Interstitial Lung Disease in Systemic Sclerosis: Focus on Early Detection and Intervention

Abstract

Systemic sclerosis (SSc) is a progressive and often devastating disease characterized by autoimmune dysfunction, vasculopathy, and fibrosis. Interstitial lung disease (ILD) is identified in the majority of patients with SSc and is the leading cause of SSc-related mortality. Although clinical manifestations and ILD severity vary among patients, lung function typically declines to the greatest extent during the first 3-4 years after disease onset. We aim to provide an overview of SSc-associated ILD (SSc-ILD) with a focus on current and emerging tools for early diagnosis of ILD and current and novel treatments under investigation. Early detection of ILD provides the opportunity for early therapeutic intervention, which could improve patient outcomes. Thoracic high-resolution computed tomography is the most effective method of identifying ILD in patients with SSc; it enables detection of mild lung abnormalities and plays an important role in monitoring disease progression. Cyclophosphamide and mycophenolate mofetil are the most commonly prescribed treatments for SSc-ILD. Recently, nintedanib (an antifibrotic) was approved by the Food and Drug Administration for patients with SSc-ILD; it is indicated for slowing the rate of decline in pulmonary function. However, there is a need for additional effective and well-tolerated disease-modifying therapy. Ongoing studies are evaluating other antifibrotics and novel agents. We envision that early detection of lung involvement, combined with the emergence and integration of novel therapies, will lead to improved outcomes in patients with SSc-ILD.

Keywords: disease progression; early diagnosis; interstitial lung diseases; systemic sclerosis; treatment outcome.

Figure 1

HRCT scans of lungs from patients with SSc-ILD of different severities. Notes: Patient with mild severity: coronal view (A) and axial view (C); patient with severe disease: coronal view (B) and axial view (D). Both patients participated in the SLS II trial. Abbreviations: HRCT, high-resolution computed tomography; SLS, Scleroderma Lung Study; SSc-ILD, systemic sclerosis with associated interstitial lung disease.

Figure 2

Key pathogenic pathways involved in SSc-ILD and purported targets of existing and potential therapeutic agents. Notes: Khanna D, Tashkin DP, Denton CP, et al, Ongoing clinical trials and treatment options for patients with systemic sclerosis–associated interstitial lung disease, Rheumatology 2019; 58 (4): 567–579, doi:10.1093/rheumatology/key151. Reprinted by permission of Oxford University Press on behalf of the British Society for Rheumatology. © The Author(s) 2018. All rights reserved. For permissions, please email: journals.permissions@oup.com. aMultiple growth factor receptors. Abbreviations: ADCC, antibody-dependent cell-mediated toxicity; CD, cluster of differentiation; CMC, complement-mediated cytotoxicity; DNA, deoxyribonucleic acid; FGF, fibroblast growth factor; IL, interleukin; LPA, lysophosphatidic acid; MMF, mycophenolate mofetil; PDGF, platelet-derived growth factor; SSc-ILD, systemic sclerosis with associated interstitial lung disease; TGF, tumor growth factor; VEGF, vascular endothelial growth factor.