Possible link between Hashimoto's thyroiditis and oral lichen planus: a novel association found

Objectives

Hashimoto's thyroiditis as well as lichen planus has been associated to a number of disorders, generally of auto-immune origin. A novel possible association between oral lichen planus (OLP) and Hashimoto's thyroiditis (HT) is here proposed on the basis of a cross-sectional survey.

Materials and methods

One hundred and five unrelated OLP patients were considered. Diagnosis of HT was based on positive serum anti-TPO, anti-Tg, TSH levels and the typical ultrasound pattern of the thyroid gland.

Results

In the present survey, the prevalence of HT in the OLP group was 14.3 % whereas the prevalence of HT-related hypothyroidism in the general population was reported to be equal to 1 %. By Fisher's exact test, it was revealed that the difference between our data and historical prevalence of HT was found statistically significant.

Conclusion

Actually, there is no definitive hypothesis that could explain the coexistence of OLP and HT. However, considering the onset timing of HT followed by OLP in 93.3 % of our series, we suspected a causal or predisposing role for HT. Specifically, we believe that in HT patients, circulating thyroid antibodies could contribute to trigger an organ-specific auto-immune response also in the oral mucosa or skin, leading to the development of LP lesions.

Clinical relevance

Because of the large number of cases of asymptomatic chronic auto-immune thyroiditis, it would be useful that women over 40 years of age affected by OLP were screened for thyroid dysfunction, particularly HT.     

Prevalence of Candida spp., xerostomia,and hyposalivation in oral lichen planus – A controlled study

Objective

To determine the frequency of Candida spp., xerostomia, and salivary flow rate (SFR) in three different groups: patients with OLP (OLP group), patients with oral mucosal lesions other than OLP (non‐OLP group), and subjects without oral mucosal lesions (control group).

Material and methods

Xerostomia as well as SFR was investigated in the three groups. Samples for isolation of Candida spp. were collected from OLP lesions (38 patients), non‐OLP lesions (28 patients), and healthy subjects (32 subjects).

Results

There was no statistically significant difference regarding the frequency of xerostomia and hyposalivation among the three groups (P > 0.05). A higher prevalence for colonization by Candida spp. was found in the healthy subject as compared to that of patients with OLP (P = 0.03) and non‐OLP (P = 0.02) groups. Low SFR was not a factor for colonization by Candida spp.

Conclusions

Xerostomia and hyposalivation occur with similar frequency in subjects with and without oral lesions; also, the presence of oral lesions does not increase the susceptibility to colonization by Candida spp. It seems that any study implicating Candida spp. in the malignant transformation of oral lesions should be carried out mostly on a biochemical basis, that is, by testing the capability of Candida spp. to produce carcinogenic enzyme.     

The clinical impact of direct-acting antiviral treatment on patients affected by hepatitis C virus-related oral lichen planus: a cohort study

Objectives

Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disease. Literature supports an association between OLP and Hepatitis C virus (HCV) infection. The current treatment for HCV infection with direct-acting antivirals (DAAs) is highly effective and safe. The aim of this study is to evaluate the clinical impact of viral eradication with DAAs in patients with HCV and OLP.

Materials and methods

For this cohort observational study, 18 patients with HCV and OLP were recruited; all patients received DAAs. Nineteen patients with OLP without HCV were recruited as controls. Both groups received an oral clinical examination, taking photographs of the oral mucosa, at three time points. Size and type of lesions, clinical and efficacy scores, were evaluated at each time point with ImageJ software. Changes were assessed by a general linear model repeated measures analysis. Kruskal–Wallis H and Mann–Whitney U tests were used to evaluate the differences between subgroups.

Results

All patients of the study group reached a sustained virological response. The study group showed a correlation between viral load and clinical status (p?<?0.05), higher clinical scores at baseline (p?=?0.001) and higher efficacy index than controls (p?<?0.001), improving over time (p?<?0.001); controls did not show significant changes (p?=?0.196). One patient of the experimental group developed oral squamous cell carcinoma (OSCC) of the tongue during the DAAs treatment.

Conclusions

In this study, patients with HCV and OLP showed a worst clinical oral status than controls at baseline. However, treatment for virus eradication can improve the oral lichen planus clinical course.

Clinical relevance

HCV eradication can improve the clinical course of patients with HCV-related OLP.

     

High percentage of oral lichen planus and lichenoid lesion in oral squamous cell carcinomas

Objective: Oral lichen planus (OLP) and lichenoid lesions (OLL) are regarded as precursor lesions of oral squamous cell carcinoma (OSCC) with potential for malignant transformation. This potential is not clear due to difficulties in diagnosis of OLP and OLL. Our aim was therefore to evaluate previously identified OLP and OLL as precursor lesions in OSCC and to identify cancer related etiological factors such as smoking and alcohol consumption.

Material and methods: We retrospectively reviewed all cases (total 323, comprising 164 females and 159 males) with OSCC treated at the Department of Oral and Maxillofacial Diseases and Surgery, Helsinki University Hospital during 2015. Confirmed by histopathological biopsy, 58 (17.9%) had OLP and 13 had OLL (4.0%) as precursor lesion.

Results: Patients with OLP were slightly older than those without it. OLP was more common in females than in males (p?p?=?.006) and cancer relapses less common (p?=?.005). Smoking was less frequent in patients with OLP and OLL (p?p?Conclusion: Our findings confirm the importance of active follow-up of all patients with OLP and OLL even in patients who do not fit a traditional high-risk category for OSCC.     

Effect of a structured plaque control on MMP-1 and MMP-9 crevicular levels in patients with desquamative gingivitis associated with oral lichen planus

Objectives

No data are available in the literature on the extent to which the immune host-response and bacterial-elicited inflammation separately contributes to the increase in gingival crevicular fluid (GCF) levels of inflammatory biomarkers in patients affected by desquamative gingivitis (DG) secondary to oral lichen planus (OLP). The aim of this study was to investigate the effect of a structured plaque control intervention on GCF levels of MMP-1 and MMP-9 in OLP patients with DG and to compare them with those of non-OLP patients.

Materials and methods

The study population consisted of 18 unrelated Caucasian patients with DG, while 18 periodontally healthy subjects were recruited for the control group. Periodontal parameters and GCF biomarker amounts were evaluated at baseline and 2 months after a structured plaque control intervention, comprising professional oral hygiene sessions, manual toothbrushing, and interdental cleaning advice, only for DG patients. Determination of MMP-1 and MMP-9 levels was carried out by means of an enzyme-linked immunosorbent assay.

Results

Plaque control program led to improvement in all examined clinical parameters and resulted in significant decrease in GCF total amount and concentration of MMP-1 and MMP-9 in comparison to baseline (p < 0.001). However, MMP-1 and MMP-9 levels in DG patients were still significantly higher than those in the healthy control group (p < 0.01).

Conclusions

These findings would seem to support an intrinsic upregulated expression of MMPs in DG patients that is exacerbated by bacterial plaque.

Clinical relevance

The present outcomes provide further scientific grounds for the importance of strict professional oral hygiene sessions in DG patients.

     

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.     

Increased melatonin in oral mucosal tissue of oral lichen planus (OLP) patients: A possible link between melatonin and its role in oral mucosal inflammation

ObjectiveThe existence of extra-pineal melatonin has been observed in various tissues. No prior studies of melatonin in human oral mucosal tissue under the condition of chronic inflammation have been reported. The aim of this study was to investigate the presence of melatonin in oral mucosal tissue of patients with oral lichen planus (OLP) which was considered as a chronic inflammatory immune-mediated disease causing oral mucosal damage and ulcerations.Materials and methodsSections from formalin-fixed and paraffin-embedded oral mucosal tissue of OLP patients (n = 30), and control subjects (n = 30) were used in this study. Immunohistochemical staining was performed and the semiquantitative scoring system was used to assess the levels of arylalkylamine-N-acetyltransferase (AANAT: a rate-limiting enzyme in the biosynthesis pathway of melatonin), melatonin, and melatonin receptor 1 (MT1) in oral mucosa of OLP patients and normal oral mucosa of control subjects.ResultsAANAT, melatonin, and MT1were detected in oral mucosal tissue of OLP patients and control subjects. Immunostaining scores of AANAT, melatonin, and MT1 in oral mucosal tissue of OLP patients were significantly higher than those in control subjects (p = 0.002, p < 0.001, and p = 0.031, respectively).ConclusionsIncreased levels of AANAT, melatonin, and MT1 in the inflamed oral mucosal tissue of OLP patients imply that chronic inflammation may induce the local biosynthesis of melatonin via AANAT, and may enhance the action of melatonin via MT1.     

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.     

Clinicopathological features and malignant transformation of oral lichen planus: A 12-years retrospective study

Abstract

Objective. Oral lichen planus (OLP) is known to be associated with the risk of developing oral squamous cell carcinoma (OSCC). The objective of this study was to investigate the clinicopathological features of OLP and the prevalence of malignant transformation in this setting. Materials and methods. This retrospective study was carried out on 204 medical records of patients with histologically proven OLP who received long-term follow-up (range 6 months–12 years). Data were entered in an informatic database. The statistical analysis, when needed, was performed with the chi-squared test for significance (p < 0.05). Results. At the moment of the diagnosis, out of 204 patients (163 female and 41 male; mean age 54.5 years), 107 patients (52.45%) suffered from systemic chronic diseases, in particular 46 (22.5%) from hepatitis C. Clinically, the reticular form of OLP was the predominant one and most patients had multiple oral sites of involvement. Fourteen patients showed extra-oral lesions. A percentage of malignant transformation less than 1% was found. In fact, two patients (0.98%) underwent a malignant transformation at a site previously diagnosed as OLP. Conclusions. At present, OLP is accepted as being a potential malignant disorder, therefore lifelong follow-up is recommended.     

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??Objective    To investigate the expression of miR-590 in the tissues of patients with oral lichen planus and oral squamous carcinoma and study its role in the carcinogenesis of oral mucosal cells. Methods    Twenty female and twelve male OLP patients??OLP group??and seventeen female and eleven male OSCC patients??OSCC group??were selected??who were pathologically diagnosed in Jinzhou Stomatological Hospital from March 2014 to December 2015. Twenty healthy matched volunteers served as control group. The expressions of miR-590 in oral tissues of the three groups were examined by realtime PCR. The difference among the three groups was statistically analyzed. Results    The relative expressions of miR-590 were significantly higher in OLP??1.96 ± 0.52??and OSCC patients??2.75 ± 0.78??than those in the healthy controls??0.77 ± 0.34????P < 0.05??. There were significant differences in the expression of miR-590 between the OLP group and OSCC group??P < 0.05??. Conclusion    The expressions of miR-590 are higher in OLP and OSCC patients than those in normal controls??miR-590 may play a role in the carcinogenesis of oral mucosal cells.     

口腔扁平苔藓及口腔鳞癌患者口腔黏膜组织中微小RNA-590表达研究

目的    研究口腔扁平苔藓（oral lichen planus,OLP）及口腔鳞癌（oral squamous carcinoma,OSCC）患者口腔黏膜组织中微小RNA-590（miR-590）的表达,探讨其在口腔黏膜细胞癌变中的作用及意义。方法    选择2014年3月至2015年12月间锦州市口腔医院收治且经病理学确诊的OLP患者32例（OLP组）和OSCC患者28例（OSCC组）,所有OLP患者均为初诊且经病理学确诊取材,OSCC患者均为术中病理确诊后开始取材。另选择20名健康志愿者作为对照组。采用实时荧光定量PCR技术检测3组受试者口腔黏膜组织中miR-590的表达水平并进行统计学分析。结果    OSCC组患者的miR-590相对表达水平（2.75 ± 0.78）最高,OLP组的相对表达水平（1.96 ± 0.52）次之,均显著高于对照组（0.77 ± 0.34）,差异有统计学意义（P < 0.05）。OSCC组与OLP组的miR-590表达差异有统计学意义（P < 0.05）。结论    与正常对照比较,miR-590的表达在OSCC和OLP组中显著升高,miR-590可能参与了口腔黏膜细胞癌变过程。     

Abnormal EBV immune status in oral lichen planus

OBJECTIVE: To investigate any possible association between oral lichen planus (OLP) and the humoral immune response to Epstein-Barr virus (EBV). MATERIAL AND METHODS The population consisted of 22 patients with histologically verified OLP and 22 healthy sex- and age-matched controls without any oral mucosal diseases. Specific serum IgG antibodies (Ab) towards EBV early antigen (EA) and nuclear antigen-I (EBNA) and IgM Ab towards EBV EA were determined by ELISA.
RESULTS: The optometric density (OD) IgG anti-EA Ab levels were significantly higher in OLP patients than in controls and a significantly negative correlation between duration of symptoms from OLP and IgG anti-EA OD Ab values was demonstrated. IgM anti-EA and IgG anti-EBNA OD Ab levels were not significantly different between the two groups.
CONCLUSION: The hypothesis of any possible association between EBV and OLP has never been tested but the present results seem to lend support for an aberration in the humoral response to EBV in OLP patients.     

TLR2, TLR3, TLR4 and CD14 gene polymorphisms associated with oral lichen planus risk

The aim of this study was to assess whether polymorphisms in toll‐like receptor (TLR) and cluster of differentiation 14 (CD14) genes are associated with oral lichen planus (OLP) risk and clinical course of the disease. The study group consisted of 101 patients with confirmed OLP and 104 healthy blood donors without systemic or oral mucosal diseases. Single nucleotide polymorphisms of TLR2 (rs3804099), TLR3 (rs3775291 and rs5743312), TLR4 (rs4986790 and rs4986791), and CD14 (rs2569190) genes were genotyped using real‐time PCR or PCR‐restriction fragment length polymorphism (PCR‐RFLP). The rs5743312 TLR3 gene polymorphism was associated with increased OLP risk in comparison with the wild type genotype (OR = 15.984, P = 0.011). No association with OLP risk was observed for the polymorphisms studied in TLR2, TLR4 and CD14 genes or for the rs3775291 polymorphism of the TLR3 gene. The polymorphisms of the TLR3 gene were in linkage disequilibrium (D′ = 1, r² = 0.1). Identified haplotypes were not associated with the risk of OLP. The findings of the current study suggest that the TT genotype of the rs5743312 TLR3 gene polymorphism may play a significant role in the aetiology of OLP.     

Overexpression and varied clinical significance of Th9 versus Th17 cells in distinct subtypes of oral lichen planus

ObjectiveOral lichen planus (OLP) presents with large numbers of T lymphocytes accumulating beneath the epithelium of the oral mucosa; however, its aetiology remains obscure. A potential role for an emerging novel T cell subset, Th9, in OLP has recently been suggested but remains to be clarified. The current aim was to investigate the expression and potential clinical significance of Th9 cells in distinct subtypes of OLP.Materials and methodsPeripheral blood samples were collected from 41 OLP patients and 18 healthy controls (HCs). Flow cytometric analysis was used to detect the CD4+ T helper subset Th9 (IL-9⁺IL-17⁻CD4⁺ Th cells) and Th17 (IL-9⁻IL-17⁺CD4⁺ Th cells) expression levels.ResultsFlow cytometry results showed significantly elevated levels of Th9 cells in reticular and erosive OLP compared to HCs. Th9 expression in erosive OLP was less than in reticular OLP, indicating that Th9 but not Th17 cells may play a predominant role in reticular disease. However, in erosive OLP patients, we found much higher levels of Th17 cells compared to reticular OLP patients and HCs, indicating that Th17 dominates in erosive OLP. Statistical analysis showed positive correlations of Th9 cells and Th17 cells in patients with reticular or erosive OLP but none in HCs.ConclusionsTh9 and Th17 cells may take the predominant roles in reticular and erosive OLP respectively, and their numbers were positively correlated in reticular and erosive OLP patients. Elevated circulating Th9 cells may help maintain immune balance in OLP immunopathogenesis, which requires further investigation.     

Validity,reliability and optimisation of the TOPICOP questionnaire for oral lichen planus

Abstract

Objectives: Due to their anti-inflammatory and immunosuppressive effects, topical corticosteroids (TCs) are commonly used for the treatment of patients with oral lichen planus (OLP) with an erosive or ulcerative component. It has been suggested that many of these patients may suffer from fear or anxiety as a result of prolonged treatment with TCs. The objective of this study was twofold: (1) to optimise a patient reported outcome measure (PROM) in order to explore this feature, and (2) to evaluate this PROM in the treatment of OLP patients.

Methods: A group of qualitative researchers adapted the TOPICOP questionnaire in order for it to be used as a PROM for OLP via structural equation modelling (SEM) and internal consistency (IC) analysis. Consequently, 34 patients with symptomatic OLP who were undergoing treatment with TCs completed a questionnaire and underwent a clinical assessment.

Results: SEM presented an adequate fit (RMSA = 0.07, CFI = 0.94 and WRMR = 1.18), as well as a high IC (α?=?0.81). A total of 16 patients (47.1%) reported TCs phobia. The receiver operating characteristic analysis (ROC) revealed that a TOPICOP value ≥50% predicted the presence of TCs phobia with a sensitivity of 93% and a specificity of 100%.

Conclusions: The optimised TOPICOP scale proved valuable as a PROM in OLP. TCs phobia can be a real consideration in OLP, nonetheless, it does not appear to be an impediment to treatment adherence.     

玉屏风口服液对口腔扁平苔藓组织表皮生长因子受体表达影响的研究

目的探讨玉屏风口服液对表皮生长因子受体(EGFR)在口腔扁平苔藓(OLP)组织中表达的影响。方法采用免疫组化法检测EGFR在OLP组织和口服玉屏风液2个月后OLP组织中的表达,正常口腔黏膜组织作为对照。结果OLP组织中EGFR的表达高于正常黏膜组织;用药后OLP组织EGFR的表达与正常黏膜组织差异无显著性。结论玉屏风口服液能下调EGFR在OLP组织中的表达。     

Unstimulated whole salivary flow rate and anxiolytics intake are independently associated with oral Candida infection in patients with oral lichen planus

Many factors have been proposed to influence oral infection with yeast. The aim of this study was to determine the prevalence of oral yeasts in oral lichen planus (OLP) patients and control subjects, and to perform a multiple logistic regression analysis to identify factors that influence oral Candida infection in OLP patients. In this cross‐sectional study, 90 new patients with OLP and 90 sex‐ and age‐matched control subjects with no mucosal lesions were interviewed about their health status, use of medication, and smoking and alcohol habits. Swab and unstimulated whole saliva samples were collected and salivary pH was measured. A positive Candida culture was more prevalent among OLP patients (48.9%) than among control subjects (26.7%). Candida albicans was the most frequently isolated species in both groups. By logistic regression analysis, unstimulated whole salivary flow rates of 0.11–0.24 ml min^?1 (OR = 5.90) and 0.25–0.32 ml min^?1 (OR = 3.51) and benzodiazepine anxiolytics intake (OR = 8.30) were independently associated with the presence of Candida among OLP patients. Age, denture wearing, levels of dentition, decreased salivary pH, antihypertensive drugs, and alcohol consumption were not associated with oral Candida infection in OLP patients. The results indicate that data on benzodiazepine anxiolytics intake and evaluation of unstimulated whole salivary flow rate should be considered as part of the clinical evaluation to identify OLP patients at risk for Candida infection.     

Lack of evidence of hepatitis in patients with oral lichen planus in China: A case control study

Background

China has been one of the countries with high prevalence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) liver disease. And lichen planus is an extrahepatic manifestation of patients with chronic HCV infection. This case-control study was conducted to investigate the relationship between oral lichen planus (OLP) and HBV/HCV infection in China.

Material and Methods

A total of 776 patients, including 150 patients with OLP (Group OLP), 429 inpatients from the Trauma Ward of Oral and Maxillofacial Surgery Department (Group A), 110 patients with other oral mucosal diseases, but without a reported association with HCV infection (Group B) and 87 patients with oral lichenoid lesion (Group OLL), were compared with their seroprevalence of anti-HCV antibody (HCVAb), hepatitis B surface antigen (HBsAg) and the parameters of liver functions. Moreover, the clinical characteristics of OLP were also observed, such as gender, age, chief complaint, course of the disease, clinical type, sites involved and so on.

Results

The positive rates of HCVAb and HBsAg in OLP patients were 0.7% and 4%, respectively. Neither HCVAb nor HBsAg was associated with OLP as demonstrated by both the univariate and the multivariate analyses. The clinical features and liver functions of OLP patients with negative or positive HBsAg were nearly the same.

Conclusions

Our findings verify that there is no association between OLP and hepatitis and there is no need to run a screening test for HCV or HBV in OLP patients in China. Key words:Oral lichen planus, hepatitis C virus, hepatitis B virus.     

Analysis of the expression of heat‐shock protein 27 in patients with oral lichen planus

Oral Diseases (2012) 19 , 65–72 Objective: Heat‐shock protein 27 (hsp27) has been implicated in several biological events. In this experimental study, we aimed at analysing, for the first time, the expression of hsp27 in the diverse stages of oral lichen planus (OLP) lesions. Materials and methods: Thirty‐six biopsy specimens of patients with OLP and 10 of healthy patients were selected. OLP specimens were divided into three groups: G1 – moderate or mildly active OLP; G2 – active or moderately active atrophic OLP; G3 – mild or inactive atrophic OLP. Hsp27 expression was analysed by immunohistochemistry (staining intensity and percentage of stained cells), and results of staining were compared between the different groups. Gender, age and anatomical location were also studied. Results: In the basal layer, an increase of hsp27 expression in both G2 and G3 was observed when compared to G1 and control group. In contrast, a decrease of hsp27 expression in the superficial layer was observed in all groups when compared to control group. Conclusion: The increased expression of Hsp27 in the basal layer observed during the OLP evolution and the less staining in the superficial layers in all cases of OLP suggest that hsp27 may have a role in the OLP pathogenesis.