{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:38:33Z","timestamp":1792827513551,"version":"4.5.0"},"reference-count":91,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":2194,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Systemic sclerosis (SSc) is a complex, multiorgan, autoimmune disease. Lung fibrosis occurs in \u223c80% of patients with SSc; 25% to 30% develop progressive interstitial lung disease (ILD). The pathogenesis of fibrosis in SSc-associated ILD (SSc-ILD) involves cellular injury, activation\/differentiation of mesenchymal cells, and morphological\/biological changes in epithelial\/endothelial cells. Risk factors for progressive SSc-ILD include older age, male sex, degree of lung involvement on baseline high-resolution computed tomography imaging, reduced DlCO, and reduced FVC. SSc-ILD does not share the genetic risk architecture observed in idiopathic pulmonary fibrosis (IPF), with key risk factors yet to be identified. Presence of anti\u2013Scl-70 antibodies and absence of anti-centromere antibodies indicate increased likelihood of progressive ILD. Elevated levels of serum Krebs von den Lungen-6 and C-reactive protein are both associated with SSc-ILD severity and predict SSc-ILD progression. A promising prognostic indicator is serum chemokine (C-C motif) ligand 18. SSc-ILD shares similarities with IPF, although clear differences exist. Histologically, a nonspecific interstitial pneumonia pattern is commonly observed in SSc-ILD, whereas IPF is defined by usual interstitial pneumonia. The course of SSc-ILD is variable, ranging from minor, stable disease to a progressive course, whereas all patients with IPF experience progression of disease. Although appropriately treated patients with SSc-ILD have better chances of stabilization and survival, a relentlessly progressive course, akin to IPF, is seen in a minority. Better understanding of cellular and molecular pathogenesis, genetic risk, and distinctive features of SSc-ILD and identification of robust prognostic biomarkers are needed for optimal disease management.<\/jats:p>","DOI":"10.1164\/rccm.201903-0563ci","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T11:31:46Z","timestamp":1576495906000},"page":"650-660","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":189,"title":["Etiology, Risk Factors, and Biomarkers in Systemic Sclerosis with Interstitial Lung Disease"],"prefix":"10.1093","volume":"201","author":[{"given":"Dinesh","family":"Khanna","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, University of Michigan Scleroderma Program, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald P.","family":"Tashkin","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Denton","sequence":"additional","affiliation":[{"name":"University College London Centre for Rheumatology and Connective Tissue Diseases, Royal Free Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta A.","family":"Renzoni","sequence":"additional","affiliation":[{"name":"Interstitial Lung Disease Unit and"},{"name":"National Institute for Health Research Clinical Research Facility, Royal Brompton Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujal R.","family":"Desai","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United 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