Pathogenesis of Male Genital Lichen Sclerosus: Autoimmunity versus the Urine/Occlusion Hypothesis - A Narrative...

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 prevalence 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 males. Conversely, the urine/occlusion hypothesis is supported by the near-universal association of MGLSc with intact foreskin, high prevalence of post-micturition micro-incontinence, 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 MGLSc cases, with autoimmune phenomena likely representing secondary responses to tissue injury rather than primary etiological mechanisms.