{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:16:37Z","timestamp":1783523797181,"version":"3.55.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Male genital lichen sclerosus (MGLSc) is a chronic inflammatory dermatosis with significant morbidity, yet its pathogenesis remains incompletely understood. Two main hypotheses have emerged: an autoimmune model, and the urine\/occlusion hypothesis, specific to male genital anatomy. This narrative review critically analyses evidence supporting each paradigm. Epidemiological data reveal that autoimmune comorbidities occur significantly less frequently in men with MGLSc than in women with vulvar disease, with some studies reporting a prevalence of the former no higher than general population rates. Histopathologically, cytotoxic CD8+ and CD57+ T-lymphocyte infiltration suggests immune-mediated tissue injury, yet extracellular matrix protein 1 autoantibodies show no significant seroreactivity in MGLSc. Conversely, the urine\/occlusion hypothesis is supported by the near-universal association of MGLSc with intact foreskin, high prevalence of postmicturition microincontinence, anatomical mapping demonstrating disease concentration in maximally occluded preputial regions, and case series showing disease resolution following urinary diversion and induction at urostomy sites. Microbiome studies demonstrate convergence between balanopreputial and urinary microbial communities in affected patients, while molecular evidence shows urea-induced fibroblast changes consistent with fibrogenesis. Recent transcriptomic analyses identifying distinct molecular subtypes suggest heterogeneity, with autoimmune mechanisms potentially operative in only a subset of patients. The evidence reviewed supports urine exposure and occlusion as the predominant pathogenic drivers in most cases of MGLSc, with autoimmune phenomena likely representing secondary responses to tissue injury rather than primary aetiological mechanisms.<\/jats:p>","DOI":"10.1093\/ced\/llag237","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:46:20Z","timestamp":1780487180000},"source":"Crossref","is-referenced-by-count":1,"title":["Pathogenesis of male genital lichen sclerosus: autoimmunity vs. the urine\/occlusion hypothesis: a narrative review"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7769-3234","authenticated-orcid":false,"given":"Andrei","family":"Tanasov","sequence":"first","affiliation":[{"name":"Carol Davila University of Medicine and Pharmacy , Bucharest ,","place":["Romania"]},{"name":"2nd Department of Dermatology, Colentina Clinical Hospital , Bucharest ,","place":["Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8719-6952","authenticated-orcid":false,"given":"George-Sorin","family":"Tiplica","sequence":"additional","affiliation":[{"name":"Carol Davila University of Medicine and Pharmacy , Bucharest ,","place":["Romania"]},{"name":"2nd Department of Dermatology, Colentina Clinical Hospital , Bucharest ,","place":["Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"2026070810370790900_llag237-B1","doi-asserted-by":"crossref","first-page":"238","DOI":"10.2340\/00015555-1512","article-title":"Association of autoimmune diseases with lichen sclerosus in 532 male and female patients","volume":"93","author":"Kreuter","year":"2013","journal-title":"Acta Derm Venereol"},{"key":"2026070810370790900_llag237-B2","doi-asserted-by":"crossref","first-page":"365","DOI":"10.2340\/00015555-2537","article-title":"Clinical features, complications and autoimmunity in male lichen sclerosus","volume":"97","author":"Kantere","year":"2017","journal-title":"Acta Derm Venereol"},{"key":"2026070810370790900_llag237-B3","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1111\/j.1468-3083.2011.04155.x","article-title":"Clinical parameters in male genital lichen sclerosus: a case series of 329 patients","volume":"26","author":"Edmonds","year":"2012","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"2026070810370790900_llag237-B4","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/j.1365-2133.2010.10091.x","article-title":"Risk factors for genital lichen sclerosus in men","volume":"164","author":"Bjeki\u0107","year":"2011","journal-title":"Br J Dermatol"},{"key":"2026070810370790900_llag237-B5","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1097\/LGT.0000000000000769","article-title":"Comorbidities in male patients with lichen sclerosus: a case\u2013control study","volume":"27","author":"Hieta","year":"2023","journal-title":"J Low Genit Tract Dis"},{"key":"2026070810370790900_llag237-B6","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.3390\/jcm13102761","article-title":"Lichen sclerosus \u2013 incidence and comorbidity: a nationwide Swedish register study","volume":"13","author":"Jerkovi\u0107 Gulin","year":"2024","journal-title":"J Clin Med"},{"key":"2026070810370790900_llag237-B7","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1186\/s40001-023-01335-9","article-title":"Comorbidity in patients with lichen sclerosus: a retrospective cohort study","volume":"28","author":"Gulin","year":"2023","journal-title":"Eur J Med Res"},{"key":"2026070810370790900_llag237-B8","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.3390\/biomedicines11071986","article-title":"Immunohistological analysis of lichen sclerosus of the foreskin in pediatric age: could it be considered a premalignant lesion?","volume":"11","author":"Arena","year":"2023","journal-title":"Biomedicines"},{"key":"2026070810370790900_llag237-B9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/00000372-200002000-00002","article-title":"Comparative immunophenotypic study of lichen sclerosus: epidermotropic CD57+ lymphocytes are numerous \u2013 implications for pathogenesis","volume":"22","author":"Carlson","year":"2000","journal-title":"Am J Dermatopathol"},{"key":"2026070810370790900_llag237-B10","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1097\/JU.0000000000000155","article-title":"Insights into the pathophysiology of urethral stricture disease due to lichen sclerosus: comparison of pathological markers in lichen sclerosus induced strictures versus nonlichen sclerosus induced strictures","volume":"201","author":"Levy","year":"2019","journal-title":"J Urol"},{"key":"2026070810370790900_llag237-B11","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13578-025-01453-3","article-title":"Multi-omics analysis unveiled fibroblast-mediated pathogenesis in male genital lichen sclerosus","volume":"15","author":"Lin","year":"2025","journal-title":"Cell Biosci"},{"key":"2026070810370790900_llag237-B12","doi-asserted-by":"crossref","first-page":"104206","DOI":"10.1016\/j.labinv.2025.104206","article-title":"Molecular subtypes of balanopreputial and urethral male genital lichen sclerosus: distinct transcriptomic and clinicopathological profiles","volume":"105","author":"Xiu","year":"2025","journal-title":"Lab Invest"},{"key":"2026070810370790900_llag237-B13","doi-asserted-by":"crossref","first-page":"14212","DOI":"10.3390\/ijms232214212","article-title":"The importance of immunological disorders in the pathogenesis of lichen sclerosus in pediatric patients: a systematic review","volume":"23","author":"Torres","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026070810370790900_llag237-B14","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.3390\/diagnostics12123070","article-title":"Lichen sclerosus: a current landscape of autoimmune and genetic interplay","volume":"12","author":"Oyama","year":"2022","journal-title":"Diagnostics (Basel)"},{"key":"2026070810370790900_llag237-B15","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1111\/j.1365-2133.2004.06142.x","article-title":"Oxidative stress is implicated in the pathogenesis of lichen sclerosus","volume":"151","author":"Sander","year":"2004","journal-title":"Br J Dermatol"},{"key":"2026070810370790900_llag237-B16","doi-asserted-by":"crossref","first-page":"367","DOI":"10.4103\/0378-6323.95461","article-title":"Occlusion, urine and genital lichen sclerosus","volume":"78","author":"Bunker","year":"2012","journal-title":"Indian J Dermatol Venereol Leprol"},{"key":"2026070810370790900_llag237-B17","doi-asserted-by":"crossref","first-page":"111","DOI":"10.4103\/0019-5154.152501","article-title":"Male genital lichen sclerosus","volume":"60","author":"Bunker","year":"2015","journal-title":"Indian J Dermatol"},{"key":"2026070810370790900_llag237-B18","doi-asserted-by":"crossref","first-page":"246","DOI":"10.2340\/00015555-1481","article-title":"Urinary voiding symptomatology (micro-incontinence) in male genital lichen sclerosus","volume":"93","author":"Bunker","year":"2013","journal-title":"Acta Derm Venereol"},{"key":"2026070810370790900_llag237-B19","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s11255-022-03130-7","article-title":"The role of occlusion and micro-incontinence in the pathogenesis of penile lichen sclerosus: an observational study of pro-inflammatory cytokines\u2019 gene expression","volume":"54","author":"Czajkowski","year":"2022","journal-title":"Int Urol Nephrol"},{"key":"2026070810370790900_llag237-B20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/jdv.14488","article-title":"The diagnosis and management of male genital lichen sclerosus: a retrospective review of 301 patients","volume":"32","author":"Kravvas","year":"2018","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"2026070810370790900_llag237-B21","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.urology.2020.11.027","article-title":"Lichen sclerosus and phimosis \u2013 discrepancies between clinical and pathological diagnosis and its consequences","volume":"148","author":"Czajkowski","year":"2021","journal-title":"Urology"},{"key":"2026070810370790900_llag237-B22","doi-asserted-by":"crossref","first-page":"780","DOI":"10.21037\/tau-22-29","article-title":"Prevalence and sequelae of penile lichen sclerosus in males presenting for circumcision in regional Australia: a multicentre retrospective cohort study","volume":"11","author":"Kwok","year":"2022","journal-title":"Transl Androl Urol"},{"key":"2026070810370790900_llag237-B23","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1111\/ced.15127","article-title":"Male genital lichen sclerosus, microincontinence and occlusion: mapping the disease across the prepuce","volume":"47","author":"Kravvas","year":"2022","journal-title":"Clin Exp Dermatol"},{"key":"2026070810370790900_llag237-B24","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1111\/bjd.12014","article-title":"Peristomal lichen sclerosus: the role of occlusion and urine exposure?","volume":"168","author":"Al-Niaimi","year":"2013","journal-title":"Br J Dermatol"},{"key":"2026070810370790900_llag237-B25","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/skinhd\/vzaf028","article-title":"Urine and occlusion in the pathogenesis of lichen sclerosus: insights from a case of post-urethrectomy remission","volume":"5","author":"Mendis","year":"2025","journal-title":"Skin Health Dis"},{"key":"2026070810370790900_llag237-B26","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1177\/0956462416688159","article-title":"Genital lichen sclerosus developing around \u2018ectopic\u2019 urethral orifices supports the role of occlusion and urine in its pathogenesis","volume":"28","author":"Gupta","year":"2017","journal-title":"Int J STD AIDS"},{"key":"2026070810370790900_llag237-B27","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/ced.14869","article-title":"Male genital lichen sclerosus associated with urological interventions and microincontinence: a case series of 21 patients","volume":"47","author":"Panou","year":"2022","journal-title":"Clin Exp Dermatol"},{"key":"2026070810370790900_llag237-B28","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1177\/09564624221079068","article-title":"Lichen sclerosus following genital piercing","volume":"33","author":"Chan","year":"2022","journal-title":"Int J STD AIDS"},{"key":"2026070810370790900_llag237-B29","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/ijd.15252","article-title":"Balanopreputial sac and urine microbiota in patients with male genital lichen sclerosus","volume":"60","author":"Watchorn","year":"2021","journal-title":"Int J Dermatol"},{"key":"2026070810370790900_llag237-B30","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1186\/s12866-024-03659-w","article-title":"Unique genital microbiota in male lichen sclerosus urethral stricture associated with urine exposure","volume":"24","author":"Wang","year":"2024","journal-title":"BMC Microbiol"},{"key":"2026070810370790900_llag237-B31","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1007\/s00345-023-04490-0","article-title":"Urinary microbiome differences between lichen sclerosus induced and non-lichen sclerosus induced urethral stricture disease","volume":"41","author":"Jamil","year":"2023","journal-title":"World J Urol"},{"key":"2026070810370790900_llag237-B32","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1111\/j.1365-2133.2010.09980.x","article-title":"Nuclear magnetic resonance spectroscopy of urine in male genital lichen sclerosus","volume":"163","author":"Edmonds","year":"2010","journal-title":"Br J Dermatol"}],"container-title":["Clinical and Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ced\/advance-article-pdf\/doi\/10.1093\/ced\/llag237\/68477262\/llag237.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ced\/advance-article-pdf\/doi\/10.1093\/ced\/llag237\/68477262\/llag237.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T14:37:17Z","timestamp":1783521437000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ced\/advance-article\/doi\/10.1093\/ced\/llag237\/8702607"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":32,"URL":"https:\/\/doi.org\/10.1093\/ced\/llag237","relation":{},"ISSN":["0307-6938","1365-2230"],"issn-type":[{"value":"0307-6938","type":"print"},{"value":"1365-2230","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]},"article-number":"llag237"}}