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Our objectives were to identify systems of SSc subset classification and synthesize novel concepts to inform development of new criteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Medline, Cochrane MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Web of Science were searched from their inceptions to December 2019 for studies related to SSc subclassification, limited to humans and without language or sample size restrictions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 5686 citations, 102 studies reported original data on SSc subsets. Subset classification systems relied on extent of skin involvement and\/or SSc-specific autoantibodies (n = 61), nailfold capillary patterns (n = 29), and molecular, genomic, and cellular patterns (n = 12). While some systems of subset classification confer prognostic value for clinical phenotype, severity, and mortality, only subsetting by gene expression signatures in tissue samples has been associated with response to therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Subsetting on extent of skin involvement remains important. Novel disease attributes including SSc-specific autoantibodies, nailfold capillary patterns, and tissue gene expression signatures have been proposed as innovative means of SSc subsetting.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.201594","type":"journal-article","created":{"date-parts":[[2021,5,15]],"date-time":"2021-05-15T12:20:19Z","timestamp":1621081219000},"page":"1698-1717","source":"Crossref","is-referenced-by-count":16,"title":["Systematic Analysis of the Literature in Search of Defining Systemic Sclerosis Subsets"],"prefix":"10.3899","volume":"48","author":[{"given":"Tatiana","family":"Nevskaya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1479-5302","authenticated-orcid":false,"given":"Janet E.","family":"Pope","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew 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