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This study aimed to evaluate its clinical effectiveness in either gel in orabase or mouthwash, on pain reduction, ulcer healing, recurrence rates, and salivary IL-2 level in patients with RAS. In this randomized clinical trial, 60 patients with RAS were equally divided into 3 groups: EPO oral gel, EPO mouthwash, or a placebo. Ulcer size, the Pain Visual Analog Scale (P-VAS), and salivary IL-2 levels were evaluated at baseline, day 3, and day 7. When compared to a placebo, both EPO formulations significantly decreased pain, ulcer size, and salivary IL-2 levels (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). With nearly total pain relief, significant ulcer healing, and the lowest post-treatment IL-2 concentration, the EPO gel group showed the greatest improvement. In comparison to mouthwash and a placebo, patients treated with EPO gel also had noticeably longer recurrence-free intervals (median 5 months). No negative effects noted. These findings suggest that EPO gel is a therapeutic option for RAS that is both safe and effective, with the potential to modify the disease in addition to relieving symptoms.\n                  <\/jats:p>\n                  <jats:p>Trial registration: The study was registered at Clinical Trials.gov (NCT06923605) on 11\/4\/2025.<\/jats:p>","DOI":"10.1038\/s41598-026-40440-7","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T15:33:31Z","timestamp":1773848011000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy of topical erythropoietin gel and mouthwash for recurrent aphthous stomatitis in a randomized clinical trial"],"prefix":"10.1038","volume":"16","author":[{"given":"Mai Talaat","family":"Elgendi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radwa R.","family":"Hussein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nivine","family":"Ragy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada M.","family":"El Hoffy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nevine H. 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