隐性梅毒患者中神经梅毒患病率分析

目的 探讨广州市神经梅毒流行情况,比较未经治疗隐性梅毒患者和血清固定的隐性梅毒患者中神经梅毒的患病率.方法 以横断面研究的方法,对初次诊断为隐性梅毒患者(未治疗或经治疗后出现血清固定)抽取脑脊液,进行性病研究实验室试验,筛查神经梅毒患者.结果 未经治疗隐性梅毒患者中有21.98%(60/273)为神经梅毒,其中10.99%(30/273)为无症状神经梅毒,10.99%(30/273)为有症状神经梅毒.经抗梅毒治疗血清固定隐性梅毒患者83例中1.20%(1/83)符合神经梅毒诊断,为无症状神经梅毒病例.在未经治疗隐性梅毒组中,无神经梅毒病例年龄与有神经梅毒病例年龄差异有统计学意义,前者年龄低于后者.结论 在抗梅毒治疗后产生梅毒血清固定患者神经梅毒发生的可能性相对未经治疗的隐性梅毒小,神经梅毒仍主要发生于未经治疗的潜伏梅毒人群中,提示未经治疗的隐性梅毒是神经梅毒发生的主要危险因素.     

隐性梅毒患者中神经梅毒患病率分析

目的 探讨广州市神经梅毒流行情况,比较未经治疗隐性梅毒患者和血清固定的隐性梅毒患者中神经梅毒的患病率.方法 以横断面研究的方法,对初次诊断为隐性梅毒患者(未治疗或经治疗后出现血清固定)抽取脑脊液,进行性病研究实验室试验,筛查神经梅毒患者.结果 未经治疗隐性梅毒患者中有21.98%(60/273)为神经梅毒,其中10.99%(30/273)为无症状神经梅毒,10.99%(30/273)为有症状神经梅毒.经抗梅毒治疗血清固定隐性梅毒患者83例中1.20%(1/83)符合神经梅毒诊断,为无症状神经梅毒病例.在未经治疗隐性梅毒组中,无神经梅毒病例年龄与有神经梅毒病例年龄差异有统计学意义,前者年龄低于后者.结论 在抗梅毒治疗后产生梅毒血清固定患者神经梅毒发生的可能性相对未经治疗的隐性梅毒小,神经梅毒仍主要发生于未经治疗的潜伏梅毒人群中,提示未经治疗的隐性梅毒是神经梅毒发生的主要危险因素.     

Lichen sclerosus of lips: a clinical and histopathologic study of 27 cases

Background & Methods Oral lichen sclerosus (LS) has been considered uncommon and involvement of lips extremely rare. We reviewed the clinical and histologic features of 72 cases of LS with oral/genital involvement, seen in our institute from 2002 to 2007. Results Lichen sclerosus was diagnosed with exclusive genital lesions in 45, exclusive lip involvement in 20, and orogenital involvement in seven cases. Fifteen of 27 histologically confirmed lip LS lesions were considered as early inflammatory or presclerotic, eight were intermediate/progressive, and four as late resolved lesions. Lip LS presented as asymptomatic vitiligoid lesions in 70% and dermal sclerosis was demonstrable in only 44%, which was limited to the papillary layer. This was in contrast with genital LS lesions which were asymptomatic in only 12% and demonstrated both papillary and reticular dermal sclerosis in 69%. Conclusion Lip LS is far less symptomatic and destructive with limited dermal sclerosis compared with genital LS. Greater awareness and histologic assessment are essential for diagnosis because of the misleading vitiligoid appearance. “Vitiligoid LS” a superficial variant proposed by Borda can be aptly applied to lip LS. Dermatologists need to be aware of this rarely reported manifestation of LS as it adds to the spectrum of oral lichenoid lesions and lichenoid dysplasia, which are suspected to have a malignant potential.     

The high rate of familial lichen sclerosus suggests a genetic contribution: an observational cohort study

Background Familial lichen sclerosus (LS) has been described in only 37 families. We feel that the association is under‐reported. Objectives To determine the percentage of patients with LS who have a positive family history. Method A large observational‐cohort study of a total of 1052 females at vulval clinics within a University Hospital with a diagnosis of LS of the vulva (clinical diagnosis was confirmed in 80% of cases by histology). Patients were questioned as to family history of LS or balanitis xerotica obliterans; male circumcision for medical reasons; vulval cancer; and routine medical and family history. The outcome was the presence or absence of personal or family history of LS, autoimmune disorder or vulval cancer. Results In total 1052 patients were investigated. Of these, 126 (12%) had a positive family history of LS. These patients belonged to 95 families. Vulval cancer was significantly increased in those with a family history of LS compared with those without (4.1% vs. 1.2%, P < 0.05). There was more associated autoimmune disease in familial LS than in sporadic LS, although this was not statistically significant. (7% vs. 5%, P > 0.2). Conclusion Our data from a large cohort of patients with LS provide evidence of an increased risk for family members to develop LS. This indicates a likely genetic component in the aetiology of LS.     

Genital verrucous carcinoma is associated with lichen sclerosus: a retrospective study and review of the literature

Background The association of lichen sclerosus (LS) with genital squamous cell carcinoma is well recognized. However, the relationship between LS and verrucous carcinoma remains unclear. Objective To evaluate the associations of genital and perianal verrucous carcinomas with LS. Methods We conducted a retrospective study on patients with a genital or perianal verrucous carcinoma and reviewed their histopathology specimens and clinical notes. We also conducted a literature review. Results We identified a total of 13 patients (including 6 women and 7 men) with a genital or perianal verrucous carcinoma. All 5 women with vulval verrucous carcinoma had coexisting LS (5/5), and 1 man with penile verrucous carcinoma had coexisting LS (1/3). In contrast, no coexisting LS was found in all 5 cases of perianal verrucous carcinoma (0/5). Half of the cases of verrucous carcinoma with coexisting LS had recurrences (3/6), while no recurrences were found in those without coexisting LS (0/7). Conclusions Our study and review of the literature demonstrate that vulval verrucous carcinoma is strongly associated with LS. In contrast, perianal verrucous carcinoma is not associated with LS. When genital verrucous carcinoma is diagnosed, it is important to consider LS as a potential concomitant diagnosis and offer appropriate treatments and close follow‐up to detect recurrence of verrucous carcinoma.     

Possible mechanisms of hypopigmentation in lichen sclerosus

Lichen sclerosus (LS) shares with vitiligo a milky-white appearance. By biopsy, pathognomonic dermal sclerosis readily distinguishes LS from vitiligo and other causes of leukoderma. To determine what the mechanism of hypopigmentation is in LS, we examined samples from LS cases for alterations in melanin content (Fontana-Masson stain) and melanocyte number (HMB-45 [PMEL-17/gp100], Mel-5 [TRP-1], Mart-1 [Melan A]) and compared these findings with those in controls of normal skin, acute scars, vitiligo, and lichen planus (LP; a common inflammatory cause of hyperpigmentation). The degree and extent of melanization found in LS overlapped with that in acute scars showing predominantly hypomelanized keratinocytes, with that in LP containing regions with numerous melanophages, and with that in vitiligo exhibiting focal regions of keratinocytes devoid of melanin pigment. By hematoxylin-eosin staining and immunocytochemistry for Mel-5 and Mart-1, LS had a lower mean count of melanocytes than acute scars, LP, and normal skin per 200 basal keratinocytes. In addition, a few LS cases had a significant loss of melanocytes comparable to that of vitiligo. Surprisingly, Mart-1 identified rare melanocytes in 67% of vitiligo cases and a significantly larger pool of melanocytes in LS and controls other than those labeled by Mel-5. Furthermore, LP and evolving lesions of LS contained the highest Mart-1 counts. HMB-45-immunoreactive melanocytes were found in the majority of acute scars and in LP and late-stage LS lesions at significantly lower levels than Mel-5- and Mart-1- labeled melanocytes, but they were not found in vitiligo or normal skin. We propose that several mechanisms may play a role in the production of leucoderma in LS: 1) decreased melanin production; 2) block in transfer of melanosomes to keratinocytes; and 3) melanocyte loss. The latter finding may be the pathogenic connection (lichenoid dermatitis of LS triggering an autoimmune reaction to melanocytes) that underlies the documented association of LS with vitiligo.     

Nail dystrophy due to lichen sclerosus?

Lichen sclerosus (LS) affects anogenital skin alone in 80% of cases. When extragenital disease occurs, it usually affects the trunk, neck, axillae and wrist flexures. Nail involvement with LS is rare. In contrast, lichen planus (LP) commonly affects extragenital skin. Mucosal lesions occur in 50% of cases, affecting the mouth and genitalia. Nail disease in LP is common, and, if severe, can lead to destruction of the nail bed. LS and LP can coexist. We report two cases of LS with nail involvement. In the Case 1 disease was confined to the nail, and nail biopsy confirmed LS. In the Case 2, the nail changes formed part of the widespread genital and extragenital LS, confirmed histologically. We review existing literature on nail disease in LS and discuss the possible aetiology of the nail changes.     

High incidence of lichen sclerosus in patients with squamous cell carcinoma of the penis

BACKGROUND: There is a well-documented association between lichen sclerosus (LS) and vulval carcinoma in women; however, until recently, there have only been anecdotal reports of penile squamous cell carcinoma (SCC) occurring in men with LS. OBJECTIVE: The incidence of penile carcinoma occurring on a background of LS remains uncertain, and we wished to examine this possible association further. METHOD: To address this, all the cases (n = 20) of penile SCC held on our pathology database (4 years) were examined. Histology was reviewed, blind to the clinical picture, for evidence of LS, applying strict histological criteria. Subsequently, clinical notes were reviewed for history of LS before the SCC presented, and history of previous circumcision, treatments, node involvement, metastases and death. RESULTS: In eight cases, evidence of LS was found in the excision specimen. Seven of these had well-differentiated SCC. In the 12 cases with no evidence of LS, only three were well differentiated. With case note review, seven had a history of LS (four with histological LS), sometimes preceding the SCC by 10 years. These all had well-differentiated SCC. Ten of the 20 patients are dead, seven from metastatic disease. Four deaths occurred in the 'well-differentiated LS' group, but only one from penile SCC metastatic disease. CONCLUSIONS: There appears to be a definite association between SCC of the penis and the presence of LS, similar to that reported between LS and vulval SCC in women. Of the 20 patients with penile SCC studied, 11 had a clinical history and/or histological evidence of LS. However, clinical presentation of the LS or need for circumcision may precede the SCC by many years. As follow-up is impractical, counselling at the time of diagnosis is very important, and it is essential that medical practitioners are aware of this association so that the subsequent risk from SCC is reduced.     

Simultaneous Occurrence of Lichen Striatusin Siblings

Abstract: Lichen striatus (LS) is a self-limiting linear papular dermatosis of unknown eliology seen mostly in children. We report LS occurring in two pairs of siblings: two sisters who had LS at an interval of 6 months and a brother and sister who had the dermatosis contemporaneously after an epidose of flulike fever. In all four patients family history was positive for atopy. LS is frequently associated with atopic diseases. The abnormal immune status of patients with atopy may be a predisposing factor in the induction of LS. In our patients the simultaneous occurrence of LS in siblings after a flulike fever appears to corroborate the hypothesis that a viral infection is a possible candidate, as other authors have proposed. The rarity of familial cases of LS is, in our opinion, due to the exceptional confluence of difference sporadic events (atopy, viral infection caught at a specific period of life such as childhood, and a genetic predisposition) simultaneously present in the same patient     

硬化性苔藓合并扁平苔藓、硬斑病一例并文献复习

硬化性苔藓(LS),扁平苔藓(LP)和硬斑病是三种病因不明的皮肤病,已有多篇任意两种疾病合并的报道,但患者同患LS、LP和硬斑病少见,目前未见国内有相关报道。本文报道1例LS合并LP和硬斑病,并对国外已报道的7例病例进行回顾性分析。结果示8例患者中男2例,女6例,平均年龄(60.3±15.1)岁。8例患者的LS与硬斑病同时发生或硬斑病发病早于LS,同一皮损的病理切片同时具有LS与硬斑病的特征,LP发病可早于或晚于LS和硬斑病;8例患者皮损主要表现为生殖器外LS、泛发型硬斑病、经典或糜烂型LP;6例有免疫相关异常指标,4例合并其他自身免疫性疾病。     

Treatment of lichen sclerosus with carbon dioxide laser vaporization

We have treated 10 patients (five women and five men) with lichen sclerosus (LS), verified by histopathological studies from skin biopsies, with CO₂ laser vaporization. All men studied had LS of the penile skin, of the women, three had extragenital lesions and two LS of the perineal skin. The mean follow-up time was 32 months (range 3-79 months). One man had both penile and urethral LS. All penile lesions of the five men were clinically cured by laser treatment: however, urethral lesions of one patient recurred despite three separate treatments. The two women with perineal LS improved after laser treatment. However, LS recurred on the treated area in one and on the margins of the treated area in another. Two women with LS on the skin of the breast became asymptomatic after treatment. One woman had several lesions on the skin of the trunk that improved after treatment but were not cured completely. The present study suggests that carbon dioxide vaporization may be an effective treatment of skin lesions in LS.     

Altered p53 expression and epidermal cell proliferation is seen in vulval lichen sclerosus

Aberrant p53 immunoreactivity has been found in skin premalignancies and dysplasias such as Bowen's disease and actinic keratoses. Vulval lichen sclerosus (LS) has been reported to be pre-malignant, with an association of vulval carcinoma in 3% to 6% of patients. In contrast, non-genital LS appears to have no malignant potential. In this immunocytochemical study, we investigated p53 expression in 10 cases of histologically proven vulval LS and 9 cases of non-genital LS using the murine monoclonal antibody Do-1 raised against recombinant human p53 which reacts with both wild-type and mutant p53. None of the vulval specimens had epithelial dysplasia or malignancy. Normal vulval (7 cases) and non-genital skin (5 cases) were used as tissue controls, respectively. The cell proliferation index was also studied using the MIB 1 monoclonal antibody which detects the cell-cycle associated Ki-67 antigen. The technique of microwave irradiation for antigen unmasking was employed on Formalin-fixed and paraffin-embedded tissues. There was a significant increase in p53 immunoreactivity in vulval LS (32.13 ± 15.11 epidermal cells per 100 basal cells) compared to normal vulval skin (7.52 ± 5.04 epidermal cells per 100 basal cells) (p < 0.001), whereas the MIB 1 labelling index was lower in vulval LS (39.45 ± 15.88 epidermal cells per 100 basal cells) than in normal controls (86.26 ± 32.31 epidermal cells per 100 basal cells) (0.001 < p < 0.01). In contrast, there was no significant difference in p53 immunoreactivity or MIB 1 labelling index between non-genital LS and normal controls. Vulval LS, when compared to non-genital LS (8.76 ± 6.61 epidermal cells per 100 basal cells), also demonstrated a significant increase in P53 immunoreactivity (p < 0.001). The reduced proliferative index in vulval LS may be directly related to its increase in p53 expression and is in keeping with the role ol p53 in the negative regulation of cell proliferation. We propose that the difference in p53 expression may represent a difference in biological behavior between vulval LS and non-genital LS. What role it plays in the evolution of vulval carcinoma in a setting of long standing LS is uncertain.     

Childhood Lichen Sclerosus—A Challenge for Clinicians

Childhood lichen sclerosus (LS) is a rare and often misdiagnosed inflammatory dermatitis with an unpredictable course. The complications of LS are architectural changes of the vulva; malignant transformation is possible. The objective of our study was to define the background and the long‐term course of childhood LS. A registery study identified 44 children with LS treated at Tampere University Hospital, Tampere, Finland, from 1982 to 2010. A questionnaire was sent to the identified patients and 15 responded. The clinical depiction of LS varied significantly. LS was diagnosed in only 16% of the patients at the referring unit. Autoimmune disorders were observed in 6 of the 44 patients. High prevalences of Turner's syndrome (2/44) and kidney disease (2/44) were noted. The majority of the patients were treated with topical corticosteroids. Eight developed architectural changes of the vulva. The questionnaire revealed that three of six patients who were asymptomatic at the end of the registery study follow‐up experienced a recurrence of symptoms. None of them were undergoing follow‐up. Nine of the 15 patients reported reduced quality of life. Childhood LS is a heterogeneous disease with a remarkable effect on quality of life. The misdiagnosis of childhood LS is common. The association between LS and autoimmune diseases should be noted. The high prevalence of Turner's syndrome raises questions regarding the influence of low estrogen levels on the development of LS. The prognosis cannot be predicted, so long‐term follow‐up is recommended. New tools for diagnosis and surveillance are needed.     

Hypoxia–ischaemia is involved in the pathogenesis of vulvar lichen sclerosus

Background. Lichen sclerosus (LS) is a chronic inflammatory skin disease, the pathogenesis of which is poorly understood. Aim. To evaluate the role of hypoxia–ischaemia (HI) in vulvar LS. Methods. Samples from five patients with vulvar LS and five control subjects were collected for analysis by transmission electron microscopy (TEM) to reveal the ultrastructural changes of organelles and dermal blood capillaries. Samples from 37 patients with vulvar LS and 12 control subjects were collected for immunohistochemistry to detect the expression of vascular endothelial growth factor (VEGF) and the hypoxia markers hypoxia‐inducible factor (HIF)‐1α and glucose transporter (Glut)‐1. Results. Using TEM, the mitochondria of basal cells and vascular endothelial cells in vulvar LS tissue were found to be swollen with loss of cristae, and the rough endoplasmic reticulum had luminal swelling and ribosomal detachment. Damage to vascular endothelial cells, disorganization of capillary architecture and loss of capillaries were also seen. By immunohistochemistry, moderate to intense staining of VEGF was seen in almost 90% of control sections vs. about 55% of LS sections. Glut‐1 expression was negative or weak in 75% of control sections vs. moderate to very strong in about 80% of vulvar LS sections. Nuclear staining of HIF‐1α was not found in LS or control tissue. Conclusions. HI is involved in the pathogenesis of vulvar LS.     

Microinvasive squamous cell carcinoma arising on lichen sclerosus of the penis

The case of a 70-year-old white man with a 10-year history of penile lichen sclerosus (LS) who developed microinvasive squamous cell carcinoma on LS is described. A high incidence of penile cancer arising on genital LS has recently been observed. The authors stress the importance of an adequate diagnosis and long-term follow-up in patients with penile LS because of the malignant potential of the disease.     

Thirteen-megahertz ultrasound probe: its role in diagnosing localized scleroderma

BACKGROUND: Ultrasound imaging has been shown to be useful for the evaluation of systemic and localized scleroderma (LS). However, its specificity and sensitivity have not been studied. OBJECTIVES: To define morphological ultrasound diagnostic criteria in LS and to test their sensitivity and specificity with a 13-MHz ultrasound probe. METHODS: Forty plaques in 26 consecutive patients with LS were examined and compared blindly with 17 control plaques in 16 patients with skin diseases where LS was in the differential diagnosis. Data were also compared with a normal control group. Five patients were re-evaluated 12-18 months after the first examination. RESULTS: Ultrasound examination disclosed a characteristic dense image resembling a flattened 'yo-yo'. Undulations of the dermis, disorganization, loss of thickness and thickened hyperechoic bands in the hypodermis, and the 'yo-yo' image had a high sensitivity and a high specificity for LS. A 92% sensitivity and a 100% specificity for LS were found when at least four of these five signs were present. CONCLUSIONS: Thirteen-megahertz ultrasound is a valuable tool for diagnosing LS. Morphological ultrasound diagnostic criteria had a high specificity and a high sensitivity.     

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.     

The possible role of human papillomavirus infection in the development of lichen sclerosus

Lichen sclerosus (LS) is a chronic inflammatory skin disease of unknown origin predominantly affecting the anogenital area that causes pruritus and pain and is associated with an increased risk of malignancy. In some cases, LS vanishes after application of imiquimod, raising the question whether human papillomavirus (HPV) may have an etiopathogenic role in anogenital LS. The databases MEDLINE and Embase were systematically searched using the PRISMA guidelines. Twenty‐seven papers were included that reported the prevalence of HPV in LS and in LS associated with neoplasia. HPV was identified in 0–80% (median 22%) of all LS cases. The prevalence of HPV was higher among male patients with LS (median 29%) than among female patients (median 8%). HPV16 was the most prevalent genotype, but the distribution of genotypes indicates that even low‐risk HPV can cause LS. The diverging detection rates are probably due to small sample sizes in the reviewed papers and different detection methods. Factors possibly underestimating the prevalence of HPV are a selective search for high‐risk HPV, DNA destruction in fixed tissue, focally residing HPV, and possibly a clearing of HPV before the time of biopsy. Seventy‐five percent of sexually active people acquire HPV during their lifetime, thus HPV alone is not a cause of LS. Genetic and immunological host factors and viral factors other than type are likely to contribute. Future studies should include patients with a short duration of symptoms, and biopsies should be multiple and fresh.     

硬化萎缩性苔藓15例皮肤镜特征

目的 探讨硬化萎缩性苔藓的皮肤镜表现。 方法 对15例门诊确诊为硬化萎缩性苔藓患者的27处生殖器及生殖器外瓷白色皮损进行皮肤镜特征分析。 结果 皮肤镜检查显示,27处皮损中24处见黄白色无结构区,25处可见线状血管,27处见白色斑片,17处见角栓样结构;4例患者的7处皮损见特征性四叶草样结构,符合硬化萎缩性苔藓。 结论 硬化萎缩性苔藓临床表现不典型,在皮肤镜下可表现出部分特异性模式。     

Coexistence of HLA-B*08 and HLA-B*18 in four siblings with Lichen sclerosus

BACKGROUND: Lichen sclerosus (LS), is characterized by localized patches of atrophy and whitening of the skin. The cause of LS remains unknown, but genetic, hormonal, immunologic factors and autoimmune mechanisms have been incriminated. There are conflicting data regarding the association between LS and human leukocyte antigens (HLA). METHODS: We have analyzed the HLA alleles of a family, in which 4 of 5 children have lichen sclerosus. RESULTS: HLA-B*08 and HLA-B*18 alleles were detected in children with LS, but not in a healthy sister. None of the patients had autoimmune disease. CONCLUSION: In our opinion, coexistence of these two alleles may play a role in the development of LS.