{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:45:26Z","timestamp":1793371526717,"version":"4.5.0"},"reference-count":7,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors can cause diverse immune-related adverse events, the early recognition of which is critical. Intestinal pseudo-obstruction caused by immune-mediated gastrointestinal dysautonomia is a rare, potentially fatal, and under-recognized toxicity that may be difficult to distinguish from more common gastrointestinal complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We describe the clinical course, investigation, and management of a patient with metastatic esophageal mucosal melanoma who developed sequential gastrointestinal toxicities following combination ipilimumab and nivolumab therapy, focusing on early recognition and the diagnostic challenges associated with recognizing immune-mediated intestinal dysmotility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Following four cycles of immunotherapy, the patient developed intractable nausea, vomiting, and constipation. Computed tomography demonstrated diffuse small bowel dilatation without a mechanical transition point, raising suspicion of immune checkpoint inhibitor-induced ileus. Despite intravenous corticosteroids, the clinical phenotype evolved over the following week to high-frequency diarrhea, with repeat imaging and endoscopy supporting superimposed enterocolitis. Following an initial response to prolonged corticosteroid treatment, diarrhea recurred and ultimately improved after infliximab therapy. The sequential presentation of dysmotility and inflammatory colitis complicated the assessment of disease evolution and decisions regarding the escalation of immunosuppression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      This case highlights intestinal pseudo-obstruction as an important but easily overlooked immune-related adverse event and demonstrates how rare gastrointestinal dysautonomia may precede, coexist with, or be masked by more familiar immune-mediated colitis. Recognition of the contrasting clinical phenotypes, particularly otherwise unexplained nausea, vomiting, constipation, and bowel dilatation without mechanical obstruction, is essential because the underlying mechanisms and therapeutic responses may differ. Greater awareness of these early warning features, coupled with prompt investigation and multidisciplinary assessment, may reduce diagnostic delays and enable earlier treatment of this potentially life-threatening toxicity\n                      <jats:bold>.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1966665","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:30:45Z","timestamp":1790224245000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Immune checkpoint inhibitor-induced gastrointestinal toxicity: the diagnostic challenge of sequential ileus and colitis"],"prefix":"10.3389","volume":"13","author":[{"given":"Mouhamad","family":"Ismail","sequence":"first","affiliation":[{"name":"Department of Oncology, Cambridge University Hospital","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Oncology, Cambridge University Hospital","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent","family":"O\u2019Carrigan","sequence":"additional","affiliation":[{"name":"Department of Oncology, Cambridge University Hospital","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa","family":"Corrie","sequence":"additional","affiliation":[{"name":"Department of Oncology, Cambridge University Hospital","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3163","DOI":"10.1038\/s41467-019-11107-x","article-title":"Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets","volume":"10","author":"Newell","year":"2019","journal-title":"Nat Commun"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1200\/JCO.2017.77.6385","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice guideline","volume":"36","author":"Brahmer","year":"2018","journal-title":"J Clin Oncol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"387","DOI":"10.6004\/jnccn.2022.0020","article-title":"Management of immunotherapy-related toxicities, version 1.2022, NCCN clinical practice guidelines in oncology","volume":"20","author":"Thompson","year":"2022","journal-title":"J Natl Compr Cancer Network"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3413","DOI":"10.1007\/s00415-023-11667-5","article-title":"Dysautonomia associated with immune checkpoint inhibitors","volume":"270","author":"Tezuka","year":"2023","journal-title":"J Neurol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e70212","DOI":"10.1111\/nmo.70212","article-title":"Gastrointestinal dysautonomia after immune checkpoint inhibitor therapy: a case series and systematic review","volume":"38","author":"Sennf\u00e4lt","year":"2026","journal-title":"Neurogastroenterol Motil"},{"key":"B6","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s40425-018-0396-9","article-title":"Fatal enteric plexus neuropathy after one dose of ipilimumab plus nivolumab: a case report","volume":"6","author":"Appelbaum","year":"2018","journal-title":"J Immunother Cancer"},{"key":"B7","first-page":"2667","article-title":"Vedolizumab or infliximab: treatment option in immune checkpoint inhibitor-induced colitis","volume-title":"J Clin Oncol","author":"Shambhavi","year":"2025"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1966665\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:31:08Z","timestamp":1790224268000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1966665\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":7,"alternative-id":["10.3389\/fmed.2026.1966665"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1966665","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"article-number":"1966665"}}