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Among autoimmune rheumatic diseases, <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c has the highest mortality rate among all rheumatic diseases, though there are exciting new therapeutic targets that appear to halt the progression of <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c manifestations such as skin or lung fibrosis. In selected patients, high\u2010intensity regimens with autologous stem cell transplantation can favorably modify the course. In what was once thought to be an untreatable disease, targeted therapies have now changed the outlook of <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c to a treatable disorder. Herein, we discuss the targeted therapies modifying the outlook on selected organ involvement and creating opportunities for future treatment. 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