Exploring Genital Lichen Sclerosus: Navigating from Pathophysiology to Precise Diagnostic Approaches

Lichen sclerosus (LS) is a chronic, relapsing skin disease that predominantly affects the perineal and genital regions, although extragenital manifestations can occur. Despite its significant impact on patients' quality of life, particularly affecting sexual and urinary function, LS remains underdiagnosed. Multiple factors, including genetic predisposition, hormonal changes, immunological abnormalities, trauma, and urine irritation, contribute to its development and persistence. This review aims to clarify the complex pathophysiology of LS by exploring three main mechanisms: autoimmune dysregulation, sclerotic tissue formation, and oxidative stress. Autoimmune dysregulation involves T-cell infiltration and the roles of miR-155 and extracellular matrix protein 1 dysfunction, leading to chronic inflammation. miR-155 contributes to sclerotic tissue formation alongside galectin-7, promoting fibroblast proliferation and collagen synthesis. Oxidative stress results in tissue damage, autoimmunity, chronic inflammation, and an increased risk of carcinogenesis. Understanding these mechanisms is crucial for developing targeted therapies and improving LS management. Further research is needed to unravel the genetic basis, immune responses, and interactions between key mediators, ultimately advancing innovative therapeutic strategies and precision medicine in LS.