{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:24:33Z","timestamp":1791559473090,"version":"4.3.4"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"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>Pembrolizumab, an anti\u2013programmed cell death protein 1 immune checkpoint inhibitor, has been associated with immune-related sicca manifestations, although its course during ongoing treatment and after cessation remains incompletely defined. We report a 78-year-old man with metastatic upper tract urothelial carcinoma who developed abrupt, severe xerostomia and xerophthalmia 45\u202fdays after pembrolizumab initiation, with no preceding sicca symptoms. Schirmer\u2019s testing and salivary gland scintigraphy confirmed bilateral lacrimal and parotid-predominant salivary hypofunction. Autoimmune serology and IgG4 were unremarkable, other causes of sicca were excluded, and minor salivary gland biopsy was offered but declined. The findings supported a presumptive diagnosis of biopsy-unconfirmed pembrolizumab-associated seronegative sicca syndrome, without fulfilling the 2016 ACR-EULAR classification criteria for Sj\u00f6gren\u2019s disease. Causality was probable (Naranjo score 6, rising to 7 after drug withdrawal). Symptoms were moderate (CTCAE grade 2) but functionally burdensome, managed with artificial tears, saliva substitutes, and intermittent pilocarpine. Pembrolizumab was continued for 19 additional cycles with ongoing disease control; sicca persisted without escalating to a treatment-limiting grade, and treatment was eventually discontinued for cancer progression rather than sicca. Xerostomia improved substantially, and the patient regained the ability to swallow dry foods without added fluid, a patient-reported improvement consistent with a positive dechallenge. This case is informative less for its seronegativity than for its prolonged, manageable course during continued therapy and subsequent improvement after withdrawal. It suggests that, in carefully selected patients, moderate ICI-associated sicca syndrome may be managed symptomatically while immunotherapy continues, but this approach should not be generalized without close monitoring and further evidence.<\/jats:p>","DOI":"10.3389\/fmed.2026.1906210","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:27:46Z","timestamp":1785817666000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Pembrolizumab-associated seronegative sicca syndrome during continued immunotherapy and after drug withdrawal in metastatic urothelial carcinoma"],"prefix":"10.3389","volume":"13","author":[{"given":"Yunjung","family":"Choi","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Jeonbuk National University Medical School","place":["Jeonju, Republic of Korea"]},{"name":"Research Institute of Clinical Medicine of Jeonbuk National University \u2013 Biomedical Research Institute, Jeonbuk National University","place":["Jeonju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1056\/NEJMcp1702514","article-title":"Primary Sj\u00f6gren\u2019s syndrome","volume":"378","author":"Mariette","year":"2018","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/s41571-019-0218-0","article-title":"Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance","volume":"16","author":"Martins","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"ref3","first-page":"114","article-title":"Sicca\/Sj\u00f6gren\u2019s syndrome triggered by PD-1\/PD-L1 checkpoint inhibitors","volume":"37","author":"Ramos-Casals","year":"2019","journal-title":"Clin Exp Rheumatol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1634\/theoncologist.2018-0823","article-title":"Sicca syndrome associated with immune checkpoint inhibitor therapy","volume":"24","author":"Warner","year":"2019","journal-title":"Oncologist"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1177\/10781552241271753","article-title":"Sjogren's syndrome due to immune checkpoint inhibitors (ICIs): insights from a single-institution series and systematic review of the literature","volume":"31","author":"Soliman","year":"2025","journal-title":"J Oncol Pharm Pract"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1159\/000533302","article-title":"Sj\u00f6gren\u2019s syndrome caused by PD-1 inhibition in a lung cancer patient","volume":"16","author":"Caeyman","year":"2023","journal-title":"Case Rep Oncol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"4073","DOI":"10.1200\/JCO.21.01440","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update","volume":"39","author":"Schneider","year":"2021","journal-title":"J Clin Oncol"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.64898\/2026.01.21.26344113","article-title":"ICI-induced granulomatous sialadenitis is responsive to prednisone","author":"Kulchar","year":"2026","journal-title":"medRxiv"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2825","DOI":"10.1200\/JCO.21.01208","article-title":"Salivary gland hypofunction and\/or xerostomia induced by nonsurgical cancer therapies: ISOO\/MASCC\/ASCO guideline","volume":"39","author":"Mercadante","year":"2021","journal-title":"J Clin Oncol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e1435","DOI":"10.1093\/oncolo\/oyae177","article-title":"Ocular adverse events associated with antibody-drug conjugates for cancer: evidence and management strategies","volume":"29","author":"Dy","year":"2024","journal-title":"Oncologist"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1906210\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:27:49Z","timestamp":1785817669000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1906210\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":10,"alternative-id":["10.3389\/fmed.2026.1906210"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1906210","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]},"article-number":"1906210"}}