Extensive Extragenital Lichen Sclerosus-Like Lesions in a Patient with Junctional Epidermolysis Bullosa.

Epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders characterized by the formation of blisters either spontaneously or at the sites of trauma. These heal with post-inflammatory hypopigmentation, scarring, or milia formation. We hereby present a child who presented with widespread hypopigmented atrophic areas, blistering at trauma-prone sites, and nail dystrophy. The significance of this particular case lies in the challenge of distinguishing between epidermolysis bullosa and bullous extragenital lichen sclerosus et atrophicus.

Dermatoscopic features of vulvar lichen sclerosus in children: A retrospective study.

OBJECTIVES: To explore the dermoscopic features of lichen sclerosus in different parts of the external genitalia in children. METHODS: A retrospective analysis of the dermoscopic features of 42 female children with vulvar lichen sclerosus treated in the Department of Dermatology of Shanxi Children's Hospital from January 2020 to May 2023. RESULTS: Among the 42 female children, aged 3-14 years (mean: 7.24 ± 2.43 years), the duration of vulvar lichen sclerosus ranged from 3 months to 2 years (mean: 9.83 ± 4.93 months). Clinical lesions occurred in the labia minora in 18 cases (42.9%), labia majora in 38 cases (90.5%), posterior fourchette in 36 cases (85.7%), perianal area in 13 cases (31.0%), anterior fourchette in 17 cases (40.5%), clitoris in seven cases (16.7%), and interlabial sulcus in 11 cases (26.2%). Dermoscopic findings common in the labia majora included follicular keratotic plugs, cloverleaf-like structures, comedo-like openings, and linear vessels (p < .05); however, purple-red globules and patches and white linear streaks were more common in the posterior fourchette (p < .05), whereas dotted vessels were more common in the labia minora (p < .05). CONCLUSIONS: Common dermoscopic findings in pediatric vulvar lichen sclerosus were yellow-white structureless areas, white linear streaks, follicular keratotic plugs, and cloverleaf-like structures; yellow-white structureless areas and white linear streaks showed the highest specificity. The dermoscopic findings varied among different affected areas, which provides a basis for further understanding of the characteristics of different sites of vulvar lichen sclerosus in the pediatric population.

Selective Histopathology Examination for Circumcision Specimens: A Retrospective Observational Study.

Background Circumcision is a widely performed surgical procedure all over the globe. This can be for religious, cultural, or medical reasons. Routine histological examination of circumcision specimens is a standard practice in many healthcare systems, despite the relatively low incidence of premalignant or malignant lesions. The primary objective of this study was to evaluate the necessity of routine histopathological examination of foreskin specimens following adult circumcision. Secondary objectives included determining the frequency of malignancy in these specimens, comparing malignancy rates between clinically suspicious and non-suspicious cases, and assessing the correlation between preoperative clinical suspicion and histopathological findings. Aim This study aimed to evaluate the necessity of routine histopathological evaluation for the foreskin after circumcision. We investigated the frequency of malignancy upon histopathological examination, in clinically suspicious cases compared to non-suspicious cases. Method A retrospective observational study was conducted at the Royal Bournemouth Hospital, analyzing data from 334 consecutive adult male patients who underwent circumcision between January 2012 and December 2016. The cohort was retrospectively divided into two groups: those with preoperative suspicious clinical features and those without it. Clinical records on electronic patient records (EPR) were used for follow-up and to identify the percentage of malignancy after final histopathological examinations in both groups. Results Among the 334 patients, only nine patients (2.7%) were deemed as having suspicious clinical features preoperatively, of which, only three (0.9% of the total study sample) showed malignancy upon histological examination. The other six patients in this group were found to have balanitis xerotica obliterans (BXO). The other 325 patients (97.3%) were without clinically suspicious lesions preoperatively, and none were found to have any malignant lesions upon histopathological examination. Conclusion The low incidence of malignancy in circumcision specimens indicates that routine histological examination may not be essential for all cases. Among 334 samples, only three (0.9%) were malignant, and all were clinically suspected. Routine histopathological examination of the remaining 331 cases did not impact management or follow-up. Selectively submitting specimens for histology based on clinical suspicion could reduce opportunity costs and time, optimize resource allocation, and maintain appropriate diagnostic evaluation.

5-Aminolevulinic acid photodynamic therapy is a safe and effective treatment for female patients with intractable vulvar lichen sclerosus.

BACKGROUND: Female vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disease of the vulva and its etiology is unknown. The main clinical symptoms are itching, burning and dyspareunia, and there is a lack of effective treatment. METHODS: Clinical and follow-up data of women with VLS who underwent 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) from January 2023 to December 2023 in the department of obstetrics and gynecology, Qilu Hospital of Shandong University, were retrospectively analyzed. According to the inclusion and exclusion criteria, 36 patients with VLS who received ineffective conventional treatment (intractable VLS) were enrolled. Objective signs and subjective symptoms of vulvar lesions were recorded before treatment and 6 months after the end of treatment according to corresponding scoring criteria. Quality of life was evaluated using the Dermatology Life Quality Index (DLQI). RESULTS: All patients received six sessions of ALA-PDT treatment and follow-up visits. After ALA-PDT treatment, 24 of 36 (66.67 %) patients' itching symptoms completely disappeared, 10 of 36 (27.78 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients' symptoms were not significantly relieved. 16 of 36 (44.4 %) patients' itching symptoms completely disappeared, 9 of 36 (25 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients still had severe pain. Compared to 22 patients with dyspareunia before treatment, only 9 patients still had dyspareunia with varying degrees of dyspareunia relief after treatment. Clinical signs improved significantly in the patients after ALA-PDT treatment. The total scores of clinical signs were (5.31 ± 1.67 vs 3.67 ± 1.71) before and after treatment. All patients showed improvement in DLQI after treatment. The main side effects of ALA-PDT were pain, erythema and swelling which were transient and tolerable. All patients were "satisfied" or "very satisfied" with the results of the treatment. CONCLUSIONS: ALA-PDT is a safe and effective treatment for women with intractable vulva lichen sclerosus.

Possible Role of NRF2 in Cell Response to OZOILE (Stable Ozonides) in Children Affected by Lichen Sclerosus of Foreskin.

Lichen sclerosus (LS) is a chronic inflammatory disease of the skin, and the gold standard for treatment is the use of the very potent topical steroids, but they can have side effects. Previously, we demonstrated that OZOILE (stable ozonides) were effective in children affected by LS, reducing the inflammatory process and stimulating tissue regeneration of the foreskin, showing a similar efficacy to steroid treatment. In this study, the modulation of inflammatory and oxidative stress pathways was evaluated by qRT-PCR and Western blotting in foreskins affected by LS removed from patients untreated or treated with OZOILE or corticosteroid cream formulations for 7 days before circumcision. OZOILE induced a significant increase in NRF2 and SOD2 levels, while it did not produce change in MIF, NF-kB subunits, and MMPs in comparison to untreated foreskins. Conversely, steroid topical treatment produced a significant reduction in the expression of p65, MIF, and MMP9, but it did not cause variation in NRF2 and SOD2 levels. These results demonstrate that the use of OZOILE as cream formulation exhibits effects on NRF2 signaling, and it does not induce NF-κB activation, unlike corticosteroids. On the basis of our biochemical data, further studies evaluating the role of NRF2 signaling cascade are necessary.

Squamous Cell Carcinoma In Situ-The Importance of Early Diagnosis in Bowen Disease, Vulvar Intraepithelial Neoplasia, Penile Intraepithelial Neoplasia, and Erythroplasia of Queyrat.

Cutaneous squamous cell carcinoma (cSCC) is the second-most-prevalent malignancy in humans. A delayed diagnosis of cSCC leads to heightened invasiveness and positive surgical margins. Bowen's disease (BD) represents an early form of cSCC and presents as a small erythematous, photo-distributed, psoriasiform plaque. Although certain dermoscopy features in BD are quite characteristic, histopathology remains the gold standard for diagnosis and provides a severity-scoring system that assists in guiding appropriate treatment strategies. The classification of precancerous lesions of the vulva and penis has undergone multifarious transformations due to variations in clinical and histopathological characteristics. Presently, erythroplasia of Queyrat is categorized as a clinical variant of penile intraepithelial neoplasia (PeIN). The diagnoses of vulvar intraepithelial neoplasia (VIN) and PeIN present significant challenges and typically necessitate one or more biopsies, potentially guided by dermoscopy. Aceto-white testing demonstrates a notably high negative predictive value for genital precancerous lesions. Histopathological examination represents the gold-standard diagnosis in VIN and PeIN, while p16 and p53 immunostainings alongside HPV testing provide crucial diagnostic clues. The histopathologic features, degree of differentiation, and associations with lichen planus, lichen sclerosus, and HPV guide the selection of conservative treatments or surgical excision.

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.

Loss, shame and secrecy in women's experiences of a vulval skin condition: A qualitative study.

Vulval lichen sclerosus (LS) is a chronic dermatological condition affecting the anogenital area, causing intense itching, pain and bleeding. It can change the terrain of the vulva, causing loss of vulval anatomy and altered texture and appearance of the skin. There has been little research into how women experience the materialities of a dermatological vulval disease. We aimed to understand experiences of living with LS, using a feminist lens to examine the influence of societal attitudes towards women's bodies and the vulva. We conducted qualitative interviews with 20 women with vulval LS, taking a critical feminist grounded theory approach. While we found that women's experiences of vulval LS symptoms was normalised as a part of womanhood, there was a silencing of speech about the vulva generally, and vulval symptoms more specifically. This caused profound shame and loneliness, and was a barrier to disclosing and seeking help for vulval symptoms, leading to delayed diagnosis and disease progression. Loss of vulval architecture resulted in a loss of (feminine) self and the sense of a body which was whole.

Anogenital Erosive Lichen Sclerosus in a Male With Multiple Autoimmune Conditions.

Lichen sclerosus (LS) is a chronic inflammatory disorder primarily affecting the anogenital region, with a higher prevalence in females and often linked to autoimmunity. This association is not clearly elucidated in males, with LS commonly presenting in uncircumcised males. The most affected areas include the glans penis, prepuce, and coronal sulcus. In this report, we present an 11-year case of treatment-resistant LS in a male patient with an extensive history of autoimmune disorders, manifesting in the intergluteal cleft as a hypertrophic plaque, a rare location. The patient had a complex autoimmune history, including porphyria cutanea tarda, discoid lupus, and Sjogren's syndrome. Histopathological analysis confirmed a diagnosis of erosive LS. Despite numerous treatments, including intralesional corticosteroids and various topicals, the lesion persisted. This case highlights the challenges in managing LS, particularly in uncommon sites and in patients with extensive autoimmune backgrounds. Treatment goals for LS focus on symptom relief, cosmetic improvement, and disease prevention. Although topical corticosteroids are commonly used, systemic options like hydroxychloroquine may be beneficial in resistant cases, although clear guidelines are lacking. Our case underscores the importance of a multidisciplinary approach in addressing LS and its associated autoimmune conditions.

Single-Cell RNA Sequencing Reveals a Unique Fibroblastic Subset and Immune Disorder in Lichen Sclerosus Urethral Stricture.

Purpose: Lichen sclerosus urethral stricture disease (LS USD) is a refractory and progressive disease primarily affecting the anterior urethra in males. Various potential etiological factors, such as genetics, autoimmunity, infection, and exposure to infectious urine, have been suggested. However, the accurate etiology of LS in the male urethra remains unclear. Patients and Methods: In this study, we conducted single-cell RNA sequencing to identify the transcriptional profiles of three patients with LS USD and three patients with non-LS USD. Immunofluorescence was used to confirm the single-cell sequence results. Results: Our study revealed distinct subsets of vein endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FBs) with high proportions in LS USD, contributing to the tissue microenvironment primarily involved in proinflammatory and immune responses. In particular, FBs displayed a unique subset, Fib7, which is exclusively present in LS USD, and exhibited high expression levels of SAA1 and SAA2. The accumulation of macrophages, along with the dysregulated ratios of M1/M2-like phenotype macrophages, may be engaged in the pathogenesis of LS USD. Through cell-cell communication analysis, we identified significant interactions involving CXCL8/ACKR1 and CCR7/CCL19 in LS USD. Remarkably, Fib7 exhibited exclusive communication with IL-1B macrophages through the SAA1/FPR2 receptor-ligand pair. Conclusion: Our study provides a profound understanding of the tissue microenvironment in LS USD, which may be valuable for understanding the pathogenesis of LS USD.

Study of 138 vulvar lichen sclerosus patients and the malignant risk transformation.

Objective: To report the prevalence of malignant transformation of vulvar lichen sclerosus (VLS) and possible risk factors. Methods: This is a cohort study with data analysis from medical records of 138 patients with histological diagnosis of VLS registered at the Vulvar Pathology Outpatient Clinic of the University Hospital, between 2007 and 2017. Predominance of risk factors was performed using logistic regression analysis. The variables studied were the length of follow-up, age, regular or irregular follow up; presence of symptoms (dyspareunia, pruritus and/or vulvar burning); histology characteristics, the presence of epithelial hyperplasia; and the presence of autoimmune diseases. Results: There were 138 patients included in the study, and among them five progressed to malignant transformation. The patients had a median age of 59 years and 83% were symptomatic. The most frequent symptom was itching with 72%. Autoimmune diseases were present in 11.6%, the most prevalent being thyroid disease. All five case of malignant transformation (0.6%) had an irregular follow up. The logistic regression analysis was used among the studied variables, and no statistical significance was found among them (p ≥ 0.05). The relationship between hyperplasia and the clinical outcome of malignant transformation, in which non-significant but acceptable p value close to 0.05 was observed. Conclusion: The prevalence of malignant transformation in patients with VLS was 0.6%, and common factors were the lack of adherence to medical treatments and the loss of follow-up.

Acral Folliculocentric Extragenital Lichen Sclerosus: A Case Report.

Introduction: Lichen sclerosus is a chronic inflammatory dermatological condition of unknown etiology, primarily impacting the genital epidermis in individuals of all genders, with a higher prevalence observed among postmenopausal women and prepubescent girls. Additionally, extragenital manifestations occur in approximately 20% of the patients diagnosed with genital lichen sclerosus. Notably, folliculocentric extragenital lichen sclerosus is rare and unusual, with only limited instances documented in existing literature. Case Description: We report a 33 years old lady presented with multiple asymptomatic lesions on the dorsal feet for 1 year and similar lesions on the left hand for 4 months. On examination: folliculocentric, shiny, atrophic papules coalescing into reticulated plaques over the dorsum of both feet and few shiny, flat-topped, pink papules over the dorsum of the left hand. A skin biopsy was performed and confirmed the diagnosis of extragenital lichen sclerosus. Conclusion: Acral folliculocentric extragenital lichen sclerosus is an unusual and rare clinical variant. Clinicopathologic correlation is necessary to establish the correct diagnosis. Contribution to the Literature: Herein, we present an unusual presentation of extragenital lichen sclerosus, and we highlight the importance of considering it in the differential diagnosis of guttate acral skin lesions. We also review and summarize relevant cases from the literature in hope to aid physicians, especially dermatologists, to consider and swiftly reach the diagnosis and offer appropriate management. We also hope to bring about new insights and broaden future research efforts regarding lichen sclerosus especially and atrophic skin disease in general.

Biopsy-verified vulvar lichen sclerosus and the risk of non-vulvar cancer: A nationwide cohort study.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory mucocutaneous disease known to be associated with human papillomavirus-independent vulvar squamous cell carcinoma. Evidence on the association with other types of cancer, however, is sparce. We conducted a large nationwide cohort study examining the incidence of non-vulvar cancers among women with biopsy-verified VLS compared with the general female population. By using the nationwide Pathology Registry, we identified all women in Denmark with a biopsy-verified VLS diagnosis during 1978-2019 (n = 16,921). The cohort was followed up in the Danish Cancer Registry until 2022 for a subsequent non-vulvar cancer diagnosis. Standardized incidence ratios (SIRs) were computed with 95% confidence intervals (CIs) as relative risk estimates of all specific non-vulvar cancer sites. Compared with general female population rates, women with biopsy-verified VLS had decreased rates of several non-vulvar cancers, including HPV-related cancers (combined estimate: SIR = 0.5; 95% CI: 0.3-0.7), and lung (SIR = 0.6; 95% CI: 0.5-0.7), liver (SIR = 0.5; 95% CI: 0.2-0.9), and thyroid cancer (SIR = 0.5; 95% CI: 0.3-0.9). The decreased SIRs tended to sustain throughout the follow-up period following the VLS diagnosis. This large nationwide cohort study shows that women with biopsy-verified VLS may have a long-term reduced risk of developing HPV-related (cervical, vaginal, oropharyngeal, and anal) and smoking-associated cancers (lung, liver, and cervical) as well as thyroid cancer. Future studies focusing on the mechanisms behind the decreased cancer risk are needed.

Effect of Health Status and Heat-Induced Inactivation on the Proteomic Profile of Plasma Rich in Growth Factors Obtained from Donors with Chronic Inflammatory Skin Conditions.

Atopic dermatitis, psoriasis and lichen sclerosus are among the most challenging conditions treated by dermatologists worldwide, with potentially significant physical, social and psychological impacts. Emerging evidence suggests that autologous-platelet-rich plasma could be used to manage skin inflammation. However, the presence of soluble autoimmune components could hinder their therapeutic potential. The aim of this study was to analyze the proteomic profile of plasma rich in growth factors (PRGFs) obtained from donors with inflammatory skin conditions to evaluate the impact of skin health status on the composition and bioactivity of PRGF-based treatments. Venous blood from healthy volunteers and patients with psoriasis, lichen sclerosus and atopic dermatitis was processed to produce PRGF supernatant. Half of the samples were subjected to an additional thermal treatment (56 °C) to inactivate inflammatory and immune molecules. Proteomic analysis was performed to assess the protein profile of PRGFs from healthy and non-healthy patients and the effect of Immunosafe treatment. Differential abundance patterns of several proteins related to key biological processes have been identified, including complement activation, blood coagulation, and glycolysis- and gluconeogenesis-related genes. These results also demonstrate that the thermal treatment (Immunosafe) contributes to the inactivation of the complement system and, as a consequence, reduction in the immunogenic potential of PRGF products.

Assessing the inclusion of women of color in lichen sclerosus treatment studies: a scoping review.

Background: Vulvar lichen sclerosus (VLS) is an underrecognized chronic inflammatory skin condition with significant clinical features and potential for malignant transformation. To date, there are no studies comparing the course of this disease in women of color to other racial groups. Objective: The objective of this study was to provide a scoping review examining racial demographic data in VLS treatment studies and specifically assessing for the inclusion of women of color. Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a primary literature search was conducted using 4 databases: Ovid Medline(R), Scopus, Cochrane, and Web of Science from all years to December 2022. We included published studies with adult women diagnosed with VLS and containing a treatment arm using topical corticosteroids. Single case reports, literature reviews, systemic reviews, meta-analyses, and reports not available in English were excluded. Results: Overall, 1340 nonduplicate studies were assessed for eligibility criteria. In total, 65 publications were included. Only 6 included racial demographic data. Black women made up at most 3.8% of the sample population and Latinx women made up at most 5.7%. Limitations: Our review focused on a specific intervention (ie, the use of topical corticosteroids for the treatment of VLS), which may restrict the generalizability of our findings to other interventions. No risk of bias assessment was done due to the scoping nature of the review. Conclusion: Women of color are underrepresented in studies of topical corticosteroid use in adult women with VLS. Intentional diversity in recruitment will enable the collection of data that is both more accurate and reflective of a broader spectrum of perspectives and life experiences.

Vulval squamous cell cancer - does precursor lesion margin status affect recurrence-free survival after optimal surgical resection for early-stage disease?

OBJECTIVES: Vulval cancer accounts for around 4% of all gynaecological malignancies and most tumours ( > 90%) are of a squamous cell histotype. Most lesions arise on a background of differentiated VIN (dVIN) or lichen sclerosus (LS). Surgical treatment has undergone a paradigm shift with less radical surgery being attempted to preserve vulval structure and function, without compromising oncological outcome. MATERIAL AND METHODS: In this single site retrospective analysis, we consider the data from a tertiary oncology unit, to assess progression-free survival based on the presence of a precursor lesion at the margin of resection.123 patients with FIGO stage 1 vulvar SCC (n = 33 1A, n = 90 1B) were included. RESULTS: One Hundred Five patients (85%) had an associated precursor lesion (dVIN and/or LS). Within the follow-up period, 33 patients (26.8%) had invasive recurrence, of which 24 (72.7%) had surgical resection margins which were positive for a precursor lesion. In patients with an acceptable microscopically clear invasive resection margin of > 2 mm the presence of a precursor lesion at the margin conveyed a higher risk of malignant recurrence when compared to those with completely clear margins (HR = 2.42; 95% CI 1.14-5.16). CONCLUSIONS: This study adds to the available literature emphasising the clinical significance of dVIN or LS at the surgical margin of optimally resected disease. In those who have marginal involvement of a precancerous lesion, increased surveillance should be considered. Future work should explore the need for additional adjuvant therapy in this cohort.