{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:19:09Z","timestamp":1787026749543,"version":"build-2736575974"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"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>Mucous membrane pemphigoid (MMP) is an autoimmune disease affecting the oral mucosa, conjunctivae and other mucous membranes. The mainstay treatment options are local and systemic corticosteroids and immunomodulatory therapies. Current research on cancer risk in MMP is scarce and has yielded conflicting results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The aim of this study was to investigate the risk of developing skin cancer in patients with MMP by performing a large-scale, retrospective matched cohort study utilizing data from over 117 million US individuals. The risk of skin cancer in patients with MMP was observed within a 5-year follow-up period, along with three temporal difference analyses and stratification for disease severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MMP was associated with an increased risk of several types of skin cancers within the first 5 years of follow-up, particularly squamous cell carcinoma, basal cell carcinoma, and non-melanoma skin cancer. Stratification by disease severity showed significantly elevated risks in severe cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings underscore the importance of regular skin cancer screening and risk-based monitoring in MMP patients, particularly those with severe disease. Integrating dermatologic surveillance into routine care could facilitate early detection and timely intervention. Additionally, these results highlight the need for further research into cancer risks in other autoimmune blistering diseases, helping to refine long-term management strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1585167","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T01:23:15Z","timestamp":1743643395000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Increased risk of skin cancers in mucous membrane pemphigoid: a large-scale matched cohort study of 117 million US individuals"],"prefix":"10.3389","volume":"12","author":[{"given":"Amar","family":"Nouri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Olbrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enno","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf J.","family":"Ludwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Curman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"103036","DOI":"10.1016\/j.autrev.2022.103036","article-title":"Mucous membrane pemphigoid.","volume":"21","author":"Du","year":"2022","journal-title":"Autoimmun Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1111\/ddg.14905","article-title":"S2k Guideline for the diagnosis and treatment of mucous membrane pemphigoid.","volume":"20","author":"Hofmann","year":"2022","journal-title":"J Dtsch Dermatol Ges."},{"key":"B3","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1001\/jamadermatol.2021.1036","article-title":"Assessment of diagnostic strategy for mucous membrane pemphigoid.","volume":"157","author":"Rashid","year":"2021","journal-title":"JAMA Dermatol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1111\/jdv.17397","article-title":"European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part I.","volume":"35","author":"Rashid","year":"2021","journal-title":"J Eur Acad Dermatol Venereol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.20603","article-title":"Risk of oesophageal strictures in mucous membrane pemphigoid: Insights from a real-world cohort study.","author":"Olbrich","year":"2025","journal-title":"J Eur Acad Dermatol Venereol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.20499","article-title":"Risk of blindness in a global cohort of patients with mucous membrane pemphigoid.","author":"Olbrich","year":"2024","journal-title":"J Eur Acad Dermatol Venereol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3389\/fimmu.2019.00034","article-title":"The diagnosis and blistering mechanisms of mucous membrane pemphigoid.","volume":"10","author":"Kamaguchi","year":"2019","journal-title":"Front Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1001\/archderm.138.3.370","article-title":"The first international consensus on mucous membrane pemphigoid: Definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators.","volume":"138","author":"Chan","year":"2002","journal-title":"Arch Dermatol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.autrev.2019.02.005","article-title":"Pemphigus and mucous membrane pemphigoid: An update from diagnosis to therapy.","volume":"18","author":"Buonavoglia","year":"2019","journal-title":"Autoimmun Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1111\/jdv.17395","article-title":"European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part II.","volume":"35","author":"Schmidt","year":"2021","journal-title":"J Eur Acad Dermatol Venereol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1007\/s40257-020-00513-3","article-title":"A review comparing international guidelines for the management of bullous pemphigoid, pemphigoid gestationis, mucous membrane pemphigoid, and epidermolysis bullosa acquisita.","volume":"21","author":"Patel","year":"2020","journal-title":"Am J Clin Dermatol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1001\/jamadermatol.2013.1434","article-title":"Prevalence and clinical significance of anti-laminin 332 autoantibodies detected by a novel enzyme-linked immunosorbent assay in mucous membrane pemphigoid.","volume":"149","author":"Bernard","year":"2013","journal-title":"JAMA Dermatol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1097\/01.md.0000076003.64510.00","article-title":"Anti-epiligrin cicatricial pemphigoid: clinical findings, immunopathogenesis, and significant associations.","volume":"82","author":"Egan","year":"2003","journal-title":"Medicine."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jdermsci.2007.02.012","article-title":"A widening perspective regarding the relationship between anti-epiligrin cicatricial pemphigoid and cancer.","volume":"47","author":"Sadler","year":"2007","journal-title":"J Dermatol Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1600-0714.2006.00483.x","article-title":"Relationship between cancer and oral pemphigoid patients with antibodies to alpha6-integrin.","volume":"36","author":"Malik","year":"2007","journal-title":"J Oral Pathol Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1111\/j.1365-2230.2007.02463.x","article-title":"Relative risk for cancer in mucous membrane pemphigoid associated with antibodies to the beta4 integrin subunit.","volume":"32","author":"Letko","year":"2007","journal-title":"Clin Exp Dermatol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"119","DOI":"10.5826\/dpc.0902a07","article-title":"Mucous membrane pemphigoid-associated malignancies: Case series and a brief overview of the literature.","volume":"9","author":"La Placa","year":"2019","journal-title":"Dermatol Pract Concept."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1001\/archderm.135.9.1091","article-title":"Antiepiligrin cicatricial pemphigoid: An underdiagnosed entity within the spectrum of scarring autoimmune subepidermal bullous diseases?","volume":"135","author":"Leverkus","year":"1999","journal-title":"Arch Dermatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/j.1346-8138.2004.tb00497.x","article-title":"A case of anti-epiligrin cicatricial pemphigoid associated with lung carcinoma and severe laryngeal stenosis: Review of Japanese cases and evaluation of risk for internal malignancy.","volume":"31","author":"Matsushima","year":"2004","journal-title":"J Dermatol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1111\/bjd.17202","article-title":"A sensitive and specific assay for the serological diagnosis of antilaminin 332 mucous membrane pemphigoid.","volume":"180","author":"Goletz","year":"2019","journal-title":"Br J Dermatol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"771766","DOI":"10.3389\/fimmu.2021.771766","article-title":"The second study of clinical and immunological findings in anti-laminin 332-type mucous membrane pemphigoid examined at Kurume University-diagnosis criteria suggested by summary of 133 cases.","volume":"12","author":"Qian","year":"2021","journal-title":"Front Immunol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1001\/jamadermatol.2021.4773","article-title":"Evaluation of site- and autoantigen-specific characteristics of mucous membrane pemphigoid.","volume":"158","author":"van Beek","year":"2022","journal-title":"JAMA Dermatol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1250115","DOI":"10.3389\/fimmu.2023.1250115","article-title":"Autoimmunity against laminin 332.","volume":"14","author":"Patzelt","year":"2023","journal-title":"Front Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1111\/bjd.18129","article-title":"Keratinocyte footprint assay discriminates antilaminin-332 pemphigoid from all other forms of pemphigoid diseases.","volume":"182","author":"Giurdanella","year":"2020","journal-title":"Br J Dermatol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.jaad.2024.10.063","article-title":"COVID-19 infection is associated with an elevated risk for autoimmune blistering diseases while COVID-19 vaccination decreases the risk: A large-scale population-based cohort study of 112 million individuals.","volume":"92","author":"Curman","year":"2025","journal-title":"J Am Acad Dermatol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"104639","DOI":"10.1016\/j.ebiom.2023.104639","article-title":"Cutaneous lupus erythematosus is associated with an increased risk of cardiac and vascular diseases: A large-scale, propensity-matched global retrospective cohort study.","volume":"93","author":"Olbrich","year":"2023","journal-title":"EBioMedicine."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1516126","DOI":"10.3389\/fphar.2025.1516126","article-title":"A comprehensive review of methodologies and application to use the real-world data and analytics platform TriNetX.","volume":"16","author":"Ludwig","year":"2025","journal-title":"Front Immunol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"ooad035","DOI":"10.1093\/jamiaopen\/ooad035","article-title":"A global federated real-world data and analytics platform for research.","volume":"6","author":"Palchuk","year":"2023","journal-title":"JAMIA Open."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.3390\/cancers12041007","article-title":"Insights into genetic susceptibility to melanoma by gene panel testing: Potential pathogenic variants in ACD, ATM, BAP1, and POT1.","volume":"12","author":"Pastorino","year":"2020","journal-title":"Cancers."},{"key":"B30","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1097\/00003226-200007000-00033","article-title":"Remission of antiepiligrin (laminin-5) cicatricial pemphigoid after excision of gastric carcinoma.","volume":"19","author":"Uchiyama","year":"2000","journal-title":"Cornea."},{"key":"B31","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1111\/cup.12348","article-title":"Remission of anti-epiligrin cicatricial pemphigoid after excision of cervical adenocarcinoma.","volume":"41","author":"Ding","year":"2014","journal-title":"J Cutan Pathol."},{"key":"B32","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1076\/0271-3683(200008)2121-VFT646","article-title":"Influence of intravenous immunoglobulin therapy on serum levels of anti-beta 4 antibodies in ocular cicatricial pemphigoid. A correlation with disease activity. A preliminary study.","volume":"21","author":"Letko","year":"2000","journal-title":"Curr Eye Res."},{"key":"B33","first-page":"2283","article-title":"The role of antibody to human beta4 integrin in conjunctival basement membrane separation: Possible in vitro model for ocular cicatricial pemphigoid.","volume":"40","author":"Chan","year":"1999","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"7707","DOI":"10.1167\/iovs.12-11404","article-title":"Identification of epitopes within integrin \u03b24 for binding of auto-antibodies in ocular cicatricial and mucous membrane pemphigoid: Preliminary report.","volume":"54","author":"Rashid","year":"2013","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1189680","DOI":"10.3389\/fmed.2023.1189680","article-title":"Skin cancer in solid organ transplant recipients: Still an open problem.","volume":"10","author":"Granata","year":"2023","journal-title":"Front Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.det.2018.07.009","article-title":"Skin cancer and immunosuppression.","volume":"37","author":"Collins","year":"2019","journal-title":"Dermatol Clin."},{"key":"B37","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1111\/j.1365-2133.1991.tb06033.x","article-title":"The epidermal basement membrane in basal cell carcinoma: An immunohistochemical study.","volume":"125","author":"Markey","year":"1991","journal-title":"Br J Dermatol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1585167\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T01:23:18Z","timestamp":1743643398000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1585167\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,3]]},"references-count":37,"alternative-id":["10.3389\/fmed.2025.1585167"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1585167","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,3]]},"article-number":"1585167"}}