Oral lichenplanus: Etiology, pathogenesis, diagnosis, and management

Oral Lichen planus(OLP) is a common chronic mucocutaneous disorder with an immune mediated pathogenesis. Its appearance may vary from presence of keratotic to erythematous areas. Etiology of OLP is unknown, but it is thought to be the result of an autoimmune process with an unknown predisposing factor. Oral lichen planus is a complex and poorly understood clinicalcondition with periods of remissions and exacerbations. Management of the OLP is diversified with few lesions requiring treatment for years and few others are mild, requiring no treatment.

Predicting the Activity of Oral Lichen Planus with Glycolysis-related Molecules:A Scikit-learn-based Function

Objective Oral lichen planus(OLP)is one of the most common oral mucosa diseases,and is mainly mediated by T lymphocytes.The metabolic reprogramming of activated T cells has been shown to transform from oxidative phosphorylation to aerobic glycolysis.The present study investigated the serum levels of glycolysis-related molecules(lactate dehydrogenase,LDH;pyruvic acid,PA;lactic acid,LAC)in OLP,and the correlation with OLP activity was assessed using the reticular,atrophic and erosive lesion(RAE)scoring system.Methods Univariate and multivariate linear regression functions based on scikit-learn were designed to predict the RAE scores in OLP patients,and the performance of these two machine learning functions was compared.Results The results revealed that the serum levels of PA and LAC were upregulated in erosive OLP(EOLP)patients,when compared to healthy volunteers.Furthermore,the LDH and LAC levels were significantly higher in the EOLP group than in the nonerosive OLP(NEOLP)group.All glycolysis-related molecules were positively correlated to the RAE scores.Among these,LAC had a strong correlation.The univariate function that involved the LAC level and the multivariate function that involved all glycolysis-related molecules presented comparable prediction accuracy and stability,but the latter was more time-consuming.Conclusion It can be concluded that the serum LAC level can be a user-friendly biomarker to monitor the OLP activity,based on the univariate function developed in the present study.The intervention of the glycolytic pathway may provide a potential therapeutic strategy.

Prediction of potential targets and molecular mechanisms of Tripterygium hypoglaucum for oral lichen planus based on network pharmacology and molecular docking

Objective:To explore the potential targets and molecular mechanisms of tripterygium hypoglaucum for oral lichen planus(OLP)by applying network pharmacology and molecular docking technology.Methods:The active ingredients and targets of tripterygium hypoglaucum were screened.OLP-related targets were predicted.The Protein-Protein Interaction(PPI)network was constructed for the intersection targets of tripterygium hypoglaucum and OLP.The“OLP-target-molecule-Tripterygium hypoglaucum”network was constructed and visualized.The intersection genes were screened for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking analysis and visualization were performed.Results:15 active ingredients and 78 targets of tripterygium hypoglaucum were obtained.9109 OLP-related targets were screened,and 54 intersection genes of tripterygium hypoglaucum with OLP were obtained.The top 10 key targets were screened from the constructed PPI network.The top 10 active ingredients of tripterygium hypoglaucum were screened from the constructed“OLP-targets of actionactive ingredients-tripterygium hypoglaucum”network.The GO and KEGG analyses of the 54 intersection targets indicated that tripterygium hypoglaucum may play a therapeutic role by regulating one carbon pool by folate,pathways in cancer,et al.Molecular docking analysis showed that dihydrofolate reductase(DHFR),phosphoribosylglycinamide formyltransferase(GART),estrogen receptor 1(ESR1),et al are the key targets for the treatment of OLP in tripterygium hypoglaucum.Conclusion:The potential key targets and molecular mechanisms of tripterygium hypoglaucum in treating OLP provide a theoretical basis for new drug development and clinical applications.

Periodontopathogen profile of healthy and oral lichen planus patients with gingivitis or periodontitis

Oral lichen planus （OLP） is a chronic inflammatory disease that is frequently detected in oral tissues. The aim of our study was to identify the prevalence of the detection of periodontopathogenic microorganisms （Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia and Treponema denticola in OLP patients and to compare with this prevalence of periodontopathogenic microorganisms in healthy non-OLP patients. Our study included 27 （18 chronic periodontitis （OLPP） and 9 gingivitis （OLPG）） patients diagnosed with OLP along with 26 （13 chronic periodontitis （HP） and 13 gingivitis （HG）） healthy non-OLP patients. The multiplex polymerase chain reaction （PCR）with subsequent reverse hybridization method （micro-IDent） was used for identifying periodontopathogenic microorganisms present in subgingival plaque samples. The percentages of detection for A. actinomycetemcomitans, P. gingivalis, P. intermedia, T. forsythia and T. denticola in subgingival plaque samples taken from OLP patients （OLPG and OLPP） were 18.5%, 85.1%, 81.4%, 88.8% and 74%, respectively. Meanwhile, in the non-OLP patients （HG and HP）, these values were 7.6%, 50%, 46.1%, 73% and 57.7%, respectively. Thus, comparing the non-OLP groups with the OLP groups, the periodontopathogens＇ percentages of detection in the OLP groups were higher than those in the non-OLP groups. According to our study results, OLP patients have higher levels of infection with A. actinomycetemcomitans, P. gingivalis, P. intermedia, T. forsythia and T. denticola than non-OLP patients. We argue that the high percentages in patients with OLP may help identify the importance of periodontopathoRenic microorganisms in the progress of periodontal diseases of OLP.

Interferon-c and interleukin-4 detected in serum and saliva from patients with oral lichen planus

Our previous salivary study had demonstrated an apparent T helper 2 （Th2）-predominance in saliva of oral lichen planus （OLP） patients and suggested a potential of salivary interleukin-4 （IL-4） as a biomarker for monitoring disease severity. To further determine the consistency of Th1/Th2 bias of OLP, this study investigated the expression profile of interferon-γ （IFN-γ） and IL-4 in serum and the relationship of the serum levels of these cytokines with their saliva partners. Sixty ethnic Chinese patients with OLP （40 of the erythematous/ulcerative form and 20 of the reticular form） were recruited for this study, with 40 age-sex-matched healthy volunteers as control group. IFN-γ and IL-4 levels in serum and paired saliva samples were screened by enzyme-linked immunosorbent assay. OLP patient showed a low-level IFN-γ but high-level IL-4 expression profile in both serum and saliva, with a lower IFN-γ/IL-4 ratio. Serum IL-4 level in the erythematous/ulcerative group was significantly higher than that in the reticular group. Serum levels of IFN-γ and IL-4 were significantly and positively correlated with their saliva partners. These results provided more evidence for Th2 cytokine- predominant immune imbalance in OLP, as well as the potential of IL-4 as the biomarker for monitoring severity of OLP.

COX-2, MMP-7 expression in oral lichen planus and oral squamous cell carcinoma

Objective: To observe cyclooxygenase (COX)-2 expression in normal oral mucosa (NOM), oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC) and explore its significance in the incidence of oral cancer. Methods: The immunohistochemical method and RT-PCR method were applied to detect the expression of COX-2 and MMP-7 in 10 cases with NOM, 33 cases of with OLP and 38 cases with OSCC. Results: The expression of COX-2 mRNA in OSCC tissues (68.4%, 26/38) was significantly higher than in the OLP (24.2%, 8/33) and NOM (0.0%, 0/10) ( P<0.01). The expression of MMP-7 mRNA in OSCC tissues (65.8%, 25/38) was significantly higher than in the OLP (30.3%, 10/33) and NOM (0.0%, 0/10) ( P<0.01). The expression of MMP-7 in OLP was significantly higher than in the NOM ( P<0.05). There was no significant expression of COX-2 protein in NOM, and the positive rate was 42.4% (14/33) and 89.5% (34/38) in OLP and OSCC group, respectively. The COX-2 expression in cancer tissues was significantly higher than in NOM and OLP ( P<0.05). The MMP-7 protein expression in cancer tissues (84.2%, 32/38) was significantly higher than in NOM (10.0%, 1/10) and in OLP (42.4%, 14/33), and the positive rate in OLP was significantly higher than in NOM ( P<0.01). The COX-2 expression was associated with clinical stage ( P<0.05), the MMP-7 expression was associated with clinical stage and lymph node metastasis ( P<0.05). The expressions of COX-2 and MMP-7 mRNA were positively correlated with OSCC. Conclusions: The abnormal expressions of COX-2 and MMP-7 are closely related to the biological behavior of OSCC, the MMP-7 may be induced by COX-2, and further lead to the invasion and metastasis of OSCC.

Implications of Th1 and Th17 Cells in Pathogenesis of Oral Lichen Planus

Oral lichen planus （OLP） is considered a T cell-mediated autoimmune disease with unknown aetiology. T helper cells appear to play an important role in the pathogenesis of OLP. We investigated the possible role of T helper cells, Th1 and Th17, in the lesions and circulation of patients with OLP. Forty patients with OLP and 15 healthy volunteers were recruited. Double immunofluorescence staining was used to detect Th1 and Th17 cells in the OLP lesions, and intracellular cytokine staining and flow cytometry to evaluate the proportion of Th1 and Th17 cells in peripheral blood. The levels of serum interferon （IFN）-γ and interleukin （IL）-17 were assessed by using an enzyme-linked immunosorbent assay. It was found that Th17 cells, as well as Th1 cells, were present in OLP lesions. The proportion of peripheral Th1 and Th17 cells was significantly increased in patients with OLP. The proportion of Th17 cells in atrophic-erosive OLP was elevated as compared with that in reticular OLP. Serum IL-17 levels in OLP patients were significantly higher than in controls, and those in the atrophic-erosive OLP group were increased as compared with the reticular OLP group. However, the levels of serum IFN-γ were slightly decreased in OLP patients. Our data suggested that Th1 and Th17 cells in the local lesions and peripheral blood may be associated with the pathogenesis of OLP, and that IL-17 may be an important proinflammatory cytokine in OLP. These findings enhance our understanding of OLP pathogenesis.

The Prevalence of Hepatitis C Virus Infection in Oral Lichen Planus in an Ethnic Chinese Cohort of 232 Patients

Aim Oral lichen planush （OLP） is a chronic inflammatory disease, and has been reported to have a correlation with hepatitis Cvirus （HCV） infection in some regional investigations. In this study, we investigated the prevalence of HCV in patients with oral lichen planus in an ethnic Chinese cohort. Methodology The antibody of HCV infection was detected by using enzymelinked immunosorbent assay. Moreover, the clinical characteristics of whole the cohort have also been studied, such as the gender, age, clinical type, habits and social factors. Results Of all 232 patients, the antibody of HCV infection was detected positive in 4 patients （1.72%） using enzyme-linked immunosorbent assay. It was lower than that in control group of 2.5%, but not significant （P=0.309）. The positive rate of HCV antibody in the erosive type ones （4.2%） was higher than that in the reticular type ones （1.0%）, but this difference was proved to be not significant （P=0.389）. The clinical characteristics of whole cohort, such as the gender, age, clinical type, habits and social factors, showed the outcome obtained in the present study were similar to thao of our previous study. Conclusion HCV may play no etiological role in oral lichen planus in ethnic Chinese OLP patients.

Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis

The Merkel cell-neurite complex initiates the perception of touch and mediates Ap slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry （the avidin-biotin-peroxidase complex and double immunofluorescence methods）using pan cytokeratin, cytokeratin 20 （K20, a Merkel cell marker）, and neurofilament 200 （NF200, a myelinated Aβ- and Aδ-nerve fibre marker） antibodies. N F200-immunoreactive （ir） nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hvperkeratosis.

The Expression of TNF-α and ICAM-1 in Lesions of Lichen Planus and Its Implication

In order to investigate the role of TNF-α and ICAM-1 in the pathogenesis of lichen planus, immunohistochemistry was used to detect the expression of TNF-α and ICAM-1 in skin lesions of the patients with lichen planus and skin tissues of normal subjects. The results showed that positive rates of TNF-α and ICAM-1 expressions in lichen planus were significantly higher than those in normal skins （both P〈0.05）. Meanwhile, there was a obvious correlation between the increase of TNF-α and that of ICAM-1 in lichen planus. The expression of TNF-α and ICAM-1 might play an important role in the development of lichen planus.

Case report and review of esophageal lichen planus treated with fluticasone

Lichen planus is a fairly common chronic idiopathic disorder of the skin,nails and mucosal surfaces.Esophageal involvement of this disease on the other hand is rare and only about 50 cases have been reported in literature.Given its rarity,it can be difficult to diagnose and may be easily misdiagnosed as reflux esophagitis.Currently,there are no clear recommendations on the optimal management of this disease and little is known about the best treatment approach.Systemic steroids are usually the first line treatment and offer a favorable response.In this report,we would like to present a novel approach in the management of esophageal lichen planus in a middle-aged woman treated successfully with swallowed fluticasone propionate 220 mcg twice a day for 6 wk,as evidenced by objective clinical findings.Based on our review of related literature and experience in this patient,we feel that a trial of swallowed fluticasone may be a prudent approach in the management of these patients since it has a more favorable side effect profile than systemic treatment.

Esophageal lichen planus:A case report and review of the literature

Esophageal involvement by lichen planus(ELP),previously thought to be quite rare,is a disease much more common in women and frequently the initial manifestation of mucocutaneous lichen planus(LP).Considering that the symptoms of ELP do not present in a predictable manner,ELP is perhaps more under-recognized than rare.To date,four cases of squamous cell carcinoma in association with ELP have been reported,suggesting that timely and accurate diagnosis of ELP is of importance for appropriate follow-up.In this case report,a 69-year-old female presented with dysphagia and odynophagia.She reported a history of oral LP but had no active oral or skin lesions.Endoscopic examination revealed severe strictures and web-like areas in the esophagus.Histologic examination demonstratedextensive denudation of the squamous epithelium,scattered intraepithelial lymphocytes,rare eosinophils and dyskeratotic cells.Direct immunofluorescence showed rare cytoid bodies and was used to exclude other primary immunobullous disorders.By using clinical,endoscopic,and histologic data,a broad list of differential diagnoses can be narrowed,and the accurate diagnosis of ELP can be made,which is essential for proper treatment and subsequent follow-up.

Efficacy of Topical Tacrolimus for Erosive Oral Lichen Planus: A Meta-analysis

Objective To assess the efficacy and safety of topical tacrolimus for erosive oral lichen planus(EOLP). Methods Literatures published up to December 2013 were searched from Pub Med, Embase, CENTRAL, Chinese Bio Medical Literature Database(CBM), and System for Information on Grey Literature in Europe(SIGLE). All randomized controlled trials(RCTs) of topical tacrolimus for EOLP which compared with other interventions or a placebo were considered in this Meta-analysis. Two researchers collected data independently. The assessment of methodological quality was based on Cochrane Handbook and the materials were analyzed with the software Revman 5.2.5. The primary outcome measures were the symptoms(e.g. pain, discomfort) complained by patients. The secondary outcome measures included the improvement rate of clinical signs assessed by the investigators and the incidence of adverse effects(e.g. clinical candidiasis). Results A total of 9 RCTs involving 476 patients were finally included. The pooled odds ratio(OR) of clinical improvement for topical tacrolimus vs. topical corticosteroids was 1.19 [95% confidence interval(CI): 0.64-2.22, I2: 44%]. Regarding to 0.1% tacrolimus and 0.03% tacrolimus, the pooled OR were 1.87(95 % CI: 0.60-5.82) and 1.47(95 % CI: 0.14-16.04) respectively in subgroup analysis. No serious adverse events were reported in topical tacrolimus group. Conclusions There was no evidence to support that topical tacrolimus for EOLP was more effective and safer than topical corticosteroids in this Meta-analysis. Clinical assessment criteria should be established and accepted by clinicians and researchers before further RCTs are undertaken.

Photodynamic therapy of oral leukoplakia and orallichen planus using methylene blue:A pilot study

Premalignant lesions like oral lichen planus(OLP),oral leukoplakia(OL)has a fair probability of transforming into malignancy and they are perverse toward conventional therapies.Photody-namic therapy(PDT)has been considered as an alternative/complimentary therapeutic mo-dality for the management of premalignant lesions.In this study,methylene blue mediated photodynamic therapy(MB-PDT)was used as a possible alternative method for the treatment of OLP and OL.A total of 15 OLP lesions and 13 OL lesions were enrolled in the study.The patients were irradiated 1using metal halide lamp filtered at 630土10nm,with a light exposure dose of 120 J/cm^(2) per stting.For the OLP lesions,MB-PDT was performed once a week for four weeks and for the OL lesions,MB-PDT was performed twice a week for three weeks.Lesions were evaluated pre-and post-and at follow-u sessions by changes in sign and symptom scores,and size of lesions.We have observed a 53.3%of complete reduction in the treated OLP lesions and their decrease in size,sign and symptom score after treatment and at follow-up session was statistially signifcant.We have also observed complete response for one OL lesion of the 13 treated lesions.The result indicates that MB-PDT is an effective modality in management of OLP and OL.Among the two types of premalignancies treated with MB-PDT,OLP lesions responded much better than that of OL.

Expression of Apoptosis Related Protein in Skin Lesions of Lichen Planus and Its Implication

In order to investigate the role of Caspase-3 and Bax in the pathogenesis of lichen planus, immunohistochemistry was used to detect the expression of Caspase-3 and Bax in skin lesions of the patients with lichen planus and skin tissues of normal subjects. The results showed that positive rate of Caspase-3 and Bax expression in lichen planus were significantly higher than that in normal skins （both P〈0.05）. Meanwhile, there was a obvious correlation between the increase of Caspase-3 and that of Bax in lichen planus. The expression of Caspase-3 and Bax might play an important role in the development of lichen planus.

Comparative Observation on the Effects of Radix Tripterygium Hypoglaucum Tablet and Tripterygium Glycosides Tablet in Treating Erosive Oral Lichen Planus

Objective: To compare the therapeutic effects of Radix Tripterygium hypoglaucum tablet (THT) and Tripterygium glycosides tablet (TGT) in treating erosive oral lichen planus(EOLP).Methods: The patients were randomized into two groups, and they were treated with THT (n=47) or TGT (n=47), respectively. The therapeutic effects were evaluated after 3 months treatment.Results: For the patients of grade 1, the total efficacy in TGT group was 85.71%, compared with 52.38% in THT group, the efficacy was statistically greater in the group receiving TGT (P=0.043). However, for the patients of grade 2, the difference was not statistically significant (P=0.173).Conclusion: TGT is more effective in treating EOLP than THT for grade 1 patients. However, TGT is not suitable for patients of child bearing age.

Methylation and Expression Status of <i>SOCS</i>1 and <i>SOCS</i>3 in Oral Lichen Planus

Oral lichen planus (OLP) is a disease of unknown etiology affecting oral mucosa by mediated chronic inflammation and is classified as a potentially malignant oral disorder. SOCS1 and SOCS3 in the SOCS family have been identified as negative regulators of the cytokine-activated JAK/STAT pathway responsible for inflammatory reaction. The DNA methylation in the promoter regions of SOCS1 and SOCS3 have been reported to correlate with carcinogenesis. In this study, we performed methylation-specific PCR (MSP) to investigate the methylation status of the promoter regions in SOCS1 and SOCS3 genes using biopsy samples from OLP and oral squamous cell carcinoma (OSCC) patients. SOCS1 was methylated in 14/29 (48.3%) cases with OLP and 7/15 (46.7%) cases with OSCC. At the same time, SOCS3 was methylated in 25/29 (86.2%) cases with OLP and 11/15 (73.3%) cases with OSCC. We didn’t recognize any DNA methylation in SOCS1 or SOCS3 genes from the exfoliated cytological specimens of normal buccal mucosa. Furthermore, mRNA expression level was analyzed using real-time RT-PCR method to evaluate the correlation with DNA methylation status. DNA methylation status of SOCS1 seemed not to affect the expression level of SOCS1 mRNA. At the same time, DNA methylation status of SOCS3 was negatively correlated with the expression level of SOCS3 mRNA (p < 0.05). We posit frequent methylation of the SOCS3 gene promoter, theoretically resulting in the increase of cytokines expression, might be associated with the etiological mechanism of OLP.

Treatment of cutaneous lichen planus with ALA-mediated topical photodynamic therapy

Purpose:To evaluate the efectiveness of topical 5-aminolevulinie acid(ALA)-mediated pho-todynamic therapy(PDT)for the treatment of cutaneous lichen planus(LP).Methods:A total of 17 symptomatic LP lesions in 7 Chinese patients were assessed.ALA cream(10%)was applied topically to LP lesions for 3h.The lesions were iradiated with a 635 nm diode laser at the dose level of 100J/cm^(2).The treatment was repeated at two week intervals.Clinical assessmnent was conducted before each treatment.Follow-up was performed once a month for up to six months.Results:Lesions showed significant improvement after one to four courses of treatments.Complete response was achieved in 13 lesions(five patients)and partial remission in four lesions(two patients).The complete response rate was 71%.There was no significant side ffects except the feeling of pain that most patients could tolerate.Follow-up of five patients who achieved complete response showed no signs of recurrence.Conclusion:Topical ALA PDT is effective in the treatment of cutaneous LP.

Lichen planus affecting a 12-year-old girl

Lichen planus (LP) is a chronic inflammatory mucocutaneous condition which is relatively common in adults but rarely affects children. In addition, few cases with oral lesions affecting children have been reported in the literature. The purpose of this study is to report an unusual case of oral LP involving the tongue and buccal mucosa in a child. A 12-year-old girl complained of painless oral lesions with 18 months of evolution. On clinical evaluation, multiple white lesions in tongue and buccal mucosa were observed with no cutaneous lesions. Diagnosis was made based on clinical examination and histopathological features. No active treatment was necessary. The patient is currently under regular evaluation. Although rarely reported in childhood, lichen planus should be considered in a differential diagnosis of hyperkeratotic and/or reticular lesions of the oral mucosa in children.

A Retrospective and Comparative Study of Familial and Non-familial Bullous Lichen Planus

In order to compare the clinical characteristics of familial and non-familial bullous lichen planus (BLP), the archival data of 36 BLP patients with positive family history and 21 BLP patients with negative family history diagnosed according to the clinical features and histopathology were collected in our department from 1956 to 2003. The clinical features were analyzed and compared. There were significant differences between familial and non-familial BLP in age of onset, duration of disease and extension of eruption (P<0.01). It was concluded that familial BLP appeared to differ from the non-familial form in its earlier age of onset, longer duration of the disease, more extensive eruption and more tendency to involve nails. Hereditary factors may play a role in the pathogenesis of familial BLP.