{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:34:37Z","timestamp":1781649277784,"version":"3.54.5"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Ulcerative colitis (UC) is classically regarded as a disease limited to the colon; however, upper gastrointestinal (UGI) involvement has been increasingly recognized. We report a rare and clinically severe case of UC with marked UGI involvement that was successfully treated with tacrolimus and subsequently maintained with upadacitinib. A 19-year-old man presented with epigastric pain, diarrhea, and elevated inflammatory markers. Computed tomography demonstrated diffuse gastric wall thickening, whereas colonic involvement was relatively mild. Esophagogastroduodenoscopy revealed extensive erythema, spontaneous bleeding, and ulcerations in the stomach and duodenum, whereas ileocolonoscopy showed findings consistent with moderate UC. Histopathological examination of gastric and duodenal biopsies demonstrated dense inflammatory cell infiltration with crypt abscesses, supporting a diagnosis of UC-associated UGI involvement. The patient was refractory to high-dose corticosteroids and unable to tolerate oral therapy. Continuous intravenous tacrolimus was initiated, resulting in clinical and endoscopic improvement. Due to tacrolimus-related adverse effects, maintenance therapy was transitioned to upadacitinib, leading to sustained clinical and endoscopic remission. This case highlights the importance of recognizing severe UGI involvement as a rare UC phenotype and suggests that aggressive immunomodulatory therapy, including calcineurin inhibitors and Janus kinase inhibitors, may be effective in selected patients.<\/jats:p>","DOI":"10.3389\/fmed.2026.1812628","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:55:29Z","timestamp":1778219729000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Severe upper gastrointestinal involvement in ulcerative colitis successfully treated with sequential therapy using intravenous tacrolimus and upadacitinib: a case report"],"prefix":"10.3389","volume":"13","author":[{"given":"Kenji","family":"Kinoshita","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hakodate Municipal Hospital","place":["Hakodate, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisei","family":"Koishi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hakodate Municipal Hospital","place":["Hakodate, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Nagaya","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hakodate Municipal Hospital","place":["Hakodate, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Higashino","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hakodate Municipal Hospital","place":["Hakodate, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonoe","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hakodate Municipal Hospital","place":["Hakodate, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hakodate Municipal Hospital","place":["Hakodate, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hakodate Municipal Hospital","place":["Hakodate, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuteru","family":"Hatanaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hakodate Municipal Hospital","place":["Hakodate, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiya","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hakodate Municipal Hospital","place":["Hakodate, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiko","family":"Katsurada","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1016\/s0140-6736(16)32126-2","article-title":"Ulcerative colitis.","volume":"389","author":"Ungaro","year":"2017","journal-title":"Lancet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5913","DOI":"10.3748\/wjg.v12.i36.5913","article-title":"Diffuse gastroduodenitis and pouchitis associated with ulcerative colitis.","volume":"12","author":"Ikeuchi","year":"2006","journal-title":"World J Gastroenterol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.path.2010.05.004","article-title":"Upper gastrointestinal tract in inflammatory bowel disease.","volume":"3","author":"Goldstein","year":"2010","journal-title":"Surg Pathol Clin."},{"key":"B4","doi-asserted-by":"publisher","first-page":"396521","DOI":"10.1155\/2012\/396521","article-title":"Two cases of diffuse duodenitis associated with ulcerative colitis.","volume":"2012","author":"Endo","year":"2012","journal-title":"Case Rep Gastrointest Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"6684806","DOI":"10.1155\/2021\/6684806","article-title":"Gastroduodenal ulcerative colitis in association with ulcerative pancolitis.","volume":"2021","author":"San Aye","year":"2021","journal-title":"Case Rep Gastrointest Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2963","DOI":"10.3748\/wjg.v27.i22.2963","article-title":"Mucosal lesions of the upper gastrointestinal tract in patients with ulcerative colitis: a review.","volume":"27","author":"Sun","year":"2021","journal-title":"World J Gastroenterol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2228","DOI":"10.1111\/apa.16882","article-title":"Severe upper gastrointestinal involvement in paediatric ulcerative colitis.","volume":"112","author":"Fioretti","year":"2023","journal-title":"Acta Paediatr."},{"key":"B8","doi-asserted-by":"publisher","first-page":"128","DOI":"10.15403\/jgld-5903","article-title":"Colitis trouble up high: a case of gastroduodenal ulcerative colitis and literature review.","volume":"34","author":"Cauchi","year":"2025","journal-title":"J Gastrointestin Liver Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"33","DOI":"10.14309\/crj.2014.76","article-title":"Tacrolimus therapy for ulcerative colitis-associated post-colectomy enteritis.","volume":"2","author":"Rush","year":"2014","journal-title":"ACG Case Rep J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2477","DOI":"10.2169\/internalmedicine.53.1910","article-title":"Severe diffuse duodenitis successfully treated with intravenous tacrolimus after colectomy for ulcerative colitis.","volume":"53","author":"Saito","year":"2014","journal-title":"Intern Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e70217","DOI":"10.1002\/deo2.70217","article-title":"Severe gastroduodenitis associated with ulcerative colitis after total colectomy successfully treated with endoscopic hemostasis and oral tacrolimus.","volume":"6","author":"Fujimoto","year":"2026","journal-title":"DEN Open."},{"key":"B12","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1002\/ibd.21853","article-title":"Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid-refractory ulcerative colitis.","volume":"18","author":"Ogata","year":"2012","journal-title":"Inflamm Bowel Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1093\/ecco-jcc\/jjv221","article-title":"Efficacy and safety of tacrolimus therapy for active ulcerative colitis; a systematic review and meta-analysis.","volume":"10","author":"Komaki","year":"2016","journal-title":"J Crohns Colitis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/s41598-024-77365-y","article-title":"Effectiveness of tacrolimus therapy in refractory ulcerative colitis compared to infliximab with propensity score matching.","volume":"15","author":"Yoshihara","year":"2025","journal-title":"Sci Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/s2468-1253(21)00377-0","article-title":"Efficacy and safety of biologics and small molecule drugs for patients with moderate-to-severe ulcerative colitis: a systematic review and network meta-analysis.","volume":"7","author":"Lasa","year":"2022","journal-title":"Lancet Gastroenterol Hepatol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1016\/s0140-6736(22)00581-5","article-title":"Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials.","volume":"399","author":"Danese","year":"2022","journal-title":"Lancet."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1812628\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:55:30Z","timestamp":1778219730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1812628\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":16,"alternative-id":["10.3389\/fmed.2026.1812628"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1812628","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]},"article-number":"1812628"}}