The role of granzyme B-expressing CD8-positive T cells in apoptosis of keratinocytes in lichen planus

Received: 3 September 1996     

扁平苔藓皮损中钙激活蛋白酶Ⅰ和半胱氨酸天冬氨酸蛋白酶3的表达及其与细胞凋亡的关系

目的 探讨凋亡相关蛋白钙激活蛋白酶Ⅰ（Calpain Ⅰ）和半胱氨酸天冬氨酸蛋白酶3（Caspase-3）在扁平苔藓皮损中的表达及其与细胞凋亡的关系。方法 分别采用脱氧核糖核苷酸末端转移酶介导的原位缺口末端标记（TUNEL）法和免疫组化法对20例扁平苔藓患者皮损组织和10例健康人皮肤组织中细胞凋亡和Calpain Ⅰ、Caspase-3表达进行检测。采用SPSS 13. 0软件,两组凋亡指数比较采用t检验,两组Calpain Ⅰ和Caspase-3表达量比较采用秩和检验,Calpain Ⅰ和Caspase-3表达量与凋亡指数相关性分析采用 Spearman 等级相关分析。结果 扁平苔藓组表皮层角质形成细胞的凋亡指数（67.59 ± 13.50）显著高于健康对照组（28.26 ± 7.56）,两组比较,差异有统计学意义（t = 8.52,P < 0.01）;Calpain Ⅰ和Caspase-3表达均高于健康对照组（T = 78.00 和77.00,P < 0.01）。扁平苔藓皮损中Calpain Ⅰ和Caspase-3阳性表达强度均与其自身角质形成细胞的凋亡指数呈正相关（r = 0.71和0.74,P < 0.01）。结论 扁平苔藓皮损中Calpain Ⅰ和Caspase-3表达上调,且与角质形成细胞凋亡亢进关系密切。     

Esophageal lichen planus

Lichen planus is a chronic inflammatory disease that affects the skin, mucous membranes, nails and scalp. Esophageal lichen planus is a rarely reported manifestation of lichen planus, presenting itself commonly in middle-aged women, with symptoms such as dysphagia. We report a case of esophageal lichen planus in a 54-year-old woman associated with oral, cutaneous and ungual lichen planus. Although lichen planus is a disorder well known by dermatologists, reports of esophageal lichen planus are rare in dermatologic literature. The esophageal lichen planus is little known and underdiagnosed, with a significant delay between the onset of symptoms and diagnosis.     

Autocytotoxic T-cell clones in lichen planus

We examined the in vitro cytotoxic activity of cutaneous T-cell lines and clones from lichen planus (LP) patients against autologous epidermal keratinocytes. T cells were cultured from LP lesions and adjacent clinically normal skin and cloned by limiting dilution. Keratinocytes were cultured from LP lesions and adjacent clinically normal skin and immortalized by transfection with the E6 and E7 genes from human papillomavirus 16 (HPV16). The lesional T-cell line from one LP patient contained 27% gammadelta+ T cells and was significantly more cytotoxic against autologous lesional keratinocytes than the T-cell line from clinically normal skin. Clones isolated from the lesional T-cell line were significantly more cytotoxic against autologous lesional keratinocytes than clones isolated from the non-lesional T-cell line. Most cytotoxic clones from LP lesions were CD8+ and most non-cytotoxic clones from LP lesions were CD4+. One cytotoxic clone was CD4- and CD8- and expressed the gammadelta T-cell receptor. Two CD8+ LP lesional T-cell clones showed dose-dependent killing of HPV16 E6/E7-immortalized autologous lesional and normal keratinocytes, but no cytotoxic activity against Epstein-Barr virus-transformed autologous B-cell blasts. The cytotoxic activity of CD8+ lesional T-cell clones against autologous lesional keratinocytes was partially blocked with anti-major histocompatibility complex (MHC) class I monoclonal antibodies. These data support the hypothesis that CD8+ lesional T cells recognize an antigen associated with MHC class I on lesional keratinocytes and that CD8+ cytotoxic T cells lyse keratinocytes in LP lesions.     

Macrophage — T-lymphocyte interaction in lichen planus

Summary Papular lichen planus lesions from 12 patients were studied by a double-step immunocyto-chemical method to detect T-lymphocytes. Semithin sections were studied by light microscopy and ultrathin sections examined by electron microscopy. In the dermal infiltrate, many T-lymphocytes appeared closely juxtaposed to macrophages or Langerhans cells, frequently arranged in a rosette-like pattern. In the epidermis, T-lymphocytes were juxtaposed to macrophages or Langerhans cells and to degenerated keratinocytes. The close relationship between T-lymphocytes, macrophages or Langerhans cells and degenerated keratinocytes supports the hypothesis that lichen planus is immunological in nature: T-lymphocytes, after interacting with macrophages or Langerhans cells, become cytotoxic for keratinocytes.Supported in part by the Consiglio Nazionale delle Ricerche; Roma, Italia, grant no 790181604The ultrastructural findings have been presented by prof. Giannotti in occasion of the VII European Meeting of the SCUR Vienna, 8–10 May 1980     

乳腺癌放疗后扁平苔藓一例

患者女,51岁,因左胸部丘疹伴痒2个月就诊。患者1年前行左乳腺癌改良切除术,术后间断辅以放射治疗25次,照射范围为左胸部、左锁骨上区及左腋窝％,累积剂量50 Gy……     

Perforin expression in peripheral blood lymphocytes and skin-infiltrating cells in patients with lichen planus

BACKGROUND: Current evidence suggests that lichen planus is a T-cell-mediated autoimmune disease in which cytotoxic mechanisms have been poorly investigated. OBJECTIVES: We investigated the expression of perforin in subpopulations of peripheral blood lymphocytes (PBL) in exacerbation and remission phases of the disease as well as in skin lesions. METHODS: We performed a simultaneous detection of perforin (intracellular molecule) and cell surface antigens on PBL by flow cytometry, and skin lesions were investigated by immunohistochemistry. RESULTS: The most interesting finding was a significant increase of perforin expression in cytotoxic T lymphocytes (CD3+ perforin+ cells) in the exacerbation phase of disease (P < 0.05), which was mostly located in the CD8+ subpopulation (CD8+ perforin+) (P < 0.01). Using immunohistochemistry we confirmed the infiltration of T lymphocytes in skin lesions, especially of CD4+ and CD8+ phenotypes, compared with uninvolved (P < 0.05) and healthy skin (P < 0.01). The expression of perforin was also significantly higher in lesional skin compared with nonlesional and healthy skin (P < 0.05). CONCLUSIONS: Our results clearly show the upregulation of perforin expression in peripheral blood as well as in lesions of patients with lichen planus and therefore suggest an important role for perforin in this autoimmune disease.     

Bcl-2、p53在扁平苔藓病变组织中的表达

为了探讨扁平苔藓的发病机理，采用标记抗链菌卵蛋白生物素（ＬＳＡＢ）的方法，检测了３５例扁平苔藓Ｂｃｌ２和ｐ５３蛋白的表达。结果发现，在扁平苔藓组织中Ｂｃｌ２和ｐ５３蛋白有广泛的表达（分别为８５７１％和６０％），Ｂｃｌ２阳性表达率和强度均高于ｐ５３（两者Ｐ＜００５），并呈平行关系（Ｐ＜００５）。提示Ｂｃｌ２和ｐ５３可能是协同参与扁平苔藓病变的重要因素。     

甲扁平苔藓研究进展

甲扁平苔藓临床少见,可伴有皮肤扁平苔藓或独立存在.甲扁平苔藓的流行病学研究较少,其流行病学特点尚未完全阐明.甲扁平苔藓分5型:Ⅰ型为典型皮损伴有甲损害,Ⅱ型为不典型皮损伴有甲损害,Ⅲ型为头皮损害伴有甲损害,Ⅳ型为黏膜损害伴有甲损害,Ⅴ型为单纯甲损害.甲扁平苔藓有许多特征性临床表现,如翼状胬肉.临床上需与甲真菌病及其他可引起甲营养不良的疾病鉴别.甲扁平苔藓的组织病理特征与其他部位的扁平苔藓类似,皮肤镜有助于辅助诊断本病.本病治疗困难,缺少特效治疗方法.系统应用激素是唯一有循证研究支持的疗法.阿维A治疗甲扁平苔藓有效.甲氨蝶呤、环孢素等免疫抑制剂也可有效治疗甲扁平苔藓.甲扁平苔藓预后差,复发率高.     

扁平苔藓的皮肤镜学表现

扁平苔藓的主要皮肤镜学表现包括具有诊断意义的叶脉状、网状Wickham纹,和非特异性点状或线状血管及点状、球状或线状色素沉着;偶尔可见其他一些变异表现。使用皮肤镜可以更清楚观察到肉眼能辨认的Wickham纹和肉眼看不到Wickham纹、血管和色素表现,因此皮肤镜有助于扁平苔藓的诊断及与银屑病、皮炎湿疹、红斑狼疮等相似疾病的鉴别诊断。     

Impairment of myocardial functions and arterial stiffness in patients with lichen planus

BackgroundLichen planus is a chronic inflammatory mucocutaneous disease. Recent studies have suggested that it is associated with an increased risk of cardiovascular comorbidities.ObjectiveThe purpose of this study was to assess and compare arterial stiffness and cardiovascular hemodynamics in patients with lichen planus and a healthy control group.MethodsFifty-five patients with lichen planus and 42 healthy controls were enrolled. All patients underwent echocardiographic examination, and arterial stiffness was measured using applanation tonometry.ResultsNo statistically significant difference was determined between the patient and control groups in terms of arterial stiffness, but stiffness was markedly higher in patients with erosive lichen planus compared to the control group and other patients (p = 0.006, and p = 0.023, respectively). Moderate positive correlation was determined between duration of disease and arterial stiffness. Impairment of systolic and diastolic functions was also determined in patients with lichen planus compared to the control group (p < 0.001, and p = 0.005, respectively).Study limitationsRelatively low number of patients.ConclusionThe positive correlation observed between duration of disease and arterial stiffness in patients with lichen planus suggests that these patients should be followed-up in terms of cardiovascular risk in the presence of resistant and long-term disease, particularly in case of erosive lichen planus.     

Male genital lichen planus: A retrospective study of 89 cases

BackgroundUnlike other types of lichen planus (LP), there are no series concerning male genital LP.ObjectiveTo describe the clinical characteristics, diagnosis, and response to treatment of male genital LP.Patients and methodsA retrospective study of male patients with genital LP consulting a dermatologist specialized in anogenital diseases between January 2010 and 2019. Demographic data, history, functional signs, clinical characteristics, pathology, complications, and treatment efficacy were collected.ResultsEighty-nine patients were included at four centers. The median age was 51 years. Most patients were uncircumcised and asymptomatic. In 88.8% of cases, only the genital mucosa was involved. Erythema (71%), papules (21.3%), lacy network (15.7%), atrophic lesions (15.7%), erosions (14.6%), and post-inflammatory hyperpigmentation (2.2%) were less frequently observed. Biopsy results confirmed LP in 61.3% of cases but could not rule out other inflammatory genital dermatoses in other cases. Anatomic complications were observed in 30.3% of patients. Topical corticosteroids (TCS) induced remission in most cases. Tacrolimus efficacy was comparable to that of TCS.ConclusionMale genital LP is a rare inflammatory disorder chiefly affecting uncircumcised men. It is found predominantly on the mucosal component of the penis and presents as non-erosive inflammatory balanitis in most cases, with frequent partial or complete remission on treatment with TCS.     

20甲扁平苔藓11例临床分析

目的：了解11例20甲扁平苔癣的临床特点，以提高对该病的认识。方法：对11例20甲扁平苔癣患者的临床资料、真菌学和组织病理检查进行分析，并对相关文献进行复习。结果：11例患者中男6例，女5例，平均年龄27．9岁，均表现为20指趾甲全部受累，真菌镜检、培养均阴性，经组织病理检查明确诊断为甲扁平苔癣。结论：甲扁平苔癣好发年龄为青少年和40～60岁，无性别差异。单独发生于甲部，特别是20甲受累的扁平苔癣十分少见，容易误诊，确诊需要组织病理活检。     

Delayed type hypersensitivity is abnormal in patients with lichen planus

Summary Lichen planus is characterized by the histological features of a cell-mediated attack on the epidermis. To see whether there is any defect in cutaneous immunity in non-lesional skin, we measured the response to a contact sensitizer in 17 patients with lichen planus and 27 control subjects. Sensitization was induced with 30 g dinitrochlorobenzene applied to the thigh. The subjects were challenged 4 weeks later with three doses of dinitrochlorobenzene (8.8, 12.5 and 17.7 g), and responses were quantified with calipers as the change in skinfold thickness at 48 h. Patients with lichen planus were significantly less responsive with smaller reactions at all challenge doses. These abnormalities suggest that the skin is abnormal in areas unaffected by the rash, and raise the possibility that there may be a primary defect in the cutaneous immune system in lichen planus.     

Erosive lichen planus: a therapeutic challenge

Erosive lichen planus is an uncommon variant of lichen planus. Chronic erosions of the soles, accompanied by intense and disabling pain, are some of its most characteristic manifestations. We present the case of a woman who developed oral and plantar erosive lichen planus associated with lichen planus pigmentosus and ungueal lichen planus that were diagnosed after several years. The patient failed to respond to multiple therapies requiring longstanding medication but remained refractory. Knowledge of the treatment options for erosive lichen planus is insufficient. Further research is required to clarify their effectiveness, ideally adopting an evidence-based methodology.     

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.     

血管内皮生长因子在扁平苔藓及银屑病皮损中的表达

目的探讨扁平苔藓及银屑病患者皮损表皮血管内皮生长因子(VEGF)表达情况。方法用抗VEGF及CD34抗体行免疫组化染色,对扁平苔藓及银屑病皮损标本进行观察,计数表皮下方真皮的毛细血管密度。结果正常人表皮VEGF基本阴性,扁平苔藓及银屑病患者非病变部VEGF阴性,移行部表皮上层VEGF染色逐渐由弱到强,由间断到连续;病变部表皮VEGF阳性,以表皮上层细胞质的细颗粒状染色为主。CD34染色各部分真皮上层毛细血管密度为;扁平苔藓的非病变部(45.61±15.70)个/mm²、移行部(68.63±15.36)个/mm²、病变部(92.07±16.84)个/mm²;银屑病的非病变部(43.73±14.55)个/mm²、移行部(72.12±18.81)个/mm²、病变部(100.29±21.93)个/mm²,各病种三个部位之间比较差异均有统计学意义。结论扁平苔藓及银屑病皮损表皮分泌VEGF,并与真皮毛细血管增生扩张密切相关。     

Multiple keratoacanthomas in hypertrophic lichen planus: treatment with systemic retinoids (etretinate)

A 75-year-old woman was referred for treatment of multiple keratoacanthomas and hypertrophic lichen planus. Surgical excision was considered but was not possible given the multiplicity of the lesions. Etretinate, potent topical corticosteroids and gradient support stockings were initiated. Complete resolution was achieved in four months and oral and topical therapy was discontinued. Four months after discontinuation of all therapy there has been no recurrence.