Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen Sclerosus.
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ABSTRACT:
SUBMITTER: Tan X
PROVIDER: S-EPMC8465596 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Vulvar lichen sclerosus (LS) is a chronic, inflammatory dermatosis that may lead to scarring of the vulva and sexual dysfunction. LS affects women of all ages and often goes unrecognized and underreported. Uncertainty continues to exist around its pathogenesis, histologic diagnosis, and treatment. However, there have been great advances in our understanding of autoimmunogenic targets in disease formation and progression. In addition, there has been recent investigation of potential non-steroid-based treatments, including platelet-rich plasma therapy and energy-based modalities such as the fractional CO2 laser, photodynamic therapy, and high intensity focused ultrasound. Refinement of surgical techniques for restoring vulvar anatomy and treating clitoral phimosis, introital stenosis, and vulvar granuloma fissuratum is leading to improved patient outcomes. This review summarizes current perspectives on the pathogenesis, symptomatology, diagnosis, and treatment for vulvar lichen sclerosus.
| S-EPMC6970240 | biostudies-literature
Project description:Lichen sclerosus (LS) is an underdiagnosed inflammatory mucocutaneous condition affecting the anogenital areas. Postmenopausal women are predominantly affected and, to a lesser extent, men, prepubertal children, and adolescents. The etiology of LS is still unknown. Hormonal status, frequent trauma and autoimmune diseases are well-known associations for LS, yet infections do not seem to be clear risk factors. LS pathogenesis involves factors such as a genetic predisposition and an immune-mediated Th1-specific IFNγ-induced phenotype. Furthermore, there is a distinct expression of tissue remodeling associated genes as well as microRNAs. Oxidative stress with lipid and DNA peroxidation provides an enabling microenvironment to autoimmunity and carcinogenesis. Circulating IgG autoantibodies against the extracellular matrix protein 1 and hemidesmosome may contribute to the progression of LS or simply represent an epiphenomenon. The typical clinical picture includes chronic whitish atrophic patches along with itching and soreness in the vulvar, perianal and penile regions. In addition to genital scarring, and sexual and urinary dysfunction, LS may also lead to squamous cell carcinoma. Disseminated extragenital LS and oral LS are also reported. The diagnosis is usually clinical; however, a skin biopsy should be performed in case of an unclear clinical picture, treatment failure or suspicion of a neoplasm. The gold-standard therapy is the long-term application of ultrapotent or potent topical corticosteroids and, alternatively, topical calcineurin inhibitors such as pimecrolimus or tacrolimus. Collectively, LS is a common dermatological disease with a so far incompletely understood pathogenesis and only limited treatment options. To foster translational research in LS, we provide here an update on its clinical features, pathogenesis, diagnosis and (emerging) treatment options.
| S-EPMC9978401 | biostudies-literature
Project description:The comorbidities of lichen sclerosus (LS) are presumed but have not been analysed in detail. The purpose of this review was to identify evidence-based associated diseases in patients with LS and explore the potential need for sex-dependent screening protocols. A comprehensive search of the MEDLINE, Embase, and PsycINFO databases from inception to 29 February 2024 was conducted using the key search terms LS and all its synonyms. Pooled odds ratios and 95% confidence intervals of comorbidities were generated using the DerSimonian and Laird random-effects model. A total of 21 case-control studies met the inclusion criteria. Of the 75 comorbidities analysed, only 16 (21.3%) were studied in both sexes, revealing no contrasting associations based on sex. Both female and male LS patients showed significantly increased odds of common dermatological conditions (i.e., lichen planus, vitiligo, alopecia areata, atopic dermatitis, and psoriasis), various cardiovascular risk factors (i.e., essential hypertension, obesity, dyslipidaemia, diabetes mellitus, and diabetes mellitus type 2), genital warts, and hypothyroidism compared with controls. Overall, the scarcity of data currently does not support the implementation of sex-dependent screening strategies. The findings do, however, present significant associations with a range of potentially serious comorbidities, which warrants further elucidation and clinical vigilance.
| S-EPMC11321451 | biostudies-literature
Project description:Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of genital and extragenital skin. LS is a debilitating disease, causing itch, pain, dysuria and restriction of micturition, dyspareunia, and significant sexual dysfunction in women and men. Many findings obtained in recent years point more and more towards an autoimmune-induced disease in genetically predisposed patients and further away from an important impact of hormonal factors. Preceding infections may play a provocative part. The role for Borrelia is still controversial. Trauma and an occlusive moist environment may act as precipitating factors. Potent and ultrapotent topical corticosteroids still head the therapeutic armamentarium. Topical calcineurin inhibitors are discussed as alternatives in the treatment of LS in patients who have failed therapy with ultrapotent corticosteroids, or who have a contraindication for the use of corticosteroids. Topical and systemic retinoids may be useful in selected cases. Phototherapy for extragenital LS and photodynamic therapy for genital LS may be therapeutic options in rare cases refractory to the already mentioned treatment. Surgery is restricted to scarring processes leading to functional impairment. In men, circumcision is effective in the majority of cases, but recurrences are well described. Anogenital LS is associated with an increased risk for squamous cell carcinoma of the vulva or penis. This review updates the epidemiology, clinical presentation, histopathology, pathogenesis, and management of LS of the female and male genitals and extragenital LS in adults and children.
| S-EPMC3691475 | biostudies-literature
Project description: Not available
| S-EPMC9201736 | biostudies-literature
Project description:PurposeTo better understand the pathophysiology of lichen sclerosus (LS) urethral stricture disease (USD), we aimed to investigate expression profiles of microRNAs (miRNAs) in tissue samples from men undergoing urethroplasty.MethodsUrethral stricture tissue was collected from 2005-2020. Histologic features diagnostic of LS were the basis of pathologic evaluation. Foci of areas diagnostic for LS or non-LS strictures were chosen for RNA evaluation. In an initial screening analysis, 13 LS urethral strictures and 13 non-LS strictures were profiled via miRNA RT-qPCR arrays for 752 unique miRNA. A validation analysis of 23 additional samples (9 LS and 14 non-LS) was performed for 15 miRNAs. Statistical analyses were performed using SPSS v25. Gene Ontology (GO) analysis was performed using DIANA-mirPath v. 3.0.ResultsIn the screening analysis 143 miRNAs were detected for all samples. 27 were differentially expressed between the groups (false discovery p-value <0.01). 15 of these miRNAs individually demonstrated an area under the curve (AUC)>0.90 for distinguishing between between LS and non-LS strictures. 11-fold upregulation of MiR-155-5p specifically was found in LS vs. non-LS strictures (p<0.001, AUC = 1.0). In the validation analysis, 13 of the 15 miRNAs tested were confirmed to have differential expression (false discovery p-value <0.10).ConclusionsTo our knowledge this is the first study evaluating miRNA expression profiles in LS and non-LS USD. We identified several miRNAs that are differentially expressed in USD caused by LS vs other etiologies, which could potentially serve as biomarkers of LS USD. The top eight differentially expressed miRNAs have been linked to immune response processes as well as involvement in wound healing, primarily angiogenesis and fibrosis.
| S-EPMC8673646 | biostudies-literature
Project description:Vulvar lichen sclerosus (VLS) is a chronic inflammatory disorder, which affects women of all ages. The aim of this review is to focus on first-line, second-line, and maintenance therapies as well as follow-up of women with VLS. With numerous controversies, we decided to conduct a scoping review on this subject. A review protocol was developed, and the Knowledge Resource Services website was used to run a search of articles pertaining to VLS with keywords "Vulvar," "Vulval," and "Lichen Sclerosus." The search was limited to published data from the last 10 years, i.e., July 2009 onward, and researches published in English language. A total of 338 articles pertaining to VLS were obtained. Out of this, 62 were original articles related to management of VLS. Effective treatments such as high-potency topical steroids are now the standard of care and first-line treatment. Follow-up may be done every three to six months for the first two years and then at least yearly to ensure adequacy of treatment and encourage compliance. Long-term follow-up in specialist clinics is recommended for women who have persistent complaints, thickened skin, or history of neoplastic lesion. Monitoring young patients yearly is recommended as there are chances of recurrence.
| S-EPMC7995233 | biostudies-literature
Project description: Not available
| S-EPMC9014314 | biostudies-literature
Project description:BackgroundVulval lichen sclerosus (VLS) is a chronic inflammatory condition predominantly affecting the anogenital skin. Symptoms can be distressing and affect quality of life and everyday activities. Very little research has been undertaken to explore the experience of living with VLS from the perspective of people with the condition.ObjectivesTo understand individuals' experiences of VLS and its impact on their lives.Participants and methodsSemi-structured remote (telephone or video) interviews were conducted with a purposive sample of 20 women living in the UK with VLS recruited via online support groups and social media. Data collection and analysis was informed by social constructionist grounded theory, using a constant comparison method.ResultsWe developed three themes to interpret the experience of living with VLS: missed opportunities (participants experienced delayed diagnosis, lack of information and disempowering encounters with healthcare professionals); learning to live with a long-term condition (the amount of work involved in learning how to self-manage the disease and the impact on everyday life); a secret life (experiences of the condition were often shrouded in secrecy, and there was stigma associated with a vulval skin condition resulting in them feeling isolated and lonely).ConclusionsPatients attending healthcare appointments with vulval complaints should be examined and LS should be considered as a diagnosis. Healthcare professionals' awareness and knowledge of VLS needs to be improved and they should avoid language which is blaming or minimizing of patients' experiences. VLS is a chronic condition and patients need to be supported in self-management. Support groups may be a source of support and information but can also be challenging when hearing others' difficult experiences. Wider public health educational activities are needed to change societal attitudes towards female genitals and tackle the stigma around vulval conditions. What is already known about this topic? Vulval lichen sclerosus (VLS) can have a profound impact on quality of life and self-identity but is relatively underexplored from the perspective of those living with the condition. What does this study add? In-depth findings about the experiences of living with VLS including ongoing issues with timely diagnosis, learning to live with a long-term condition and the secrecy and stigma about the condition. The needs of women with symptoms of and diagnoses of VLS are not being met sufficiently by the healthcare system. What are the clinical implications of this work? Healthcare professionals should consider addressing knowledge gaps in vulval conditions including VLS to prevent delayed diagnosis and avoid the use of certain terminology which can minimize patients' experiences. Patients with vulval complaints should be examined and LS should be considered as a diagnosis. Regular follow-up would reflect its chronic nature and could provide patients with reassurance and confidence in self-management. Wider public health activities are needed to change societal attitudes and tackle stigma around vulval conditions.
| S-EPMC10087446 | biostudies-literature
Project description:Lichen sclerosus (LS) is an acquired chronic inflammatory dermatosis predominantly affecting the anogenital area with recalcitrant itching and soreness. Progressive or persistent LS may cause urinary and sexual disturbances and an increased risk of local skin malignancy with a prevalence of up to 11%. Investigations on lipoid proteinosis, an autosomal recessive genodermatosis caused by loss-of-function mutations in the extracellular matrix protein 1 (ECM1) gene, led to the discovery of a humoral autoimmune response to the identical molecule in LS, providing evidence for an autoimmune and genetic counterpart targeting ECM1. This paper provides an overview of the fundamental importance and current issue of better understanding the immunopathology attributed to ECM1 in LS. Furthermore, we highlight the pleiotropic action of ECM1 in homeostatic and structural maintenance of skin biology as well as in a variety of human disorders possibly associated with impaired or gained ECM1 function, including the inflammatory bowel disease ulcerative colitis, Th2 cell-dependent airway allergies, T-cell and B-cell activation, and the demyelinating central nervous system disease multiple sclerosis, to facilitate sharing the concept as a plausible therapeutic target of this attractive molecule.
| S-EPMC9777366 | biostudies-literature