https://doi.org/10.4081/monaldi.2024.2957
Assessing disease activity in scleroderma-related interstitial lung disease: a review and practical guide to management
Submitted: February 13, 2024
Accepted: August 5, 2024
Published: September 25, 2024
Accepted: August 5, 2024
Abstract Views: 177
PDF_EARLY VIEW: 89
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Systemic sclerosis (SSc) is a heterogeneous disease with a propensity to involve multiple organ systems. There is a significant proportion of these patients with interstitial lung disease (ILD) who are at risk of mortality and morbidity. There are limited available tools to assess the severity of parenchymal lung involvement and are subject to confounding factors, including the presence of pulmonary hypertension and concomitant smoking history. The diagnostic tools include careful clinical history, examination, thoracic imaging, and pulmonary function tests. One of the limitations of assessing disease severity in SSc-ILD is the lack of standardized definitions for disease activity and serum biomarkers to predict future progression. Although there has been significant progress in managing SSc-related ILD over the last couple of decades with a few randomized double-blind clinical trials assessing the role of immunosuppression (mainly Cyclophosphamide and Mycophenolate Mofetil), the efficacy of these therapies is at best modest and is associated with significant toxicities. Furthermore, Nintedanib has shown promise in reducing forced vital capacity decline in SSc-ILD and in progressive fibrotic-ILD of a range of etiologies. Data are emerging for therapies like Rituximab and Tocilizumab, and we are likely to see further evidence of similar drugs being efficacious in this disease cohort. A relatively simplified algorithm is proposed in this review to guide clinicians dealing with ILD and SSc. It is imperative that clinicians take a multi-disciplinary approach to managing this complex disease in a changing therapeutic landscape.
Walker UA, Tyndall A, Czirják L, et al. Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database. Ann Rheum Dis 2007;66:754-63.
DOI: https://doi.org/10.1136/ard.2006.062901
Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis 2007;66:940-4.
DOI: https://doi.org/10.1136/ard.2006.066068
Wangkaew S, Euathrongchit J, Wattanawittawas P, et al. Incidence and predictors of interstitial lung disease (ILD) in Thai patients with early systemic sclerosis: inception cohort study. Mod Rheumatol 2016;26:588-93.
DOI: https://doi.org/10.3109/14397595.2015.1115455
Hamaguchi Y. Autoantibody profiles in systemic sclerosis: predictive value for clinical evaluation and prognosis. J Dermatol 2010;37:42-53.
DOI: https://doi.org/10.1111/j.1346-8138.2009.00762.x
Kuwana M, Bando M, Kawahito Y, et al. Identification and management of connective tissue disease-associated interstitial lung disease: evidence-based Japanese consensus statements. Expert Rev Respir Med 2023;17:71-80. Erratum in: Expert Rev Respir Med 2024;18:67.
DOI: https://doi.org/10.1080/17476348.2023.2176303
Denton CP, Hughes M, Gak N, et al. BSR and BHPR guideline for the treatment of systemic sclerosis. Rheumatology 2016;55:1906-10.
DOI: https://doi.org/10.1093/rheumatology/kew224
Hannah J, Rodziewicz M, Mehta P, et al. The diagnosis and management of systemic autoimmune rheumatic disease-related interstitial lung disease: British Society for Rheumatology guideline scope. Rheumatol Adv Pract 2024;8:rkae056.
DOI: https://doi.org/10.1093/rap/rkae085
Jokerst C, Yaddanapudi K, Chaudhary S, et al. Imaging innovations in the screening, diagnosis, and monitoring of systemic autoimmune disease-related interstitial lung disease. EMJ 2024;5:71-81.
DOI: https://doi.org/10.33590/emjradiol/11000033
van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 2013;65:2737-47.
DOI: https://doi.org/10.1002/art.38098
Avouac J, Fransen J, Walker UA, et al. Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group. Ann Rheum Dis 2011;70:476-81.
DOI: https://doi.org/10.1136/ard.2010.136929
Daimon T , Johkoh T, Honda O, et al. Nonspecific interstitial pneumonia associated with collagen vascular disease: analysis of CT features to distinguish the various types. Intern Med 2009;48:753-61.
DOI: https://doi.org/10.2169/internalmedicine.48.1714
Bouros D, Wells AU, Nicholson AG, et al. Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome. Am J Respir Crit Care Med 2002;165:1581-6.
DOI: https://doi.org/10.1164/rccm.2106012
Walkoff L, White DB, Chung JH, et al. The four corners sign: a specific imaging feature in differentiating systemic sclerosis-related interstitial lung disease from idiopathic pulmonary fibrosis. J Thorac Imaging 2018;33:197-203.
DOI: https://doi.org/10.1097/RTI.0000000000000319
Champtiaux N, Cottin V, Chassagnon G, et al. Combined pulmonary fibrosis and emphysema in systemic sclerosis: a syndrome associated with heavy morbidity and mortality. Semin Arthritis Rheum 2019;49:98-104.
DOI: https://doi.org/10.1016/j.semarthrit.2018.10.011
Bonifazi M, Sverzellati N, Negri E, et al. Pleuroparenchymal fibroelastosis in systemic sclerosis: prevalence and prognostic impact. Eur Respir J 2020;56:1902135.
DOI: https://doi.org/10.1183/13993003.02135-2019
Palmucci S, Galioto F, Fazio G, et al. Clinical and radiological features of lung disorders related to connective-tissue diseases: a pictorial essay. Insights Imaging 2022;13:108.
DOI: https://doi.org/10.1186/s13244-022-01243-2
Shah RM, Jimenez S, Wechsler R. Significance of ground-glass opacity on HRCT in long-term follow-up of patients with systemic sclerosis. J Thorac Imaging 2007;22:120-4.
DOI: https://doi.org/10.1097/01.rti.0000213572.16904.40
Launay D, Remy-Jardin M, Michon-Pasturel U, et al. High resolution computed tomography in fibrosing alveolitis associated with systemic sclerosis. J Rheumatol 2006;33:1789-801.
Walsh SL, Calandriello L, Sverzellati N, Wells AU, Hansell DM; UIP Observer Consort. Interobserver agreement for the ATS/ERS/JRS/ALAT criteria for a UIP pattern on CT. Thorax. 2016 Jan;71(1):45-51. doi: 10.1136/thoraxjnl-2015-207252. Epub 2015 Nov 19. PMID: 26585524.
DOI: https://doi.org/10.1136/thoraxjnl-2015-207252
Walsh SL, Sverzellati N, Devaraj A, et al. Connective tissue disease related fibrotic lung disease: high resolution computed tomographic and pulmonary function indices as prognostic determinants. Thorax 2014;69:216-22.
DOI: https://doi.org/10.1136/thoraxjnl-2013-203843
Fischer A, Swigris JJ, Groshong SD, et al. Clinically significant interstitial lung disease in limited scleroderma: histopathology, clinical features, and survival. Chest 2008;134:601-5.
DOI: https://doi.org/10.1378/chest.08-0053
Konopka KE, Myers JL. Interstitial lung disease pathology in systemic sclerosis. Ther Adv Musculoskelet Dis 2021;13:1759720X211032437.
DOI: https://doi.org/10.1177/1759720X211032437
Goh NS, Hoyles RK, Denton CP, et al. Short-term pulmonary function trends are predictive of mortality in interstitial lung disease associated with systemic sclerosis. Arthritis Rheumatol 2017;69:1670-8.
DOI: https://doi.org/10.1002/art.40130
Wells AU, Hansell DM, Rubens MB, et al. Fibrosing alveolitis in systemic sclerosis: indices of lung function in relation to extent of disease on computed tomography. Arthritis Rheum 1997;40:1229-36.
DOI: https://doi.org/10.1002/art.6
Lacedonia D, Carapgnano GE, Galgano G, et al. Utility of FVC/DLCO ratio to stratify the risk of mortality in unselected subjects with pulmonary hypertension. Intern Emerg Med 2017;12:319-26.
DOI: https://doi.org/10.1007/s11739-016-1573-9
Moore OA, Goh N, Corte T, et al. Extent of disease on high-resolution computed tomography lung is a predictor of decline and mortality in systemic sclerosis-related interstitial lung disease. Rheumatology 2013;52:155-60.
DOI: https://doi.org/10.1093/rheumatology/kes289
Tashkin DP, Elashoff R, Clements PJ, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006;354:2655-66.
DOI: https://doi.org/10.1056/NEJMoa055120
Peelen DM, Zwezerijnen BGJC, Nossent EJ, et al. The quantitative assessment of interstitial lung disease with positron emission tomography scanning in systemic sclerosis patients. Rheumatology 2020;59:1407-15.
DOI: https://doi.org/10.1093/rheumatology/kez483
Meyer KC. Scleroderma with fibrosing interstitial lung disease: where do we stand? Ann Am Thorac Soc 2018;15:1273-5.
DOI: https://doi.org/10.1513/AnnalsATS.201808-544ED
Antoniou KM, Margaritopoulos GA, Goh NS, et al. Combined pulmonary fibrosis and emphysema in scleroderma-related lung disease has a major confounding effect on lung physiology and screening for pulmonary hypertension. Arthritis Rheumatol 2016;68:1004-12.
DOI: https://doi.org/10.1002/art.39528
Orlandi M, Meliante LA, Damiani A, et al. The role of bronchoalveolar lavage in systemic sclerosis interstitial lung disease: a systematic literature review. Pharmaceuticals 2022;15:1584.
DOI: https://doi.org/10.3390/ph15121584
Kase K, Watanabe S, Saeki K, et al. Fractional analysis of bronchoalveolar lavage in systemic sclerosis-associated interstitial lung disease. J Thorac Dis 2021;13:4146-55.
DOI: https://doi.org/10.21037/jtd-20-2596
Nevskaya T, Baron M, Pope JE. Predictive value of European Scleroderma Group Activity Index in an early scleroderma cohort. Rheumatology 2017;56:1111-22.
DOI: https://doi.org/10.1093/rheumatology/kex015
Medsger TA Jr, Silman AJ, Steen VD, et al. A disease severity scale for systemic sclerosis: development and testing. J Rheumatol 1999;26:2159-67.
Amjadi S, Maranian P, Furst DE, et al. Course of the modified Rodnan skin thickness score in systemic sclerosis clinical trials: analysis of three large multicenter, double-blind, randomized controlled trials. Arthritis Rheum 2009;60:2490-8.
DOI: https://doi.org/10.1002/art.24681
Ho KT, Reveille JD. The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther 2003;5:80-93.
DOI: https://doi.org/10.1186/ar628
Muangchan C, Harding S, Khimdas S, et al. Association of C-reactive protein with high disease activity in systemic sclerosis: results from the Canadian Scleroderma Research Group. Arthritis Care Res 2012;64:1405-14.
DOI: https://doi.org/10.1002/acr.21716
Gourh P, Arnett FC, Assassi S, et al. Plasma cytokine profiles in systemic sclerosis: associations with autoantibody subsets and clinical manifestations. Arthritis Res Ther 2009;11:R147.
DOI: https://doi.org/10.1186/ar2821
Bernstein EJ, Denton CP, Huang S, Khanna D. Baseline absolute monocyte count predicts lung function decline among patients with systemic sclerosis-associated interstitial lung disease: a post hoc analysis from the focuSSced trial. Semin Arthritis Rheum 2024;65:152376.
DOI: https://doi.org/10.1016/j.semarthrit.2024.152376
Roofeh D, Brown KK, Kazerooni EA, et al. Systemic sclerosis associated interstitial lung disease: a conceptual framework for subclinical, clinical and progressive disease. Rheumatology 2023;62:1877-86.
DOI: https://doi.org/10.1093/rheumatology/keac557
Distler O, Assassi S, Cottin V, et al. Predictors of progression in systemic sclerosis patients with interstitial lung disease. Eur Respir J 2020;55:1902026.
DOI: https://doi.org/10.1183/13993003.02026-2019
Goh NS, Desai SR, Veeraraghavan S, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med 2008;177:1248-54.
DOI: https://doi.org/10.1164/rccm.200706-877OC
Hax V, Bredemeier M, Didonet Moro AL, et al. Clinical algorithms for the diagnosis and prognosis of interstitial lung disease in systemic sclerosis. Semin Arthritis Rheum 2017;47:228-34.
DOI: https://doi.org/10.1016/j.semarthrit.2017.03.019
Chatterjee S, Perelas A, Yadav R, et al. Viewpoint: a multidisciplinary approach to the assessment of patients with systemic sclerosis-associated interstitial lung disease. Clin Rheumatol 2023;42:653-61.
DOI: https://doi.org/10.1007/s10067-022-06408-4
Cottin V, Martinez FJ, Smith V, Walsh SL. Multidisciplinary teams in the clinical care of fibrotic interstitial lung disease: current perspectives. Eur Respir Rev 2022;31:220003.
DOI: https://doi.org/10.1183/16000617.0003-2022
Raghu G, Montesi SB, Silver RM, et al. Treatment of systemic sclerosis-associated interstitial lung disease: evidence-based recommendations. An official American Thoracic Society Clinical practice guideline. Am J Respir Crit Care Med 2024;209:137-52.
DOI: https://doi.org/10.1164/rccm.202306-1113ST
Hoyles RK, Ellis RW, Wellsbury J, et al. A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheum 2006;54:3962-70.
DOI: https://doi.org/10.1002/art.22204
Omair MA, Alahmadi A, Johnson SR. Safety and effectiveness of mycophenolate in systemic sclerosis. A systematic review. PLoS One 2015;10:e0124205.
DOI: https://doi.org/10.1371/journal.pone.0124205
Yilmaz N, Can M, Kocakaya D, et al. Two-year experience with mycophenolate mofetil in patients with scleroderma lung disease: a case series. Int J Rheum Dis 2014;17:923-8.
DOI: https://doi.org/10.1111/1756-185X.12399
Tashkin DP, Roth MD, Clements PJ, et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med 2016;4:708-19.
DOI: https://doi.org/10.1016/S2213-2600(16)30152-7
Jordan S, Distler JH, Maurer B, et al. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis 2015;74:1188-94.
DOI: https://doi.org/10.1136/annrheumdis-2013-204522
Maher TM, Tudor VA, Saunders P, et al. Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial. Lancet Respir Med 2023;11:45-54.
DOI: https://doi.org/10.1016/S2213-2600(22)00359-9
Khanna D, Lin CJ, Furst DE, et al. Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med 2020;8:963-74.
DOI: https://doi.org/10.1016/S2213-2600(20)30318-0
Ciaffi J, van Leeuwen NM, Boonstra M, et al. Evolution of systemic sclerosis-associated interstitial lung disease one year after hematopoietic stem cell transplantation or cyclophosphamide. Arthritis Care Res 2022;74:433-41.
DOI: https://doi.org/10.1002/acr.24451
Distler O, Highland KB, Gahlemann M, et al. Nintedanib for systemic sclerosis-associated interstitial lung disease. N Engl J Med 2019;380:2518-28.
DOI: https://doi.org/10.1056/NEJMoa1903076
Denton CP, Goh NS, Humphries SM, et al. Extent of fibrosis and lung function decline in patients with systemic sclerosis and interstitial lung disease: data from the SENSCIS trial. Rheumatology 2023;62:1870-6.
DOI: https://doi.org/10.1093/rheumatology/keac535
Khanna D, Maher TM, Volkmann ER, et al. Effect of nintedanib in patients with systemic sclerosis-associated interstitial lung disease and risk factors for rapid progression. RMD Open 2023;9:e002859.
DOI: https://doi.org/10.1136/rmdopen-2022-002859
Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med 2019;381:1718-27.
DOI: https://doi.org/10.1056/NEJMoa1908681
Rahaghi FF, Hsu VM, Kaner RJ, et al. Expert consensus on the management of systemic sclerosis-associated interstitial lung disease. Respir Res 2023;24:6.
DOI: https://doi.org/10.1186/s12931-022-02292-3
How to Cite
Adizie, Tochukwu, Lauren Dolan, Aqusa Zahid, and Ahmed Fahim. 2024. “Assessing Disease Activity in Scleroderma-Related Interstitial Lung Disease: A Review and Practical Guide to Management”. Monaldi Archives for Chest Disease, September. https://doi.org/10.4081/monaldi.2024.2957.
Copyright (c) 2024 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.