Dental Implants in Patients with Oral Lichen Planus: A Systematic Review.

Background and Objectives: To integrate the available published data on patients with oral lichen planus (OLP) rehabilitated with dental implants, as well as to review the recommendations for OLP patients receiving implants. Materials and Methods: An electronic search was undertaken in February 2019 using five databases. Publications reporting cases of patients with OLP and rehabilitated with implant-supported oral prosthesis were included. Results: Twenty-two publications were included (230 patients, 615 implants). The overall implant failure rate was 13.9% (85/610). In patients with oral squamous cell carcinoma (OSCC) the failure rate was 90.6% (29/32), but none of these implants lost osseointegration; instead, the implants were removed together with the tumor. One study presented a very high implant failure rate, 76.4% (42/55), in patients with "active lichen planus", with all implants failing between 7-16 weeks after implant placement, and its conflicting and incongruent results are discussed in detail. There was a statistically significant difference between the failure rates in implants installed in different jaws (maxilla/mandible) and when implants of different surfaces were used (turned/moderately rough), but not between patients with reticular or erosive OLP types, or between male and female patients. If OSCC patients and the cases of the latter study are not considered, then the failure rate becomes very low (2.7%, 14/523). The time between implant placement and failure was 25.4 ± 32.6 months (range 1-112). The mean ± SD follow-up was 58.9 ± 26.7 months (1-180). Conclusions: When the results of the one study with a very high failure rate and of the cases that developed OSCC are not considered, the dental implant failure rate in OLP patients was 2.7% after a follow-up of approximately five years. Recommendations are given when treating OLP patients with dental implants.

Impact of oral potentially malignant disorders on quality of life.

BACKGROUND: Oral potentially malignant disorders (OPMDs) could have a significant psychological impact on patients, principally because of the unknown risk of malignant transformation, while the physical and functional impairments could differ. This study aimed to assess the impact of three different OPMDs and their disease stages on the quality of life (QoL) of affected patients. METHODS: Oral leukoplakia (OL), oral lichen planus (OLP) and oral submucous fibrosis (OSF) patients who were undergoing treatment at an oral medicine clinic of a dental teaching hospital in India were the study population. All subjects completed the recently developed OPMDQoL questionnaire and a short form 12 item (version 2) health survey questionnaire (SF-12v2). OPMDQoL questionnaire consists of 20 items over four dimensions. A higher score denotes poor OHRQoL. SF-12v2 has two components, a Physical Component Summary (PCS) and Mental Component Summary (MCS). RESULTS: A total of 150 subjects (50 each of OL, OLP and OSF) participated. OL patients (37.7 ± 7.9) reported significantly better OPMDQoL scores than OLP (47.3 ± 5.8) and OSF (45.4 ± 9.2) patients. OLP patients reported significant problems in obtaining a clear diagnosis for their condition, more so than the other OPMDs. OL patients reported fewer problems for the dimension, "physical impairment and functional limitations" than the OLP and OSF patients. A significant trend was observed with the overall OPMDQoL and MCS, deteriorating as the disease stage increased. CONCLUSIONS: OLP and OSF have a significant impact on the QoL of affected individuals: OL less so. Increasing stage of the disease is associated with worsening QoL.

Salivary Cortisol and Salivary Flow Rate in Clinical Types of Oral Lichen Planus.

Patients with oral lichen planus (OLP) may develop immune sialadenitis that causes a dry mouth. The role of cortisol in autoimmune diseases is well known; yet studies on this subject are controversial. In this study, the salivary flow rate and salivary cortisol level were compared among subtypes of OLP. This study involved three groups of patients: (1) 11 with reticular OLP, (2) 20 with atrophic-erosive OLP, and (3) 30 with no apparent oral lesion. The salivary flow rate in the control group was significantly higher than in OLP patients. The mean level of cortisol in atrophic-erosive cases was higher than in reticular cases and in the control group; however, there was no significant difference between the three study groups. In a previous study, there was moderate to severe acinar atrophy in two-thirds of patients with OLP, which may explain the decreased salivary flow rate in these patients.

Alterations in Factors Involved in Differentiation and Barrier Function in the Epithelium in Oral and Genital Lichen Planus.

Lichen planus is a chronic recurrent inflammatory disease affecting both skin and mucosa, mainly in oral and/or genital regions. Keratinocytes go through a well-regulated process of proliferation and differentiation, alterations in which may result in defects in the protective epithelial barrier. Long-term barrier impairment might lead to chronic inflammation. In order to broaden our understanding of the differentiation process in mucosal lichen planus, we mapped the expression of 4 factors known to be involved in differentiation. Biopsies were collected from oral and genital lichen planus lesions and normal controls. Altered expression of all 4 factors in epithelium from lichen planus lesions was found, clearly indicating disturbed epithelial differentiation in lichen planus lesions.

Allelic loss in amalgam-associated oral lichenoid lesions compared to oral lichen planus and mucosa.

BACKGROUND: The amalgam-associated oral lichenoid lesion (AAOLL) shows clinical and histopathological features similar to oral lichen planus (OLP). Molecular researches to improve knowledge of pathogenesis and clinical behavior of AAOLL are still scarce. OBJECTIVE: We investigated for the first time the use of loss of heterozygosity (LOH) as a molecular approach for genetic characterization of AAOLL in comparison with OLP and evaluated the cell proliferation index. MATERIALS AND METHODS: The sample comprised nine AAOLLs, 10 OLPs, and eight NOMs matched by patients' gender and age. LOH was assessed using polymorphic microsatellite markers at chromosomes 9p (D9S157, D9S162, D9S171), 11q (D11S1369), and 17p (TP53, AFM238WF2). Cell proliferation was assessed by immunohistochemical expression of Ki-67 (MIB-1). The association between LOH and Ki-67 was investigated. RESULTS: Loss of heterozygosity occurred in 5/9 AAOLLs and in 2/10 OLPs in at least one marker each, while NOM showed no LOH. Cell proliferation index in AAOLL ranged from 2 to 23%. There was no association between cell proliferation and LOH, independent of the marker. CONCLUSION: Our study shows that the profile of molecular changes in AAOLL and OLP, evaluated by LOH and Ki-67 expression, is similar. Additional studies including larger samples should be performed to confirm or to refute our findings.

Gustatory function and taste perception in patients with oral lichen planus and tongue involvement.

OBJECTIVES: The aim of the study was to evaluate if patients with oral lichen planus (OLP) and tongue involvement have impaired taste function and if there is an association to the perception of pain. MATERIAL AND METHODS: The test group included patients with OLP and involvement of the tongue without treatment (n = 20). Control subjects had no mucosal or systemic disease affecting taste function and were matched for age and gender (n = 20). Patients' intraoral pain and subjective perception of taste were recorded on a visual analog scale. Taste function was assessed by means of the "taste strips." RESULTS: Measured taste function was slightly but significantly decreased in OLP patients compared to control subjects (p = 0.01). Self-rated taste perception did not differ in both groups (p = 0.8). Post hoc analysis showed that particularly the taste quality "sour" was most affected by the OLP status (p = 0.01). There were no correlations between pain and subjective/objective taste perception. CONCLUSION: Untreated OLP subjects have lower gustatory function, which they are not aware of. CLINICAL RELEVANCE: Impaired gustatory function in patients with OLP may affect patient's quality of life. Further studies on larger samples sizes are requested.

Dental implants in patients with oral mucosal diseases - a systematic review.

To reveal dental implants survival rates in patients with oral mucosal diseases: oral lichen planus (OLP), Sjögren's syndrome (SjS), epidermolysis bullosa (EB) and systemic sclerosis (SSc). A systematic literature search using PubMed/Medline and Embase databases, utilising MeSH and search term combinations identified publications on clinical use implant-prosthetic rehabilitation in patients with OLP, SjS, EB, SSc reporting on study design, number, gender and age of patients, follow-up period exceeding 12 months, implant survival rate, published in English between 1980 and May 2015. After a mean observation period (mOP) of 53·9 months (standard deviation [SD] ±18·3), 191 implants in 57 patients with OLP showed a survival rate (SR) of 95·3% (SD ±21·2). For 17 patients with SjS (121 implants, mOP 48·6 ± 28·7 months), 28 patients with EB (165 implants, mOP 38·3 ± 16·9 months) and five patients with SSc (38 implants, mOP 38·3 ± 16·9 months), the respective SR was 91·7 ± 5·97% (SjS), 98·5 ± 2·7% (EB) and 97·4 ± 4·8% (SSc). Heterogeneity of data structure and quality of reporting outcomes did not allow for further comparative data analysis. For implant-prosthetic rehabilitation of patients suffering from OLP, SjS, EB and SSc, no evidence-based treatment guidelines are presently available. However, no strict contraindication for the placement of implants seems to be justified in patients with OLP, SjS, EB nor SSc. Implant survival rates are comparable to those of patients without oral mucosal diseases. Treatment guidelines as for dental implantation in patients with healthy oral mucosa should be followed.

Low basal salivary flow and burning mouth syndrome: new evidence in this enigmatic pathology.

BACKGROUND: Burning mouth syndrome remains a puzzling condition. One symptom commonly associated with the burning sensation is xerostomia. The current study measured basal and stimulated salivary flow in a group of burning mouth syndrome patients. METHODS: Three groups of patients were recruited: 44 burning mouth syndrome patients, 27 oral lichen planus patients and 40 healthy patients. We chose to measure basal salivary flow and stimulated salivary flow in the three groups of patients using the 'spitting' method. Thus, the patients were asked to spit every minute for 5 min. Afterwards, they were asked to repeat the procedure a second time, but a drop of citric acid was positioned on their tongue every minute to stimulate salivary secretion. After 14 days, the same procedure was repeated for 15 min. RESULTS: Although there was no significant difference between the burning mouth syndrome group and the other two groups regarding the stimulated volumes, an important difference was found in the basal volumes, with the burning mouth syndrome patients showing lower values. CONCLUSIONS: The outcomes of our research demonstrate the presence of very low basal salivary flow in burning mouth syndrome patients compared with the other two groups, but the stimulated salivary flow was equal, if not higher, in the burning mouth syndrome patients. This study contributes new topics for further investigation of a solution to the very mysterious pathology represented by burning mouth syndrome.

Evaluation of the Effects of Dental Implants on Oral Lesions.

OBJECTIVE: To determine whether dental implants impress oral lesions, and to evaluate the nature of their effect on the lesions. MATERIALS AND METHODS: A comprehensive search was done via Google and PubMed for articles (including case reports and literature reviews) containing the keywords 'oral squamous cell carcinoma' (OSCC), 'oral lichen planus' (OLP), 'lichenoid contact reaction' (LCR), 'osseointegrated implants', and 'dental implants' , in the last 10 years (2002-2012). RESULTS: The study included 24 articles involving patients with dental implants, and some oral lesions (e.g. oral lichen planus and oral squamous cell carcinoma) or with a history of lesions. In these publications, there is evidence suggesting the possibility of emergence, exacerbation, recurrence, or even malignant transformation of the oral lesions after implant placement in some cases. CONCLUSION: Based on our review of the literature, implant treatment does not seem to be completely safe under any circumstances, but may have some complications in subjects with certain diseases (e.g. oral lesions, autoimmune diseases, malignancies, allergic reactions, etc.). Therefore prior to treatment, patients should be fully informed of the risks. CLINICAL SIGNIFICANCE: Implant treatment is best done with caution in patients with cancer or mucocutaneous disorders.

Diurnal trajectories of salivary cortisol, salivary α-amylase and psychological profiles in oral lichen planus patients.

Although many reports have been published on the link between oral lichen planus (OLP) and the stress-related neuro-psycho-endocrine clinical features of the disease over the last 20 years, the data still remain controversial. Therefore, the aim of this study was to explore the personality traits of OLP subjects and assess the subjects' capability of coping with stress challenges. Cortisol and alpha-amylase were measured as reliable markers of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) activities in salivary samples collected by the participants at their home during the sampling day (07:30, 12:00, and 19:30). Compared with the healthy controls, the OLP patients demonstrated a less effective coping ability, had higher scores in stress perception and loneliness, and had no significant variation in their anxiety and depressive symptoms. The OLP patients also showed dysregulation of the HPA axis activity with a significant reduction of diurnal salivary cortisol production, which was particularly significant in the morning hours. No significant variation was found in the OLP salivary alpha-amylase diurnal fluctuation and production, which was measured at the same time point as that for cortisol. In conclusion, we report that OLP subjects had a reduced capability of coping with stress events and presented a dysregulation of HPA axis activity with hypocortisolism detected in the morning hours.

Association of autoimmune diseases with oral lichen planus: a cross-sectional, clinical study.

BACKGROUND: The aim of this study was to investigate the association between autoimmune disease and oral lichen planus (OLP), comparing OLP patients with a control population. METHODS: This cross-sectional clinical study evaluated the prevalence of autoimmune diseases in male and female patients with OLP. The variables analysed were age, sex, tobacco and alcohol consumption, the clinical form of OLP, time of evolution and the presence of autoimmune diseases. RESULTS: Autoimmune diseases were present in 7% of OLP patients (10/130) and 4% of the control group (6/130) without statistically significant difference (P = 0.67). The estimated odds ratios (with 95% confidence intervals) of the presence of autoimmune disease in OLP sufferers was 1.033 (0.97-1.10). A logistic regression model for presence/absence of the risk autoimmune disease found statistically significant differences in relation to age. CONCLUSIONS: At present, there is no definitive hypothesis that explains the coexistence of OLP and autoimmune disease; further research is required into the mechanisms whereby this coexistence occurs.

Oral health-related quality of life of patients with oral lichen planus, oral leukoplakia, or oral squamous cell carcinoma.

PURPOSE: To compare oral health-related quality of life (OHRQoL) of patients with oral lichen planus (OLP), oral leukoplakia (OL), or oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Seventy-three patients with OLP, 44 with OL, and 37 with OSCC participated in this prospective study. The German version of the 14-item Oral Health Impact Profile (OHIP-G 14) was used to measure OHRQoL. Descriptive statistics and multivariate analysis of clinical forms, age, gender, alcohol consumption, and smoking habits were evaluated. RESULTS: No association to cumulative OHIP-14 score (P = .086) among the 3 groups was found. However, patients with OLP showed a higher "physical pain" score and a lower "social disability" score (P = .026) than patients with OSCC, followed by patients with OL. Women with OLP had a lower OHRQoL than men. After differentiation of clinical forms of OLP (symptomatic vs asymptomatic), an impact on these patients' OHRQoL in the dimensions "physical pain" and "physical disability" was found. CONCLUSION: Patients with OLP or OSCC and high OHIP-G 14 scores reported physical pain, which emphasizes the need for physical therapy. For improved OHRQoL, patients with symptomatic forms of OLP would gain more from a treatment compared with those with asymptomatic forms. In contrast, patients with asymptomatic OLP or OL and thus with a minimal impact on their OHRQoL might be at risk of delayed consultation, diagnosis, and treatment of their condition.

Clinical evaluation of the efficiency of low-level laser therapy for oral lichen planus: a prospective case series.

Oral lichen planus (OLP) is an inflammatory disease that can be painful, mainly in the atrophic and erosive forms. Numerous drugs have been used with dissimilar results, but most treatments are empirical. However, to date, the most commonly employed and useful agents for the treatment of OLP are topical corticosteroids. The study objective was to detail the clinical effectiveness of low-level laser therapy (LLLT) for the management of OLP unresponsive to standard topical therapy. The authors studied a prospective cohort of 30 patients affected by OLP, who received biostimulation with a 980-nm gallium-aluminum-arsenide (GaAIAs) diode laser (DM980, distributed by DMT S.r.l., Via Nobel 33, 20035, Lissone, Italy). Outcome variables, statistically evaluated, were: the size of lesions; visual analogue score of pain and stability of the therapeutic results in the follow-up period. Eighty-two lesions were treated. We reported significant reduction in clinical scores of the treated lesions and in reported pain. No detailed complications or therapy side effects were observed during the study. As previously reported by our group with a preliminary report, this study suggests that LLLT could be a possible treatment choice for patients with unresponsive symptomatic OLP, also reducing the possible invasiveness correlated with other therapies.

New perspectives on the dynamic behaviour of oral lichen planus.

Lichen planus, a chronic inflammatory disease that affects the skin and mucous membranes, is one of the most frequent dermatological disorders of the oral cavity. The prevalence of oral lichen planus ranges from 0.2% to 4%. The triggering factors remain unknown. Oral lichen planus can be considered to be a chronic disease of long duration with a dynamic evolution and frequent changes in clinical appearance. Three successive active stages can be distinguished, without sharp limits between them: an initial stage; a protracted intermediate stage with alternate periods of variable activity and quiescence, which carries a progressively increasing risk of malignant transformation; and a late stage that often ends in a clinically little-known, inactive cicatricial post-lichen stage, which does not respond to steroid treatment but retains the same risk.

The possible roles of OPN-regulated CEACAM1 expression in promoting the survival of activated T cells and the apoptosis of oral keratinocytes in oral lichen planus patients.

Oral lichen planus is a chronic inflammatory disorder of the oral mucosa that represents T cell-mediated autoimmune diseases. The regulation and roles of carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1), a novel immune molecule, in the immunopathogenesis of T cell-mediated autoimmune diseases remain unclear. In the current paper, CEACAM1 was found to be overexpressed in peripheral T cells and epithelial cells in oral lichen planus patients. A fraction of infiltrating inflammatory mononuclear cells in the lamina propria of the oral lichen planus mucosa also expressed CEACAM1. Importantly, for the first time, CEACAM1 expression in T cells and in normal human oral keratinocytes was demonstrated to be regulated differently by osteopontin in vitro. Furthermore, the apoptosis of oral keratinocytes and activated T cells can be markedly suppressed by CEACAM1-specific monoclonal antibodies. In conclusion, OPN-regulated CEACAM1 expression may play a critical role in the immunopathogenesis of oral lichen planus.

Upregulation of transient receptor potential vanilloid type-1 receptor expression in oral lichen planus.

OBJECTIVES: Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa. Its etiology is still unclear. Neurogenic components might contribute to the inflammatory process. The oral mucosa is richly innervated by sensory fibers. Mediators secreted by inflammatory cells activate sensory nerves via transient receptor potential vanilloid receptor 1 (TRPV1) and lead to the release of neuropeptides. So far, TRPV1 receptor expression was detected on neurons. Only recently, TRPV1 receptors were identified in nonneuronal tissues. The aim of the present study was to detect the presence of TRPV1 receptors and peripheral expression of receptor mRNA in normal oral mucosa and mucous membranes from OLP patients. METHODS: Presence of TRPV1 receptor proteins in the mucosal tissue was assessed by immunohistochemistry. Expression of TRPV1 receptor mRNA was determined by quantitative RT-PCR. RESULTS: We provided qualitative and quantitative immunohistochemical evidence that TRPV1 receptors are present in normal human oral mucosa and that their expression is increased in OLP. The number of immunopositive cells was elevated in the epithelium, and vascular endothelial cells, lymphocytes and fibroblasts of the subepithelium were also labeled in samples obtained from OLP patients. The local expression of nonneuronal TRPV1 receptors was proven at mRNA level using quantitative real-time RT-PCR. CONCLUSIONS: Since the number of TRPV1 receptor-positive nonneural cells is increased in inflammatory conditions, we hypothesize that TRPV1-receptor-mediated processes might play role in the pathogenesis of OLP.

Research trends and characteristics of oral lichen planus: A bibliometric study of the top-100 cited articles.

BACKGROUND: Bibliometric analysis highlights the key topics and research trends which have shaped the understanding and management of a concerned disease. The objective of this study was to identify and characterize the most-cited articles on oral lichen planus (OLP), and highlight the analysis of key topics and research trends. METHODS: A comprehensive search was performed and identified in the Scopus database from 1907 to 5 March 2019 for the top-100 most-cited articles on OLP. RESULTS: The number of citations of the 100 selected articles varied from 101 to 570, with a mean of 178.7 citations per article. Malignant potential, immunopathogenesis, and topical drug therapy were the top-3 study topics, and the majority of high-quality articles were the research of the 3 topics. Journal of Oral Pathology and Medicine (n = 19) and Oral Surgery Oral Medicine Oral Pathology Oral Radiology (n = 14) were 2 journals with the most articles published. Both van der Waal I. and Scully C. were the most frequently contributing authors (n = 9). United States (n = 27) and Academic Centre for Dentistry Amsterdam (n = 7) was the most contributing country and institution, respectively. Systematic reviews (n = 2), randomized controlled trial (n = 1), cohort studies (n = 17) were study designs with higher evidence level, but the large majority (n = 80) were considered lower level. CONCLUSIONS: The results of this first citation analysis of the 100 most cited articles on OLP provide a historical perspective on scientific evolution, and suggest further research trends and clinical practice in the field of OLP.

Common benign and malignant oral mucosal disease.

BACKGROUND: Mucosal diseases of the oral cavity are relatively common, and patients often seek initial assessment from their general practitioner. OBJECTIVE: The aim of this article is to provide an overview of common oral mucosal diseases to help with formulating a differential diagnosis and stratifying the urgency of referral. DISCUSSION: Pathological mucosal conditions of the oral cavity and jaws commonly present as a mucosal ulcer or a white, red or pigmented lesion. In this review, the authors outline the most common conditions organised according to their clinical presentation and describe their typical appearance and management.

Differential gene expression profiles of whole lesions from patients with oral lichen planus.

BACKGROUND: The molecular biological properties of oral lichen planus (OLP) are largely unknown. The aim of this study was to identify the genes responsible for its pathogenesis at the genome scale using DNA microarray technology. METHODS: The RNA samples extracted from the specimens of nine OLP patients and nine controls were analyzed with Affymetrix GeneChip. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis was applied to confirm GeneChip results. RESULTS: A total of 985 differentially expressed genes (629 up-regulated and 356 down-regulated) were identified. These genes were involved in many function classifications and biochemical pathways. The results of quantitative RT-PCR analysis of FOXP3, VEGFA, ANGPT1, MMP1, and SCGB2A2 were consistent with their changes demonstrated by GeneChip. CONCLUSIONS: This study showed the gene expression profiles of OLP, which were quite distinct from that of healthy controls. These results presented a global view of physiopathologic processes in lesions, which will give important clues to understand pathogenesis and identify new therapeutic targets of OLP.