{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:26:02Z","timestamp":1777983962398,"version":"3.51.4"},"reference-count":23,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Scleroderma and Related Disorders"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Systemic sclerosis is a rare autoimmune disease characterized by skin and organ fibrosis, and vasculopathy. Raynaud\u2019s phenomenon is almost universally present in systemic sclerosis and can be the most debilitating symptom. Raynaud\u2019s phenomenon may lead to the development of digital ulcers, potentially complicated by infection, tissue necrosis, and auto-amputation. Recommended treatments have variable efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We report the case of a 30-year-old woman with diffuse systemic sclerosis suffering from severe Raynaud\u2019s phenomenon and digital ulcers with digital tissue necrosis who was treated with combination therapy of an endothelin receptor antagonist and phosphodiesterase 5 inhibitor. In addition, we reviewed the literature on the topic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Previous therapy with calcium-channel blockers, intravenous iloprost, and bosentan had all failed to control symptoms. We added sildenafil in combination with bosentan and observed a rapid and sustained treatment effect. Raynaud\u2019s phenomenon severity, number of attacks, and attack duration decreased within 2\u2009weeks of initiating treatment. Furthermore, this resulted in the healing of established digital ulcers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our case report suggests that combination therapy may be a feasible treatment for the most severely affected and refractory patients. In our literature review, we found one retrospective study and three additional cases with similarly encouraging results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/2397198319876738","type":"journal-article","created":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T06:00:07Z","timestamp":1568872807000},"page":"159-164","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Combination therapy with bosentan and sildenafil for refractory digital ulcers and Raynaud\u2019s phenomenon in a 30-year-old woman with systemic sclerosis: Case report and literature review"],"prefix":"10.1136","volume":"5","author":[{"given":"Jan-Gerd","family":"Rademacher","sequence":"first","affiliation":[{"name":"Department of Nephrology and Rheumatology, University Medical Center G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Wincup","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University College London, London, UK"},{"name":"Arthritis Research UK Centre for Adolescent Rheumatology, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn","family":"Tampe","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, University Medical Center G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6065-5680","authenticated-orcid":false,"given":"Peter","family":"Korsten","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, University Medical Center G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2019,9,19]]},"reference":[{"key":"bibr1-2397198319876738","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.2"},{"key":"bibr2-2397198319876738","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200742"},{"issue":"4","key":"bibr3-2397198319876738","first-page":"S47","volume":"33","author":"Brand M","year":"2015","journal-title":"Clin Exp 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