Oral lichen planus and lichenoid reactions: etiopathogenesis, diagnosis, management and malignant transformation

Lichen planus, a chronic autoimmune, mucocutaneous disease affects the oral mucosa (oral lichen planus or OLP) besides the skin, genital mucosa, scalp and nails. An immune mediated pathogenesis is recognized in lichen planus although the exact etiology is unknown. The disease most commonly affects middle-aged females. Oral lichenoid reactions (OLR) which are considered variants of OLP, may be regarded as a disease by itself or as an exacerbation of an existing OLP, by the presence of medication (lichenoid drug reactions) or dental materials (contact hypersensitivity). OLP usually presents as white striations (Wickham's striae), white papules, white plaque, erythema, erosions or blisters. Diagnosis of OLP is established either by clinical examination only or by clinical examination with histopathologic confirmation. Direct immunofluorescence examination is only used as an adjunct to the above method of diagnosis and to rule out specific autoimmune diseases such as pemphigus and pemphigoid. Histopathologic features of OLP and OLR are similar with suggestions of certain discriminatory features by some authors. Topical corticosteroids are the treatment of choice for OLP although several other medications have been studied including retinoids, tacrolimus, cyclosporine and photodynamic therapy. Certain OLP undergo malignant transformation and the exact incidence and mechanisms are still controversial. In this paper, etiopathogenesis, diagnosis, management and malignant transformation of OLP and OLR have been reviewed.     

细胞自噬在口腔扁平苔藓恶变中作用的研究进展

口腔扁平苔藓(OLP)是一种常见的口腔黏膜炎症性疾病,易复发并存在恶变的可能,具体的病因和发病机制尚不清楚。细胞自噬是真核细胞生物中高度保守的生命现象,作为程序性细胞死亡的方式之一,在维持细胞内环境的稳态方面起到重要作用。目前关于细胞自噬与OLP发病及恶变的关系的相关报道较少,本文就细胞自噬与口腔扁平苔藓的联系作一探讨。     

Pathogenesis of oral lichen planus – a review

J Oral Pathol Med (2010) 39 : 729–734 Oral lichen planus (OLP) is a T‐cell‐mediated chronic inflammatory oral mucosal disease of unknown etiology. OLP presents as white striations, white papules, white plaques, erythema, erosions, or blisters affecting predominantly the buccal mucosa, tongue and gingiva. Both antigen‐specific and non‐specific mechanisms are hypothesized to be involved in the pathogenesis of oral lichen planus (OLP). Antigen‐specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen‐specific keratinocyte killing by CD8⁺ cytotoxic T cells. Non‐specific mechanisms include mast cell degranulation and matrix metalloproteinase activation in OLP lesions. These mechanisms may combine to cause T cell accumulation in the superficial lamina propria, basement membrane disruption, intra‐epithelial T cell migration and keratinocyte apoptosis in OLP. The various hypotheses proposed for pathogenesis of oral lichen planus are discussed in this review.     

The immunopathogenesis of oral lichen planus—Is there a role for mucosal associated invariant T cells?

Oral lichen planus (OLP) is a chronic, T‐cell‐mediated, immune condition of unknown cause. OLP may present with painful symptoms requiring treatment, as well as lesions outside the oral cavity. It is likely that what initiates the OLP disease process is a complex interaction of host susceptibility and environmental triggers. While it is possible that OLP represents a true autoimmune condition against an epithelial autoantigen, the mechanisms that lead to this immune dysregulation are still poorly understood. In this review article, we discuss current concepts relating to the immunopathogenesis of OLP, as well as the potential contributory roles the oral microbiota and mucosal‐associated invariant T (MAIT) cells.     

Detection of antibodies against p63 and p73 isoforms in sera from patients diagnosed with oral lichen planus

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease of oral mucosa. Despite numerous publications and intense research, the etiology of OLP is still unknown, however, autoimmunity as a possible causative factor has been discussed. METHODS: In the present study sera from 20 patients clinically and histologically diagnosed with OLP were analyzed for antibodies directed toward p53, p63, and p73 using Western blot. RESULTS: Sera from two patients reacted with all six p63 isoforms, and one also with p73. The strongest reaction was noted against the TAp63beta protein, which is the most potent transactivator of all p63 proteins and is implicated in the differentiation of stratified epithelia. CONCLUSIONS: This is the first demonstration of antibodies directed against all p63 and some p73 isoforms in sera from patients diagnosed with OLP.     

Immune mechanisms in oral lichen planus

Although we still don't know the cause, there has been much research into the immune and pathological mechanisms that underlie oral lichen planus (OLP) and it is now possible to piece together a much clearer picture of the disease process. There is consensus that in OLP there is chronic, cell-mediated, immune damage to basal keratinocytes in the oral mucosa that are recognized as being antigenically foreign or altered. In most cases, however, the identity of the target antigen remains unknown. It is likely that cytokines released by the affected keratinocytes, and the associated inflammatory infiltrate, play a key role in the selective recruitment of the T-cell-dominated infiltrate that characterizes OLP, through their ability to induce adhesion molecule expression as well as further cytokine and chemokine release. In susceptible individuals, chronic presentation of antigen by basal keratinocytes may perpetuate the condition and direct cell-mediated immune damage on the keratinocytes.     

Gene polymorphism in oral lichen planus

口腔扁平苔藓（OLP）是一种常见的口腔黏膜慢性炎症性疾病,成年人患病率为0.5%~2%。OLP的病因和发病机制尚不明确,研究显示其发病可能与某些基因的遗传多态性相关,目前研究较多的有肿瘤坏死因子、干扰素、白细胞介素、酶类、受体等基因家族。本文就基因多态性与口腔扁平苔藓的相关性进行综述。     

Oral lichen planus. A review

Lichen planus is a unique but common inflammatory disorder that affects the skin, mucous membranes, nails and hair. Oral lichen planus (OLP) is among the more common mucosal conditions a clinician is likely to encounter in his or her practice. The etiology is unknown. Immunofluorescence studies have provided some insight into a proposed immunopathogenesis. Buccal mucosa, tongue and gingiva are more commonly involved. The question of malignant transformation of OLP remains controversial. Management of lichen planus can be challenging and discouraging for both the patient and physician. Treatment options should be assessed for attendant risks and benefits, and tailored to the extent and severity of disease.     

Immunohistopathological study of the oral lichenoid lesions of chronic GVHD

BACKGROUND: Chronic graft-vs.-host disease (cGVHD) is a common and serious complication after bone marrow transplantation (BMT). However, the detailed process of oral lichenoid lesions of cGVHD is still unknown. Therefore, we investigated the immunohistopathological features of cGVHD compared with oral lichen planus (OLP) and healthy controls. METHODS: Nineteen allogenic BMT recipients with a histopathological diagnosis of cGVHD were investigated. We investigated the immunohistopathological features of cGVHD compared with OLP and healthy controls. RESULTS: Immunohistopathological features showed that the infiltrations of CD4-positive T cells of cGVHD and OLP were significantly larger than those of the normal oral mucosa (P < 0.005). A larger number of CD8-positive T cells was infiltrated in cGVHD and OLP compared with the normal oral mucosa (P < 0.001). The difference in the number of CD4- and CD8-positive T cells between cGVHD and OLP was not significant. The infiltrations of Langerhans cells (CD1a) in cGVHD and OLP were significantly larger than those in the normal oral mucosa (P < 0.005). The difference in the number of Langerhans cells between cGVHD and OLP was not significant. CD68-positive macrophages were more frequently seen in cGVHD and OLP than in the normal oral mucosa (P < 0.0001). The difference in the number of CD68-positive macrophages between cGVHD and OLP was not significant. CONCLUSIONS: It is suggested that Langerhans cells and CD8-positive T cell may play a major role in the pathogenesis of the oral lichenoid lesions of cGVHD, and the immune response was inducted in OLP as well as the oral lichenoid lesion of cGVHD in this study.     

血管生成与口腔扁平苔藓关系的研究进展

［摘要］ 口腔扁平苔藓是一种常见口腔黏膜慢性炎性疾病,但关于口腔扁平苔藓的病因机制仍不明确。已知血管生成参与到很多免疫介导的慢性炎症疾病中。近年来已有很多研究关注血管生成在口腔扁平苔藓发生发展中的作用,因此本文就血管生成在口腔扁平苔藓发生发展及其癌变和治疗中的作用进行综述。     

Immune mechanisms in oral lichen planus

Although we still don't know the cause, there has been much research into the immune and pathological mechanisms that underlie oral lichen planus (OLP) and it is now possible to piece together a much clearer picture of the disease process. There is consensus that in OLP there is chronic, cell-mediated, immune damage to basal keratinocytes in the oral mucosa that are recognized as being antigenically foreign or altered. In most cases, however, the identity of the target antigen remains unknown. It is likely that cytokines released by the affected keratinocytes, and the associated inflammatory infiltrate, play a key role in the selective recruitment of the T-cell-dominated infiltrate that characterizes OLP, through their ability to induce adhesion molecule expression as well as further cytokine and chemokine release. In susceptible individuals, chronic presentation of antigen by basal keratinocytes may perpetuate the condition and direct cell-mediated immune damage on the keratinocytes.     

口腔扁平苔藓免疫学因素的研究现状

口腔扁平苔藓(OLP)是一种严重影响患者身心健康的发生于口腔黏膜的非传染性炎症性疾病.OLP的病因尚不明确,可能与多种因素有关.目前的研究表明,OLP的发病与免疫因素密切相关,它是一种以T淋巴细胞介导的免疫应答为特征的慢性疾病.抗原特异性机制和非特异性机制可能参与OLP的免疫过程.首先由树突状细胞摄取、处理未知抗原触发...     

口腔白斑、扁平苔藓细胞凋亡相关蛋白Bax表达的研究

目的 :探讨口腔白斑、扁平苔藓的癌变机理及发病机制。方法 :采用免疫组化法检测 10例正常口腔黏膜上皮 ,18例扁平苔藓 ,2 3例白斑 ,2 2例口腔鳞癌上皮组织中凋亡相关蛋白Bax的表达水平。结果 :白斑中上皮单纯增生、轻度、中度不典型增生和低分化鳞癌及糜烂型扁平苔藓的Bax蛋白显过度表达 ,与正常口腔黏膜上皮相比有显著性差异。结论 :Bax参与了口腔白斑癌变的早期过程 ,Bax的表达水平可作为临床监测白斑癌变倾向的参考指标。扁平苔藓的发病机制可能与细胞免疫亢进刺激Bax过度表达诱导角朊细胞凋亡有关 ,扁平苔藓的癌变机理有待进一步研究     

Composition of hemidesmosomes in basal keratinocytes of normal buccal mucosa and oral lichen planus

Oral lichen planus (OLP) is a chronic inflammatory disease displaying ultrastructural disturbances in epithelial hemidesmosomes. The expression of several key hemidesmosomal components in OLP as well as in normal buccal mucosa is, however, unknown. The aim of the study was therefore to examine intracellular and extracellular components involved in hemidesmosomal attachment, in OLP (n = 20) and in normal buccal mucosa (n = 10), by immunofluorescence. In normal buccal mucosa, laminin-α3γ2, integrin-α6β4, CD151, collagen α-1(XVII) chain, and dystonin showed linear expression along the basal membrane, indicating the presence of type I hemidesmosomes. Plectin stained most epithelial cell membranes and remained unphosphorylated at S4642. In OLP, most hemidesmosomal molecules examined showed disturbed expression consisting of discontinuous increases, apicolateral location, and/or intracellular accumulation. Plectin showed S4642-phosphorylation at the basement membrane, and deposits of laminin-α3 and laminin-γ2 were found within the connective tissue. The disturbed expression of hemidesmosomal proteins in OLP indicates deficient attachment of the basal cell layer, which can contribute to detachment and cell death of basal keratinocytes seen in the disease.     

口腔黏膜扁平苔藓患者口腔黏膜组织中cyclin D1,ki-67及凋亡的表达研究

目的　检测口腔黏膜扁平苔藓 (OLP)患者口腔黏膜上皮凋亡增殖状况及细胞周期调控蛋白表达水平的变化 ,探讨OLP发病机制。方法　采用甲基绿 -派诺宁法及免疫组化SABC法分别检测 30例OLP患者及 2 0例正常对照者口腔黏膜组织的凋亡情况及细胞周期蛋白 (cyclinD1)、增殖细胞核抗原 (ki 6 7)的表达并进行细胞计数及统计学分析。结果　OLP组与对照组凋亡、ki 6 7、cyclinD1表达阳性率差异有显著性 (P <0 .0 5 ) ;与凋亡呈正相关。结论　OLP病变中 ,部分细胞受损进入凋亡性细胞死亡 ,同时发生了细胞周期紊乱、细胞增殖     

Mast cell/T cell interactions in oral lichen planus

Lichen planus is a disorder characterized by lesions of the skin and oral mucous membranes. Although many patients have involvement of both skin and oral mucosa at some stage during the progress of the disease, a larger group has oral involvement alone. It has been reported that oral lichen planus (OLP) affects one to two percent of the general population and has the potential for malignant transformation in some cases (1, 2). Like many chronic inflammatory skin diseases, it often persists for many years. Numerous disorders may be associated with OLP such as graft-vs.-host disease and Hepatitis C virus infection (3), however, it is unclear how such diverse influences elicit the disease and indeed whether they are identical to idiopathic OLP. Available evidence supports the view that OLP is a cell-mediated immunological response to an induced antigenic change in the mucosa (4-6). Studies of the immunopathogenesis of OLP aim to provide specific novel treatments as well as contributing to our understanding of other cell-mediated inflammatory diseases. In this paper, the interactions between mast cells and T cells are explored from the standpoint of immune regulation. From these data, a unifying hypothesis for the immunopathogenesis of OLP is then developed and presented.     

Immune mechanisms in oral lichen planus

Oral lichen planus (OLP) is a T cell-mediated inflammatory disease of the oral mucosa that has been extensively researched over many years but as yet the mechanisms of pathogenesis are still not fully understood. Whilst the specific aetiological factors driving OLP remain ambiguous, evidence points to the development of a chronic, dysregulated immune response to OLP-mediating antigens presented by innate immune cells and oral keratinocytes leading to increased cytokine, chemokine and adhesion molecule expression. These molecules recruit T cells and mast cells to the diseased site and orchestrate a complex interplay between cells that culminates in keratinocyte cell death, mucosal basement membrane destruction and long-term chronicity of the disease. The main lymphocytes involved are thought to be CD8+ cytotoxic and CD4+ Th1 polarised T cells although recent evidence indicates the involvement of other Th subsets such as Th9, Th17 and Tregs, suggesting that a more complex immune cell relationship exists during the disease process. This review provides an overview of the immune mechanisms at play in OLP pathogenesis with particular emphasis on the role of the different Th subsets and how these recent discoveries may guide research towards identifying potential therapeutic targets.     

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口腔扁平苔藓(oral lichen planus,OLP)是一种常见的口腔黏膜慢性炎性疾病,WHO将其列入潜在恶性病变(potentially malignant disorders)的范畴。有关OLP癌变的研究目前主要集中在流行病学调查、癌变危险性预测、癌变机制、化学预防等方面,而对其是否癌变近年产生疑问和争议。本文就OLP癌变的相关研究进展进行综述。     

Oral lichen planus: A retrospective study of 633 patients from Bucharest,Romania

Objective: In this retrospective study, patients’ medical records were reviewed to investigate the profiles of 633 OLP cases in a group of Romania. Material and Methods: In this retrospective study, the following clinical data were obtained from the medical charts of patients: gender, age, clinical presentation of OLP, site affected, presence of symptoms, extraoral manifestations of lichen planus, presence of systemic diseases, and history of medications. Results: Most (78.67%) OLP patients were female and the mean age at presentation was 52 years. The white type of the disease (reticular/papular/plaque lesions) was the main form encountered in this sample (48.97%). Among patients with available hepatitis C virus test results, 9.6% were serum-positive. OLP was associated with gallbladder disease (i.e. cholecystitis, cholelithiasis) in 19% of patients. Six patients (0.95%) developed squamous cell carcinoma at a site with confirmed OLP lesions. Conclusions: To the best of our knowledge, no similar study has been conducted in a Romanian population. The present investigation revealed the predominance of OLP among middle-aged white women and the prevalence of bilateral involvement of the buccal mucosa with reticular white lesions. Anti-HCV circulating antibodies were more common in patients with OLP than in the general population and, notably, OLP was associated with gallbladder disease (cholecystitis, cholelithiasis) in 19% of patients. Key words:Oral lichen planus, oral mucosal diseases, retrospective study.     

端粒酶逆转录酶mRNA在OLP和OSCC中的表达

目的：探讨端粒酶逆转录酶（TERT）mRNA在口腔扁平苔藓（OLP）和口腔鳞状细胞癌（OSCC）中的表达以及在OLP癌变过程中的作用。方法：应用mRNA原位杂交法对正常口腔黏膜12例,非糜烂型OLP20例,糜烂型OLP20例及OSCC20例,进行hTERTmRNA的检测。结果：正常口腔黏膜、非糜烂型OLP、糜烂型OLP及OSCC中hTERTmRNA阳性表达率分别为8.33％（1／12）、15％（3／20）、45％（9／20）、80％（16／20）。其中,除正常口腔黏膜与非糜烂型OLP中hTERT mRNA阳性率无显著性差异外,其余各组间均有显著性差异（P〈0.05）。而且,正常口腔黏膜与非糜烂型OLP的hTERT mRNA染色强度明显低于糜烂型OLP及OSCC（P〈0.05）。结论：hTERT mRNA可能在糜烂型OLP的癌变过程起着一定的作用。