Prevalence of vulval lichen planus in a cohort of women with oral lichen planus: an interdisciplinary study

BACKGROUND: Lichen planus (LP) is a mucocutaneous inflammatory dermatosis that frequently involves the oral and genital mucosae. Patients with LP affecting these sites are often seen by oral medicine specialists or gynaecologists who work in isolation and depend heavily on histopathologists to help them in confirming the diagnosis. There are few studies in the literature combining the experiences of these specialists who share the care of patients with both oral and genital LP. OBJECTIVES: To estimate the prevalence of vulval LP (VLP) in a cohort of patients with histologically confirmed oral LP (OLP). METHODS: The study group consisted of 42 women histologically diagnosed with OLP. The mean age was 60.5 years (range 27-81). They underwent genital examination, colposcopy and vulvoscopy. For the histological confirmation of clinical VLP biopsies were performed whenever a clinical lesion was found. Oral and genital biopsy specimens were processed through histological and immunohistochemical staining. Histological diagnoses of LP were made according to the modified World Health Organization histopathological criteria proposed by van der Meij and van der Waal for the diagnosis of OLP, and extended to VLP. Patients with clinical evidence, but without the histological confirmation of OLP and VLP, were excluded from the study group. RESULTS: Thirty-two vulval and one vaginal biopsy specimens were obtained. Histological diagnoses were confirmed in 24 of 32 (75%) patients who underwent a vulval biopsy: these represent 57% (24 of 42) of the study group. Of the 12 patients free of symptoms such as itching, burning and dyspareunia, but with clinical vulval lesions, 11 (92%) had histological confirmation of VLP. Vulval lichen sclerosus was ascertained in five of 32 (16%) cases. CONCLUSIONS: This study showed a 57% prevalence of VLP in selected patients with OLP. The high prevalence of VLP of 92% in the women who were free of vulval symptoms confirmed the usefulness of this careful integrated approach.     

Potential human papillomavirus reactivation following topical corticosteroid therapy of genital lichen sclerosus and erosive lichen planus

Using a highly sensitive polymerase chain reaction (PCR) technique, based on general GP5+/GP6+ PCR primers covering 34 different human papillomavirus (HPV) types, the presence of HPV DNA was studied in paraffin-embedded penile biopsies from 20 men treated topically with corticosteroids. Clobetasol propionate was applied for 2-16 (mean 7) weeks by 19 men (age 18-73; mean 40) with lichen sclerosus. High-risk HPV was detected prior to therapy in three patients (16%) who lacked clinical or histopathological signs of HPV infection. Following therapy high-risk HPV was detected in biopsies from four men (21%), of whom three also exhibited clinical and/or light microscopic signs of HPV infection. Low-risk HPV DNA was not detected in any of these samples. Four biopsies were collected during a 5-year period from a 51-year-old man who was treated repeatedly with topical mild-moderate potent corticosteroids at intervals of up to 10 weeks for penile erosive lichen planus, followed by nine clinical outbreaks of typical condylomas that consistently showed the presence of low-risk HPV DNA only. These observations indicate that long-lasting topical corticosteroid therapy occasionally may be associated with opportunistic reactivation of a latent high- and low-risk mucosotrophic HPV type infection. The importance of clinical follow-up is underlined.     

Histology of lichen sclerosus varies according to site and proximity to carcinoma.

To investigate why vulvar but not extragenital lichen sclerosus is associated with squamous cell carcinoma, we performed a histologic study of extragenital lichen sclerosus, vulvar lichen sclerosus without carcinoma, and vulvar lichen sclerosus with carcinoma adjacent to and distant from the carcinoma. We compared epidermal thickness, rete ridge length, mitotic activity, atypia, dermal collagen change, dermal inflammation, and presence of other dermatoses in 30 women in each group. Extragenital lichen sclerosus showed thinner epidermis (mean thickness of 0.13 mm versus 0.41 mm; P < 0.0005), shorter rete ridges (P = 0.0001), more dermal edema (P = 0.16), and absence of associated dermatoses of spongiotic dermatitis and lichen planus (P < 0.005) compared with vulvar lichen sclerosus. The epidermal thickening seen in vulvar lichen sclerosus was indistinguishable from lichen simplex chronicus. Vulvar lichen sclerosus without carcinoma was generally similar to that distant from carcinoma. Vulvar lichen sclerosus adjacent to carcinoma showed increased epidermal thickness (0.61 mm versus 0.26 mm; P < 0.005), more dermal fibrosis (P < 0.0005), more inflammation (P < 0.0005), and more simplex (differentiated) vulvar intraepithelial neoplasia (18 cases versus 1 case; P < 0.0005) compared with that distant from carcinoma. We concluded that (1) the classic histologic features of lichen sclerosus are seen in both vulvar and extragenital sites; (2) vulvar lichen sclerosus without associated carcinoma has a mean epidermal thickness more than three times that of extragenital lichen sclerosus; (3) the epidermal thickening is histologically indistinguishable from lichen simplex chronicus; (4) there is a tendency for vulvar lichen sclerosus to have a more sclerotic and inflamed dermis; (5) lichen sclerosus 10 mm from cancer is more similar to vulvar lichen sclerosus without carcinoma than lichen sclerosus 1 mm from carcinoma; and (6) lichen sclerosus adjacent to carcinoma tends to show exaggerated epidermis thickness, basal atypia, and loss of the edematous-hyaline layer.     

Vulvar squamous cell carcinoma and lichen sclerosus

There are two clinicopathological types of vulvar squamous cell carcinoma, human papillomavirus (HPV)-positive and HPV-negative, which can be distinguished to some degree on routine histology. Human papillomavirus-positive carcinomas account for one-quarter to one-third of cases, occur in women on average 20 years younger than in HPV-negative, and are associated with multiple lower genital tract neoplasia. Human papillomavirus negative carcinoma is linked to lichen sclerosus. Of all carcinomas, 7-96% show lichen sclerosus in skin adjacent to the carcinoma, the majority being the first presentation of lichen sclerosus, and up to 5% of patients with lichen sclerosus develop carcinoma after long-term follow up. Where lichen sclerosus is associated with malignancy, it is often hyperplastic, may show a subtle form of intraepithelial neoplasia termed 'differentiated vulvar intraepithelial neoplasia', and may lose its pathognomonic oedematous-hyaline layer. The local additional factors causing lichen sclerosus to develop malignancy on the vulva are not known.     

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.     

【开放获取】儿童外阴硬化性苔藓79例皮肤镜特征分析

【摘要】 目的 探讨儿童外阴硬化性苔藓的皮肤镜特征。方法 回顾2019年1月至2021年5月昆明市儿童医院79例外阴硬化性苔藓初诊及复诊时的皮肤镜特征。结果 外阴硬化性苔藓女性患儿79例，年龄2.4 ~ 12岁，发病年龄（5.6 ± 2.12）岁，病程（14.23 ± 12.36）个月，其中30例规律复诊及治疗。初诊329处皮损中，149处（45.3％）可见特征性血管形态，包括线状血管（129处）、点状血管（25处）、盘绕状血管（19处）、发夹样血管（12处）等；207处（62.92%）可见退行性结构及色素异常，包括蓝灰色色素结构（136处）、褐色色素结构（51处）、胡椒粉样模式（15处）等；280处（85.1％）见黄白色无结构区，97处（29.5％）毛囊角栓，66处（20％）紫红色小球、斑片等。复诊238处皮损中，100处（42％）可见特征性血管形态，其中线状血管87处、树枝状血管21处、点状血管4处，未见发夹样血管；154（64.70%）处见退行性结构及色素异常，其中褐色色素结构93处、蓝灰色色素结构57处、胡椒粉样模式4处；165处（69.3％）见黄白色无结构区，62处（26.1％）毛囊角栓，8处（3.4％）紫红色小球、斑片。复诊皮损中观察到的蓝灰色色素结构、黄白色无结构区、紫红色小球、斑片及点状血管、发夹样血管、盘绕状血管比例均低于初诊（均P < 0.05），而褐色色素结构高于初诊（均P < 0.05）。结论 儿童硬化性苔藓皮肤镜下黄白色无结构区具较高特异性，监测镜下褐色色素结构及蓝灰色色素结构、黄白色无结构区、紫红色小球、斑片及血管结构等特征可反映疗效，在辅助诊断及随访观察中有一定应用价值。     

Successful treatment of vulvar lichen sclerosus in a child with low-concentration topical tacrolimus ointment

Lichen sclerosus is a chronic inflammatory skin disorder that has a predilection for the anogenital area. Topical corticosteroid is occasionally effective; however, continuous treatment is often required and recurrence after its stoppage is frequent. Herein, we report a case of vulvar lichen sclerosus in a 5-year-old girl, which was refractory to topical corticosteroids. After 14 weeks of treatment with 0.03% tacrolimus ointment once daily, the lesions completely resolved without side-effects. Of interest, the number of milia within the plaque of lichen sclerosus was reduced in tandem with the improvement of lichen sclerosus. This is the first report of topical low-concentration tacrolimus treatment showing a dramatic effect in the treatment of childhood vulvar lichen sclerosus.     

Familial lichen sclerosus et atrophicus in association with CREST syndrome: a case report

Lichen sclerosus et atrophicus is an uncommon disease which appears to be multifaetorial in aetiology. We describe a case of a young woman with CREST syndrome (calcinosis, Raynaud's phenomenon, oesophageal dysfunction, sclerodactyly and telangiectasial who has a documented family history of two sisters with lichen sclerosus et atrophicus. She presented with vulvar pruritas in association with dyspareunia. and biopsy of atrophic white vulvar lesions was consistent with lichen sclerosus et atrophicus. Lichen sclerosus et atrophicus has been previously noted to occur in association with morphoea and lichen planus, although it has never been reported in conjunction with CREST syndrome.     

Genital lichen sclerosus associated with morphoea or systemic sclerosis: clinical and HLA characteristics

Although patients with both morphoea and lichen sclerosus have been reported previously, in the majority of these reports the lichen sclerosus has been extragenital. We report nine patients in whom genital lichen sclerosus coexisted with scleroderma spectrum disorders including seven with morphoea, one with morphoea and lichen planus, and one with systemic sclerosis. The clinical features, associated autoimmune disease, autoantibodies and HLA type are reported. Antibodies to Borrelia burgdorferi were not detected in any of the patients. The coexistence of these diseases raises a number of intriguing questions about the relationship between them.     

Oral lichen planus: case series and experience in a tertiary dermatology service in Brazil

BackgroundLichen planus is an inflammatory disease that can affect both the skin and mucous membranes, including the oral mucosa. There is very little original Brazilian dermatology literature about oral lichen planus.ObjectiveTo describe the clinical, pathological, and treatment data of 201 patients diagnosed with oral lichen planus followed at the Stomatology Outpatient Clinic of Hospital das Clínicas, Universidade de São Paulo, from 2003 to 2021.MethodThe patients demographic profile, the morpho-topographic features of the lesions, the treatment employed, and the possible presence of squamous cell carcinoma were analyzed.ResultsThe disease was more common in women over 50 years of age, tending to be chronic, with a large number of cases showing cicatricial sequelae in the mucosa. Topical treatment with potent corticosteroids was shown to be effective in the vast majority of cases. Squamous cell carcinoma in oral lichen planus cicatricial sequelae was observed in eight cases.Study limitationsRetrospective study of medical records, with gaps regarding the filling out of data; unequal observation time among the studied cases.ConclusionsThis is the largest Brazilian dermatology series on oral lichen planus. The response to topical corticoid therapy was excellent in the vast majority of cases. The high prevalence of atrophic lesions, demonstrating the chronicity and tissue destruction potential of this disease, may explain the large number of cases of squamous cell carcinoma.     

Oral lichen planus in children: An Italian case series

Oral lichen planus usually occurs in adults; there are no clear data regarding the incidence and the clinical features of oral lichen planus in children. This paper reports clinical findings, treatments, and outcomes of 13 Italian patients with oral lichen planus in childhood diagnosed between 2001 and 2021. The most common finding was keratotic lesions with reticular or papular/plaque-like patterns, confined to the tongue in seven patients. Although oral lichen planus in childhood is rare and the malignant transformation index is unknown, specialists must be aware of its characteristics and oral mucosal lesions must be correctly diagnosed and managed.     

外阴硬化性苔藓患者的生活质量及影响因素：基于198例成年女性问卷调查

目的 了解成年女性外阴硬化性苔藓(VLS)患者生活质量现状,并探究其影响因素,为改善成年女性VLS患者生活质量提供依据。方法 2019年6月—2021年4月,采用便利抽样法,选择198例河南省人民医院就诊的成年女性VLS患者[年龄(40.98±7.43)岁],采用一般资料调查表、皮肤病生活质量指数量表、女性性功能指数量表、医院用焦虑抑郁量表进行调查,将单因素分析有统计学意义的变量进行多元线性回归分析。结果 成年女性VLS患者生活质量量表得分为(11.31±6.22)分,多元线性回归分析显示性功能障碍、焦虑、抑郁、病程、以往治疗过及绝经是成年女性VLS患者生活质量的主要危险因素(P<0.05)。结论 成年女性VLS患者生活质量较低,护理人员应重点关注患者生活质量的生理及心理健康相关因素并针对性地进行干预和照护,以提高患者生活质量。     

Conscious sedation with inhaled 50% nitrous oxide/oxygen premix in photodynamic therapy sessions for vulvar lichen sclerosus treatment

Photodynamic therapy has been described as an effective therapeutic option in selected cases of anogenital lichen sclerosus that are refractory to first-line treatments. However, procedure-related pain is a limiting factor in patient adherence to treatment. The authors report the case of a 75-year-old woman with highly symptomatic vulvar lichen sclerosus, successfully treated with photodynamic therapy. An inhaled 50% nitrous oxide/oxygen premix was administered during sessions, producing a pain-relieving, anxiolytic, and sedative effect without loss of consciousness. This ready-to-use gas mixture may be a well-tolerated and accepted alternative to classical anesthetics in Photodynamic therapy, facilitating patients'' adherence to illumination of pain-prone areas.     

Two cases of palmoplantar lichen planus with various clinical features

Two cases of palmoplantar lichen planus with various clinical features. Palmoplantar lichen planus is a rare, localized variant of lichen planus. Although several clinical features of palmoplantar lichen planus may be seen, the erythematous scaly form is most common. We present two cases of palmoplantar lichen planus that show vesicle-like and petechia-like features, which are uncommon variants of palmoplantar lichen planus.     

Topical tacrolimus ointment for the treatment of lichen sclerosus, comparing genital and extragenital involvement

Lichen sclerosus is a chronic inflammatory dermatosis presenting with significant sclerosis, atrophy and pruritus. The treatment for this condition remains unsatisfactory, with potent corticosteroids being the most effective therapy. In this study, we investigated the efficacy and safety of tacrolimus ointment in patients with genital and extragenital lichen sclerosus. Sixteen patients with active lichen sclerosus (10 with anogenital and six with extragenital localization) were treated with topical tacrolimus ointment twice daily. The therapeutic effects were evaluated according to 3 grades: complete response (>75% improvement), partial response (25-75% improvement), or no response (<25% improvement). Applications were continued until complete disappearance or stabilization of the cutaneous lesions. In addition, we conducted telephone surveys to determine the long-term treatment outcome and relapse rate. Objective response to therapy occurred in nine of 10 patients (90%) with anogenital and one of six patients (16.7%) with extragenital lesions. Out of 10 patients with anogenital lichen sclerosus, five showed more than 75% improvement. Complete, partial and no response were achieved in five (50%), four (40%) and one (10%) patient, respectively. During the follow-up period of a mean of 29.3 months, six of nine patients had a relapse of symptoms. However, most patients with extragenital involvement did not respond to tacrolimus, except one patient showing partial response. No significant adverse effects were observed. Topical tacrolimus ointment was a safe and effective treatment for genital lichen sclerosus and should be used for long-term duration to prevent relapse. However, it was not useful for patients with extragenital lichen sclerosus.     

A study on the association with hepatitis B and hepatitis C in 1557 patients with lichen planus

Background Previous reports have demonstrated contradicting results on the association between lichen planus and hepatitis. Objectives The aim of this study was to investigate the association between lichen planus and viral hepatitis. Methods Patients with lichen planus were compared with controls regarding the prevalence of viral hepatitis in a case‐control study using logistic multivariate regression models. The study was performed utilizing the medical database of Clalit Health Services. Results The study included 1557 lichen planus patients over the age of 20 years and 3115 age‐ and gender‐matched controls. The prevalence of hepatitis C in patients with lichen planus was higher than that in the control group (1.9%, 0.4% respectively, P < 0.001). In a multivariate analysis, lichen planus was associated with hepatitis C (OR 4.19, 95% CI 2.21; 7.93). The prevalence of hepatitis B in patients with lichen planus was similar to that in the control group (0.9%, 0.5% respectively, P = 0.12). A multivariate analysis revealed that lichen planus was not associated with hepatitis B (OR 1.69, 95% CI 0.82; 3.47). Conclusion Lichen planus is associated with hepatitis C but not with hepatitis B. Physicians who care for patients with lichen planus should consider screening patients with lichen planus for hepatitis C.     

Cytokine alterations in lichen sclerosus: an immunohistochemical study

BACKGROUND: Although the histology of lichen sclerosus is characteristic, the precise nature of the inflammatory changes and the signals provoking them is uncertain. OBJECTIVES: To delineate the inflammatory changes in lichen sclerosus more accurately by studying cytokine changes. METHODS: An immunohistochemical study of 12 specimens of genital lichen sclerosus and one specimen of extragenital lichen sclerosus was undertaken using monoclonal antibodies to interferon (IFN)-gamma, IFN-gamma receptor, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-2 receptor (CD25), intercellular adhesion molecule-1 (ICAM-1) and its ligand CD11a. Control specimens were seven specimens of normal vulva obtained during gynaecological procedures, three specimens of normal skin, adjacent uninvolved thigh from three of the patients with lichen sclerosus, five specimens of nonvulval psoriasis, four specimens of nonvulval lichen planus and two specimens from chronic wounds. RESULTS: The lichen sclerosus specimens demonstrated slightly increased staining for IFN-gamma within the epidermis compared with the normal vulva and nonvulval skin. There was increased dermal staining for IFN-gamma both within the pale zone of the upper dermis and within the inflammatory zone below this. We confirmed our previous demonstration that in lichen sclerosus HLA-DR immunostaining is increased in association with vascular endothelium, the inflammatory cell infiltrate and around the keratinocytes. The areas of the epidermis with the strongest immunostaining for HLA-DR generally also had the strongest staining for IFN-gamma. In the lichen sclerosus specimens the zone of inflammation also demonstrated increased immunostaining for TNF-alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 while the zone of sclerosus demonstrated a smaller increase in immunostaining for IFN-gamma receptor, TNF-alpha, CD11a and ICAM-1, and the epidermis demonstrated increased staining for ICAM-1. CONCLUSIONS: The increased staining for IFN-gamma, TNF-alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 suggest that the cytokine response in lichen sclerosus shares characteristics of the cytokine response in lichen planus and chronic wounds.