Vulvar Lichen Sclerosus from Pathophysiology to Therapeutic Approaches: Evidence and Prospects

Abstract

Vulvar lichen sclerosus (VLS) is a chronic, distressing, inflammatory disease with an enormous impact on quality of life. Treatment goals are relieving symptoms, reversing signs and preventing anatomical changes. Despite the availability of numerous therapeutic options, treatment outcome may not be entirely satisfactory and a definitive cure does not exist. This may be due to the fact that the exact VLS etiopathogenesis remains unknown. The objectives of this paper were to review the most up-to-date knowledge on VLS etiopathogenesis and to consider the available therapies through the lens of a plausible pathogenetic model. An electronic search on both VLS etiopathogenesis and its treatment was performed using the National Library of Medicine PubMed database. Based on current knowledge, it is conceivable that various, heterogeneous environmental factors acting on a genetic background trigger an autoimmune, Th-1 response, which leads to a chronic inflammatory state. This, in turn, can determine both tissue and micro-vascular injury and activation of signaling pathways involved in fibroblast and collagen metabolism. This pathogenetic sequence may explain the effectiveness of anti-inflammatory treatments, mostly topical corticosteroids, in improving VLS clinical-pathological changes. Further deepening of the disease pathways will presumably allow key mediators to become new therapeutic targets and optimize the available treatments.

Early Diagnostics of Vulvar Intraepithelial Neoplasia

“…It is conceivable that various, heterogeneous environmental factors acting on a genetic background trigger an autoimmune Th-1 response, which leads to a chronic inflammatory state [ 33 ]. LS affects women of all ages and often goes unrecognized and underreported [ 35 ]. Studies have also described lesions of uncertain malignant potential adjacent to dVIN and SCC, qualifying them as “vulvar aberrant maturations” (VAMs) [ 36 ].…”

Photodynamic Therapy in the Treatment of Vulvar Lichen Sclerosus: A Systematic Review of the Literature

“…However, the exact mechanism of action of PDT in the treatment of VLS remains uncertain. It is thought to primarily target skin sclerosis as PDT has been shown to induce apoptosis of lymphocytes and keratinocytes and to alter the expression of both cytokines and metalloproteinases that play a role in skin remodeling [ 48 ]. However, Olejek et al described the effect of PDT on the immune status of patients after the procedures, that is, a significant reduction in antinuclear antibody titers, which places PDT as a method with immuno-modulatory potential [ 37 ].…”

Genital Wound Repair and Scarring

“…In both sexes, chronic inflammation leads to skin atrophy and phimosis in men or tissue shrinkage in women followed by itchiness, pain and dyspareunia. An increased autoimmune response with formation of auto-antibodies against ECM-1 protein are features of this multifactorial disease [ 60 ]. Interestingly, a higher dermal inflammatory infiltrate with immune cells degrading elastic fibers was found in extra-genital LSC compared with genital skin [ 61 ].…”