Systemic Sclerosis Associated Interstitial Lung Disease: A Comprehensive Overview

Abstract

Interstitial lung disease (ILD) is a common complication of systemic sclerosis (SSc). SSc-ILD adversely impacts quality of life and is currently the leading cause of death in this multisystem disease. Identifying clinically significant SSc-ILD is critically important. Accurate staging and prognostication remain difficult; however, significant advances have been made in the last decade. Evidence supports the need to treat patients with extensive and/or progressive SSc-ILD, while only a subset of patients with limited ILD may require treatment. Research is urgently required to allow improved prediction of patients at risk of ILD progression at an early point in the disease, and ideally prior to its onset, to allow prevention. The last decade has seen the publication of landmark clinical trials for SSc-ILD. More effective strategies with less toxicity are under investigation. For those with refractory or very advanced disease, studies into disease-specific palliative approaches are in their infancy. Lung transplantation as an option for SSc-ILD remains patient- and center-specific, with data to suggest equivalent outcomes to other fibrotic lung diseases, in carefully selected cases. This review aims to provide a comprehensive overview of all key aspects of SSc-ILD.

The Spectrum of Interstitial Lung Disease Associated with Autoimmune Diseases: Data of a 3.6-Year Prospective Study from a Referral Center of Interstitial Lung Disease and Lung Transplantation †

“…This frequency was higher than in former reports [43][44][45]. Therefore, our data support the claim that the presence of anti-Scl 70 in patients with SSc is an important reason for monitoring lung involvement in these patients [8,46]. All patients with anti-synthetase syndrome had positive myositis-associated antibodies, the most frequent being, in decreasing order, anti-Ro 52, anti-Pl 7, anti-Pl 12 and anti-Jo 1.…”

Molecular mapping of interstitial lung disease reveals a phenotypically distinct senescent basal epithelial cell population

“…Interstitial lung disease (ILD) associated with systemic sclerosis (SSc-ILD), despite arising from autoimmune vasculitis, shares many pathophysiological features in advanced stages with IPF (8).…”

“…The biological manifestations of disease are spatially and temporally heterogeneous, whereby normal lung tissue is adjacent to areas of fibroblast accumulation with active fibrosis or mature scar tissue with honeycomb cysts ( 7 ). Interstitial lung disease (ILD) associated with systemic sclerosis (SSc-ILD), despite arising from autoimmune vasculitis, shares many pathophysiological features in advanced stages with IPF ( 8 ). ILD, on the whole, is heterogeneous, which is reflected in the highly variable course of disease progression, and while it is well established that fibrosis in IPF and SSc-ILD is characterized by activity of myofibroblast-activating pathways such as TGF signaling, the events that lie upstream of and precipitate these pathways are not well characterized.…”

Bioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma‐Associated Interstitial Lung Disease

“…SSc‐associated interstitial lung disease (SSc‐ILD), a frequent complication of SSc, results in significant morbidity and mortality (2). The clinical trajectory of SSc‐ILD is highly variable, as some patients experience rapid deterioration in their ventilatory function while others remain stable or improve (3,4). Although prognostic models with clinical parameters (5) and peripheral blood biomarkers (6) have demonstrated promise in identifying patients at risk for severe disease phenotypes, the relationship between these clinical prediction models and the molecular mechanisms driving disease remains an area of ongoing investigation.…”