Interstitial lung disease in Systemic sclerosis: insights into pathogenesis and evolving therapies

Abstract

Interstitial lung disease (ILD) is a leading cause of mortality in systemic sclerosis (SSc). However, mortality is improving as pathogenesis is being better understood and new therapies emerge. The roles of the inflammasome and NETosis in fibrosis are being elucidated. Epigenetic targets like DNA methylation and microRNA show promise as new targets for anti-fibrotic agents. The IL17-23 pathway has been shown to be active in SSc-ILD. Newer biomarkers are being described like CCL18 and the anti-eIF2B antibody. Hypothesis-free approaches are identifying newer genes like the ALOX5AP and XRCC4 genes. Computer-aided interpretations of CT scans, screening with ultrasonography and magnetic resonance imaging (MRI) are gradually emerging into practice. Imaging can also predict prognosis. A plethora of studies has shown the benefit of immunosuppression in halting ILD progression. Extent of lung involvement and PFT parameters are used to initiate therapy. The best evidence is for cyclophosphamide and mycophenolate. Besides these, corticosteroids and rituximab are being used in cases refractory to the first line drugs. Stem cell transplant is also backed by evidence in SSc. Longer studies on maintenance therapy are awaited. The inflammation in SSc is mostly subclinical and there is great interest in developing anti-fibrotic drugs for SSc-ILD. Perfinidone and nintedanib are under trial. The last resort is lung transplantation.

Efficacy and Safety of Nintedanib in Patients with Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD): A Real-World Single Center Experience

“…As expected, the most common concomitant medications were corticosteroids (prednisolone < 7.5 mg/day) and MMF. Fewer patients were treated with biologic drugs such as tocilizumab, abatacept, and rituximab, as indicated by recent studies [ 51 , 52 , 53 , 54 ]. Data from the SENSCIS trial strongly suggest that the co-administration of immunosuppressive drugs and nintedanib may provide the greatest efficacy in slowing FVC decline in SSc-ILD patients.…”

Management of Connective Tissue Disease–related Interstitial Lung Disease

“…Transforming growth factor-β (TGF-β), endothelin-1, and platelet-derived growth factor (PDGF) are major players in the pathogenesis of fibrosis in the setting of SSc. These lead to an endothelial mesenchymal transition (EMT) of the epithelial cell that predisposes to fibroblasts converting to myofibroblasts and leading to fibrosis [ 22 ]. The role of autoantibodies has been proposed but not fully established [ 23 ].…”

B Cell Depletion Treatment in Resistant Systemic Sclerosis Interstitial Lung Disease

“… 2 , 3 New treatment options could be based on novel evidence in pathogenetic mechanisms of autoimmunity, vasculopathy, inflammation and fibrosis that lead to disease progression. 1 , 4 , 6 SSc ILD treatment options are few and unable to fight the disease effectively; however, studies are currently testing new drugs. 6 – 8 B cell depletion is a treatment option for SSc ILD as assessed by trials during the past 10 years .…”

“… 1 , 4 , 6 SSc ILD treatment options are few and unable to fight the disease effectively; however, studies are currently testing new drugs. 6 – 8 B cell depletion is a treatment option for SSc ILD as assessed by trials during the past 10 years . An important number of controlled and uncontrolled studies has been designed to strengthen this assertion.…”