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.

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.

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.

Chlamydia trachomatis infection in women with lichen sclerosus vulvae and vulvar cancer.

OBJECTIVE: Chronic infections in the urogenital area often precede or coexist with vulvar cancer. A strong connection between some tumours and the-appearance of Chlamydia trachomatis infection has been observed, but there is little information concerning a connection of that infection with vulvar cancer and lichen sclerosus vulvae (LS). The aim of this study was the analysis of frequency of antigens appearance and antibodies of IgM and IgG Chlamydia trachomatis in patients with vulvar cancer and LS and we wanted to find the correlation between Chlamydia trachomatis infection and vulvar cancer and LS. METHODS: 80 women treated in the Clinic of Vulva Diseases at the Department and Clinical Ward of Gynaecology, Obstetrics and Oncological Gynaecology in Bytom, in the Silesian Medical University in Katowice were divided into two groups - 30 were treated for vulvar cancer and 50 were treated because of LS. We took bacterial smears vagina and cervical smears for presence of Chlamydia trachomatis antigens and peripheral blood to mark antibodies of IgM and IgG Chlamydia trachomastis. RESULTS: Chlamydia trachomatis antigen was found in 20% women with vulvar cancer and in 12% women with LS (p>0.05). In 13,3% cases with vulvar cancer we observed IgM Chlamydia trachomatis antibodies. In the group with LS IgM antibodies appeared in 16% women (p>0.05). In 50% patients with vulvar cancer in blood serum we observed IgG Chlamydia trachomatis antibodies, and in 16% women with LS (p<0.001). CONCLUSIONS: Previous Chlamydia trachomatis infection can lead to vulvar carcinogenesis.

Langerhans cells in vulvar lichen sclerosus and vulvar squamous cell carcinoma.

INTRODUCTION: Langerhans cells (LCs), specializing in antigen presentation, are a very important part of the skin immune system (SIS). MATERIALS AND METHODS: Skin biopsies from 22 women with vulvar lichen sclerosus (LS): 15 patients with early and 7 with the late stage of the disease, were evaluated. Five women with vulvar squamous cell carcinoma (SCC) were also examined. The control group consisted of 9 women who underwent plastic surgery of the vulvar region. Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissues samples using antihuman CD1a antibody (NCL-CD1a-235, Novocastra). RESULTS: Increased numbers of LC stainings were present in early LS, whereas decreased numbers of these cells were present in late LS and in SCC compared with the control group. CONCLUSIONS: This study showed that dysregulation of the SIS may lead to suppression of LCs in the vulvar epithelium and may be one of the reasons for a higher tendency for carcinogenesis in the vulvar region.

Cytokine alterations in lichen sclerosus: an immunohistochemical study.

BACKGROUND: Although the histology of lichen sclerosus is characteristic, the precise nature of the inflammatory changes and the signals provoking them is uncertain. OBJECTIVES: To delineate the inflammatory changes in lichen sclerosus more accurately by studying cytokine changes. METHODS: An immunohistochemical study of 12 specimens of genital lichen sclerosus and one specimen of extragenital lichen sclerosus was undertaken using monoclonal antibodies to interferon (IFN)-gamma, IFN-gamma receptor, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-2 receptor (CD25), intercellular adhesion molecule-1 (ICAM-1) and its ligand CD11a. Control specimens were seven specimens of normal vulva obtained during gynaecological procedures, three specimens of normal skin, adjacent uninvolved thigh from three of the patients with lichen sclerosus, five specimens of nonvulval psoriasis, four specimens of nonvulval lichen planus and two specimens from chronic wounds. RESULTS: The lichen sclerosus specimens demonstrated slightly increased staining for IFN-gamma within the epidermis compared with the normal vulva and nonvulval skin. There was increased dermal staining for IFN-gamma both within the pale zone of the upper dermis and within the inflammatory zone below this. We confirmed our previous demonstration that in lichen sclerosus HLA-DR immunostaining is increased in association with vascular endothelium, the inflammatory cell infiltrate and around the keratinocytes. The areas of the epidermis with the strongest immunostaining for HLA-DR generally also had the strongest staining for IFN-gamma. In the lichen sclerosus specimens the zone of inflammation also demonstrated increased immunostaining for TNF-alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 while the zone of sclerosus demonstrated a smaller increase in immunostaining for IFN-gamma receptor, TNF-alpha, CD11a and ICAM-1, and the epidermis demonstrated increased staining for ICAM-1. CONCLUSIONS: The increased staining for IFN-gamma, TNF-alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 suggest that the cytokine response in lichen sclerosus shares characteristics of the cytokine response in lichen planus and chronic wounds.

Fetal microchimerism is not involved in the pathogenesis of lichen sclerosus of the vulva.

OBJECTIVES: The aim of this study was to investigate a possible relationship between fetal cell microchimerism and lichen sclerosus of the vulva. We searched for the presence of male cells and DNA in vulval tissue samples. METHODS: Paraffin-embedded skin biopsy samples from 15 women affected with vulval lichen sclerosus who gave birth to at least one son were analyzed for the presence of microchimeric male cells using fluorescence in situ hybridization (FISH) and fluorescent PCR. We included three lichen sclerosus samples originating from women without male offspring, six vulval specimens without pathological finding originating from autopsies and seven male gingival specimens as controls. RESULTS: Nucleated cells containing Y-chromosome specific sequences were neither detected at any site of the lesions nor in normal vulval specimens by using FISH. These results were confirmed by the use of PCR amplification demonstrating only DNA sequences specific for the X chromosome. No female microchimerism was detected in the male gingival samples. CONCLUSION: Despite the limited number and size of the samples, we conclude that persistent male fetal cells are not involved in the pathogenesis of lichen sclerosus of the vulva, since we consistently could not detect Y-chromosome specific sequences by using two molecular techniques.