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 frequency of Candida in oral lichen planus

ABSTRACT – Histologic material of typical lichen planus lesions from 43 patients was studied. Two sections of each specimen were stained with hematoxylin-eosin and 10 sections by the PAS method. Only 1 of 43 biopsies was invaded by Candida, and hyphae were present in all of the 10 PAS-stained sections of this case. The results show that oral lichen planus has a considerably lesser susceptibility than oral leukoplakia to invasion by Candida albicans.     

MicroRNA‐137 promoter methylation in oral lichen planus and oral squamous cell carcinoma

Oral lichen planus (OLP) is a common oral mucosal disease, which is generally considered a potentially malignant lesion. To identify efficiently prognostic biomarker, we investigated the microRNA‐137 (miR‐137) promoter methylation in OLP and compared with the samples from healthy volunteers and patients with oral squamous cell carcinoma (OSCC). A total of 20 OLP and 12 patients with OSCC as well as 10 healthy subjects were subjected to miR‐137 promoter methylation analysis using methylation‐specific PCR (MSP). To address the malignancy prediction potential from miR‐137 promoter methylation status, methylation of the p16 gene, a well‐known tumor suppressor, was investigated in the same samples. The p16 methylation and miR‐137 promoter methylation were found to be 25% and 35% in patients with OLP, 50% and 58.3% in patients with OSCC, and 0% and 0% in healthy subjects, respectively. The differences between miR‐137 and p16 methylation levels were statistically significant between healthy controls and patients. Methylation levels of the two promoters were also influenced by age, gender, and lesion duration. Interestingly, aberrant promoter methylation of the p16 and miR‐137 genes was only found in the epithelium but not in the connective tissue from patients with OLP. This raises the possibility to use miR‐137 methylation as a biomarker for malignant prediction in patients with OLP.     

CIITA rs4774 and rs6498122 polymorphisms are associated with oral lichen planus in Chinese people: a case–control study

Oral lichen planus (OLP) is a common autoimmune inflammatory disorder that is difficult to cure, and its pathogenesis is still largely unknown. The major histocompatibility complex (MHC) class II transactivator (CIITA) gene has been reported to be an important candidate in some classical autoimmune diseases, and certain single nucleotide polymorphisms (SNPs) in CIITA have been confirmed to be associated with susceptibility to some autoimmune diseases. We conducted this research to investigate the existence of any correlation between OLP and SNPs in CIITA. A case–control study was performed to genotype 15 SNPs in the CIITA gene from 42 patients with OLP and from 86 controls; this was carried out by the PCR and then by a locus‐specific single‐base extension reaction. Allele detection was performed using matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) mass spectrometry. The SNP rs4774 variant in exon 11 (+1614G/C, Gly500Ala) of CIITA is significantly associated with OLP in healthy persons, both in genotype frequency and in allele frequency. Another intronic SNP, rs6498122, showed significant differences only in allele frequency. In conclusion, our data show that the two SNPs rs4774 and rs6498122 are associated with OLP and could also indicate the autoimmune characteristics of OLP.     

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.     

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.     

Micronuclear and sister chromatid exchange analyses in peripheral lymphocytes of patients with oral lichen planus – a pilot study*

Objective: The purpose of this study was to determine the genetic instability of peripheral blood lymphocytes from patients diagnosed with oral lichen planus (OLP) by investigation of frequencies of micronuclei (MN) and sister chromatid exchange (SCE). Materials and Methods: A total of 22 newly diagnosed and untreated patients with OLP of same severity scores and twenty healthy controls participated in this study. They were all non‐smokers with no previous history or family history of cancer. The periodontal status, flow rate and buffering capacity of whole mouth saliva were recorded. SCE and MN analyses were performed on peripheral blood lymphocytes of OLP patients and healthy controls. Results: The frequencies of MN (50.00 ± 22.36) and SCE (6.89 ± 1.48) in OLP patients were found to be significantly elevated compared with that in normal individuals (25.20 ± 9.52 and 5.93 ± 1.31; z = 3.946, P = 0.0001; z = 2.346, P = 0.019). There were no significant differences in the MN frequency and SCE between the two subgroups with reticular or erosive types of OLP. Conclusion: These pilot data indicate an increased genomic instability in peripheral blood lymphocytes of a cohort of Turkish patients diagnosed with oral lichen planus as compared with that of healthy individuals. As patients with OLP may have an increased or potential risk for oral malignancy, these assays could be used in translational research to monitor beneficial effects of interventions and long‐term prognosis.     

A multicenter study of oral lichen planus in Thai patients

Abstract Aim: Oral lichen planus is an oral mucosal disease that affects middle‐aged patients. The characteristics of oral lichen planus in Thai patients from a multicenter were studied. Methods: Data of 533 patients from the oral medicine clinics at Chulalongkorn and Mahidol (central Thailand), Chiang Mai (northern Thailand), and Khon Kaen (northeastern Thailand) universities during 2002–2007 were analyzed. The diagnosis of patients with oral lichen planus was clinically and/or histopathologically confirmed. Results: There was a greater number of female patients than males (4:1). There were significant differences in age, sex, and some systemic diseases among the oral lichen planus patients from the three centers. Burning sensation was the most common symptom (72.9%), followed by pain (26.5%), roughness (6.4%), and then no other symptoms (7.9%). The most common site of lesions was found at the buccal mucosa (87.1%). Atrophic oral lichen planus was common in Thai patients. There were significant differences in the types of oral lichen planus, including reticular, atrophic, and ulcerative oral lichen planus among these patients from the three centers (P = 0.000). Nine cases (1.7%) showed dysplasia, but one case (0.2%) developed squamous cell carcinoma. Conclusion: Patients with oral lichen planus from the central, northern, and northeastern parts of Thailand presented with distinct characteristics. The malignant transformation of oral lichen planus was low in Thai patients.     

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提要：口腔扁平苔藓（oral lichen planus,OLP）是口腔黏膜病中最常见且难以治愈的疾病之一。该病反复发作,可迁延终身,对患者身心造成很大痛苦,故寻找切实有效的治疗方法是非常必要的。目前,国内外学者提出了很多治疗OLP的方法,主要有局部激素治疗、全身应用激素及免疫调节剂等方法,同时,中医中药治疗也取得了较好的疗效。本文主要就近年来国内外报道的OLP治疗进展做一综述。     

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.     

Cytologic and DNA-cytometric examination of oral lesions in lichen planus

BACKGROUND: The aim of the present study was to evaluate the diagnostic value of exfoliative cytology (EC) and DNA image cytometry applied to oral lesions of lichen planus (LP; n = 56), in order to detect or exclude malignant transformation. METHODS: Brush and excisional biopsies were obtained from 56 patients. In cases of oral LP in which brush biopsies were suspicious for tumor cells, nuclear DNA contents were measured, using a TV Image Analysis System. RESULTS: In 50 patients EC yielded tumor cell-negative, doubtful in four cases and suspicious results obtained in two cases. DNA image cytometry revealed DNA-aneuploidy only in the two suspicious cases. The comparison between cytologic/DNA-cytometric diagnosis and biopsy histology resulted in a total agreement (LP without dysplasia: 54 and squamous cell carcinoma in LP: two cases). CONCLUSIONS: In conclusion, cytology with DNA-cytometry is a highly sensitive, specific, and non-invasive method, which can be used for periodical follow up of oral LP lesions in order to early detect or exclude malignancy.     

微小RNA在口腔扁平苔藓中的作用

微小RNA家族在调控基因表达中的重要作用日益受到关注,其调控的基因涉及细胞增殖、凋亡、生长、分化和代谢、血管化和免疫应答等多种生物过程,其表达谱和表达量的变化与多种疾病如肿瘤、炎症性疾病、自身免疫性疾病的发生、发展密切相关.本文对口腔扁平苔藓中微小RNA的研究现状作一综述.