Natural history of systemic sclerosis–related interstitial lung disease: How to identify a progressive fibrosing phenotype

Abstract

The natural history of interstitial lung disease in patients with systemic sclerosis is highly variable. Historical observational studies have demonstrated that the greatest decline in lung function in systemic sclerosis occurs early in the course of the disease; however, not all patients experience a decline in lung function even in the absence of treatment. Furthermore, among patients who do experience a decline in lung function, the rate of decline can be either rapid or slow. The most common clinical phenotypes of systemic sclerosis–related interstitial lung disease are, therefore, as follows: (1) rapid progressors, (2) gradual progressors, (3) stabilizers, and (4) improvers. This review summarizes the features of systemic sclerosis–related interstitial lung disease patients who are more likely to experience rapid progression of interstitial lung disease, as well as those who are more likely not to experience interstitial lung disease progression. Understanding the clinical, biological, and radiographic factors that consistently predict interstitial lung disease–related outcomes in systemic sclerosis is central to our ability to recognize those patients who are at heightened risk for interstitial lung disease progression. With new options available for treating patients with systemic sclerosis–related interstitial lung disease, it is more important than ever to accurately identify patients who may derive the most benefit from aggressive systemic sclerosis–related interstitial lung disease therapy. Early therapeutic intervention in patients with this progressive fibrosing phenotype may ultimately improve morbidity and mortality outcomes in patients with systemic sclerosis–related interstitial lung disease.

Prognostic role of KL‐6 in SSc‐ILD patients with pleuroparenchymal fibroelastosis

“…Systemic sclerosis (SSc) is a rare immune-mediated disorder, characterized by microvascular injury, circulating autoantibodies and fibroblast activation, leading to fibrosis of the skin and visceral organs. [1][2][3][4] In SSc, interstitial lung disease (ILD) is the leading cause of morbidity and mortality. 5 High-resolution computed tomography (HRCT) is the imaging tool which is the gold standard parameter in routine clinical practice.…”

“…6 In fact, HRCT may allow to distinguish the two main pathological patterns in SSc-ILD, either the usual interstitial pneumonia or the most frequent one which is nonspecific interstitial pneumonia. [1][2][3][4] Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease featuring pleural thickening with associated subpleural fibrosis involving the upper lobes. 7 It has recently been described in patients with systemic sclerosis, and its prognostic determinants are the subject of ongoing studies.…”

“…High‐resolution computed tomography (HRCT) is the imaging tool which is the gold standard parameter in routine clinical practice 6 . In fact, HRCT may allow to distinguish the two main pathological patterns in SSc‐ILD, either the usual interstitial pneumonia or the most frequent one which is nonspecific interstitial pneumonia 1‐4 …”

Pulmonary magnetic resonance imaging in systemic sclerosis: a jump in the future to unravel inflammation in interstitial lung disease

“…Inflammation and vascular injury, leading to vasculopathy, are the early cornerstones, thereafter, resulting in fibrosis of internal organs and their functional failure [2][3][4]. These events occur also in the lung, resulting in interstitial lung disease (ILD) [5,6]. In SSc, ILD is a severe organ complication [7] and chest computed tomography (CT) is the most suitable, rapid, reliable technique for its evaluation and follow-up [8].…”

Are serum biomarkers useful in the management of systemic sclerosis‐associated interstitial lung disease?

“…Interstitial lung disease (ILD) is the leading cause of mortality 1 in patients with systemic sclerosis (SSc), also causing significant morbidity, with resultant disability and reduced quality of life 2 . Unlike idiopathic pulmonary fibrosis in which lung function declines inexorably, there is considerable variation in the natural history of SSc‐related ILD (SSc‐ILD) and its response to therapy 3 . In some patients, ILD progresses rapidly to life‐threatening disease, typically within the first 5 years after the onset of SSc, while others experience a more gradual decline in lung function and some never develop clinically significant ILD.…”