Slim University Hospital, Tunis, Faculty of Medicine of Tunis, University of Tunis El Manar, 1068, Tunis, Tunisia
Thara Larbi
Internal medicine department, Mongi Slim University Hospital, Tunis, Faculty of Medicine of Tunis, University of Tunis El Manar, 1068, Tunis, Tunisia

Abstract

Introduction: Screening for interstitial lung disease (ILD) at the onset of systemic sclerosis (SSc) as well as during follow-up is mandatory. The aim of our study was to define the risk factors of SSc-ILD onset and progression in a Tunisian population.
Methods: This was a bicentric, descriptive, retrospective study that included patients with SSc. Data from the initial evaluation and from a 3-year follow-up (FUT) were collected. The patients' chest tomography (CT) scans were reinterpreted by a radiologist specialized in thoracic imaging using the Goh score.
Results: Forty-nine patients were included. ILD was diagnosed at FUT in 31 patients (63%), of whom 35% had progressive disease. The most common radiological pattern was nonspecific interstitial pneumonia (68%). The mean values for the global extension and overall severity score
of ILD at FUT were 33.3% and 5.61, respectively. Factors associated with ILD onset included: A higher modified Rodnan skin score (p=0.008; OR=1.16, 95% CI [1.04–1.3]), pulmonary hypertension (p=0.004; OR=9.35, 95% CI [1.093–30.011]), esophageal involvement (p=0.044; OR=3.650,
95% CI [0.494–26.945]), anti-topoisomerase I antibodies (p=0.001; OR=9.344, 95% CI [2.352–37.123]) and a lower hemoglobin level (p=0.04; OR=8.576, 95% CI [1.481–15.912]). ILD progression factors included: a lower forced vital capacity (p=0.002; OR=0.797, 95% CI [0.637–0.998]), anti-
topoisomerase I antibodies (p=0.015), elevated C-reactive protein (p=0.038; OR=5.07, 95% CI [1.09–30.3]), an indeterminate radiological pattern (p=0.048).
Conclusion: A higher mRSS, esophageal involvement, pulmonary hypertension, anti-topoisomerase I antibodies and anemia were factors associated with ILD onset. Progression risk factors were reduced baseline respiratory volumes and biological inflammatory syndrome.

Keywords:

Systemic sclerosis, Interstitial lung disease, onset, progression, chest tomography

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References

  1. Van den Hoogen F, Khanna D, Fransen J et al. (2013). 2013 classification criteria for systemic sclerosis: an American college of
  2. rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis, 72(11):1747-55. doi: 10.1136/
  3. annrheumdis-2013-204424.
  4. Perelas A, Silver RM, Arrossi AV, Highland KB. (2020). Systemic sclerosis-associated interstitial lung disease. Lancet Respir Med,
  5. (3):304-320. doi: 10.1016/S2213-2600(19)30480-1.
  6. Steen VD, Medsger TA. (2007). Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis, 66(7):940-4. doi:
  7. 1136/ard.2006.066068.
  8. Sierakowska M, Doroszkiewicz H, Sierakowska J et al. (2019). Factors associated with quality of life in systemic sclerosis: a cross-
  9. sectional study. Qual Life Res, 28(12):3347-3354. doi: 10.1007/ s11136-019-02284-9.
  10. Lescoat A, Jouneau S, Uzunhan Y, Jégo P, Cottin V, Hachulla E. (2022). Pneumopathie interstitielle diffuse associée à la sclérodermie
  11. systémique : prise en charge diagnostique et thérapeutique à la lumière des essais thérapeutiques récents. Rev Med Interne,
  12. (6):365-74. doi: 10.1016/j.revmed.2021.12.003
  13. Sobanski V, Giovannelli J, Allanore Y et al. (2019). Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective
  14. European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis. Arthritis Rheumatol, 71(9):1553-1570. doi:
  15. 1002/art.40906.
  16. Pokeerbux MR, Giovannelli J, Dauchet L et al. (2019). Survival and prognosis factors in systemic sclerosis: data of a French multicenter
  17. cohort, systematic review, and meta-analysis of the literature. Arthritis Res Ther, 21(1):86. doi: 10.1186/s13075-019-1867-1.
  18. Aringer M, Costenbader K, Daikh D et al. (2019). 2019 European League Against Rheumatism/American College of Rheumatology
  19. Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol, 71(9):1400-1412. doi: 10.1136/
  20. annrheumdis-2018-214819.
  21. Edey AJ, Devaraj AA, Barker RP, Nicholson AG, Wells AU, Hansell DM. (2011). Fibrotic idiopathic interstitial pneumonias: HRCT
  22. findings that predict mortality. Eur Radiol, 21(8):1586-93. doi: 10.1007/s00330-011-2098-2
  23. Goh NS, Desai SR, Veeraraghavan S et al. (2008). Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir
  24. Crit Care Med, 177(11):1248-54. doi: 10.1164/rccm.200706- 877OC.
  25. Flaherty KR, Wells AU, Cottin V et al. (2019). Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med,
  26. (18):1718-27. doi: 10.1056/NEJMoa1908681.
  27. Santosa A, Tan CS, Teng GG et al. (2016). Lung and gastrointestinal complications are leading causes of death in SCORE, a multi-ethnic Singapore systemic sclerosis cohort. Scand J Rheumatol, 45(6):499- 506. doi: 10.3109/03009742.2016.1153141.
  28. Freire M, Alonso M, Rivera A et al. (2015). Clinical peculiarities of patients with scleroderma exposed to silica: A systematic review
  29. of the literature. Semin Arthritis Rheum, 45(3):294-300. doi: 10.1016/j.semarthrit.2015.06.004.
  30. Ballerie A, Cavalin C, Lederlin M et al. (2020). Association of silica exposure with chest HRCT and clinical characteristics in systemic
  31. sclerosis. Semin Arthritis Rheum, 50(5):949-56. doi: 10.1016/j. semarthrit.2020.08.014.
  32. Rivas Vargas D. (2020). Analysis of body mass index and risk factors of interstitial lung disease in systemic sclerosis patients. Rev
  33. Colomb Reumatol, 27(1):9-19. DOI: 10.1016/j.rcreue.2020.02.001
  34. Takei R, Arita M, Kumagai S et al. (2018). Radiographic fibrosis score predicts survival in systemic sclerosis-associated interstitial lung disease. Respirology, 23(4):385-91. doi: 10.1111/resp.13175.
  35. Wulani V, Budianto T, Amal MY. (2021). Variation of usual interstitial pneumonia using HRCT in scleroderma patients. Radiol Case Rep, 17(2):336-9. doi: 10.1016/j.radcr.2021.10.057.
  36. Sambataro D, Sambataro G, Pignataro F et al. (2020) Quantification of Ground Glass Opacities Can Be Useful to Describe Disease
  37. Activity in Systemic Sclerosis. Diagnostics (Basel), 10(4):225. doi: 10.3390/diagnostics10040225.
  38. Khanna D, Tseng CH, Farmani N et al. (2011). Clinical course of lung physiology in patients with scleroderma and interstitial lung
  39. disease: analysis of the scleroderma lung study placebo group. Arthritis Rheum, 63(10):3078-85. doi: 10.1002/art.30467.
  40. Hoffmann Vold AM, Aaløkken TM, Lund MB et al. (2015). Predictive value of serial high-resolution computed tomography analyses
  41. and concurrent lung function tests in systemic sclerosis. Arthritis Rheumatol, 67(8):2205-12. doi: 10.1002/art.39166.
  42. Fairley JL, Goh NSL, Nikpour M. (2024). Systemic sclerosis-associated interstitial lung disease: Diagnostic approaches and challenges. Rev Colomb Reumatol, 31:15-25. DOI: 10.1016/j.rcreue.2023.07.004
  43. Ibrahim IH, Gamal SM, Salama AM, Khairy MA. (2020). Systemic sclerosis: correlation between lung abnormalities on high-
  44. resolution computed tomography (HRCT) and pulmonary function tests (PFTs). Egypt J Radiol Nucl Med, 51(1):1-13. doi: 10.1186/
  45. s43055-020-00220-3.
  46. Renaud A, Pautre R, Morla O et al. (2022). Thoracic lymphadenopathies in diffuse systemic sclerosis: an observational
  47. study on 48 patients using computed tomography. BMC Pulm Med, 22(1):1-9. doi: 10.1186/s12890-022-01837-y.
  48. Ben Salah R, Frikha F, Hachicha H et al. (2019). Clinical and serological profile of systemic sclerosis in Tunisia: a retrospective
  49. observational study. Presse Med, 48(10):284-91. doi: 10.1016/j. lpm.2019.07.037.
  50. Ashmore P, Tikly M, Wong M, Ickinger C. (2018). Interstitial lung disease in South Africans with systemic sclerosis. Rheumatol Int,
  51. (4):657-62. doi: 10.1007/s00296-017-3893-0.
  52. Scolnik M, Catoggio LJ, Lancioni E et al. (2014). Are There Clinical Differences in Limited Systemic Sclerosis according to Extension
  53. of Skin Involvement? Int J Rheumatol, 2014:716358. doi: 10.1155/2014/716358.
  54. De Figueiredo AD, Costa JF, Matos AP, Ramalho M. (2021). Esophageal dilatation as a predictor of systemic sclerosis in patients
  55. with interstitial lung disease. Turk Thorac J, 22(3):231-6. doi: 10.5152/TurkThoracJ.2021.19162.
  56. Wangkaew S, Losuriya P, Euathrongchit J. (2021). Worsening of esophageal dilatation is associated with increase in a high-
  57. resolution computed tomography (HRCT) score in early systemic sclerosis-associated interstitial lung disease (SSc-ILD). Clin
  58. Rheumatol, 40(3):955-63. doi: 10.1007/s10067-020-05346-3.
  59. MolinaRios S, Ordoñez CE, QuintanaLopez G. (2020). Osteoarticular manifestations of systemic sclerosis: a systematic review of the
  60. literature. Rev Colomb Reumatol, 27:85-110. DOI: 10.1016/j. rcreue.2020.01.001.
  61. Muraru S, Mihai C, Elhai M et al. (2024). Arthritis in patients with very early systemic sclerosis: a comprehensive clinical
  62. and prognostic analysis. Rheumatology, 247:1-8. doi: 10.1093/ rheumatology/keae247.
  63. Yayla ME, İlgen U, Okatan İE et al. (2020). Association of simple hematological parameters with disease manifestations, activity,
  64. and severity in patients with systemic sclerosis. Clin Rheumatol, 39(1):77-83. doi: 10.1007/s10067-019-04685-0.
  65. Li Z, Xu D, Jiang X, Li T, Su Y, Mu R. (2022). Anemia is an indicator for worse organ damage trajectories in patients with systemic
  66. sclerosis: a retrospective study. J Clin Med, 11(17):1-13. doi: 10.3390/jcm11175013.
  67. Aydi Z, Rachdi I, Ben Dhaou B et al. (2016). Particularités épidémiologiques, cliniques et évolutives des pneumopathies
  68. interstitielles au cours de la sclérodermie systémique. Rev Pneumol Clin, 72(2):122-8. doi: 10.1016/j.pneumo.2015.09.003.
  69. Guler S, Sarbu AC, Stalder O et al. (2023). Phenotyping by persistent inflammation in systemic sclerosis associated interstitial lung
  70. disease: a EUSTAR database analysis. Thorax, 78(12):1188-96. doi: 10.1136/thorax-2023-220541.
  71. Damoiseaux J, Potjewijd J, Smeets RL, Bonroy C. (2022). Autoantibodies in the disease criteria for systemic sclerosis: the
  72. need for specification for optimal application. J Transl Autoimmun, 5:1-5. doi: 10.1016/j.jtauto.2022.100141.
  73. Możdżan M, Węgiel A, Biskup L, Brzezińska O, Makowska J. (2024). Anti-Th/To antibodies in scleroderma: good prognosis or serious
  74. concern? J Clin Med, 13(11):1-22. doi: 10.3390/jcm13113022.