Lichen Sclerosus Patients Research Articles

The Association between Cardiovascular Risk Factors and Lichen Sclerosus: A Systematic Review and Meta-Analysis.

Background/Objective: Lichen sclerosus is a chronic inflammatory skin disease that affects people of all ages and sexes. Evidence of cardiovascular risk factors in lichen sclerosus has been continuously reported; however, the definitive association remains inconclusive. This meta-analysis aimed to summarize the association between cardiovascular risk factors and lichen sclerosus. Methods: Electronic databases, including MEDLINE and EMBASE, were systematically searched from inception to May 2024 to identify the literature reporting the association between cardiovascular risk factors and lichen sclerosus. A random-effects model was used for the meta-analysis. Results: We included 16 eligible studies: nine case-control studies, six retrospective cohort studies, and one cross-sectional study. A total of 432,457 participants were included. Lichen sclerosus was significantly associated with type 2 diabetes mellitus with an odds ratio of 2.07 (95% CI: 1.21-3.52). Although not statistically significant, a trend of increasing risk in hypertension, dyslipidemia, obesity, and metabolic syndrome was observed among lichen sclerosus patients, with odds ratios of 1.56 (95% CI: 0.90-2.70), 1.44 (95% CI: 0.94-2.23), 5.84 (95% CI: 0.37-92.27), and 1.36 (95% CI: 0.52-3.54), respectively. Conclusions: Lichen sclerosus was associated with diabetes mellitus and potentially correlated with hypertension, dyslipidemia, obesity, and metabolic syndrome. Population-based prospective observational studies are required to further elucidate these findings and assess the impact of these associations.

DNA Methylation and p53 Immunohistochemistry as Prognostic Biomarkers for Vulvar Lichen Sclerosus

Vulvar lichen sclerosus (LS) is an inflammatory dermatosis that can progress to human papillomavirus (HPV)-independent vulvar intraepithelial neoplasia (HPVi VIN) and vulvar squamous cell carcinoma (VSCC). Although LS has a much lower cancer risk compared with HPVi VIN (5% vs 50%, respectively), its incidence is significantly higher. Therefore, there is a clinical need to identify LS patients with an increased cancer risk. Our objective was to study the value of DNA methylation and p53 immunohistochemistry (IHC) as prognostic biomarkers for progression to cancer in patients with LS. Vulvar tissues from 236 patients were selected, including 75 LS and 68 HPVi VIN, both with and without cancer development, 32 VSCC, and 61 healthy vulvar controls. Samples were subjected to p53 IHC and DNA methylation analysis of a 3-gene marker panel containing ZNF582, SST, and miR124-2. Methylation levels and p53 IHC status (mutant or wild-type) were assessed and compared among all disease categories. Odds ratios were determined to identify whether the biomarkers were associated with progression to cancer in patients with LS. The highest methylation levels were found in HPVi VIN and VSCC, followed by LS and healthy vulvar controls. The largest heterogeneity in methylation levels was observed in LS cases. In fact, the 3-marker panel tested positive in 70% of LS, which progressed to VSCC vs only 17% of LS in patients without cancer development (P = .002). Also, mutant p53 IHC was observed more frequently in LS with progression to VSCC compared with nonprogressive LS cases (42% vs 3%, respectively, P = .001). Multivariable analysis identified a mutant p53 status as the only independent risk factor for cancer development in LS (odds ratio: 34.0, 95% CI: 1.4-807.4). In conclusion, DNA methylation testing and p53 IHC show strong potential as prognostic biomarkers for the identification of LS patients at high risk of progression to cancer.

EuroGuiderm guideline on lichen sclerosus-Treatment of lichen sclerosus.

Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are usually a whitening of the genital skin, sometimes preceded by redness and oedema; fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. The guideline intends to provide guidance on the diagnostic of LS (part 1), highlight important aspects in the care of LS patients, generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

EuroGuiderm guideline on lichen sclerosus-introduction into lichen sclerosus.

Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are redness and oedema, typically followed by whitening of the genital skin; sometimes fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. The guideline intends to provide guidance on the diagnostic of LS, highlight important aspects in the care of LS patients (part 1), generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

Lichen Sclerosus-Incidence and Comorbidity: A Nationwide Swedish Register Study.

Background: Data on the incidence and comorbidity of Lichen sclerosus (LS), based on validated nationwide population-based registries, remains scarce. Objective: To explore the incidence and association of comorbidities with LS in Sweden, emphasizing its potential links to malignancies and autoimmune disorders. Methods: A population-based retrospective open cohort study was conducted using the National Patient Register to identify all individuals diagnosed with LS (ICD-10 code L90.0) from 1 January 2001 to 1 January 2021. The study included 154,424 LS patients and a sex and age matched control group of 463,273 individuals to assess the incidence and odds ratios for various cancers and premalignant conditions. Results: The incidence of LS in Sweden was 80.9 per 100,000 person per year, with higher incidence in females (114.4) than in males (47.2). LS patients showed an increased odds ratio for vulvar cancer (OR = 8.3; 95% CI = 7.5-9.0), penile cancer (OR = 8.9; 95% CI = 7.3-11.0), prostate cancer (OR = 1.2; 95% CI = 1.1-1.2), testicular cancer (OR = 1.4; 95% CI = 1.1-1.7), bladder cancer (OR = 1.1; 95% CI = 1.1-1.2), breast cancer (OR = 1.4; 95% CI = 1.3-1.4), leukoplakia of the vulva (OR = 253.5; 95% CI = 221.9-289.6), and leukoplakia of the penis (OR = 5.1; 95% CI = 4.9-5.4). Conclusions: This study underscores the significantly increased association of various cancers and premalignant conditions in LS patients, highlighting the critical need for efficacious treatment and diligent follow-up. The association between LS and autoimmune diseases further necessitates comprehensive investigation to understand the underlying mechanisms and clinical management implications. Future research is essential to confirm these findings and elucidate the role of LS in cancer development.

Biopsy-verified vulvar lichen sclerosus: Incidence trends 1997-2022 and increased risk of vulvar squamous precancer and squamous cell carcinoma.

Population-based data on the epidemiology of vulvar lichen sclerosus (LS) are sparse and only few prospective studies have investigated the malignant potential of the disease. We used the nationwide Danish Pathology Registry to first assess the incidence of biopsy-verified vulvar LS in the period 1997-2022 and second to examine the incidence of vulvar high-grade squamous precancer and squamous cell carcinoma (SCC) in women with biopsy-verified vulvar LS (1978-2019) compared with that expected in the general female population. For the latter aim, we computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). During our study period, the age-standardized incidence rate of vulvar LS increased from 5.0 (1997-1998) to 35.7 (2021-2022) per 100,000 person-years. Compared with the general female population, women with biopsy-verified vulvar LS had significantly increased rates of vulvar high-grade squamous precancer (SIR = 8.5; 95% CI: 7.2-10.0) and SCC (SIR = 16.2; 95% CI: 14.2-18.4). The SIRs of vulvar high-grade squamous precancer and SCC did not vary substantially according to length of follow-up. This nationwide and population-based study shows a 7-fold increase in the incidence of biopsy-verified vulvar LS since 1997. Data also show that women with biopsy-verified vulvar LS have 8.5 and 16 times higher than expected incidence of vulvar high-grade squamous precancer and SCC, respectively. The substantially increased incidence of vulvar high-grade squamous precancer and SCC following LS is important in relation to the clinical management and follow-up of LS patients.

Obstetric, somatic and infectious risk factors for vulva sclerotic lichen

Relevance. Until now, disputes among scientists about its etiology, pathogenesis, nomenclature and risk factors for the development of vulvar lichen sclerosis have not subsided, which actualizes the need for scientific research aimed at solving these problems. The aim of the study - to establish statistically significant clinical and anamnestic risk factors for vulvar lichen sclerosis. Materials and Methods. An electronic database was formed with data from 344 patients with lichen sclerosus of the vulva and 60 women without vulvar diseases aged 20-70 years on hereditary, obstetric-­gynecological, somatic and infectious history. Astatistical comparative correlation analysis of the obtained data was carried out using the Spearman correlation coefficient (R0.15), nonparametric Mann - Whitney U test and Student t test (p0.05), Chi-square tests, Phi and Cramer statistics. Results and Discussion. Statistically significant (p0.05) risk factors for the development of vulvar lichen sclerosus (R, in descending order) were established: the presence of fibrocystic mastopathy (-0.29); late menarche (15 years and older) (-0.28); onset of menopause (-0.25); recurrent vulvo-­vaginal infections (-0.18); recurrent bacterial vaginosis (-0.18); autoimmune thyroiditis(-0.16) and stage II obesity (-0.16). Also, the average number of abortions and births (1.23 and 1.49, respectively) in the group of patients with lichen sclerosis of the vulva is statistically significantly greater (p0.05) than the average value (0.27 and 1.13, respectively) in control group. Conclusion. The data obtained on the impact of obesity and autoimmune thyroiditis on the risk of developing vulvar sclerotic lichen are consistent with the results of global studies and confirm the association of the disease with autoimmune and metabolic disorders. Recurrent vulvo-­vaginal infections and dysbiotic processes in the vagina can be both acause and aconsequence of vulvar lichen. The relationship between fibrocystic mastopathy and vulvar lichen sclerosus remains debatable and requires further research. Late menarche, the onset of menopause, alarge number of abortions and childbirth can also be considered triggers for vulvar lichen sclerosus in patients with agenetic predisposition to the disease.

Vulvodynia, Genital Eczema and Lichen Sclerosus: What are the Successful Treatments from a Patient's Perspective?

Genital pain treatment regimens range from local or systemic pharmacological to non-pharmacological, manual and psychosexual therapies with poor to moderate evidence for their efficiency. The aim of this study was to evaluate the subjective therapeutic response (genital pain relief) of different treatment modalities for vulvodynia and the most prevalent other vulvar pathologies, chronic vulvar eczema and lichen sclerosus by means of a cross-sectional survey. A questionnaire-based cohort study that included 128 vulvodynia, 116 eczema and 79 lichen sclerosus patients was used. All patients attended the vulvar clinic at the University Hospital of Zurich. The patients who had been treated were surveyed from January to October 2022, using a customized online questionnaire consisting of 37 questions on symptoms and treatment outcomes for guideline-recommended treatment modalities. The study was approved by the Cantonal Ethics Review Board of Zurich. Altogether, 41 patients with vulvodynia, 37 with vulvar eczema and 23 with lichen sclerosus returned the questionnaire. The three groups were similar regarding pain characteristics and comorbidities. All three patient groups reported having benefited from non-pharmacological treatment (improvement rate vulvodynia 54%; eczema 51%; lichen sclerosus 58%), from topical (55%; 55%; 75%) and from locally invasive (46%; 66%; 50%) treatments. Overall, there was no significant difference in subjective treatment outcome between non-pharmacological, locally invasive, and topical treatments for vulvodynia, eczema, and lichen sclerosus. However, the use of oral medication was reported to be significantly less effective (p-value 0.050). In conclusion, we found that in the patients' perception, topical, invasive and non-pharmacological treatments, but not oral medications, are helpful for genital pain relief in women with vulvodynia, vulvar eczema, and lichen sclerosus. Therefore, we recommend an escalating therapy approach with first-line non-pharmacological treatments together with topical therapies.

Prevalence of prescribing topical corticosteroids to patients with lichen sclerosus following surgery for vulvar cancer: a survey among gynaecologic oncologists in The Netherlands

Background Vulvar lichen sclerosus (LS) is a chronic inflammatory dermatosis which can progress to precursor lesion differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar squamous cell carcinoma (VSCC). The risk of developing recurrent vulvar cancer following LS-associated VSCC is high. Evidence suggests that treatment of LS with topical corticosteroids (TCS) can prevent progression to dVIN, VSCC and recurrences. However, current guidelines do not give any recommendation on the management of LS following surgery for VSCC. The aim of this study was to conduct a survey among all registered gynaecologic oncologists (GOs) in the Netherlands to evaluate the current management of LS patients without a history of VSCC (LSnoVSCC) and patients with LS following surgery for VSCC (LSVSCC). Methods An online survey was distributed to all registered GOs in the Netherlands. Primary outcome measures were the frequency, type and duration of TCS treatment prescribed for LSnoVSCC and LSVSCC patients, separately. As a secondary outcome measure, reasons for treating or not treating patients with LSnoVSCC and LSVSCC with TCS were analysed. Results Forty-four GOs completed the survey, resulting in a response rate of 75%. TCS were prescribed more often to patients with LSnoVSCC as compared to patients with LSVSCC (86% versus 52%, respectively, p < 0.001). If treatment was initiated, ultra-potent (class IV) TCS were most commonly prescribed for an indefinite period of time for both patient groups. The most reported reason for treating patients in both groups with TCS was symptoms, followed by clinical aspects of the lesion and prevention of progression to dVIN and VSCC. Conclusion The majority of GOs who participated in our study endorse the utilisation of long-term ultra-potent TCS therapy in both patients with LSnoVSCC and LSVSCC. Nevertheless, Dutch GOs are currently prescribing TCS more frequently to patients with LSnoVSCC than to patients with LSVSCC.

Insights from a joint pediatric dermatology-gynecology vulvar clinic: A retrospective study.

Pediatric vulvar disease has not been widely explored in the medical literature. Few studies focus on vulvar disease in skin of color. The vulvar disease can be distressing for young patients given the sensitive location, and providers may lack experience in diagnosing and managing vulvar dermatoses. We sought to characterize the conditions seen, diagnostic challenges encountered, and the racial and ethnic factors associated with vulvar diseases in our multidisciplinary pediatric dermatology-gynecology vulvar clinic at Children's National. Medical records of 220 patients who presented to our multidisciplinary pediatric dermatology-gynecology clinic were reviewed retrospectively. Lichen sclerosus (LS) (36%, n = 80), inflammatory vulvitis (11%, n = 23), and vitiligo (9%, n = 19) were the three most frequent conditions observed. These conditions were often misdiagnosed as one another. There was a mean delay in diagnosis after symptom onset in LS patients of 16.43 months. LS, inflammatory vulvitis, and vitiligo are common vulvar diseases among pediatric patients. Accurate diagnosis is important because LS must be treated aggressively to prevent sequelae. Further studies are warranted to help differentiate LS and vitiligo with consideration of skin tone.

The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions.

The role of the vulvar microbiome in the development of (pre)malignant vulvar disease is scarcely investigated. The aim of this exploratory study was to analyze vulvar microbiome composition in lichen sclerosus (LS) and vulvar high-grade squamous intraepithelial lesions (HSIL) compared to healthy controls. Women with vulvar lichen sclerosus (n = 10), HSIL (n = 5) and healthy controls (n = 10) were included. Swabs were collected from the vulva, vagina and anal region for microbiome characterization by metagenomic shotgun sequencing. Both lesional and non-lesional sites were examined. Biophysical assessments included trans-epidermal water loss for evaluation of the vulvar skin barrier function and vulvar and vaginal pH measurements. Healthy vulvar skin resembled vaginal, anal and skin-like microbiome composition, including the genera Prevotella, Lactobacillus, Gardnerella, Staphylococcus, Cutibacterium, and Corynebacterium. Significant differences were observed in diversity between vulvar skin of healthy controls and LS patients. Compared to the healthy vulvar skin, vulvar microbiome composition of both LS and vulvar HSIL patients was characterized by significantly higher proportions of, respectively, Papillomaviridae (p = 0.045) and Alphapapillomavirus (p = 0.002). In contrast, the Prevotella genus (p = 0.031) and Bacteroidales orders (p = 0.038) were significantly less abundant in LS, as was the Actinobacteria class (p = 0.040) in vulvar HSIL. While bacteria and viruses were most abundant, fungal and archaeal taxa were scarcely observed. Trans-epidermal water loss was higher in vulvar HSIL compared to healthy vulvar skin (p = 0.043). This study is the first to examine the vulvar microbiome through metagenomic shotgun sequencing in LS and HSIL patients. Diseased vulvar skin presents a distinct signature compared to healthy vulvar skin with respect to bacterial and viral fractions of the microbiome. Key findings include the presence of papillomaviruses in LS as well as in vulvar HSIL, although LS is generally considered an HPV-independent risk factor for vulvar dysplasia. This exploratory study provides clues to the etiology of vulvar premalignancies and may act as a steppingstone for expanding the knowledge on potential drivers of disease progression.

Incidence of Vulvar Lichen Sclerosus and of Cancer Among Vulvar Lichen Sclerosus Patients: Does Socioeconomic Status Have a Role?

Socioeconomic status (SES) impacts on the incidence of many inflammatory diseases and cancers, but there is no evidence on its implication in vulvar lichen sclerosus (VLS). The authors aimed to assess possible associations between SES and both occurrence of VLS and cancer occurrence among VLS patients. A retrospective cohort of women resident in the province of Ferrara, Italy, affected with VLS diagnosed between 2001 and 2020, was investigated for assessing any association of SES with VLS and cancer incidence. The SES was expressed through an ecological-based deprivation index identifying 5 subgroups. Four-hundred women were diagnosed with VLS during the study period, with double the number of cases in the second decade (2011-2020) compared with the first (2001-2010). More VLS patients belonged to the high rather than the low SES groups (p = .032). From VLS diagnosis to 2018 (1,958.4 total person*years at risk), 22 patients received their first diagnosis of cancer, mainly the skin, breast, and vulva. No significant differences in cancer incidence were found between high/medium-high and low/medium-low SES subjects. The fact that more VLS patients belonged to the highest socioeconomic classes may be due to a more frequent diagnosis in those with greater health seeking behavior and resources. An involvement of SES-related factors in VLS pathophysiological background can also be taken into consideration. Both the lack of marked social and economic differences in the study area and the availability of free visits and screening may account for the lack of association between SES and cancer development.

(070) Treatment of Genitourinary Syndrome of Menopause is Beneficial for Lichen Sclerosus Patients

Abstract Introduction Postmenopausal women with Lichen Sclerosus frequently report vulvar symptoms consistent with genitourinary syndrome of menopause (GSM) including pruritus, dyspareunia, or non-provoked pain. Our data revealed not surprising vulvar itching as the most frequently reported symptom of LS, second most frequent was general irritation, followed by vaginal dryness, and vulvar burning. Distinguishing these symptoms from GSM which occurs in 27-84% of postmenopausal women can be problematic. Objective The purpose of this study was to understand the symptoms of postmenopausal women with LS. We specifically surveyed them regarding their symptoms and treatments they had tried including both prescription and over the counter. Methods We interviewed 25 women with biopsy proven LS. This was part of a larger study on the microbiome and genetics of postmenopausal women with LS. Results Our data revealed that while the majority of the women in our study were using standard treatments such as high or medium potency steroid ointments or calcineurin inhibitor, less than 25% reported using hormonal medicines in their vulva (4 of 17), a common treatment for postmenopausal symptoms of vulvar burning, general irritation and dryness; Our data revealed that 50% of the women reported they had used at least more than one prescription or over the counter product to manage symptoms, none of which were hormone related. Conclusions Our data suggests that while these women were treated for their LS, their menopausal symptoms were not addressed. These findings lead us to believe perhaps their menopausal symptoms had been undertreated and that LS symptoms may be difficult to manage exclusively with standard treatments such as steroids and/or calcineurin inhibitors in postmenopausal women. Treatment of GSM with standard recommended treatments is beneficial for LS patients. Disclosure No

A Potential Protective Effect of Alcohol Consumption in Male Genital Lichen Sclerosus: A Case-Control Study.

A nested case-control study design was chosen. Subjects enrolled were adult male patients who had a circumcision between January 2010 and December 2020 at our university hospital, with a confirmed LSc diagnosis on pathology. Cases were matched with controls by age with a ratio of 1 : 1, all of whom were circumcised and had a negative pathology report. Data collection consisted of sociodemographic, behavioral, and past medical and familial history characteristics. A total of 94 patients were enrolled. The mean age was 49.81 (±22.92) in the group of men with LSc. No significant differences in sociodemographic characteristics (age and BMI) were found between the two compared groups. Smoking cannot predict LSc as opposed to alcohol consumption, which we found to be a protective factor against the appearance of LSc (p=0.027). Men with LSc had significantly higher rates of diabetes (p=0.021) and hypertension (p=0.004). No associations were found between LSc and the presenting chief complaints, family history of LSc, and past penile trauma. In this study, we were able to compare multiple variables between 47 circumcised patients diagnosed with LSc and a control group. We found that LSc patients showed higher rates of diabetes and hypertension. A potential protective effect of alcohol consumption is to be explored in future projects with bigger sample sizes and higher statistical powers.

A study on clinical spectrum of lichen sclerosus in a tertiary care Centre in North India

Introduction:Lichen sclerosus (LS) is a chronic dermatosis frequently located over labial, perineal, and perianal areas. The etiology is multifactorial and includes genetic, autoimmune, hormonal, and infectious aspects.Materials and Methods:A series of twenty genital LS patients was carried out to evaluate the signs, symptoms, complications, and affliction of quality of life.Results:Eighteen out of twenty patients were female between 30 and 73 years and showed smooth, glistening, and whitish plaques. The mean duration was 8.4 years. Itching and burning was the most common symptom (75%) corresponding to excoriation and fissuring of genitalia (75%). Malignancy was seen in two cases (10%). The mean Vulvar Quality of Life Index was 9.2, higher in younger patients.Discussion:LS is a disorder of older age group with female preponderance. It is a source of significant morbidity, and long-standing cases predispose to vulvar malignancy.Conclusion:To conclude, early diagnosis with proper counselling of the patient and his/her partner regarding various aspects of disease are essential for a wholesome approach.

Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen Sclerosus.

Lichen sclerosus (LS) is a chronic inflammatory skin disorder with unknown pathogenesis. The aberrant expression of microRNAs (miRNAs) is considered to exert a crucial role in LS. We used the next-generation sequencing technology (RNASeq) for miRNA profiling and Ingenuity Pathway Analysis (IPA) for molecular network analysis. We performed qRT-PCR, miRNA transfection and Matrigel assays for functional studies. We identified a total of 170 differentially expressed miRNAs between female LS and matched adjacent normal tissue using RNASeq, with 119 upregulated and 51 downregulated. Bioinformatics analysis revealed molecular networks that may shed light on the pathogenesis of LS. We verified the expression of a set of miRNAs that are related to autoimmunity, such as upregulated miR-326, miR-142-5p, miR-155 and downregulated miR-664a-3p and miR-181a-3p in LS tissue compared to the matched adjacent normal tissue. The differentially expressed miRNAs were also verified in blood samples from LS patients compared to healthy female volunteers. Functional studies demonstrated that a forced expression of miR-142-5p in human dermal fibroblast PCS-201-010 cells resulted in decreased cell proliferation and migration. These findings suggest that differentially expressed miRNAs may play an important role in LS pathogenesis; therefore, they could serve as biomarkers for LS management.

Human beta defensin levels and vaginal microbiome composition in post-menopausal women diagnosed with lichen sclerosus

Human beta defensins (hBDs) may play an important role in the progression of lichen sclerosus (LS), due to their ability to induce excessive stimulation of extracellular matrix synthesis and fibroblast activation. The genetic ability of the individual to produce defensins, the presence of microbes influencing defensin production, and the sensitivity of microbes to defensins together regulate the formation of an ever-changing balance between defensin levels and microbiome composition. We investigated the potential differences in postmenopausal vaginal microbiome composition and vaginal hBD levels in LS patients compared to non-LS controls. LS patients exhibited significantly lower levels of hBD1 (p = 0.0003), and significantly higher levels of hBD2 (p = 0.0359) and hBD3 (p = 0.0002), compared to the control group. The microbiome of the LS patients was dominated by possibly harmful bacteria including Lactobacillus iners, Streptococcus anginosus or Gardnerella vaginalis known to initiate direct or indirect damage by increasing defensin level production. Our observations highlight that correcting the composition of the microbiome may be applicable in supplementary LS therapy by targeting the restoration of the beneficial flora that does not increase hBD2-3 production.

One-Stage Buccal Mucosal Graft Urethroplasty for Lichen Sclerosus-Related Urethral Stricture Disease: A Systematic Review and Pooled Proportional Meta-Analysis.

Performing 1-stage urethroplasty in patients with urethral strictures caused by lichen sclerosus (LS) is hotly debated among reconstructive urologists due to conflicting reports of success. Therefore, the objective of this study was to determine the pooled incidence of stricture recurrence following 1-stage buccal mucosal graft (BMG) urethroplasty in patients with LS, to determine the impact of surgical technique on recurrence and to compare recurrence risk between patients with and without LS after 1-stage repairs. A systematic review was conducted in accordance with PRISMA criteria. The primary outcome was pooled incidence of recurrence, which was calculated using a Der-Simonian-Laird binary random effects model with a Freeman-Tukey arcsine transformation. A total of 21 studies were included, of which 15 provided data for comparative analyses. Pooled data from 625 LS patients revealed a stricture recurrence rate of 10% (95% CI 6-14). Among studies with longer followup (≥24 months), this increased to 18%. Among patients with penile urethral involvement, studies utilizing a penile skin incision had significantly higher pooled recurrence rates than those utilizing penile invagination (p=0.004). Across all studies, there was no evidence to suggest a difference in pooled recurrence rate between patients with and without LS (p=0.36). However, across only long-term studies, recurrence risk was significantly higher for patients with LS (OR 1.83, p=0.05). One-stage BMG urethroplasty is likely a viable surgical option for patients with LS-related strictures; however, high-quality data are limited. Future multi-institutional, long-term prospective studies are needed to assess durability of 1-stage repair.

Evaluation of genital self-image and sexual dysfunction in women with vulvar lichen planus or lichen sclerosus

Introduction Vulvar lichen planus (LP) and vulvar lichen sclerosus (LS) are chronic inflammatory diseases that affect women’s sexual health. In this study, our aim was to investigate sexual function, anxiety level and genital self-image in vulvar LP and vulvar LS patients. Methods This study was conducted on a total of 178 women who presented to the gynecology clinic between February 2019 and January 2020. The patients were divided into the following groups: group 1, vulvar LP (n = 21); group 2, vulvar LS (n = 59); group 3, fungal vulvitis controls (n = 48); and group 4, healthy controls (n = 50). The validated Female Sexual Function Index (FSFI), Beck Anxiety Index (BAI), and Female Genital Self-Image Scale (FGSIS) questionnaires were assessed in all women. Results There were no significant differences among the groups with respect to age, parity, menopausal status, body mass index (BMI), vaginal intercourse past 1 month, marital status or educational status (p > .05). There were statistically significant differences between the vulvar LP and vulvar LS groups compared to control groups in terms of FSFI total scores and subscores (p < .001). When FGSIS and BAI scores were analyzed, significant statistical differences were found among the study groups (p < .001). A positive correlation was found between the FSFI and FGSIS scores in patients with vulvar LP and LS. Additionally, a negative correlation was found between the FSFI and BAI scores in patients with vulvar LP and LS. Conclusions Our study showed that sexual function, genital self-image and anxiety level were associated in vulvar LP and vulvar LS patients. Vulvar LP and vulvar LS patients with worse genital self-image have more sexual problems and anxious conditions.

Alteration of gene expression related to vulvar smooth muscle, extracellular matrix and innervation in vulvar lichen sclerosus: A pilot study.

Lichen sclerosus (LS) is a chronic inflammatory disease with a potential for atrophy, destructive scarring, functional impairment, and increased risk of malignant evolution. 1 , 2 Notably, a significant number of LS patients are asymptomatic. It is most frequently seen in the anogenital area. 3 Women with vulvar LS often present with severe pruritus and soreness of the vulvar and perianal areas. 4 In advanced stages, there is destruction of the vulvar anatomy. 2 If untreated, it is associated with a 2% to 6% lifetime risk of malignant squamous neoplasia of the vulva. 5 , 6 , 7 Otherwise, potent topical corticosteroid is the gold standard for obtaining remission and reducing malignancy in vulvar LS. 7 , 8 Despite the possibility for treatment, the true etiology of LS remains unknown. 7 In long‐standing and classic LS, the lymphocytic infiltrate is located under a band of homogenized collagen below the dermo‐epidermal junction. 9 One study showed a significantly increase of pro‐inflammatory cytokines in LS patients. 10 We hypothesize that the elevated inflammation of LS leads to alteration of smooth muscle, subcutaneous adipose tissue, extracellular matrix (ECM), and innervation of the vulva and aim to evaluate the changes of tissues by testing the expression of marker genes. To avoid the disturbance of various treatments, only untreated patients were included for this study.