HCV poly U/UC sequence-induced inflammation leads to metabolic disorders in vulvar lichen sclerosis.

Vulvar lichen sclerosis (VLS) is a dermatologic disorder that affects women worldwide. Women with VLS have white, atrophic papules on the vulva. They suffer from life-long intense pruritus. Corticosteroids are the first-line of treatments and the most effective medicines for VLS. Although VLS has been speculated as an autoimmune disease for a long time, its pathogenesis and the molecular mechanism is largely unknown. We performed a comprehensive multi-omics analysis of paired samples from VLS patients as well as healthy donors. From the RNA-seq analysis, we found that VLS is correlated to abnormal antivirus response because of the presence of Hepatitis C Virus poly U/UC sequences. Lipidomic and metabolomic analysis revealed that inflammation-induced metabolic disorders of fatty acids and glutathione were likely the reasons for pruritus, atrophy, and pigment loss in the vulva. Thus, the present study provides an initial interpretation of the pathogenesis and molecular mechanism of VLS and suggests that metabolic disorders that affect the vulva may serve as therapeutic targets for VLS.

Novel Therapeutic Approaches and Targets for Treatment of Vulvar Lichen Sclerosus.

BACKGROUND: Vulvar Lichen Sclerosus (VLS) is a chronic inflammatory disease with a huge impact on a person's quality of life. A correct therapy is required for relieving symptoms, reversing signs and preventing further anatomical changes. OBJECTIVE: The main objective of the present paper is to provide suggestions for the best treatment approach, based on the available evidence. Treatment strategies are divided on the basis of the treatment phase, distinguishing options for initial, acute or attack treatment and those for long-term, maintenance treatment. METHODS: An electronic search was performed using the National Library of Medicine PubMed database. All the studies evaluating treatment of vulvar lichen sclerosus published in the English literature were analyzed, including controlled studies, case series, guidelines and reviews. RESULTS: Current evidence identifies ultra-potent and potent corticosteroids, administered for 12 weeks, as the first-line recommended treatment for active VLS. Topical calcineurin inhibitors, tacrolimus and pimecrolimus, are effective and safe alternatives. Long-term maintenance strategies aimed at preventing recurrences are required, after the initial treatment phase. Maintenance treatment mostly consists in topical corticosteroids, administered i) on an "as needed" basis ("reactive" scheme), ii) on a continuative regimen, iii) on a low-dose, intermittent regimen ("proactive" scheme). Further investigations are needed for better defining the placement of other options within the VLS therapeutic algorithm, including retinoids, physical and systemic treatments. CONCLUSION: The available evidence provides useful indications for the management of VLS. Both the identification of new therapeutic targets and the optimization of the available options represent the main objectives of future research.

Structured analysis of histopathological characteristics of vulvar lichen sclerosus in a juvenile population.

Genital lichen sclerosus (LS), a chronic noninfectious dermatosis, is not rare in pediatric dermatology. The histopathological diagnosis in children and adults in both genital and nongenital LS is considered to be the same and encompasses a broad range of possible characteristics. Clinical manifestations and treatment options of genital LS in children are different depending on gender. The vast majority of boys are treated with circumcision, making for a larger amount of information on the histopathology of genital LS in boys, whereas substantial information on the histopathology of juvenile vulvar LS is lacking. In girls, vulvar LS almost always persists beyond puberty and, therefore, presents a particular challenge to clinicians and cause for concern for the patient. Vulvar LS in childhood and adolescence (juveniles) is underreported, and there are uncertainties with regard to the long-term course of the disease when it occurs at an age when the vulva is still developing. The present study investigates biopsies of 100 juvenile cases of vulvar LS and analyzes the presence or absence of the most salient histopathological characteristics of LS that are described in the literature. We found that the range of histopathological characteristics known for adult LS are also present in juvenile vulvar LS, even at very young ages, including histopathological features associated with autoimmune disease, in support of the idea of a similar pathogenesis.

An autoimmune phenotype in vulvar lichen sclerosus and lichen planus: a Th1 response and high levels of microRNA-155.

Vulvar lichen sclerosus and lichen planus are T-cell-mediated chronic skin disorders. Although autoimmunity has been suggested, the exact pathogenesis of these disorders is still unknown. Therefore, the aim of the current study was to investigate the molecular and immunological mechanisms critical to the pathogenesis of vulvar lichen sclerosus and lichen planus. By using gene expression profiling and real-time RT-PCR experiments, we demonstrated a significantly increased expression of the pro-inflammatory cytokines (IFNγ, CXCR3, CXCL9, CXCL10, CXCL11, CCR5, CCL4, and CCL5) specific for a Th1 IFNγ-induced immune response. In addition, BIC/microRNA-155 (miR-155)--a microRNA involved in regulation of the immune response--was significantly upregulated in lichen sclerosus and lichen planus (9.5- and 17.7-fold change, respectively). Immunohistochemistry showed a significant T-cell response, with pronounced dermal infiltrates of CD4(+), CD8(+), and FOXP3(+) cells. In conclusion, these data demonstrate an autoimmune phenotype in vulvar lichen sclerosus and lichen planus, characterized by increased levels of Th1-specific cytokines, a dense T-cell infiltrate, and enhanced BIC/miR-155 expression.

Lichen sclerosus: a review of literature and a case of an atypic surgical treatment.

Lichen sclerosus is a chronic immuno-mediated skin disease of the genital region in men and women. The treatment may be pharmacological or surgical, the choice depending on the extension of the involved area, the histological pattern and the level of functional disease complained by the patient. If the biopsy is negative for neoplastic degeneration the treatment may be pharmacological only. In our paper, we describe the case of a patient with vulvar disease and labial fusion, burial of the clitoris and severe introital stenosis. In this case, the treatment was surgical.

Vulval lichen sclerosus and lichen planus.

Lichen sclerosus (LS) and lichen planus (LP) are both immunologically mediated diseases with a preference for the genitalia. The basic principles of management of vulval LS and vulvovaginal LP are the same and involve explanation of the disease, emphasizing the chronic nature of the condition and outlining treatment options. The main difference between the two conditions is that LP has a propensity to involve the mucous membranes including the mouth and vagina which are rarely affected in LS. First-line treatment for LS is a super-potent topical corticosteroid ointment which has a high response rate. Erosive vulvovaginal LP is more challenging to treat. Second-line therapies include topical calcineurin inhibitors and systemic agents. There is limited evidence for systemic treatments for both conditions. The risk of vulval squamous cell carcinoma (SCC) is increased in both LP and LS, and it is not known how treatment affects this risk. We recommend teaching self-examination and longitudinal evaluation.