Medical Management of Penile and Urethral Lichen Sclerosus with Topical Clobetasol Improves Long-Term Voiding Symptoms and Quality of Life.

PURPOSE: We evaluated the success of minimally invasive management of lichen sclerosus with topical and intraurethral clobetasol, as defined by improvement in patient reported outcome measures and nonprogression to surgery. MATERIALS AND METHODS: We conducted a review of our prospective ongoing quality improvement study to determine outcomes of our current standard practice for males with penile and urethral biopsy proven lichen sclerosus. Data were collected between 2011 and 2019, and included patient demographic information, medical and surgical histories, and location and extent of lichen sclerosus related pathology. The primary outcomes for this study were voiding function and voiding related quality of life, and were assessed using the AUASS (American Urological Association Symptom Score) and quality of life bother index, respectively. RESULTS: We identified 42 patients with biopsy proven lichen sclerosus related urethral stricture disease. Of these patients 85.7% were treated with intraurethral steroids alone and did not require surgical intervention. Median AUASS significantly improved from 12 to 8, and median quality of life bother index improved from 4 ("mostly dissatisfied") to 2 ("mostly satisfied"). Average stricture length of those with penile urethral disease and bulbar urethral disease was 4.8 cm (SD 3.0) and 16.2 cm (SD 6.5), respectively. Median followup was 8.4 months (IQR 2.6-26.4). CONCLUSIONS: Lichen sclerosus related urethral stricture disease can be effectively managed with intraurethral steroids. This minimally invasive management strategy improves patient reported voiding symptoms and voiding quality of life.

Oral lichen sclerosus: a systematic review of reported cases and two new cases.

Lichen sclerosus (LS) is a chronic inflammatory mucocutaneous disease with uncertain etiology. It occurs as white plaque-like lesions mostly in the anogenital skin. Oral mucosal involvement is extremely rare. This study aims to summarize the features of published oral lichen sclerosus (OLS) and two new cases. A systematic search of the English literature from 1955 to 2016 was performed in MEDLINE, Scopus, and Web of Science, and cross-references were searched manually. Search phrases included "lichen sclerosus," "mouth," "oral," "lip," "palate," "floor of mouth," "tongue," "gingiva," "buccal mucosa," and "mouth diseases." Cases with clinical and histopathological confirmation of diagnosis of OLS were included. A total of 41 (39 published and 2 new) histologically confirmed OLS cases were available. The median age of OLS patients was 31 years, and 66% of the patients were female. Most of the OLS lesions were asymptomatic. They were located in the labial mucosa (n = 20), lip (n = 15), buccal mucosa (n = 14), gingiva (n = 12), tongue (n = 12), and palate (n = 7). OLS is rare and typically presents as asymptomatic, white, plaque-like lesions. Malignant transformation of preexisting OLS has not been reported.

Squamous Cell Carcinoma of the Bulbar Urethra Accompanied by Lichen Sclerosus: A Case Report.

Squamous cell carcinoma (SCC) of the bulbar urethra accompanied by lichen sclerosus (LS) is rarely reported. This study reports the case of a 56-year-old man with urethral squamous cell carcinoma (USCC) accompanied by a long history of genital LS. The man presented with a painful perineal mass and had a long-term history of urethral strictures and urethral dilatation. The patient developed a periurethral abscess that expanded to the perineum and formed an urethrocutaneousperineal fistula. An organ-sparing perineal resection and fistulectomy was performed according to the patient's wishes. During the operation, residue-like pus mixed with necrotic tissues drained out. A section of the prepuce and the necrotic tissues were sent for histological analysis. Hematoxylin and eosin (HE) staining of the excised prepuce revealed classical LS. HE and immunohistochemical (IHC) staining of the necrotic tissues showed well-differentiated USCC. IHC staining showed the USCC to be positive for P53 and Ki-67 and negative for P16, suggesting the USCC was probably associated with LS. The patient received high-dose chemotherapy and radiation therapy and died 10 months after surgery.

Selected inflammatory imitators of mycosis fungoides: histologic features and utility of ancillary studies.

Mycosis fungoides is the most common primary cutaneous lymphoma; however, it remains a significant diagnostic challenge, in part because of the overlap with several inflammatory dermatoses. Despite advances in immunohistochemistry and molecular diagnostics, false-positive, false-negative, and indeterminate diagnoses are not uncommon. In most cases, the overall balance of morphologic, immunophenotypic, and genetic features must be considered carefully because there are few sensitive and specific clues to the diagnosis. Moreover, an appropriate clinical presentation is essential to the diagnosis and helps to favor or exclude inflammatory/reactive processes. Herein, we discuss 3 important inflammatory dermatoses that may closely simulate mycosis fungoides, and we review the use of ancillary studies in these challenging cases.

Lichen sclerosus et atrophicus.

Morphea and lichen sclerosus et atrophicus (LSA) have similar clinical presentations. Reports of patients with overlapping clinical and histopathologic features of both conditions have led some to speculate that they may represent different presentations along the same disease spectrum. It has been postulated that there is a common etiologic agent, which may involve autoimmunity, response to trauma, or infection. The link between Borrelia infection and both morphea and LSA has been widely studied but remains controversial. We present a case of a patient with lesions characterized by overlapping features of morphea and LSA with rapid decrease in joint mobility.

Oral lichen sclerosus et atrophicus - literature review and two clinical cases.

Lichen sclerosus et atrophicus (LSA), also called Lichen sclerosus (LS) is a chronic, benign, depigmenting disease of the skin and mucous membranes, most frequently affecting genital mucosa and skin. Involvement of the oral mucosa without concurrent genital or skin lesions has very rarely been reported in the literature. Here we report on two Chinese women with LSA limited to the dorsum of the tongue, and describe the clinical manifestations and histopathological findings of these two patients.

The effect of vulvar lichen sclerosus on quality of life and sexual functioning.

Lichen sclerosus (LS) is a chronic skin disorder mostly seen on the female anogenital skin. The aim of this study was to evaluate the quality of life (QoL) and sexuality in female patients with LS and to compare their scores with healthy controls. In addition, we wanted to find factors associated with impaired sexual functioning in patients with LS. Members of the Dutch LS foundation and support group were asked to fill in three questionnaires: the Dermatology Quality of Life Index, Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS). 215 of 368 patients returned their questionnaire (58.4%). Their scores were compared to a control group which consisted of 61 women of similar age (p = 0.472) without a skin disorder. Of all domains of QoL, LS interfered most with sexual functioning. Patients significantly scored lower on all subscales of the FSFI (desire (p = 0.016), arousal (p < 0.001), lubrication (p < 0.001), orgasm (p < 0.001), satisfaction (p < 0.001) and pain (p < 0.001), indicating worse sexual functioning. These problems with sexual functioning brought about significant sexual distress (p < 0.001). Patients who experienced more influence on their QoL had more sexual difficulties, leading to more sexual distress independent of their age.

[Lichen sclerosus]. / Liquen escleroso.

Lichen sclerosus is a chronic inflammatory mucocutaneous disease that is highly bothersome for men and women of all ages. The exact etiology is unknown, although genetic and autoimmune factors, as well as infections, have been implicated in its pathogenesis. First-line treatment is highly potent topical corticosteroid therapy for short periods. Surgery is reserved for cases of phimosis, urethral stenosis, synechiae, and squamous cell carcinoma.

The role of calcineurin inhibitors in the management of lichen sclerosus.

Lichen sclerosus is a chronic inflammatory disorder with a propensity to affect the mucocutaneous anogenital area. Topical corticosteroids remain the treatment of choice for this condition and constitute an effective therapeutic modality. However, in patients with corticosteroid-resistant disease, when long-term remission is not sustainable, or in those intolerant to these agents, topical calcineurin inhibitors may be considered. Studies have demonstrated their efficacy and tolerability; however, concerns remain with regard to their malignant potential with long-term use. As lichen sclerosus is a potentially precancerous dermatosis, topical calcineurin inhibitors should be used with caution in this disorder.

Xantogranuloma necrobiótico con paraproteinemia asociado a liquen escleroatrófico / Necrobiotic xanthogranuloma with scleroatrophic lichen associated with paraproteinemia

El xantogranuloma necrobiótico (Xn) con paraproteinemia es una histiocitoxantomatosis (histiocitosis no X) que afecta la dermis y el tejido subcutáneo de la cara y, con menor frecuencia, del tronco y las extremidades. Presentamos el caso de una mujer de 58 años con historia previa de paraproteinemia IgG lambda y múltiples patologías autoinmunes, que asocia lesiones clínica e histológicamente típicas de Xn en cara, cuello y extremidades, así como de liquen escleroatrófico (LEA) en piel y mucosas. Los tratamientos realizados fueron ineficaces, siguiendo las lesiones de Xn un curso crónico y progresivo, con aumento del número, tamaño y ulceración de las mismas. La paraproteinemia ha permanecido estable desde su diagnóstico hace 8 años. No hemos encontrado descrita en la literatura la asociación de Xn con paraproteinemia y LEA. Repasamos las características de esta rara enfermedad y sus posibles mecanismos patogénicos

Necrobiotic xanthogranuloma (Xn) with paraproteinemia is a histiocytoxanthomatosis (non-X histiocytosis) that affects the dermis and subcutaneous tissue of the face and less frequently the trunk and limbs. We present the case of a 58-year-old woman with a previous background of IgG (lambda) paraproteinemia and multiple autoimmune diseases, that associate clinically and histologically typical lesions of Xn on face, neck and limbs and of lichen sclerosus et atrophius (LEA) on skin and mucosae. The treatments performed were ineffective, the Xn lesions followed a chronic and progressive course with increased number, size and ulceration of them. The paraproteinemia has remained stable since it was diagnosed eight years ago. We have not found the association of Xn with paraproteinemia and SAL described in the literature. We review the characteristics of this rare disease and its possible pathogenic mechanisms

Oxidative stress is implicated in the pathogenesis of lichen sclerosus.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory skin disease of unknown aetiology which can be associated with secondary malignancies. Recent evidence supports an autoimmune basis for this disorder, as demonstrated by autoantibodies to extracellular matrix protein 1 (ECM-1). The pathophysiological mechanisms leading to autoimmunity and carcinogenesis are poorly understood. OBJECTIVES: We hypothesized that oxidative stress, which has been demonstrated to be involved in the pathogenesis of several autoimmune and malignant disorders, contributes to these processes in LS. METHODS: Skin biopsies from 16 patients with untreated, histologically confirmed vulval LS were examined immunohistochemically using antibodies against the lipid peroxidation products malondialdehyde and 4-hydroxynonenale and against the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine. Protein carbonyls as markers of protein oxidation were visualized using the dinitrophenylhydrazone method. Expression of antioxidant enzymes was investigated. Normal vulval tissue from 16 subjects served as control. RESULTS: In vulval LS tissue a significant increase of lipid peroxidation products was found particularly within the basal cell layers of the epidermis, thus colocalizing with ECM-1. Oxidative DNA damage was detected throughout LS biopsies. Intriguingly, protein oxidation was significantly increased within the dermis of LS lesions, indicating oxidative protein damage in the areas of sclerosis and inflammation. The enzymatic antioxidant defence in LS was found to be significantly disturbed. CONCLUSIONS: This is the first study to demonstrate oxidative damage to lipids, DNA and proteins in LS, revealing a novel pathophysiological mechanism which may contribute to sclerosis, autoimmunity and carcinogenesis. Therapeutic strategies using antioxidants might be a useful new approach in the treatment of LS and could also help to prevent secondary malignancies.

Vulvar lichen sclerosus : pathophysiology and treatment.

Lichen sclerosus is a chronic disorder of the skin and mucosal surfaces, and is most commonly seen on the female genital skin. It also occurs on other areas of the body. Any age group may be affected, although it is seen more often in elderly women. The exact cause of lichen sclerosus is unknown. There have been reports of family members with lichen sclerosus; thus it may have a genetic link. There is also the possibility of an autoimmune connection. Currently, ultra-potent topical corticosteroids are the medical treatment of choice. Other treatments that have been utilized for this condition include testosterone, progesterone, tacrolimus, surgery, and phototherapy. Surgery should be reserved for symptomatic patients who fail to respond to multiple medical treatments, as there is a high recurrence rate following surgery. The risk of developing squamous cell carcinoma of the vulva approaches 5% in women with vulvar lichen sclerosus, and therefore close surveillance by the healthcare provider and patient is needed. This review discusses the history, clinical features, pathophysiology, and treatment of lichen sclerosus of the vulva, as well as pregnancy issues and sexual function in patients with this condition. In addition, problems specific to children with lichen sclerosus are reviewed.

Lichen sclerosus: a review and practical approach.

Lichen sclerosus (LS) is a chronic dermatitis predominantly found in the anogenital area. It can be found in patients of any age group, sex, or race, but is most commonly present in Caucasian peri- or postmenopausal women. Although the etiology of LS remains uncertain, an autoimmune process is believed to underlie this condition. With many cases going unreported, its incidence is still unknown. There is no cure for LS, but treatment offers control of the condition. They are three reasons for treating LS: relief of symptoms and discomfort; prevention of any or further anatomical changes; and a theoretical prevention of malignant transformation. Although many treatments have been suggested to treat LS over the years, only potent or ultra-potent corticosteroids remain as the treatment of choice. After initial therapy, some patients might only use corticosteroids as needed, while others may require a twice-weekly maintenance therapy. There is no place for surgery in uncomplicated LS. Surgery should be limited exclusively to patients with malignancy and to correct scarring secondary to the disease. Lichen sclerosus is associated with a 4-6% risk of squamous cell carcinoma, making long-term follow-up essential in these patients.

Overexpression of wild-type p53 in lichen sclerosus adjacent to human papillomavirus-negative vulvar cancer.

Human papillomavirus is a risk factor for vulvar cancer, whereas human papillomavirus-negative late onset vulvar carcinoma is associated with the dermatologic condition, lichen sclerosus. Human papillomavirus E6 protein targets TP53 for degradation and by inference it has been assumed that human papillomavirus-negative vulvar cancer is dependent upon the acquisition of p53 somatic mutations and subsequent allelic loss. To investigate this, TP53 expression, loss of heterozygosity, and p53 genomic sequence were examined in 29 cases of human papillomavirus-negative vulvar carcinoma with adjacent lichen sclerosus. We examined 37 cases of lichen sclerosus without vulvar carcinoma, 10 cases of nongenital lichen sclerosus, and 12 cases of normal vulvar epithelium served as controls. TP53 was evident in 72% of vulvar carcinoma, 48% in epithelium adjacent to vulvar carcinoma, but was minimal in normal samples. When lichen sclerosus cases were selected to exclude samples with absolutely no TP53 expression through probable failed antigen retrieval or homozygous p53 loss the number of epithelial cells expressing TP53 increased progressively from nongenital lichen sclerosus to lichen sclerosus without vulvar carcinoma, then to lichen sclerosus with vulvar carcinoma (p<0.0001). These data suggest elevated TP53 is a feature of vulvar lichen sclerosus. Seventy-four percent of vulvar carcinoma had chromosome 17p-linked loss of heterozygosity, whereas 47% of adjacent lichen sclerosus featured loss of heterozygosity, but only 31% of vulvar carcinoma had p53 mutations, a frequency less than reported previously. Seven percent of adjacent lichen sclerosus had mutations, showing for the first time the presence of an identical mutation to the matched vulvar carcinoma. These data, however, implicate p53 mutations as a later event in vulvar carcinoma and in marked contrast to the original expectation, our loss of heterozygosity data are consistent with loss of another locus (not p53) on 17p operating as a tumor suppressor in lichen sclerosus destined to develop vulvar carcinoma.

Childhood vulvar lichen sclerosus. The course after puberty.

OBJECTIVE: To identify girls with vulvar lichen sclerosus (LS) and to follow them through puberty, documenting the course of the disease. STUDY DESIGN: Twenty-one postpubertal girls were identified from a cohort of 75 girls with LS presenting prepubertally and attending a pediatric vulvar clinic. Details of current symptoms, findings on examination and treatment needs were recorded. A database of 263 women with LS was reviewed for onset of LS premenarche. RESULTS: Of the 21 postpubertal girls, 16 reported an improvement in symptoms, but 11 stated that they still experienced occasional pruritus, requiring intermittent topical steroid application. Although the disorder appeared less active in most cases, definite physical signs persisted in 16 patients (75%); in 5 patients no physical signs of the disease remained. Of 251 postmenopausal women with LS, < 5 could recall symptoms in childhood. Of 12 young adult premenopausal patients with vulvar LS, 4 could recall symptoms in childhood. One of these, a 32-year-old with well-documented LS in childhood resolving at puberty, presented with and died of vulvar squamous cell carcinoma (SCC). CONCLUSION: Patients should be aware that LS may improve symptomatically but usually does not entirely resolve at puberty and that the disease in women may be associated with development of vulvar SCC. Ideally, long-term follow-up should be the standard of care.

Survey of genital lichen sclerosus in women and men.

We present the clinical and laboratory findings in 60 women and 42 men with lichen sclerosus.