Lichen Sclerosus: A Survey of Diagnosis and Management Among Pediatric Dermatologists and Gynecologists.

BACKGROUND/OBJECTIVES: Lichen sclerosus (LS) is a chronic condition that warrants close follow-up due to the risk of scarring. The optimal long-term management of pediatric vulvar and perianal lichen sclerosus (PVPLS) is unknown. This study aimed to identify diagnostic, treatment, and maintenance regimens among pediatric dermatologists and pediatric/adolescent gynecologists, as well as assess provider confidence and desire for guidance on long-term PVPLS management. METHODS: A cross-sectional 35-question survey was administered through the Pediatric Dermatology Research Alliance (PeDRA) and the North American Society for Pediatric and Adolescent Gynecology (NASPAG) between 7/13/2021 and 8/30/2021 to ascertain PVPLS diagnostic and management regimens. RESULTS: Most responders were attending-level pediatric/adolescent gynecologists (46%) and pediatric dermatologists (41%). Although 85% of participants felt completely or very confident in diagnosing PVPLS, the majority (86%) desired further management guidelines. While the initial treatment was similar among providers, maintenance regimens and follow-up varied considerably, with only 42% recommending lifelong monitoring despite potential persistence into adulthood. CONCLUSIONS: While initial treatment was similar among practitioners, there was variation by specialty in subsequent management and a lack of uniformity in long-term follow-up. Additional studies are needed to clarify the optimal management of PVPLS and to provide evidence-based guidelines regarding long-term follow-up.  J Drugs Dermatol. 2024;23(6):450-455.     doi:10.36849/JDD.8084.

Treatment algorithm for the comprehensive management of severe lichen sclerosus in boys based on the pathophysiology of the disease.

INTRODUCTION: It is estimated that approximately one out of 200 boys has the diagnosis of lichen sclerosus (LS), previously referred to as BXO (balanitis xerotica obliterans). Severe progressive disease is rare however, mismanagement of urethral tissues may contribute to progression of LS. STUDY DESIGN: The current literature regarding the management of severe lichen sclerosus was reviewed alongside our management of seven patients with ages ranging from six to ten years of age with severe lichen sclerosus who required surgical intervention. These patients were identified out of a busy pediatric practice that saw 5507 patients during the four-year span. Based on the pathophysiology of lichen sclerosus, urethral anatomy, and our management an algorithm was developed for medical and surgical management. RESULTS: All patients received initial medical treatment with topical steroids. Three patients underwent urethral mobilization and serial biopsy. One of these patients with severe disease required a second distal urethral mobilization. Three patients were treated with circumcision, and one is responding well to topical steroids after complex reconstruction. None developed postoperative urethral disease. DISCUSSION: Lichen sclerosus affects squamous epithelium but can extend to unaffected tissue if traumatized via the Koebner phenomenon. There are no randomized control trials for the management of the disease. Thus, appropriate early management with avoidance of urethral dilation or incision may prevent extension down the urethra that can lead to severe stricture disease. Several authors identified this as one of the worst forms of stricture diseases to manage. Based on the pathophysiology of the disease and our 4-year experience treating patients, we propose an algorithm for management of severe lichen sclerosus in boys. The diagnosis of lichen sclerosus in boys requires a high level of suspicion, and early biopsies should be obtained if suspected. If identified before circumcision or meatotomy, initial treatment should be medical. If the patient fails topical steroid therapy, circumcision and biopsy are the initial recommended surgical approach. Optimally, a biopsy with the first meatotomy establishes the diagnosis. If the disease persists, urethral mobilization may represent a curative treatment as it advances healthy urethra and allows complete removal of distal squamous epithelium instead of traumatic repeated dilations or incisions. CONCLUSION: This paper summarizes the available literature on the management of severe LS and provides a flow diagram based on the pathophysiology of the disease and our experience sever cases.

Extragenital lichen sclerosus: a comprehensive review of clinical features and treatment.

Lichen sclerosus (LS) is a chronic inflammatory skin disease commonly affecting the anogenital area with less frequent extragenital occurrence. Extragenital LS cutaneous manifestations vary and precipitating factors are not well described. Recent evidence for etiology and clinical associations of extragenital LS provide insight into disease recognition and pathogenesis. Novel diagnostic techniques as well as treatment standardization have the potential to improve management of this rare condition. This review details both past and new insights into the pathogenesis, clinical manifestations, and treatment options of extragenital LS.

The Distribution of Innervation and Immune Cell Infiltration Is Different in Genital and Extragenital Variants of Lichen Sclerosus.

Lichen sclerosus (LS) is a progressive skin disease that is characterized by chronic inflammation of either genital or extragenital skin, and it disproportionately affects women. We analyzed the distribution of nerve fibers, vanilloid receptors, cell proliferation, mast cells and macrophages in genital and extragenital LS samples, as well as in healthy skin, by using immunohistochemistry. The total amount of intraepidermal nerve fibers was lower in LS samples compared to healthy controls, while the total amount of subepidermal nerve fibers and calcitonin gene-related peptide (CGRP) positive fibers was higher in genital LS samples compared to both extragenital LS and healthy controls. Cell proliferation, macrophage and mast cell density were increased in LS samples compared to healthy controls. Genital LS had a higher macrophage density compared to the extragenital variant. Mast cell distribution significantly differed between genital and extragenital LS samples, even though their total mast cell densities were similar. These findings could explain the differences between pruritic symptoms of genital and extragenital LS and provide targets for the research of novel therapeutic strategies for LS management.

Lichen Sclerosus and Sexual Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: Lichen sclerosus (LS) is a common autoimmune dermatological condition that is often under-diagnosed in women and has been documented to affect quality of life and sexual function. AIM: To determine the prevalence of sexual dysfunction among women with vulvar lichen sclerosus. METHODS: The authors conducted a systematic review and meta-analysis of the existing research on LS and sexual function in database including PubMed using search terms: lichen sclerosus OR vulvar lichen sclerosus OR vulvar lichen sclerosus et atrophicus OR kraurosis vulvae) AND (sexual function OR sexual functions OR sexual disorder OR sexual disorders OR sexual activity OR sexual activities OR sexual dysfunction OR sexual dysfunctions OR dyspareunia OR vaginismus). OUTCOMES: Nearly 60% of women with lichen sclerosus suffer from sexual dysfunction. RESULTS: Two hundred and ten studies were initially identified. Twenty-six articles met inclusion criteria and 3 were excluded as they did not relate to sexual function, were regarding a surgical or medical intervention and sexual dysfunction and one was a review article. Therefore, 23 studies were included in the final analysis resulting in a cumulative 486 participants with LS with 208 patients experiencing any kind of sexual dysfunction. Meta-analysis presented prevalence of sexual dysfunction among LS patients as 59% (95% CI: 48 - 70%). Dyspareunia or generalized pain with intercourse was the most commonly reported type of dysfunction. CLINICAL IMPLICATIONS: Discussing sexual concerns with women with LS could empower them to seek treatment. STRENGTHS AND LIMITATIONS: Few articles met criteria for inclusion. CONCLUSION: A large proportion of women with LS experience sexual dysfunction. More research is needed, especially that which includes biopsy-proven LS and validated tools on sexual function. Pope R, Lee MH, Myers A, et al. Lichen Sclerosus and Sexual Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2022;19:1616-1624.

Autologous lipoaspirate as a new treatment of vulvar lichen sclerosus: A review on literature.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis that mostly affects the genital and anal skin areas. Symptoms may vary from pruritis and pain to sexual dysfunction; however, LS can also be asymptomatic. LS occurs at all ages and in both sexes. Approximately 5% of all women affected by vulvar LS will develop vulvar squamous cell carcinoma. Topical treatment is safe but less effective resulting in chronic course in most patients, who suffer from persistent itching and pain. In severe cases of therapy-resistant LS, there is no adequate treatment. Fat grafting is a novel regenerative therapy to reduce dermal fibrosis. The therapeutic effect of adipose tissue grafts for LS is already investigated in various pioneering studies. This review provides an overview of these studies and the putative mechanisms-of-action of fat grafting to treat LS.

The management of penile intraepithelial neoplasia (PeIN): clinical and histological features and treatment of 345 patients and a review of the literature.

INTRODUCTION: Penile intraepithelial neoplasia (PeIN) is a histological term for precancerous penile lesions. PeIN is important due to the high morbidity and mortality associated with progression to penile squamous cell carcinoma (PSSC). But PeIN is rare, contributing to a limited evidence-base for the relative efficacy of available treatment options. OBJECTIVES & METHODS: To consolidate and expand knowledge about PeIN and its treatment, we describe the clinical and histological characteristics, treatments and outcomes of 345 patients with PeIN, managed by our multidisciplinary team. Our results are compared and contrasted with those in the literature, following comprehensive review. RESULTS: 8.7% of patients had concomitant, invasive PSCC, whilst 91.3% demonstrated PeIN alone. 84% had undifferentiated PeIN, and 10.7% differentiated PeIN (5.2%, not specified). Clinical or histological evidence of HPV alone was present in 58%; features of lichen sclerosus alone in 12%; features of both in 29.4%. Only 14.4% of patients could be treated solely with topical agents or cryotherapy, whereas the remaining 85.6% underwent some form of surgical intervention, circumcision being the mainstay. Just 2.6% progressed to PSCC. CONCLUSIONS: Clinical management of PeIN can be rationally optimized with excellent outcomes. Circumcision is important. Topical treatments alone are disappointing.

Platelet-rich plasma for genital lichen sclerosus: analysis and results of 94 patients. Are there gender-related differences in symptoms and therapeutic response to PRP?

BACKGROUND: Lichen sclerosus is a chronic relapsing inflammatory dermatosis with a predilection for anogenital skin in 85%-98% of cases and is more prevalent in women (3%) than in men (> 0.07%). OBJECTIVES: The purpose of this study was to investigate gender differences in clinical presentation and therapeutic response to treatment with platelet-rich plasma (PRP), an emerging innovative strategy for LS. METHODS: Forty-three male and 51 female patients affected by LS were evaluated. Each patient was subjected to PRP treatment (1 infiltration every 15 days, for 3 times). RESULTS: The PRP procedure was well tolerated by all patients and an overall significant decrease in symptoms was reported 6 months after PRP infiltration. Reduction in pain and burning sensation was significant in both gender but more accentuated in women than in men, whereas reduction of itching was similar. On the contrary, dyspareunia evidenced sex-related difference since a significant diminution was observed only in male. CONCLUSIONS: This study demonstrates that PRP based therapy may exert a relevant role in LS patient management due to its effect on Quality of Life (QoL) and sexual function in both gender. In addition, the study underlined gender-related differences in severity of symptoms and disease age onset.

NASPAG Clinical Opinion: Diagnosis and Management of Lichen Sclerosis in Pediatric and Adolescent Patients.

This Clinical Opinion replaces the NASPAG Clinical Recommendation: Pediatric Lichen Sclerosus published in 2014. The objective of this document is to provide guidance in the diagnosis and management of vulvar lichen sclerosus (LS) in the pediatric and adolescent patient in order to treat patient symptoms and reduce long-term sequelae. LS is a chronic inflammatory condition affecting the anogenital region that may present in the prepubertal or adolescent patient. Clinical presentations include significant pruritus, loss of pigmentation and vulvar adhesions with loss of normal vulvar architecture. Management includes topical agents for induction and maintenance therapy, as well as long-term follow-up for identification and treatment of recurrence and sequelae. This document is intended for use by both primary and specialty pediatric and adolescent gynecology (PAG) providers, including specialists in pediatrics, gynecology, adolescent medicine, and dermatology.

Vulval lichen sclerosus: An Australasian management consensus.

BACKGROUND/OBJECTIVES: Vulval lichen sclerosus (VLS) is a chronic inflammatory skin condition predominantly affecting the anogenital region in women and children. To date, there is lack of agreement amongst experts on a severity scale to aid assessment, research and treatment stratification on VLS. Furthermore, literature on best practice for long-term management of VLS is lacking. The aim of this consensus is to provide broad guidelines on the short and long-term management of VLS. METHODS: An initial focus group of Australasian experts in vulval dermatology developed a draft consensus statement for the management of VLS. Based on the results of the draft statement, a consensus panel of 22 Australasian experts, comprised of the initial and additional members, participated in an anonymous four-stage eDelphi process. Round 1 involved generation and voting on statements from the draft consensus statement developed by the focus group. In Rounds 2, 3 & 4, panel members were presented formal feedback from previous rounds and asked to indicate their level of agreement. Consensus was reached if there was ≥70% agreement on the importance of an item in the 4 (agree) to 5 (strongly agree) range. RESULTS: The expert panel, with a total of 504 collective years of experience in the field of VLS, reached consensus on a core set of 51 management statements related to diagnosis, severity, initial and long-term management, follow-up, and complications of VLS. CONCLUSIONS: This study has identified a set of management statements for VLS that may be useful in clinical practice in the Australasian population.

The Diagnosis and Treatment of Lichen Sclerosus and Bulbous Urethral Squamous Cell Carcinoma: A Case Report.

Lichen sclerosus (LS) is a rare disease with malignant potential and has been identified by the European Society of Urology Guidelines as a risk factor for penile squamous cell carcinoma (SCC) cancer. LS combined with urethral squamous cell carcinoma (USCC) is extremely rare. There has been only one case report of this combination in China over the last decade. The prevalence of this combination in East Asian population is unclear. In this report, a 49-year-old patient with the presence of LS, perineal masses, and abscesses was hospitalized. He underwent anti-infectious therapy, meatotomy, perineal abscess incision, and drainage and debridement of the perineal wound. USCC was diagnosed following a series of biopsies and treated with radiation therapy. The patient remains well and alive with no recurrence of USCC 13 months after radiation treatment.

Common Benign Chronic Vulvar Disorders.

Common benign chronic vulvar conditions include genitourinary syndrome of menopause (formerly called vulvovaginal atrophy), lichen sclerosus, lichen planus, lichen simplex chronicus, and vulvodynia. Genitourinary syndrome of menopause results from the hypoestrogenic state that leads to atrophy of normal vulvar and vaginal tissues. It is typically treated with lubricants, moisturizers, and intravaginal estrogen. Lichen sclerosus is an inflammatory condition characterized by intense vulvar itching. It is treated with topical steroids or, in some cases, topical calcineurin inhibitors. Patients with lichen sclerosus are at risk of vulvar squamous cell carcinoma and should be monitored closely for malignancy. Lichen planus is an inflammatory autoimmune disorder that can affect the vulva and vagina in addition to other skin and mucosal surfaces. The first-line treatment is topical steroids, and significant scarring can occur if left untreated. Lichen simplex chronicus manifests as persistent itching and scratching of the vulvar skin that leads to thickened epithelium. Breaking the itch-scratch cycle, often with topical steroids, is the key to treatment. Vulvodynia is a common vulvar pain disorder and is a diagnosis of exclusion. A multimodal treatment approach typically includes vulvar hygiene, physical therapy, psychosocial interventions, and antineuropathy medications.

Adipose tissue stromal vascular fraction and adipose tissue stromal vascular fraction plus platelet-rich plasma grafting: New regenerative perspectives in genital lichen sclerosus.

Lichen sclerosus (LS) is a chronic relapsing, inflammatory skin disorder usually involving the anogenital region of both sexes lacking a resolutive therapy. This study compared adipose tissue derived-stromal vascular fraction (AD-SVF) and AD-SVF-enriched platelet-rich plasma (PRP) therapy in the management of genital LS patients. Additionally, in vitro evaluation of cells and growth factors contained in the injected SVF has been evaluated as possible predictive factors for treatment outcome. The study population was 40 patients diagnosed with LS who were symptomatic despite medical treatment. Patients (age 43-78 years) randomized into two groups using a 1:1 allocation ratio, were evaluated clinically and assessing dermatology life quality index (DLQI) before and 6 months after treatment. Both procedures demonstrated a strong safety profile with no complications linked to the therapy. After 6 months, both treatments allowed for a significant improvement respect to baseline. Combinatory therapy demonstrated decreased efficacy in late stage patients. No correlations have been found between clinical and biological findings. AD-SVF and AD-SVF plus PRP are safe and effective regenerative approaches for genital LS patients. Clinical results support the preferential use of combinatory therapy for early stage patients confirming a synergic effect of AD-SVF and PRP. In contrast, AD-SVF plus PRP is discouraged for late stage patients.

Platelet-rich plasma for male genital lichen sclerosus resistant to conventional therapy: First prospective study.

Ultrapotent topical corticosteroids and circumcision are usually effective for male genital lichen sclerosus (MGLSc); however, refractory cases are often referred to our Male Genital Dermatology Unit. Treatment with autologous platelet-rich plasma (TPRP) has recently been advocated as a safe and effective treatment option, but there have been no prospective studies in men to date. The objective of this study is to assess the safety and efficacy of TPRP for MGLSc resistant to conventional therapy. A prospective, open-label, single-arm, therapeutic study was carried out in this study. Inclusion criteria: resistant to conventional therapy for at least 6 months. Procedure: infiltration of 0.1 mL/cm2 PRP every 8 weeks. Monthly data recording: visual appearance with photographs and external scoring by an expert using Investigator's Global Assessment Scale (IGA scale 0-5), symptoms (scale 0-5), quality of life (QoL; Dermatology Life Quality Index [DLQI]), and complications. No. of patients included was n = 5. No. of patients excluded during treatment was n = 1. Mean initial IGA: 3.6. Mean initial DLQI: 6. TPRP n = 34 (range: 2-9; average: 6.8 per patient). Mean IGA at 18 months: 3.25. Mean DLQI at 18 months: 1.25. All patients reported being completely asymptomatic at 10 months. No. of patients with complications is n = 1 (balanitis). TPRP seems to be safe and effective, regarding symptom control and improvement in QoL; however, visual changes were minimal.

Recent advances in understanding and managing Lichen Sclerosus.

Lichen sclerosus (LS), or balanitis xerotica obliterans as it was previously known, is a chronic inflammatory lymphocyte-mediated scarring dermatosis that often affects the preputial skin and glans, leading to phimosis and urethral strictures if left untreated. We present a narrative review of the literature assessing its aetiology and pathogenesis and discuss its links to penile cancer and its medical and surgical management. Possible hypotheses for the development of LS include chronic exposure to trapped urine, leading to changes in the epithelial structure. This is supported by the fact that circumcision is often curative in the early stages of the disease. Although circumcision can be curative, the use of topical steroids is typically the first-line treatment and may preserve the foreskin and forgo the need for circumcision altogether. Patients should be made aware of a possible association with penile cancer. Although the majority of cases can be treated by medical therapy and circumcision, a significant number of patients may also require penile reconstructive procedures.

Gender differences in genital lichen sclerosus: data from a multicenter Italian study on 729 consecutive cases.

BACKGROUND: Studies specifically conducted to assess gender differences in genital lichen sclerosus (GLS) are not available. This multicenter study aimed to identify possible gender-related differences on GLS clinical features, history and course, through collecting data from a large mixed-sex sample of patients. METHODS: This was a cross-sectional study on 729 subjects (53.8% females, 46.2% males) affected with GLS, consecutively observed within a network of 15 Italian dermatology units. The following information was specifically collected: clinical features and severity of symptoms related to GLS, extragenital involvement, previous therapies, diagnostic suspicion at referral, type of referring physicians, development of genital squamous-cell carcinoma (SCC). RESULTS: Females complained of symptoms more frequent and severe than men; pallor and scarring-sclerosis-atrophy were the most frequent features without gender differences; itching-related signs were more frequent in females than in males as well as extragenital involvement; prior to receiving a definitive diagnosis, females received treatment more frequently than males; 40% of patients were referred with a misdiagnosis; the highest rate of correct suspected diagnosis at referral came from dermatologists than from other physicians; duration of the disease was found to predispose to SCC development. CONCLUSIONS: Our findings highlighted several gender differences on clinical presentation and symptom profile of GLS. In spite of some characteristic features, misdiagnosis at referrals was frequent.

Pathophysiology, Clinical Manifestations, and Treatment of Lichen Sclerosus: A Systematic Review.

OBJECTIVE: To elucidate current understanding on the pathophysiological mechanism of genital lichen sclerosus (LS), urologic manifestations, and treatment options. MATERIALS AND METHODS: The Medline/PubMed and Embase databases were systematically reviewed for publications pertaining to LS. After applying inclusion and exclusion criteria, references were assessed for relevance to the pathophysiology, presentation, and treatment of LS by title and abstract review by 2 independent reviewers, yielding 186 articles for assessment. RESULTS: The contemporary understanding of the epidemiology and histology of LS is reviewed herein. Additionally, we explore in detail the 3 hypotheses regarding the pathophysiological mechanism contributing to disease presentation: infectious etiology, primary immune dysregulation, and the isotraumatopic response. We summarize the available biological evidence supporting each hypothesis. This discussion provides context for understanding LS morbidity and may spur new avenues of research. For the clinician, we review the clinical presentation of disease, including the risk of progression to squamous cell carcinoma. The current medical and surgical treatment options are also detailed. CONCLUSION: LS remains a potentially insidious disease which may lead to debilitating urinary and sexual dysfunction. Cross disciplinary research should aim for earlier detection, as well as more effective and durable treatment. The exact cause of LS remains unknown.