Significant Improvement in Extensive Lichen Sclerosus with Tacrolimus Ointment and PUVA

Lichen sclerosus is an uncommon, chronic inflammatory skin disorder of unknown origin. It is clinically characterized by sclerotic, whitish, atrophic-type lesions. The most frequent site of the lesions is generally the genital region, with about 15-20% having additional extragenital involvement. We present the case of a 62-year-old woman with a very extensive extragenital lichen sclerosus who showed great clinical and subjective improvement with 0.1% tacrolimus ointment and psoralen plus UVA (PUVA), without any topical or systemic adverse effects. Combined treatment of 0.1% tacrolimus ointment and PUVA may be a good option in extensive cases of lichen sclerosus or when other treatment options have failed, and has a good tolerability and safety profile.     

Vulvar Lichen Sclerosus

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.     

Three-dimensional imaging reveals major changes in skin microvasculature in lipoid proteinosis and lichen sclerosus

BACKGROUND: Lipoid proteinosis is a rare autosomal recessive disorder characterized by deposition of hyaline-like material in several organs, including skin. Pathogenic mutations have been found in the extracellular matrix protein 1 gene (ECM1). Recent studies have disclosed that ECM1 is also a target antigen for autoantibodies in patients with the acquired disease, lichen sclerosus. Both conditions have been reported to show abnormalities in dermal blood vessels but these changes have not been fully assessed. OBJECTIVE: The purpose of this study was to investigate the architecture of the cutaneous microvasculature in lipoid proteinosis and lichen sclerosus to better determine the role of ECM1 in the skin pathology observed in these disorders. METHODS: Labeling of skin biopsies (lipoid proteinosis, lichen sclerosus and control skin) with antibodies to type IV collagen and laminin-1 and reconstruction of the dermal blood vessels using laser confocal microscopy and computer imaging. RESULTS: In both lipoid proteinosis and lichen sclerosus there was reduplication of the basement membranes surrounding blood vessel walls. There were enlarged vessels in the mid and deep dermis that were orientated parallel to the dermal-epidermal junction. In addition, the normal capillary loop network in the dermal papillae, as well as the subcutaneous plexus and transverse connecting vessels were lacking in both disorders. CONCLUSION: This study demonstrates that skin microvasculature is grossly altered when ECM1 is targeted by inherited mutations (lipoid proteinosis) or acquired autoantibodies (lichen sclerosus) and that this glycoprotein appears to have an important role in regulating blood vessel physiology and anatomy in the skin.     

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.     

Squamous cell carcinoma in untreated lichen sclerosus of the penis: a rare complication

Lichen sclerosus et atrophicus (LSA) is an uncommon disease of the skin and mucosae of either sex. Apart from a number of complications, SCC developing from a lesion of LSA in males is rare, although it is well known in females. We report two cases recently seen by us to alert clinicians of this potentially fatal complication in males.     

Evidence for Borrelia burgdorferi in morphea and lichen sclerosus

BACKGROUND: Borrelia burgdorferi (Bb) infection has been implicated in the development of morphea and lichen sclerosus; however, conflicting results have been reported with different investigational methods from different regions. We looked for evidence of Bb in patients with morphea and lichen sclerosus by polymerase chain reaction (PCR) analysis of of skin biopsy samples. METHODS: Formalin-fixed, paraffin-embedded skin biopsy samples from 10 patients with morphea and 12 patients with lichen sclerosus were investigated by PCR analysis for the presence of Bb. RESULTS: The presence of Bb DNA was demonstrated in three of 10 patients with morphea and six of 12 patients with lichen sclerosus by nested PCR. CONCLUSIONS: The data obtained in this study suggest that Bb may play a role in the etiopathogenesis of both morphea and lichen sclerosus at least in the western parts of Turkey.     

日本性别认同障碍的发展现状综述

性别认同障碍(gender identity disorder,GID),指对于自己的性别认同与生物解剖学上的性别不一致的情况,并且常伴随内心痛苦想要改变生物学上的性别,心理治疗对性别认同障碍的干预,即想要使患者的性别认同与生物性别一致的情况早已被证实无效,性别认同障碍的患者往往会选择荷尔蒙治疗甚至手术来使自己的生物性别与性别认同趋向一致。2013年5月美国《精神疾病诊断及统计手册》第五版(DSM-Ⅴ)将性别认同障碍修改为性别烦恼(gender dysphoria),不再认为性别认同问题是障碍或疾病,承认性别多样性的存在。本文从对日本性别认同障碍患者的一般调查研究数据,包括荷尔蒙疗法及性别转变手术在内的性别认同障碍的治疗以及生殖医疗三个方面来描述日本性别认同障碍目前的发展状况。     

Psoriasis associated with vulval scarring

Psoriasis is a chronic inflammatory skin disorder which is generally not associated with scarring. We report two patients with long-standing severe anogenital psoriasis, that was associated with loss of the labia minora, thus clinically mimicking the scarring associated with lichen sclerosus. Histopathological finding were however, consistent with psoriasis with no evidence of lichen sclerosus. Elastic fibres were present and there was no evidence of abnormal collagen or fibrous tissue. The association of vulval psoriasis with scarring has not been reported previously.     

Milia occurring in lichen sclerosus et atrophicus

Large numbers of milia were seen in areas of skin affected with bullae in a 68-year-old woman who had extensive lichen sclerosus et atrophicus. Although milia are frequently seen in other sub-epidermal bullous disorders, they have not previously been reported in lichen sclerosus et atrophicus.     

Tacrolimus ointment for the treatment of vulvar lichen sclerosus

The treatment of vulvar lichen sclerosus is generally considered difficult. Ultrapotent corticosteroids represent the most effective topical treatment, but carry the risk of side effects such as skin atrophy. We describe a 71-year-old woman with long-standing vulvar lichen sclerosus refractory to conventional treatment. After 6 consecutive weeks of treatment with tacrolimus ointment 0.1% (Protopic) twice daily, signs and symptoms of lichen sclerosus resolved. To our knowledge, this is the first report of the use of topical tacrolimus, which does not induce skin atrophy, in the treatment of vulvar lichen sclerosus.     

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.     

Lichen sclerosus et atrophicus of the scalp

A patient is described who developed pruritic lesions of the scalp with increasing hair loss and plaque formation over a period of 15 years, in association with patches if white atrophic skin on her trunk and vulva in the last 5 years. Biopsies of the scalp and trunk lesions both showed lichen sclerosus et atrophicus. This would appear to be the first recorded case of lichen sclerosus et atrophicus of the scalp in the English literature.     

闭塞性干燥性龟头炎研究进展

闭塞性干燥性龟头炎是一种病因不明的慢性萎缩性皮肤黏膜疾病,通常主要累及男女生殖器与前尿道的表皮和真皮结缔组织.临床上特征性损害是侵及包皮和阴茎的白色丘疹和斑片,可导致包皮变硬,继发性包茎及尿道口狭窄.发生在阴茎龟头的硬化萎缩性苔藓又称闭塞性干燥性龟头炎.对闭塞性干燥性龟头炎的病因、发病机制、临床表现、组织病理及治疗等方面的进展概述.     

Vulvar malignant melanoma associated with human papillomavirus DNA: report of two cases and review of literature

Oncogenic human papillomavirus (HPV) types such as HPV 16 are known to play a crucial role in the development of anogenital carcinomas. The etiology of anogenital malignant melanoma is unknown. We report two case of vulvar malignant melanoma in which multiple HPV types including HPV 16 and putative novel HPV types (alb-1, alb-2, alb-7, and alb-10) were identified by degenerated nested polymerase chain techniques (polymerase chain reaction) in both the malignant melanoma and surrounding skin. One melanoma was associated with lichen sclerosus, and the other, with melanoma in situ and pigmented vulvar squamous papillomatosis. These melanomas harbored HPV types alb-7, and HPV 16 as well as alb-1, respectively. HPV types 16, 20, 21, 36, alb-2, and AJ001060 were detected in vulvar skin affected by lichen sclerosus. Vulvar squamous papillomatosis harbored HPV types 28 and alb-10. HPV 16 was physically integrated into the host genome in lichen sclerosus skin and possibly in the melanoma associated with pigmented vulvar squamous papillomatosis. Twenty-two percent (4 of 18) of normal control specimens from skin tumor excisions were found to harbor HPV DNA (HPV types 3, 54, and alb-7); none of these control samples harbored multiple HPV DNA. These findings of multiple HPV DNA and integrated HPV 16 in skin associated with vulvar malignant melanoma indicate that HPV may play a role in the development of vulvar malignant melanoma. The role of HPV could be either direct through infection of melanocytes or indirect as a cofactor with free radicals in chronic fibroinflammatory vulvar disorders such as lichen sclerosus.     

Detection of expanded T cell clones in skin biopsy samples of patients with lichen sclerosus et atrophicus by T cell receptor-gamma polymerase chain reaction assays

Lichen sclerosus et atrophicus is a chronic dermatosis of unknown etiology and pathogenesis. Lichen sclerosus et atrophicus associated skin lesions show T cell enriched infiltrates, sometimes resembling the histologic picture of early mycosis fungoides. It is supposed that the infiltrating T cells participate in the pathogenesis of atrophy and sclerosis. We investigated skin biopsies from 39 lichen sclerosus et atrophicus patients by histology, immunohistochemistry and, in order to establish the status of T cell clonality, by polymerase chain reaction amplifying the T cell receptor-gamma rearrangements. A stage-dependent shift of the CD3-positive T cells was observed from a predominantly CD4-positive to a predominantly CD8-positive phenotype. The increase of CD8-positive cells was associated with more pronounced epidermotropism and basal degeneration. Nearly all CD8-positive cells expressed cytotoxic granules (TIA1), possibly causing the basal destruction. In the late fibrotic stage of the disease, only a weak or no infiltrate was found. Regarding the T cell receptor-gamma polymerase chain reaction, the presence of clonally expanded T cells was demonstrated in 19 of 39 patients (49%) by at least one of two different high resolution electrophoresis techniques applied to separate the amplification products. Thus, for the first time clonally expanded infiltrating T cells were detected in lichen sclerosus et atrophicus. Furthermore, this is one of the first reports on the detection of clonally expanded infiltrating T cells in an inflammatory skin disease. The clonal T cells could not be assigned to the CD4 or CD8 subtype. Most likely, their presence is not the result of a malignant transformation but a response to an as yet unknown lichen sclerosus et atrophicus associated antigen.     

Lichen sclerosus in adult men: a study of HLA associations and susceptibility to autoimmune disease

Lichen sclerosus is a skin disorder of unknown prevalence affecting both men and women, and several studies have established HLA associations in women with this disease. Autoimmune disease associations in the form of a personal and/or family history of autoimmune disease have also been shown to be related to lichen sclerosus. In this study, we examined 58 men (mean age 38 years) with lichen sclerosus, 39 of whom had histologically proven disease. HLA tissue typing by phototyping was performed on these patients and contrasted with that of 602 control subjects. There was no difference in antigen frequencies of the HLA class I loci. The patient group was found to have an increased frequency of several HLA antigens of the class II loci: DR11, 13 of 58 (22%) patients vs. 75 of 602 (13%) control subjects (P = 0.05); DR12, five of 58 (9%) patients vs. 16 of 602 (3%) control subjects (P = 0.04); DQ7, 26 of 58 (45%) patients vs. 189 of 602 (31%) control subjects (P = 0.05). There were few autoimmune disease associations: two of 58 (3%) patients had a personal history of a different autoimmune disease, two patients were found to have abnormal thyroid function and six of 58 (10%) had a first-degree relative with an autoimmune disease. There was no difference in the frequency of the autoimmune haplotype HLA A1, B8, DR3/17, DQ2 compared with the control population. HLA DQ7 has now been shown to occur more frequently in both male and female patients with lichen sclerosus, which may reflect the immunopathogenesis of the disease. Autoimmune disease associations, however, are less common in men with lichen sclerosus.     

Immunohistochemical evaluation of androgen receptors in genital and extragenital lichen sclerosus: evidence for loss of androgen receptors in lesional epidermis.

BACKGROUND: Reduction of lichen sclerosus has been seen with topical testosterone, and spontaneous resolution has been attributed to increasing androgen levels. OBJECTIVE: Our purpose was to investigate the role of androgens in lichen sclerosus by studying lesional skin and site-specific normal skin for the presence of androgen receptors. METHODS: Immunoperoxidase staining for androgen receptors was performed on lesional tissue from 31 patients and microscopically compared with site-specific normal skin. RESULTS: Androgen receptors were present in normal genital and extragenital skin. Lesional genital and extragenital areas showed decreased staining compared with site-specific controls. Finally staining was decreased in histologically well-developed lesions compared with early lesions. CONCLUSION: This study provides evidence for the loss of androgen receptors with disease progression in both genital and extragenital skin affected by lichen sclerosus. These findings support a hormonal pathogenesis of lichen sclerosus and may be significant in the treatment of the disease.     

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.     

Localized lichen sclerosus with nail loss

A 52-year-old woman who developed a pale sclerotic second left toe with loss of the nail plate is described. Biopsy showed changes of lichen sclerosus. There were no other skin or genital lesions present.