Probiotics: A non-conventional therapy for oral lichen planus

Oral lichen planus (OLP) is a common T-cell mediated chronic inflammatory disease. Although the etiology is still unclear, present studies suggest that the composition of the oral microbiota and psychological problems are implicated in the etiology of OLP. The pathogenesis of OLP includes mainly antigen-specific and non-specific mechanisms. Antigen-specific mechanisms involve T-cell activation following antigen presentation and apoptosis of basal keratinocytes triggered by CD8⁺ cytotoxic T cells, while non-specific mechanisms consist of matrix metalloproteinase over-expression and mast cell degranulation in OLP lesions. Therapies for OLP are mainly used to control symptoms and a specific cure is not yet available. Probiotics are capable of modulating the immune response in a strain-specific manner. They are able to alleviate microbial infection and suppress T-cell activation, infiltration and proliferation, as well as suppress keratinocyte apoptosis and nuclear factor-kappa B signaling. Furthermore, probiotics can also modulate the production of inflammatory cytokines and microRNAs, inhibit MMP-9 expression and mast cell degranulation, and ameliorate psychological problems, all of which are involved in the pathogenesis of OLP. Therefore, we hypothesize that probiotics may be applicable to OLP as a safe, inexpensive and non-conventional therapy.     

Biologics,an alternative therapeutic approach for oral lichen planus

J Oral Pathol Med (2011) 40 : 521–524 Oral lichen planus (OLP) is generally accepted as a chronic and T‐cell‐mediated autoimmune disease, whose immunopathogenesis may involve antigen presentation, T‐cell activation and migration as well as, possibly, tumor necrosis factor‐alpha (TNF‐α)‐induced keratinocytes apoptosis. However, present treatment options for OLP are far from being satisfactory. Recent advances in understanding the pathogenesis of OLP, progress in biologics, and the success of biologic therapies in OLP indicate that biologic agents are facing expanding indications in OLP. In this review, we mainly discuss the role of T cells in the pathogenesis of OLP and several biologic therapies that directly and/or indirectly target T cells to treat OLP.     

Role of distinct CD4+ T helper subset in pathogenesis of oral lichen planus

Oral lichen planus (OLP) is one of the most common chronic inflammatory oral mucosal diseases with T‐cell‐mediated immune pathogenesis. In subepithelial and lamina propria of OLP local lesions, the presence of CD4⁺ T helper (CD4⁺ Th) cells appeared as the major lymphocytes. These CD4⁺ T lymphocytes can differentiate into distinct Th cell types such as Th1, Th2, Treg, Th17, Th22, Th9, and Tfh within the context of certain cytokines environment. Growing evidence indicated that Th1/Th2 imbalance may greatly participate into the cytokine network of OLP immunopathology. In addition, Th1/Th2 imbalance can be regulated by the Treg subset and also greatly influenced by the emerging novel CD4⁺ Th subset Th17. Furthermore, the presence of novel subsets Th22, Th9 and Tfh in OLP patients is yet to be clarified. All these Th subsets and their specific cytokines may play a critical role in determining the character, extent and duration of immune responses in OLP pathogenesis. Therefore, we review the roles of distinct CD4⁺ Th subsets and their signature cytokines in determining disease severity and susceptibility of OLP and also reveal the novel therapeutic strategies based on T lymphocytes subsets in OLP treatment.     

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.     

DNA ploidy in oral lichen planus,determined by image cytometry

J Oral Pathol Med (2010) 39 : 206–211 Background: The objective of this study was to use image cytometry to determine the degree and frequency of DNA ploidy in biopsies of reticular and atrophic‐erosive oral lichen planus and to analyze 14 karyometric measurements of the nuclei of epithelial cells from each specimen. Methods: A total of 40 slides were analyzed, each of them representing one biopsy of one oral lichen planus (OLP) lesion from each one of the 40 patients (cases) studied. Specimens were embedded in paraffin and comprised 20 slides of reticular oral lichen planus (group R) and 20 slides of atrophic‐erosive oral lichen planus (group AE). Results: Group R, the reticular lichen samples, had 18 diploid cases and two aneuploid cases. Group AE, the atrophic‐erosive lichen samples, had 10 diploid cases, one tetraploid case, and nine aneuploid cases. Of the 14 karyometric measurements of the nuclei of OLP epithelial cells analyzed, the group R mean values for mean density and minimum density were significantly greater than the group AE mean values, and mean roundness in group AE was significantly greater than in group R (t‐test: P < 0.05). Conclusions: The most common degree of DNA ploidy in OLP lesions was diploidy. Comparing the two groups (chi‐square test of association P = 0.021) demonstrated that diploidy was associated with the reticular clinical form of OLP, while aneuploidy was associated with the atrophic‐erosive clinical form of oral lichen planus.     

Altered microRNA expression profile with miR-27b down-regulation correlated with disease activity of oral lichen planus

Oral Diseases (2012) 18 , 265–270 Background: Increasing evidence indicates that microRNAs (miRNAs) play a vital role in the pathogenesis of inflammatory and autoimmune diseases. The objective of this study was to investigate the altered miRNA expression profile in patients with oral lichen planus (OLP) and determine the miR‐27b expression. Methods: We compared miRNA expression patterns in oral biopsy specimens from patients with OLP (n = 3) with those from normal controls (n = 3) using microarray technology. We further assessed the miR‐27b expression in specimens from patients with OLP (n = 53) against controls (n = 34) using real‐time quantitative PCR (RT‐QPCR), and miR‐27b expression in specimens from patients with OLP (n = 15) against controls (n = 12) using in situ hybridization (ISH). Results: Using microarray analysis, a total of 46 differentially expressed miRNAs with more than 2‐fold change were identified, including 8 up‐regulated and 38 down‐regulated miRNAs. Both RT‐QPCR and ISH analyses revealed that miR‐27b was significantly down‐regulated in OLP tissue, and miR‐27b expression was even more suppressed in atrophic‐erosive OLP than in reticular OLP. In addition, miR‐27b was found to be expressed in the epithelial keratinocyte layer of both normal and OLP tissues. Conclusion: These data indicate that miRNAs may be the novel candidate biomarkers for the implication of miRNAs in the pathogenesis of OLP.     

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.     

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.     

The microbiology of oral lichen planus: Is microbial infection the cause of oral lichen planus?

Oral lichen planus (OLP) is a variant of lichen planus (LP), a common chronic mucocutaneous inflammatory disease. Cutaneous lesions of LP are self‐limiting, but OLP lesions are non‐remissive, alternating periods of exacerbation and quiescence, and only symptomatic treatments exist for OLP. The precise etiology and pathogenesis of OLP are hardly understood, which is a major obstacle to the development of new therapeutics for this disease. OLP is considered a T‐cell‐mediated inflammatory disease. Although various antigens have been considered, what actually triggers the inflammatory response of T cells is unknown. Suggested predisposing factors include genetic factors, stress, trauma, and infection. The aim of this review was to determine whether microbial infection can cause OLP. We first reviewed the association between OLP and microbial factors, including viral, fungal, and bacterial infections. In addition, each microbial factor associated with OLP was assessed by modified guidelines of Fredricks and Relman to determine whether it establishes a causal relationship. In conclusion, no microbial factor yet fulfills the guidelines to establish the causality of OLP. By focusing on the unclarified issues, however, the potential roles of microbial factors in the pathogenesis of OLP will be soon elucidated.     

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??Oral lichen planus ??OLP?? is a common oral mucosal chronic disease??the prevalence rate is 0.1% to 4.0% of the general population??and it occurs mostly in women aged 30 to 60. OLP pathogenesis has not yet been clear??currently it is considered as a class of T cell-mediated autoimmune diseases. It is related to genetics??drug??infection??oral irritation and mental factors. The clinical manifestations are white or gray textures??pimples??plaques??etc.??which may be accompanied by congestion??erosion??blisters and other lesions. Because 1.1% of OLP will develop into oral squamous cell carcinoma??World Health Organization lists it as a potentially malignant disease??and clinicians should pay attention accordingly. Here we summarize the pathogenesis??diagnosis and treatment of OLP.     

TLR4 and TLR9 are induced in oral lichen planus

J Oral Pathol Med (2012) 41 : 741–747 Background: The role of Toll‐like receptors (TLRs) has been elucidated in many human infectious, autoimmune and neoplastic diseases. Previously, TLR2 and TLR4 expression in oral lichen planus (OLP) was described. The aim of our study was to examine expression patterns of TLR4 and TLR9 in normal oral mucosa and OLP and describe the effect of topical tacrolimus treatment on the expression of TLR4 and TLR9 in OLP. Methods: Toll‐like receptor 4 and TLR9 expression was analysed by immunohistochemistry in five samples of normal oral mucosa and 50 samples of OLP (31 representing clinically white and 19 clinically erythematous/erosive lesions). We evaluated also the effect of topical tacrolimus on TLR4 and TLR9 expression in a patient with OLP. Results: Toll‐like receptor 4 and TLR9 expression was increased in OLP epithelium compared with normal epithelium (P < 0.001); no significant difference between the two clinical types of OLP was observed. TLR9 expression was strongest in the superficial layer of the epithelium (P < 0.001), while the expression of TLR4 was strongest in the basal layer (P < 0.001). Treatment of OLP lesions with topical tacrolimus resulted in clinical improvement but had no effect on TLR expression levels. Conclusions: Toll‐like receptor 4 and TLR9 are induced in OLP; our finding confirms the results of a previous study. TLR4 and TLR9 may play a part in the pathogenesis of OLP. Further studies are needed to dissect the definitive role of TLRs in OLP pathogenesis and progression and to determine the effect of tacrolimus on the function of TLRs.     

Langerin-expressing and CD83-expressing cells in oral lichen planus lesions

Objective. Dendritic Langerhans cells (LCs) have been attributed a role in the pathogenesis of lichen planus as autoantigen-presenting cells initiating expansion of autoreactive T cells. Langerin and CD83, which are cell molecules expressed on LCs, are associated with antigen presentation. The present study examined expression of Langerin and CD83 molecules on LCs in patients with oral lichen planus (OLP). Material and methods. Biopsies were obtained from seven patients with OLP. Oral mucosa from seven healthy subjects served as controls. Monoclonal antibodies (mAbs) were used in standard immunohistochemical procedures to visualize CD1a-, Langerin-, and CD83-molecule-expressing cells. Results. CD1a+ and Langerin+ cells were found in significantly higher frequencies in OLP epithelium compared with healthy oral epithelium (p<0.01 and p<0.05, respectively); however, the frequency of CD83+ cells did not differ (p>0.05). The connective tissue in OLP lesions showed significantly higher frequencies of CD1a+, Langerin+, and CD83+ cells compared with healthy connective tissue (p<0.01, p<0.01, and p<0.05). CD1a+ and Langerin+ cells in OLP and healthy epithelium had a dendritic morphology. Conclusions. The study shows increased numbers of CD1a- and Langerin-expressing LCs in OLP compared with healthy controls. In the connective tissue, CD83+ cells with dendritic morphology were localized to regions of lymphocyte clusters. The presence of CD83+ dendritic cells in areas of lymphocyte clusters in the connective tissue of OLP lesions indicates the possibility of ongoing autoantigen presentation.     

Expression of TGF-beta1, Smad7 and cell apoptosis in epithelium of oral lichen planus

OBJECTIVE: To examine the expression of TGF-beta1, Smad7 and cell apoptosis in oral lichen planus (OLP) and to evaluate the possible pathogenesis of oral lichen planus. METHODS: Immunohistochemical technique was used to study the expression of TGF-beta1 and Smad7 in the epithelia cells of 17 OLP cases and 7 normal oral mucosa (NOM). TUNEL was used for detecting the cell apoptosis in 17 OLP cases and 7 NOM. RESULTS: TGF-beta1 was moderately positive in the epithelia cells of OLP. All the epithelia cells in OLP showed strong cytoplasmic staining. The expression of TGF-beta1 and Smad7 were significantly increased in OLP compared with that in NOM (P < 0.05). Cell apoptotic index (AI) was remarkably increased in epithelia cells in OLP cases, and the cell apoptosis was localized in basal and suprabasal epithelial layers. There was a positive correlation between TGF-beta1 expression and cell apoptosis in the epithelia of OLP (r = 0.69, P <0.05). CONCLUSIONS: High expression of TGF-beta1 and Smad7 in the epithelia of OLP suggests that TGF-beta1-Smad7 signal pathway was disturbed in oral lichen planus. The imbalance of TGF-beta1-Smad7 pathway may contribute to the mechanisms of cell apoptosis of epithelial cells in OLP.     

Oral lichen planus and chronic junctional stomatitis: differences in lymphocyte subpopulations

Objective. Oral lichen planus (OLP) is an oral counterpart or oral manifestation of the common skin disease lichen planus. Chronic junctional stomatitis (CJS) is a relatively unknown condition characterized by a stromal lymphocyte infiltrate, which is also a diagnostic feature of OLP. The differential diagnosis of OLP and CJS is unclear and they have been suggested to represent variants of the same disease. Material and methods. To investigate possible differences in lymphocyte (sub)populations between these two conditions, we immunostained 10 OLP and 10 CJS specimens for CD1-a, and the lymphocyte markers, CD3, CD4, CD5, CD8, and CD20. We scored the staining results by a four-step grading system and used the Fisher exact test to analyze them statistically. Results. The proportional amount of (CD20 positive) B lymphocytes was higher in CJS than in OLP and the predominance of CD4 positive T lymphocytes over CD8 positive T lymphocytes was stronger in OLP than in CJS. The differences were statistically significant. Conclusion. The results reflect differences in the lymphatic infiltrate between OLP and CJS. Their significance needs further investigation.     

Perforin and granzyme B involvement in oral lesions of lichen planus and chronic GVHD

J Oral Pathol Med (2010) 39 : 741–746 Background: Oral lesions of lichen planus and chronic graft‐vs.‐host disease (cGVHD) have similar clinical and histological features, but distinct etiology. Apoptosis induced by cytotoxic T lymphocyte has been proposed as a mechanism of keratinocytes death. Cytotoxicity can be mediated by granules containing granzyme B and perforin. Since common features can reflect similarities in immunological mechanisms, we studied the role of those molecules in both diseases. Methods: We analyzed 29 cases of oral lichen planus and 27 of oral cGVHD. The sections were studied on H&E, perforin and granzyme B staining. Results: The total means (epithelium plus connective tissue number) of the granzyme B‐ and perforin‐positive cells were significantly higher in cGVHD than in oral lichen planus lesions (P < 0.05). Also, it was found that the higher the number of perforin+ cells, the higher the number of granzyme‐B+ cells in the epithelium and in the connective tissue for both groups (P < 0.05). In oral lichen planus, the number of single apoptotic bodies had a positive correlation with connective tissue granzyme immunostaining and a negative correlation with perforin (P < 0.01). On the contrary, in oral cGVHD, the number of apoptotic body clusters presented a positive correlation with connective tissue perforin (P < 0.01). Conclusions: Our findings indicate that apoptosis in oral lichen planus seems to be correlated with granzyme B release, while in oral cGVHD, perforin seems to be more important. Although these diseases present clinical and histological similarities, subtle differences seem to exist in their pathogenetic mechanisms.     

Oral lichen planus and dental hygiene: a case report

To cite this article:
Int J Dent Hygiene 9 , 2011; 163–166
DOI: 10.1111/j.1601‐5037.2010.00454.x
Scattarella A, Petruzzi M, Ballini A, Grassi FR, Nardi GM. Oral lichen planus and dental hygiene: a case report. Abstract: Background: The presence of atrophic‐erosive lesions among gingival tissues makes oral hygiene procedures difficult for several reasons. Plaque control and rigorous oral hygiene are a fundamental requisite for the treatment of any oromucosal disease. Case report: A patient suffering from a mixed atrophic‐erosive form of oral lichen planus (OLP), with serious gingival involvement, was also treated with the topical application of clobetasol propionate 0.05% using gingival trays. The highest hygiene standards of both patient and trays were of fundamental importance. Discussion: The management of the patient suffering from gingival atrophic‐erosive OLP requires the synergic treatment of both dentist and dental hygienist, whose contribution supports the corticosteroid and/or immunosuppressive treatment.     

Oral lichen planus. A review

Lichen planus is a mucocutaneous disease of unknown etiology which, according to current knowledge, may represent a cell-mediated immunological response to induced antigenic changes in the skin and mucosa. Oral lichen planus (OLP) is a disease of adulthood and as one of the most prevalent diseases affecting the oral mucosa it has been the subject of intensive research during recent years. Ultrastructural and immunohistochemical studies particularly dealing with the subepithelial inflammatory cell infiltrate and its relations to epithelial pathology, the basal cell region and the intraepithelial antigen presenting Langerhans' cells, have contributed vastly to our knowledge of the pathogenesis of OLP. However, the treatment of OLP still remains largely symptomatic because many as yet unknown factors, active in the disease process, still remain to be elucidated.     

Oral lichen planus and the p53 family: what do we know?

J Oral Pathol Med (2011) 40 : 281–285 Oral lichen planus (OLP) is a relatively common chronic disease of the oral mucosa for which the aetiopathogenesis is not fully understood. It mainly affects middle aged and elderly. The finding of autoantibodies against p63, a member of the p53 family, is a strong indication of autoimmunity as a causative or contributing factor. The WHO classified OLP as a potentially malignant disorder, but still there is an ongoing debate in the literature on this subject. The TP53 gene encodes a tumour suppressor protein that is involved in induction of cell‐cycle arrest or apoptosis of DNA‐damaged cells. The p63 gene encodes six different proteins that are crucial for formation of the oral mucosa and skin. The coordinated stabilization of p53 and decreased expression of p63 seen in OLP cause induction of apoptosis enabling removal of DNA‐damaged cells. In view of the complexity of cancerogenesis, no firm statement can at present be made about the relevance of the observed relationship between p53 and p63 and the possible malignant transformation of OLP.     

Number V Oral lichen planus: clinical features and management

Oral lichen planus (OLP) is a relatively common chronic inflammatory disorder affecting stratified squamous epithelia. Whereas in the majority of instances, cutaneous lesions of lichen planus (LP) are self-limiting and cause itching, oral lesions in OLP are chronic, rarely undergo spontaneous remission, are potentially premalignant and are often a source of morbidity. Current data suggest that OLP is a T cell-mediated autoimmune disease in which auto-cytotoxic CD8+ T cells trigger apoptosis of oral epithelial cells. The characteristic clinical aspects of OLP may be sufficient to make a correct diagnosis if there are classic skin lesions present. An oral biopsy with histopathologic study is recommended to confirm the clinical diagnosis and mainly to exclude dysplasia and malignancy. The most commonly employed and useful agents for the treatment of lichen planus (LP) are topical corticosteroids but other newer agents are available.     

口腔扁平苔藓与系统性疾病的关系

口腔扁平苔藓（oral lichen planus,OLP）是一种慢性炎症性皮肤黏膜病,病因复杂,确切病因目前尚不清楚。随着研究的进展,越来越多的研究发现,OLP与高血压、糖尿病、慢性肝病以及甲状腺疾病等一些系统性疾病关系密切。现结合国内外文献就此方面内容做一论述。