van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, 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.

PubMed  PubMed Central  Article  Google Scholar 

Nihtyanova SI, Denton CP. Pathogenesis of systemic sclerosis associated interstitial lung disease. J Scleroderma Relat Disord. 2020;5:6–16.

PubMed  PubMed Central  Article  Google Scholar 

Hoffmann-Vold AM, Fretheim H, Halse AK, Seip M, Bitter H, Wallenius M, et al. Tracking impact of interstitial lung disease in systemic sclerosis in a complete nationwide cohort. Am J Respir Crit Care Med. 2019;200:1258–66.

PubMed  Article  Google Scholar 

Steele R, Hudson M, Lo E, Baron M, Canadian Scleroderma Research Group. Clinical decision rule to predict the presence of interstitial lung disease in systemic sclerosis. Arthritis Care Res (Hoboken). 2012;64:519–24.

Article  Google Scholar 

Steen VD. Autoantibodies in systemic sclerosis. Semin Arthritis Rheum. 2005;35:35–42.

CAS  PubMed  Article  Google Scholar 

Nihtyanova SI, Schreiber BE, Ong VH, Rosenberg D, Moinzadeh P, Coghlan JG, et al. Prediction of pulmonary complications and long-term survival in systemic sclerosis. Arthritis Rheumatol. 2014;66:1625–35.

PubMed  Article  Google Scholar 

Jaeger VK, Wirz EG, Allanore Y, Rossbach P, Riemekasten G, Hachulla E, et al. Incidences and risk factors of organ manifestations in the early course of systemic sclerosis: a longitudinal EUSTAR study. PLoS One. 2016;11:e0163894.

PubMed  PubMed Central  Article  CAS  Google Scholar 

•• Hoffmann-Vold AM, Allanore Y, Alves M, Brunborg C, Airó P, Ananieva LP, et al. Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database. Ann Rheum Dis 2021;80:219–227. This analysis of the EUSTAR database showed that patients with SSc who have no established risk factors for ILD are still at risk of developing progressive ILD.

Hu S, Hou Y, Wang Q, Li M, Xu D, Zeng X. Prognostic profile of systemic sclerosis: analysis of the clinical EUSTAR cohort in China. Arthritis Res Ther. 2018;20:235.

PubMed  PubMed Central  Article  Google Scholar 

Suliman YA, Dobrota R, Huscher D, Nguyen-Kim TDL, Maurer B, Jordan S, et al. Brief report: pulmonary function tests: high rate of false-negative results in the early detection and screening of scleroderma-related interstitial lung disease. Arthritis Rheumatol. 2015;67:3256–61.

CAS  PubMed  Article  Google Scholar 

Showalter K, Hoffmann A, Rouleau G, Aaby D, Lee J, Richardson C, et al. Performance of forced vital capacity and lung diffusion cutpoints for associated radiographic interstitial lung disease in systemic sclerosis. J Rheumatol. 2018;45:1572–6.

PubMed  PubMed Central  Article  Google Scholar 

Rahaghi FF, Strek ME, Southern BD, Saggar R, Hsu VM, Mayes MD, et al. Expert consensus on the screening, treatment, and management of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), and the potential future role of anti-fibrotic drugs in a treatment paradigm for SSc-ILD: a Delphi consensus study. Poster presented at the American Thoracic Society International Conference, Dallas, TX, USA; May 17–22, 2019. Available at: https://www.usscicomms.com/respiratory/ats2019/rahaghi

•• Hoffmann-Vold AM, Maher TM, Philpot EE, Ashrafzadeh A, Barake R, Barsotti S, et al. The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements. Lancet Rheumatol 2020;2:E71–83. This article summarizes the findings of a Delphi consensus panel, including a suggested algorithm for the detection, monitoring, and management of SSc-ILD.

Goh NS, Desai SR, Veeraraghavan S, Hansell DM, Copley SJ, Maher TM, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008;177:1248–54.

PubMed  Article  Google Scholar 

Moore OA, Goh N, Corte T, Rouse H, Hennessy O, Thakkar V, 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.

PubMed  Article  Google Scholar 

Walsh SL, Sverzellati N, Devaraj A, Keir GJ, Wells AU, Hansell DM. Connective tissue disease related fibrotic lung disease: high resolution computed tomographic and pulmonary function indices as prognostic determinants. Thorax. 2014;69:216–22.

PubMed  Article  Google Scholar 

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;71:45–51.

PubMed  Article  Google Scholar 

Widell J, Lidén M. Interobserver variability in high-resolution CT of the lungs. Eur J Radiol Open. 2020;7:100228.

PubMed  PubMed Central  Article  Google Scholar 

Desai SR, Veeraraghavan S, Hansell DM, Nikolakopolou A, Goh NSL, Nicholson AG, 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.

PubMed  Article  Google Scholar 

Vonk MC, Walker UA, Volkmann ER, Kreuter M, Johnson SR, Allanore Y. Natural variability in the disease course of SSc-ILD: implications for treatment. Eur Respir Rev. 2021;30:200340.

PubMed  Article  Google Scholar 

Winstone TA, Assayag D, Wilcox PG, Dunne JV, Hague CJ, Leipsic J, et al. Predictors of mortality and progression in scleroderma-associated interstitial lung disease: a systematic review. Chest. 2014;146:422–36.

PubMed  Article  Google Scholar 

Goh NS, Hoyles RK, Denton CP, Hansell DM, Renzoni EA, Maher TM, 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.

CAS  PubMed  Article  Google Scholar 

Young A, Vummidi D, Visovatti S, Homer K, Wilhalme H, White ES, et al. Prevalence, treatment, and outcomes of coexistent pulmonary hypertension and interstitial lung disease in systemic sclerosis. Arthritis Rheumatol. 2019;71:1339–49.

PubMed  PubMed Central  Article  Google Scholar 

Khanna D, Mittoo S, Aggarwal R, Proudman SM, Dalbeth N, Matteson EL, et al. Connective tissue disease-associated interstitial lung diseases (CTD-ILD) – report from OMERACT CTD-ILD Working Group. J Rheumatol. 2015;42:2168–71.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Volkmann ER, Tashkin DP, Sim M, Li N, Goldmuntz E, Keyes-Elstein L, et al. Short-term progression of interstitial lung disease in systemic sclerosis predicts long-term survival in two independent clinical trial cohorts. Ann Rheum Dis. 2019;78:122–30.

PubMed  Article  Google Scholar 

Jhajj A, Gill HP, Hague CJ, Murphy D, Elicker B, Soon J, et al. Pulmonary physiology is poorly associated with radiological extent of disease in systemic sclerosis-associated interstitial lung disease. Eur Respir J. 2019;53:1802182.

PubMed  Article  Google Scholar 

Ley-Zaporozhan J, Giannakis A, Norajitra T, Weinheimer O, Kehler L, Dinkel J, et al. Fully automated segmentation of pulmonary fibrosis using different software tools. Respiration 2021:1–8.

Takei R, Arita M, Kumagai S, Ito Y, Tokioka F, Koyama T, et al. Radiographic fibrosis score predicts survival in systemic sclerosis-associated interstitial lung disease. Respirology. 2018;23:385–91.

PubMed  Article  Google Scholar 

Mango RL, Matteson EL, Crowson CS, Ryu JH, Makol A. Assessing mortality models in systemic sclerosis-related interstitial lung disease. Lung. 2018;196:409–16.

CAS  PubMed  Article  Google Scholar 

Roofeh D, Lescoat A, Khanna D. Treatment for systemic sclerosis-associated interstitial lung disease. Curr Opin Rheumatol. 2021;33:240–8.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Li Q, Wallace L, Patnaik P, Alves M, Gahlemann M, Kohlbrenner V, et al. Disease frequency, patient characteristics, comorbidity outcomes and immunosuppressive therapy in systemic sclerosis and systemic sclerosis-associated interstitial lung disease: a US cohort study. Rheumatology (Oxford). 2021;60:1915–25.

Article  Google Scholar 

Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLSII): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med. 2016;4:708–19.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;354:2655–66.

CAS  PubMed  Article  Google Scholar 

Barnes H, Holland AE, Westall GP, Goh NS, Glaspole IN. Cyclophosphamide for connective tissue disease-associated interstitial lung disease. Cochrane Database Syst Rev. 2018;1:CD010908.

PubMed  Google Scholar 

Khanna D, Denton CP, Jahreis A, et al. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial. Lancet. 2016;387:2630–40.

CAS  PubMed  Article  Google Scholar 

Khanna D, Lin CJF, Furst DE, Goldin J, Kim G, Kuwana M, et al. Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2020;8:963–74.

CAS  PubMed  Article  Google Scholar 

•• Roofeh D, Lin CJF, Goldin J, Kim GH, Furst DE, Denton CP, et al. Tocilizumab prevents progression of early systemic sclerosis-associated interstitial lung disease. Arthritis Rheumatol 2021;73:1301–1310. The results of a post hoc analysis of the subgroup of patients with SSc-ILD in the focuSSced trial showed that lung function was preserved over 48 weeks in patients who received tocilizumab versus placebo.

Genentech, Inc. ACTEMRA® (tocilizumab) injection prescribing information. 2021. Available at: https://www.gene.com/download/pdf/actemra_prescribing.pdf

Goswami RP, Ray A, Chatterjee M, Mukherjee A, Sircar G, Ghosh P. Rituximab in the treatment of systemic sclerosis-related interstitial lung disease: a systematic review and meta-analysis. Rheumatology (Oxford) 2020;keaa550.

Wollin L, Distler JHW, Denton CP, Gahlemann M. Rationale for the evaluation of nintedanib as a treatment for systemic sclerosis–associated interstitial lung disease. J Scleroderma Relat Dis. 2019;4:212–8.

Article  Google Scholar 

•• Distler O, Highland KB, Gahlemann M, Azuma A, Fischer A, Mayes MD, et al. Nintedanib for systemic sclerosis-associated interstitial lung disease. N Engl J Med 2019;380:2518–2528. The results of the SENSCIS trial showed that the rate of decline in FVC over 52 weeks in patients with SSc-ILD was lower in those who received nintedanib versus placebo.

Seibold JR, Maher TM, Highland KB, Assassi S, Azuma A, Hummers LK, et al. Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial. Ann Rheum Dis. 2020;79:1478–84.

CAS  PubMed  Article  Google Scholar 

Highland KB, Distler O, Kuwana M, Allanore Y, Assassi S, Azuma A, et al. Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease treated with mycophenolate: subgroup analysis of the SENSCIS trial. Lancet Respir Med. 2021;9:96–106.

CAS  PubMed  Article  Google Scholar 

Kuwana M, Allanore Y, Denton CP, Distler JHW, Steen V, Khanna D, et al. Nintedanib in patients with systemic sclerosis-associated interstitial lung disease: subgroup analyses by autoantibody status and modified Rodnan skin thickness score. Arthritis Rheumatol. 2022;74:518–26.

Kowal-Bielecka O, Fransen J, Avouac J, Becker M, Kulak A, Allanore Y, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017;76:1327–39.

PubMed  Article  Google Scholar 

Sullivan KM, Majhail NS, Bredeson C, Carpenter PA, Chatterjee S, Crofford LJ, et al. Systemic sclerosis as an indication for autologous hematopoietic cell transplantation: position statement from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2018;24:1961–4.

PubMed  PubMed Central  Article  Google Scholar 

Pradère P, Tudorache I, Magnusson J, Savale L, Brugiere O, Douvry B, et al. Lung transplantation for scleroderma lung disease: an international, multicenter, observational cohort study. J Heart Lung Transplant. 2018;37:903–11.