Is there a role for tumor necrosis factor-alpha (TNF-α) in oral lichen planus?

Oral lichen planus (OLP) is a T cell-mediated inflammatory disease of the oral mucosa. T lymphocytes accumulate within OLP lesions by extravasation from the local microvasculature and subsequent migration to the oral epithelium. Tumor necrosis factor-alpha (TNF-α) is a cytokine involved primarily in T cell-mediated immunopathological reactions, and it is implicated in diseases which bear clinical and histological similarities to OLP. This review examines the role of TNF-α in the initiation and progression of OLP, and summarises evidence for a key role for TNF-α in this disease. A unifying hypothesis for the involvement of TNF-α in the immunopathogenesis of OLP is presented. Based on this model, a variety of current therapies are explained and several alternative approaches suggested.     

核因子Kappa B与肿瘤坏死因子α在口腔扁平苔藓中的相关性

目的：研究核因子KappaB（NF—KB）和肿瘤坏死因子α（TNF—α）在口腔扁平苔藓（OLP）中的相关性,及其两种因子的表达与OLP临床特征之间的联系。方法：30例OLP患者根据其临床表现分为萎缩-糜烂型及斑纹型,采用免疫组化方法研究OLP两种临床类型NF—KBp65及TNF-α的表达,并计算阳性细胞百分率。选取10例正常组织作为对照。结果：NF—KBp65阳性表达位于OLP上皮基底层及临近细胞的胞核内,而正常组织未见胞核着色。TNF-α阳性表达位于OLP上皮基底层细胞的胞质内,正常组织中仅有散在阳性表达。NF—KBp65和TNF—α的表达在不同临床类型、年龄及病损部位中有显著性差异（P〈0．05）,但与性别无关（P〉0．05）。NF—KBp65的胞核着色与TNF-α的高表达呈正相关（r=0．676,P〈0．01）。结论：OLP中NF—KB被激活与TNF-α的高表达密切相关。在NF—KB和TNF-α之间可能存在一个正反馈调节环,这种正反馈的机制可能加重了OLP的炎性反应,同时也可能保护了上皮细胞,避免了过多的凋亡。     

Immunohistochemical study of oral keratoses including lichen planus

Biopsies of non-ulcerated oral mucosa from 13 patients with oral lichen planus and 12 patients with leukoplakia were immunohistochemically stained using monoclonal antibodies to pan T, pan B, T helper and T suppressor/cytotoxic cells and the stained lymphocytes enumerated using an image analyser. The results show the preponderance of T cells infiltrating both oral lichen planus and leukoplakia. The T helper: T suppressor/cytotoxic cell ratio was the same (1:2) for both oral lichen planus and leukoplakia. A similar proportion of T suppressor/cytotoxic cells was found infiltrating the epithelium. These data indicate that T cell subset analysis is of no value in distinguishing oral lichen planus from other oral keratoses.     

Ets-1在口腔扁平苔藓中的表达研究

目的 :分析Ets 1(E2 6transformation specific)在口腔扁平苔藓 (OLP)的表达及意义。 方法 :采用免疫组化ABC法检测Ets 1蛋白在 2 0例口腔扁平苔藓和 8例正常口腔黏膜组织中的表达。结果 :70 % (14 /2 0 )的口腔扁平苔藓病例中Ets 1呈阳性表达 ,明显高于正常黏膜组织 ,两者比较有显著性差异 (P <0 .0 5 )。阳性表达率在溃疡型OLP与斑块型OLP间亦有显著性差异 (P <0 .0 5 ) ,并与病程相关 (P <0 .0 5 )。结论 :Ets 1在口腔扁平苔藓中过表达并与其发病有关。     

Periodontal status in patients with oral lichen planus: a study of 90 cases

OBJECTIVE: This study was carried out to relate periodontal status to the oral lesions in patients with oral lichen planus (OLP). MATERIALS AND METHODS: Periodontal status was evaluated in 90 patients with OLP and in 52 controls, in terms of the plaque index (PII), simplified calculus index (CIS) and periodontal disease index (PDI). RESULTS: No significant differences were observed between the two groups as regards the different periodontal indices. The plaque and calculus indices were higher in the more extensive forms of OLP (P = 0.02 and P = 0.012, respectively), and in the presence of gingival involvement (P = 0.004 and P = 0.04). A significant association was also observed between the presence of atrophic-erosive lesions and increased periodontal deterioration (P = 0.037). CONCLUSIONS: Increased plaque and calculus deposits are associated to a significantly higher incidence of atrophic-erosive gingival lesions in patients with OLP.     

Topical clobetasol in the treatment of atrophic-erosive oral lichen planus: a randomized controlled trial to compare two preparations with different concentrations

Oral lichen planus (OLP) is a chronic inflammatory disease that can be painful, mainly in the atrophic and erosive forms. Numerous drugs have been used with dissimilar results, but most treatments are empirical and do not have adequate control groups or correct study designs. However, to date, the most commonly employed and useful agents for the treatment of LP are topical corticosteroids. A randomized, double-blind, placebo-controlled trial has been designed to compare the efficacy and safety of two different formulations of clobetasol, a very potent topical steroid, in the topical management of OLP and to evaluate which gives the longest remission from signs and symptoms. Thirty-five consecutive patients were divided into two groups: the first received clobetasol propionate 0.025% and the second was given clobetasol propionate 0.05%. Both drugs were placed in 4% hydroxyethyl cellulose bioadhesive gel. Anti-mycotic prophylaxis was also added. After the end of therapy, patients received a 2-month follow-up. In all, 14 of the 15 clobetasol 0.025% patients (93%) and 13 of the 15 clobetasol 0.05% patients (87%), had symptoms improvement after 2 months of therapy ( P  = 0.001 in both groups). Also, 13 of the 15 clobetasol 0.025% patients (87%) and 11 of the 15 clobetasol 0.05% patients (73%) had clinical improvement after 2 months of therapy ( P  < 0.05 in both groups). No statistical differences were found in comparing the two different formulations. A larger concentration of the active molecules cannot further improve the therapeutic findings or optimize the obtained results in a significant manner.     

Immunohistochemical study of oral lichen planus associated with hepatitis C virus infection,oral lichenoid contact sensitivity reaction and idiopathic oral lichen planus

OBJECTIVES: Oral lichen planus (OLP) is a common mucocutaneous disorder and might be associated to a possible pathogenic relationship with hepatitis C virus (HCV) infection or hypersensitivity to dental alloy. We examined the clinical and immunohistochemical features of OLP associated with HCV infection (OLP-HCV), oral lichenoid contact sensitivity reaction (OLCSR), and idiopathic oral lichen planus (iOLP). The immunohistochemical expressions of CD4, CD8, B cells, Class II major histocompatibility complex antigen (HLA-DR), S-100, HSP60, Proliferating cell nuclear antigen (PCNA) and Ki-67 were compared to study the pathogenic differences of the three OLP groups. MATERIALS AND METHODS: Three groups of OLP patients, (I) OLP-HCV patients (n = 17), (2) OLCSR patients (n = 10) and (3) iOLP patients (n = 14) were retrieved from clinical records and tissues examined immunohistochemically by the avidin-biotin-complex technique. RESULTS: The patients with OLP-HCV showed widespread lesions. The proportion of CD8+ cells was found to be significantly higher in the lamina propria of the OLP-HCV patients and a significantly lower proportion of CD8+ cells of the OLCSR patients was noticed in the epithelium or the connective tissue papillae than in the iOLP patients. There were no significant differences in either the number of CD4+ cells or B cells between the three OLP groups. No significant differences in the number of HLA-DR+ cells were found between the three OLP groups and some OLP-HCV patients showed a significant increase of S-100+ cells in the epithelium compared with iOLP patients. There were no significant differences in either the number of PCNA+ or Ki-67+ cells between the groups. The patients showed similar weak expressions of HSP60 in the three OLP groups. CONCLUSION: The different distributions of the CD8+ cells that could have functionally different roles might be related to the distinct pathogenic mechanisms in the three OLP groups.     

A clinical study of 674 patients with oral lichen planus in China

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease with different clinical presentations that can be classified as reticular, atrophic or erosive. Although OLP is a relatively common disorder, the reports comprising large numbers of OLP patients with specific character are lacking in the literature. The purpose of this paper was to describe the clinical characteristics of OLP in 674 Chinese patients. METHODS: A total of 674 charts of patients with histologically confirmed OLP were collected from Stomatological Hospital of Wuhan University between 1963 and 2003. RESULTS: Of the 674 patients, 65.9% were women and 34.1% were men. The most common clinical presentation was the reticular type (51.3%), and symptomatic OLP was noted in 67.5% of the patients, mainly in those with the erosive form. The erosive presentations showed significantly longer duration, more sites affected and a much greater old patients predominance than reticular or atrophic ones. About 90.9% of the patients had multiple oral sites of involvement and isolated lower lip lichen planus were observed in 60 cases (8.9%) and isolated gingiva lichen in only one case (0.2%). Skin involvement of lichen planus was found in 11.4% of patients. No statistically significant differences could be identified between OLP and diabetes, cardiovascular disease, smoking or alcohol use. Precipitating factors that resulted in an exacerbation of the disease were frequently noted and included foods, stress, dental cusp and poor oral hygiene. The transformation of OLP into malignancy was observed in four patients at sites previously diagnosed by clinical examination as erosive or atrophic lichen planus. CONCLUSIONS: Patients with OLP in China usually present with distinctive clinical morphology and characteristic distribution and few may display lesions with a confusing array of forms mimicking other diseases. A long time follow up is of utmost importance to detect its malignant transformation.     

Tumour necrosis factor‐alpha gene polymorphisms and susceptibility to oral lichen planus

Oral Diseases (2011) 17 , 206–209 Objective: This study is aimed to investigate the association between OLP susceptibility and clinical type in the Thai population and three polymorphisms within the promoter region of the TNF‐α at positions ‐863, ‐308 and ‐238 which have putative functional significances. Materials and Methods: Genomic DNA from 75 Thai patients with OLP and 154 healthy controls were genotyped for TNF‐α polymorphisms – ‐863(rs1800630), ‐308(rs1800629), and ‐238(rs361525) – using polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Results: We found a higher proportion of TNF‐alpha‐308 AA genotype (high producer genotype) among OLP patients (5/75; 6.67%) when compared to healthy controls (1/154; 0.65%; OR = 10.93; 95% CI = 1.21–251.9). For other polymorphisms (‐863 and ‐238), we did not find any significant association with OLP development; this was also the case with haplotype analysis (‐863/‐308/‐238). Conclusion: TNF‐α‐308AA may play a relevant role in the susceptibility and severity of OLP in the Thai population. However, further investigation of this study is needed.     

Expression of TNF-α in oral lichen planus treated with fluocinolone acetonide 0.1%

BACKGROUND: Oral lichen planus (OLP) is a common chronic inflammatory disease involving T cells-mediated immunity. Tumor necrosis factor (TNF)-alpha has been reported to be involved in the disease process. The purpose of this study was to investigate the effect of fluocinolone acetonide in orabase (FAO) 0.1% on the expression of TNF-alpha in patients with OLP. METHODS: Eighteen Thai patients with atrophic or erosive OLP were recruited. Biopsy specimens were taken before and 1 month after treatment with FAO 0.1% and sent for histopathologic examination where they were immunohistochemically stained with antibody to TNF-alpha. Twenty normal mucosa specimens were identically processed. Oral squamous cell carcinoma tissue was used as a positive control for TNF-alpha expression, whereas OLP sections without primary antibody were served as negative control. RESULTS: Sixteen of 18 cases (88.89%) of OLP exhibited positive staining for TNF-alpha. Most of the TNF-alpha was observed in the mononuclear cells. Ten cases (55.56%) of OLP demonstrated TNF-alpha expression in keratinocytes. The number of mononuclear cells positive for TNF-alpha before the treatment with FAO 0.1% in orabase was statistically higher than that after the treatment (P=0.000) and in the normal mucosa (P=0.000). Moreover, the number of mononuclear cells after treatment with FAO 0.1% in orabase was statistically lower than before the treatment (P=0.000). CONCLUSION: Our study exhibited that TNF-alpha may be associated with the immunopathogenesis of OLP in Thai patients and FAO 0.1% had an effect on the reduction of TNF-alpha expression.     

OLP组织中Smad7蛋白的表达研究

目的:检测Smad7蛋白在口腔扁平苔藓(OLP)组织中的表达及分布,探讨其在OLP发病机制中的作用。方法:采用免疫组化SABC法,用Smad7兔抗人多克隆抗体检测60例OLP病变组织及10例正常口腔黏膜组织中Smad7蛋白的表达及分布。结果:Smad7在OLP病变组织有明显的阳性表达,而在正常口腔黏膜组织中阴性表达(P<0.05)。结论:Smad7蛋白在OLP病变组织中高表达,其在OLP发病机制中有重要作用。     

Hepatitis C virus infection in Italian patients with oral lichen planus: a prospective case-control study

To assess the aetiology of liver disease associated with lichen planus, we prospectively studied 70 consecutive newly diagnosed patients with oral lichen planus (OLP) living in northwest Italy (Piemonte) and 70 controls matched for age and sex with other oral keratoses coming from the same district. Twenty-two patients with OLP (3.4%) and 9 controls (12.9%) were found to be affected by chronic liver disease (CLD) ( P =0.014). In sixteen of the 22 OLP patients with CLD the liver disease was hepatitis C virus (HCV)-related. whereas 2 of the 9 controls had a HCV-related CLD ( P =0.016). In another OLP case, liver damage was related to a combination of HCV and alcohol abuse. The prevalence of HCV antibodies in the whole OLP group (27.1%) was significantly higher than in controls (4.3%) ( P =0.014). whereas no difference was found between the OLP and control groups regarding hepatitis B virus markers and other common causes of CLD. HCV infection was more frequently found in patients with erosive OLP (58.8%) than in patients with non-erosive OLP (13.2%) ( P =0.004). Serum HCV-RNA was detected by polymerase chain reaction (RT-PCR) in the majority (93.7%) of OLP patients who had HCV antibodies. Excluding OLP and control patients with HCV markers, there was no difference between the two groups regarding frequency of CLD. Our data show that HCV is probably the main pathogenic factor in liver disease of Italian patients with OLP. and suggests that HCV could be involved in the pathogenesis of OLP.     

口腔扁平苔藓病损区白细胞介素12p40和干扰素-γ的表达及意义

目的 探讨白细胞介素12p40(IL-12p40)及干扰素-γ(IFN-γ)在口腔扁平苔藓(OLP)病损形成及发展中的意义.方法 正常口腔黏膜组织11例,OLP组织43例,采用免疫组织化学Envision二步法检测IL-12p40和IFN-γ的表达情况,分析其与OLP患者临床病理特征的关系.结果 1)OLP组IL-12...     

口腔白斑和扁平苔藓中TSGF的检测

目的 探讨恶性肿瘤特异性生长因（TSGF）的检测对口腔白斑和扁平苔藓的临床意义。方法 对45例鳞癌，12例白斑和32例扁平苔藓患者，测定其血中TSGF的浓度。结果 鳞癌的阳性率为53．33％，白斑为33．33％，扁平苔藓为25．00％。白斑与鳞癌的阳性率无显著性差异（P＞0．05）。扁平苔鲜与鳞癌的阳性率有显著性的差异（P＜0．05）。结论 检测患者血清中TSGF可做为临床预测口腔黏膜病是否有癌变倾向的初步手段。     

口腔扁平苔藓中细胞角蛋白19的表达及意义

目的:探讨细胞角蛋白19(keratin 19,CK19)在口腔扁平苔藓(OLP)中的表达以及其病理意义.方法:采用免疫组化法检测17例OLP和14例正常颊黏膜中CK19的表达,采用RT-PCR方法分别在OLP患者和正常人颊黏膜中比较CK19 mRNA的表达.结果:正常颊黏膜中CK19均在基底细胞胞浆内呈强阳性表达,只有5例(29.4%)OLP基底细胞呈弱阳性表达,其余为阴性表达;RT-PCR结果显示在OLP组织中CK19 mRNA表达显著高于正常黏膜(P＜0.05).结论:CK19的表达下调与颊部OLP黏膜上皮更新能力下降密切相关.     

Topical corticosteroids in association with miconazole and chlorhexidine in the long-term management of atrophic-erosive oral lichen planus: a placebo-controlled and comparative study between clobetasol and fluocinonide

OBJECTIVE: To evaluate the efficacy of a combination of topical corticosteroids with topical antimycotic drugs in the therapy of atrophic-erosive forms of oral lichen planus (OLP). PATIENTS AND METHODS: The study population consisted of 60 patients with OLP subdivided into three groups matched for sex and age. The first group (25 patients) and the second group (24 patients) received respectively 0.05% clobetasol propionate ointment or 0.05% fluocinonide ointment in an adhesive medium (4% hydroxyethyl cellulose gel) plus in each case antimycotic treatment consisting of miconazole gel and 0.12% chlorhexidine mouthwashes. The third group (11 patients), placebo group, received only hydroxyethyl cellulose gel and antimycotic treatment as above. All the treatment regimens were carried out for 6 months. Each patient was examined every 2 months during the 6-month period of active treatment and for a further 6 months of follow-up. Objective and subjective clinical progress was scored and compared between the three groups. Plasma cortisol levels were monitored in half the patients using the topical corticosteroids. RESULTS: All patients treated with clobetasol and 90% of the patients treated with fluocinonide witnessed some improvement, whereas in the placebo group only 20% of patients improved (P < 0.0001 and P = 0.00029, respectively. However, when considering complete responses, only clobetasol gave significantly better results than placebo. Clobetasol resolved 75% of the lesions whereas fluocinonide was effective in 25% of cases and placebo in none. Clobetasol achieved better results statistically than did fluocinonide (P = 0.00442) and placebo (P = 0.00049) whereas there was no statistical difference among fluocinonide and placebo (P = 0.140). Similar results were obtained for symptoms. Both drugs were shown to be effective in the treatment of erosive lesions, but clobetasol was considerably more efficacious than fluocinonide in the atrophic areas (75% vs 25% of total response, respectively) (P = 0.00442). None of the treated patients contracted oropharyngeal candidiasis. After 6 months of follow-up, 65% of the clobetasol-treated group and 55% of the fluocinonide group were stable. Estimation of plasma cortisol levels showed no significant systemic adverse effects of clobetasol or fluocinonide. CONCLUSIONS: Our results suggest that a very potent topical corticosteroid such as clobetasol may control OLP in most cases, with no significant adrenal suppression or adverse effects. Moreover, a concomitant antimycotic treatment with miconazole gel and chlorhexidine mouthwashes is a useful and safe prophylaxis against oropharyngeal candidiasis.