{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T22:25:53Z","timestamp":1767651953012,"version":"3.41.0"},"reference-count":12,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_rir-2025-0006_s_101\">\n                  <jats:title>Background and Objectives<\/jats:title>\n                  <jats:p>Raynaud\u2019s phenomenon (RP) and digital ulcers (DUs) impact the quality of life (QoL) of systemic sclerosis (SSc) patients. Calcium channel blockers (CCBs) and phosphodiesterase-5 inhibitors (PDE-5i) have been used to improve blood flow. However, vasodilators are limited in patients with low blood pressure. We aimed to determine the eficacy and safety of 2% isosorbide dinitrate (ISDN) cream as an adjunctive for treating DUs and RP.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_rir-2025-0006_s_102\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A cohort study was conducted at the Scleroderma Clinic at Khon Kaen University\u2019s Srinagarind Hospital in Khon Kaen, Thailand between January 2021 and December 2022. The study included adult SSc patients, who had received 2% ISDN cream for treatment of DUs or RP as adjuvant and with\/or without receiving CCBs and\/or PDE-5i as a background treatment for DUs and RP. Patients had to have follow-up data between 2 and 4 months after starting treatment. The median treatment duration was 2.8 months. Dosages of sustained-release nifedipine ranged from 10\u201380 mg and sildenafil ranged from 12.5\u2013150 mg. Topical 2% ISDN cream was thinly applied three times a day. The treatment responses of DUs (ulcer size and pain) and RP (frequency and duration of attack) were according to patients\u2019 self-assessment, categorized into 3 levels Improvement Stable and Worsening. Before and after the treatment period of 2% ISDN cream the Quality of life was evaluated by using the EuroQoL five dimensions (EQ-5D) assessment by attending physicians.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_rir-2025-0006_s_103\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In terms of anxiety, QoL, as evaluated by the EQ-5D, significantly improved after treatment with 2% ISDN cream in patients with DUs compared to before treatment. When used as an adjunct to CCB, 2% ISDN cream resulted in stability or improvement of RP in 43.2% of patients, DUs in 41.4% of patients, and both RP and DUs in 41.0% of patients. When used as an adjunct to PDE-5i as background therapy, it resulted in stability or improvement of RP in 13.5% of patients, DUs in 13.8% of patients, and both RP and DUs in 15.4% of patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_rir-2025-0006_s_104\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Topical 2% ISDN cream may help to reduce anxiety when DUs were improved and improve overall QoL.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/rir-2025-0006","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T07:52:04Z","timestamp":1743666724000},"page":"52-58","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and safety of 2% isosorbide cream in systemic sclerosis patients with digital ulcers and Raynaud\u2019s phenomenon"],"prefix":"10.1515","volume":"6","author":[{"given":"Suwassa","family":"Namvijit","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, Khon Kaen University , Khon Kaen , Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chingching","family":"Foocharoen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Khon Kaen University , Khon Kaen , Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siraphop","family":"Suwannaroj","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Khon Kaen University , Khon Kaen , Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patnarin","family":"Pongkulkait","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Khon Kaen University , Khon Kaen , Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tippawan","family":"Onchan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Khon Kaen University , Khon Kaen , Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7091-0259","authenticated-orcid":false,"given":"Ajanee","family":"Mahakkanukrauh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Khon Kaen University , Khon Kaen , Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"2025070208224362870_j_rir-2025-0006_ref_001","doi-asserted-by":"crossref","unstructured":"Ko J, Noviani M, Chellamuthu VR, et al. The Pathogenesis of Systemic Sclerosis: The Origin of Fibrosis and Interlink with Vasculopathy and Autoimmunity. Int J Mol Sci. 2023;24:14287.","DOI":"10.3390\/ijms241814287"},{"key":"2025070208224362870_j_rir-2025-0006_ref_002","doi-asserted-by":"crossref","unstructured":"van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology\/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013;65:2737\u20132747.","DOI":"10.1002\/art.38098"},{"key":"2025070208224362870_j_rir-2025-0006_ref_003","unstructured":"LeRoy EC, Black C, Fleischmajer R, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988;15:202-205."},{"key":"2025070208224362870_j_rir-2025-0006_ref_004","doi-asserted-by":"crossref","unstructured":"Khouri C, Lepelley M, Bailly S, et al. Comparative eficacy and safety of treatments for secondary Raynaud\u2019s phenomenon: a systematic review and network meta-analysis of randomised trials. Lancet Rheumatol. 2019;1:e237\u2013e246.","DOI":"10.1016\/S2665-9913(19)30079-7"},{"key":"2025070208224362870_j_rir-2025-0006_ref_005","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Codina A, Ca\u00f1as-Ruano E, Pope JE. Management of Raynaud\u2019s phenomenon in systemic sclerosis-a practical approach. J Scleroderma Relat Disord. 2019;4:102\u2013110.","DOI":"10.1177\/2397198318823951"},{"key":"2025070208224362870_j_rir-2025-0006_ref_006","doi-asserted-by":"crossref","unstructured":"Curtiss P, Schwager Z, Cobos G, et al. A systematic review and meta-analysis of the efects of topical nitrates in the treatment of primary and secondary Raynaud\u2019s phenomenon. J Am Acad Dermatol. 2018;78:1110\u20131118.","DOI":"10.1016\/j.jaad.2018.01.043"},{"key":"2025070208224362870_j_rir-2025-0006_ref_007","doi-asserted-by":"crossref","unstructured":"Morrisroe K, Stevens W, Sahhar J, et al. Digital ulcers in systemic sclerosis: their epidemiology, clinical characteristics, and associated clinical and economic burden. Arthritis Res Ther. 2019;21:299.","DOI":"10.1186\/s13075-019-2080-y"},{"key":"2025070208224362870_j_rir-2025-0006_ref_008","doi-asserted-by":"crossref","unstructured":"Balestroni G and Bertolotti G. EuroQol-5D (EQ-5D): an instrument for measuring quality of life. Monaldi Arch Chest Dis. 2012;78:155-159.","DOI":"10.4081\/monaldi.2012.121"},{"key":"2025070208224362870_j_rir-2025-0006_ref_009","doi-asserted-by":"crossref","unstructured":"Steen V, Denton CP, Pope JE, Matucci-Cerinic M. Digital ulcers: overt vascular disease in systemic sclerosis. Rheumatology (Oxford). 2009;48 Suppl 3:iii19-iii24.","DOI":"10.1093\/rheumatology\/kep105"},{"key":"2025070208224362870_j_rir-2025-0006_ref_010","doi-asserted-by":"crossref","unstructured":"Shah AA, Wigley FM. My approach to the treatment of sclero-derma. Mayo Clin Proc. 2013;88:377\u2013393.","DOI":"10.1016\/j.mayocp.2013.01.018"},{"key":"2025070208224362870_j_rir-2025-0006_ref_011","doi-asserted-by":"crossref","unstructured":"Au K, Singh MK, Bodukam V, et al. Atherosclerosis in systemic sclerosis: a systematic review and meta-analysis. Arthritis Rheum. 2011;63:2078\u20132090.","DOI":"10.1002\/art.30380"},{"key":"2025070208224362870_j_rir-2025-0006_ref_012","doi-asserted-by":"crossref","unstructured":"Hughes M, Pauling JD, Jones J, et al. Multicenter Qualitative Study Exploring the Patient Experience of Digital Ulcers in Systemic Sclerosis. 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