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Background: Oral Lichen Planus is a chronic inflammatory disorder that affects the oral mucosa, with the reticular and erosive forms representing the primary clinical variants of the disease. Previous studies have shown that metabolic alterations may well be involved in the pathogenesis of the disease; however, the molecular mechanisms related to the clinicopathological differences between erosive and reticular forms remain unknown., Methods: A comparative metabolomic analysis was performed on formalin-fixed and paraffin-embedded tissue samples of erosive (n = 6) and reticular (n = 10) oral lichen planus using gas chromatography-mass spectrometry., Results: The metabolomic analysis showed a distinct profile between the two clinical variants. Five metabolites (cyclohexanamine, glycine, mannitol/sorbitol, methyl palmitate and trehalose) were significantly diminished in erosive oral lichen planus as compared to the reticular form., Conclusions: Reticular and erosive forms of oral lichen planus have a distinct metabolic profile. However, further studies using a large number of fresh tissue samples are necessary to confirm this data., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: To evaluate the impact of a structured plaque control intervention on clinical and patient-centred outcomes for patients with gingival manifestations of oral lichen planus., Materials and Methods: Eighty-two patients were recruited into a 20-week randomized controlled trial. The intervention was structured plaque control comprising powered tooth brushing and inter-dental cleaning advice. Control subjects continued with their normal dental plaque control regimen. The primary outcome measure was the oral health impact profile (OHIP) with secondary outcomes of pain, plaque index, mucosal disease score and cost-effectiveness., Results: Overall, the intervention patients showed statistically significant improvements in OHIP sum ordinal and OHIP dichotomous scores compared with control. There were improvements in the functional limitation, psychological discomfort and physical disability domains at 4- and 20-weeks and in the psychological disability domain at 20-weeks. The intervention was successful in reducing plaque compared to control (p < 0.001) and improvements were observed using the mucosal disease indices at the 4- and 20-week follow-ups (p < 0.001)., Conclusion: A structured plaque control intervention was effective in improving the oral health-related quality of life and clinically observed gingival lesions. This study provides evidence to include intensive plaque control within patients' initial and on-going management., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Lichen planus together with its oral variant is a chronic, inflammatory disease of the skin and the mucosa of unclear aetiology and with an unpredictable course that still poses a major problem in terms of diagnosis and treatment. The objective of this study was to assess the concentrations of interleukin-6 (IL-6) and neopterin in saliva and serum of patients with lichen planus (including reticular and erosive form of oral lichen planus) and to compare them with the concentrations observed in healthy controls., Methods: The study material comprised serum and saliva samples from 56 patients diagnosed with lichen planus and 56 healthy volunteers. The ELISA test was used to measure concentrations of IL-6 and neopterin in the serum and saliva of the study participants., Results: The concentrations of IL-6 in saliva and serum of patients with lichen planus were significantly higher than in controls (P = 0.0002; P < 0.0001). The difference remains significant after adjustment for gingivitis and age. Patients with atrophic-erosive oral lichen planus had significantly higher IL-6 concentrations in their saliva compared to patients with reticular form of disease (P = 0.01). The concentrations of neopterin were significantly higher in the serum but not in saliva of lichen planus patients vs. controls (P <0.0001)., Conclusions: Serum levels of proinflammatory cytokines IL-6 and neopterin are increased in lichen planus as well as the salivary concentrations of IL-6. The differences observed in IL-6 levels in patients with erosive-atrophic forms of oral lichen planus may indicate a substantial role played by the cytokine in the disease., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Oral lichen planus (OLP) is an immune-mediated mucocutaneous disease of uncertain aetiology. OLP has many manifestations: reticular, erosive, atrophic, plaque like, papular, bullous, with unique etiopathogenetic working. The purpose of this study is to find a link between different clinical types of lichen and the alterations of lymphocytes on peripheral blood and oral mucosa., Materials and Methods: A total of 21 patients were enrolled in this study. The mean age of patients was 53.82 years, between 31 and 78 years. OLP Diagnosis was afterwards confirmed by histopathology. Selected patients underwent to clinical evaluation, lesion characterization, incisional biopsy, samples histological analysis, peripheral blood collection. Blood specimens were submitted to cell count determination with differential, characterization of populations and circulating lymphocyte subpopulations using monoclonal antibodies in flow cytometry. Referring to the clinical presentation of lesions, patients were divided in two groups: red lesions (RL) and white lesions (WL) and compared with an age-matched control group., Results: The results of the immunophenotypic study showed correlation between WL and the expression of CD19 lymphocytes (r = 0.693, P = 0.0005). The results of immunohistochemical study performed on histological specimens showed a significant correlation between RL group and expression of all lymphocyte tested (CD3 r = 0.722 P = 0.0002, CD4 r = 0.579 P = 0.0060, CD56 r = 0.513 P = 0.0173, CD8 r = 0.548 P = 0.0102)., Conclusions: We assume there is the responsibility of the expression of lymphocytes, not only type but also as quantity, in determining RL or WL manifestation of OLP. Circulating lymphocytes may have a role, too., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2010 John Wiley & Sons A/S.)

Objectives: This study describes the clinicopathological characteristics of a group of patients with oral lichen planus (OLP) in south-eastern Spain., Materials and Methods: A retrospective descriptive study was made of 550 patients clinically and histopathologically diagnosed with OLP in the period 1991-2007. Patient gender, age, the prevalence of hepatitis C, symptoms and malignization were recorded. The clinical forms were classified as reticular-papular and atrophic-erosive., Results: Of the 550 patients, 128 (23.3%) were men and 422 (76.7%) women. The mean age was 56.35 +/- 13.67 years (range 14-91). The prevalence of hepatitis C was 3.5%. The red clinical forms were the most frequent, with 359 cases (64.2%). The lesions were asymptomatic in 159 patients (28.9%). Five patients developed oral squamous cell carcinoma (0.9%); none of these subjects was smokers., Conclusions: Patients with OLP present different clinical manifestations. Women were more frequently affected by the disease, and the malignant transformation rate was under 1%.

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

Background: Nuclear factor-kappa B (NF-kappaB) is believed to be involved in the pathogenesis of various inflammatory diseases, including oral lichen planus (OLP). The objective of the present study was to investigate the possible relationship between NF-kappaB activation and expression of tumor necrosis factor-alpha (TNF-alpha) in OLP and their expression pattern in relation to several clinical features., Methods: Thirty OLP cases were divided into atrophic-erosive form (14 cases) and reticular form (16 cases) according to their clinical manifestations. The expression of NF-kappaB p65 and TNF-alpha of both two groups were investigated by immunohistochemical staining, and the percentage of positive cells was calculated in each case. Biopsies of 10 normal oral mucosa (NOM) also underwent the same procedure as controls., Results: Nuclear factor-kappa B p65 nuclear staining was found in nuclei of basal and suprabasal epithelial keratinocytes in OLP, however, no positive staining was found in NOM. Positive TNF-alpha staining was detected in cytoplasm of basal epithelial keratinocytes in OLP, and only scattered staining was detected in NOM. Expression of NF-kappaB p65 and TNF-alpha were significantly different with respect to clinical forms and lesion sites (P < 0.05), except for genders (P > 0.05) in 30 OLP cases. NF-kappaB nuclear staining positively correlated (r = 0.676, P < 0.01) with TNF-alpha overexpression in OLP., Conclusions: Nuclear factor-kappa B activation and its correlation with overexpression of TNF-alpha may play an important role in pathogenesis of OLP. There might be a positive regulatory loop between NF-kappaB and TNF-alpha, which may contribute to inflammation in OLP; NF-kappaB may also protect epithelial keratinocytes from excessive apoptosis.

Background: Caspase-3 (CPP32) and Bax expression levels in oral lichen planus (OLP) lesions are considered reliable markers of apoptosis. The malignant transformation of OLP remains a very controversial matter. The objective of this study was to compare histological and apoptotic phenomena between atrophic-erosive and reticular forms of OLP., Methods: Analysis was conducted of biopsy samples from 18 patients with reticular and 14 with atrophic-erosive OLP. Conventional histology techniques were used to quantify histological markers of OLP and peroxidase/anti-peroxidase techniques to determine apoptosis markers caspase-3 (CPP32) and Bax., Results: More Civatte bodies and lymphocyte exocytosis were observed in atrophic-erosive than reticular OLP samples, without any statistical difference. No statistical significant differences in caspase-3 expression were found between these OLP forms in suprabasal layer (58.3% vs. 43.8%), basal layer (83.3% vs. 68.8%) or infiltrate (69.2% vs. 46.6%). Bax expression was relatively infrequent, and no differences were observed between atrophic-erosive and reticular forms., Conclusions: The low frequency of apoptotic phenomena (caspase-3 and Bax) in epithelial cells of OLP may create a favourable substrate for malignant transformation. However, there does not seem to be an association with the clinical form (atrophic-erosive or reticular).

At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the UK issues related to terminology, definitions and classification of oral precancer were discussed by an expert group. The consensus views of the Working Group are presented here. The term, 'potentially malignant disorders', was recommended to refer to precancer as it conveys that not all disorders described under this term may transform into cancer. Critically evaluating all definitions proposed so far for oral leukoplakia, the Working Group agreed that the term leukoplakia should be used to recognize 'white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer'. An outline was proposed for diagnosing oral leukoplakia that will prevent other oral white disorders being misclassified as leukoplakia. The Working Group discussed the caveats involved in the current use of terminology and classification of oral potentially malignant disorders, deficiencies of these complex systems, and how they have evolved over the past several decades. The terminology presented in this report reflects our best understanding of multi-step carcinogenesis in the oral mucosa, and aspires to engender consistency in use.

Background: Common clinical forms of oral lichen planus (OLP) and oral lichenoid reactions (OLR) are erythematous (ERY) or reticular (RET). The purpose of this study was to find histopathological changes that differ between these forms., Methods: Epithelial thickness, epithelial proliferation rate, apoptosis, and HLA-DR expression were compared among 10 reticular and 12 erythematous lesions, and 11 normal oral mucosa samples (NOM)., Results: The epithelium in ERY was thinner than in NOM, whereas RET showed values between ERY and NOM. Cell proliferation increased significantly in ERY as compared with RET and NOM, with no difference between RET and NOM. Relative numbers of epithelial cell nuclei displaying visible chromatin condensation were reduced in ERY form., Conclusions: The markedly increased cell proliferation in ERY supports the notion that this form displays a higher disease activity as compared to RET. It can therefore be important to study each disease form separately.

Background: Oral lichen planus (OLP) is a T cell-mediated inflammatory disease. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has effects on cellular and humoral immunities. Previous studies have shown that keratinocytes and tissue-infiltrating mononuclear cells from OLP lesions can secrete IL-6. In some OLP patients, the high serum IL-6 levels are reduced after treatment, suggesting that IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP., Methods: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 in a group of 180 patients with erosive OLP (EOLP), nonerosive OLP (NEOLP), erythema multiforme (EM), traumatic ulcers (TU), oral submucous fibrosis (OSF), pemphigus vulgaris (PV), or Sjögren's syndrome (SS), and in 77 normal control subjects. Some OLP patients were treated with levamisole plus Chinese medicinal herbs or levamisole only for 0.5-5.5 months and their serum IL-6 levels were measured after treatment., Results: We found that approximately 99% of the normal control subjects and the patients with EM, TU, or OSF had a normal serum IL-6 level less than 5.0 pg/ml. However, 15% (22/149) OLP patients, 15% (20/136) EOLP patients, 20% (5/25) major type EOLP patients, 14% (15/111) minor type EOLP patients, 15% (2/13) NEOLP patients, 14% (1/7) EM patients, 43% (3/7) PV patients, and 100% (6/6) SS patients had a serum IL-6 level greater than 5.0 pg/ml. The mean serum IL-6 level in patients with OLP (3.4 +/- 3.1 pg/ml, P < 0.001), EOLP (3.4 +/- 3.2 pg/ml, P < 0.001), major type EOLP (4.9 +/- 3.5 pg/ml, P < 0.001), minor type EOLP (3.0 +/- 3.0 pg/ml, P < 0.01), or NEOLP (4.2 +/- 1.5 pg/ml, P < 0.001) was significantly higher than that in normal control subjects (2.0 +/- 1.5 pg/ml). A significant difference in the mean serum IL-6 level was also found between major type and minor type EOLP patients (P < 0.01). The mean reduction of serum IL-6 level in OLP patients treated with levamisole plus Chinese medicinal herbs was significantly higher (7.4 +/- 4.7 pg/ml) than that in OLP patients treated with levamisole only (3.8 +/- 2.3 pg/ml, P < 0.05), suggesting that the combination therapy was superior to levamisole only., Conclusion: We conclude that levamisole and levamisole plus Chinese medicinal herbs can modulate the serum IL-6 level in OLP patients. IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP.

A variety of betel/areca nut/tobacco habits have been reviewed and categorized because of their possible causal association with oral cancer and various oral precancerous lesions and conditions, and on account of their widespread occurrence in different parts of the world. At a recent workshop in Kuala Lumpur it was recommended that "quid" be defined as "a substance, or mixture of substances, placed in the mouth or chewed and remaining in contact with the mucosa, usually containing one or both of the two basic ingredients, tobacco and/or areca nut, in raw or any manufactured or processed form." Clear delineations on contents of the quid (areca nut quid, tobacco quid, and tobacco and areca nut quid) are recommended as absolute criteria with finer subdivisions to be added if necessary. The betel quid refers to any quid wrapped in betel leaf and is therefore a specific variety of quid. The workshop proposed that quid-related lesions should be categorized conceptually into two categories: first, those that are diffusely outlined and second, those localized at the site where a quid is regularly placed. Additional or expanded criteria and guidelines were proposed to define, describe or identify lesions such as chewer's mucosa, areca nut chewer's lesion, oral submucous fibrosis and other quid-related lesions. A new clinical entity, betel-quid lichenoid lesion, was also proposed to describe an oral lichen planus-like lesion associated with the betel quid habit.