Salivary cytokine profile in patients with oral lichen planus / Perfil de citoquinas salivales en pacientes con liquen plano oral

Abstract This study aimed to determine salivary concentrations of interleukin (IL)-1β, IL-2, IL-10, IL- 23, transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, nitrate (a by-product of nitric oxide oxidation), and cortisol in patients with oral lichen planus (OLP). Twenty patients diagnosed with OLP and 20 sex-matched healthy volunteers (HV) were included in this cross-sectional study. Unstimulated whole saliva was collected in the morning. Salivary cytokine and cortisol concentrations were determined by enzyme-linked immunosorbent assays (ELISA). Nitrate was measured in a nitric oxide analyzer. We found higher salivary concentrations of IL-2 (p<0.003), IL-23 ( p<0.04), and TGF-β (p=0.05) in patients with OLP compared to HV. No significant differences were found in salivary levels of TNF-α, IL-1β, or IL-10. Nitrate concentrations were markedly increased in OLP patients (1,227.0 ± 738.8 µM/mg total protein) when compared to HV (261.6 ± 166.8 µM/mg; p<0.0001). Salivary cortisol levels were also higher in OLP patients (2.79 ± 1.39 vs. 1.94 ±1.21 ng/mg; p<0.048). The markedly increased salivary levels of nitric oxide in patients with OLP suggest a relationship of this molecule with the cell death and tissue damage observed in these lesions.

Resumen Este estudio tuvo como objetivo determinar las concentraciones salivales de interleucina (IL)-1β, IL-2, IL-10, IL-23, factor de crecimiento transformante (TGF)-β y factor de necrosis tumoral (TNF)-α, nitrato (subproducto de la oxidación del óxido nítrico) y cortisol en pacientes con liquen plano oral (OLP). En este estudio transversal se incluyeron veinte pacientes diagnosticados con OLP y 20 voluntarios sanos (HV) del mismo sexo. Saliva entera no estimulada Se recolectó por la mañana, se determinaron las concentraciones de citocinas y cortisol en saliva mediante ensayo inmunoabsorbente ligado a enzimas (ELISA), se determinó nitrato mediante un analizador de óxido nítrico, se encontraron concentraciones salivales mayores de IL-2 (p<0,003), IL- 23 (p<0,04) y TGF-β (p=0,05) en pacientes con OLP en comparación con HV. No se encontraron diferencias significativas en los niveles salivales de TNF-α, IL-1β e IL-10. Las concentraciones de nitrato fueron marcadamente aumentó en pacientes con OLP (1227,0 ± 738,8 µM/mg de proteína total), en comparación con HV (261,6 ± 166,8 µM/mg; p<0,0001). Los niveles de cortisol salival también fueron más altos en los pacientes con OLP que en los controles (2,79 ± 1,39 vs. 1,94 ±1,21 ng/mg; p<0,048). Los niveles de óxido nítrico en saliva aumentaron notablemente en pacientes con OLP, lo que sugiere una relación de esta molécula con la muerte celular y el daño tisular observado en las lesiones de OLP.

Childhood lichenoid granulomatous stomatitis: a case report and literature review / 口腔疾病防治

Objective@#To investigate the classification, clinical manifestations, diagnosis, differential diagnosis and treatment of oral lichenoid lesions and provide a reference for clinical practice.@*Methods@#Hospital ethical approval and patient informed consent were obtained. We report a case of oral lichenoid lesion in children and review the diagnosis and treatment of oral lichenoid damage in the literature.@*Results@#The patient experienced repeated rupture of the dorsal surface of the tongue with pain for more than 3 years. There was a large area of tongue back surface erosion with an irregular shape, surrounded by pearly-white lines. The left erosive area was accompanied by tissue hyperplasia, which was approximately 1.5 cm × 2.0 cm, with tough texture and broad masses. The pathological diagnosis of the patient was oral lichenoid lesion. After biopsy of the dorsal surface of the tongue, the pathological diagnosis of the patient was granulomatous inflammation. The final diagnosis of lichenoid granulomatous stomatitis was made on the basis of the patient's intraoral damage features, systemic history, medication history and histopathological findings. A review of the literature suggests that oral lichenoid lesions have an unknown etiology and need to be clinically differentiated from oral lichen planus, oral lichenoid drug reactions, oral lichenoid contact damage and chronic ulcerative stomatitis. The clinical treatment of oral lichen planus is based on the topical and/or systemic use of glucocorticoids.@*Conclusion@#There are still no uniform criteria for the classification and diagnosis of oral lichenoid lesions. They rely mainly on history taking, clinical manifestations and histopathological findings, and the treatment is mainly based on the topical and/or systemic use of glucocorticoids.

Detection of molecular affecting sensitivity to local glucocorticoid therapy in oral lichen planus through transcriptome sequencing / 北京大学学报(医学版)

Objective:To detect key genes of local glucocorticoid therapy in oral lichen planus(OLP)through transcriptome sequencing.Methods:The study prospectively enrolled 28 symptomatic patients who visitied Department of Oral Mucosa,Peking University Hospital of Stomatology from November 2019 to March 2023.Topical inunction of 0.1 g/L of dexamethasone was applied for 1 min,3 times daily for 4 weeks.The patients'signs and pain symptoms were recorded and they were classified as effective group and ineffective group according to the treatment outcome.Their mucosa samples were collected before treatment.After isolating total RNA,transcriptome sequencing was performed.The gene expression data obtained by sequencing were analyzed differently using the DESeq2 package in R software,and the Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis was performed on the basis of the hypergeometric distribution algorithm to describe the biological function of differentially expressed genes(DEGs),accordingly detecting sensitivity related molecular affecting therapeutic effect of dexamethasone.Results:After 4 weeks treatment by topical dexamethasone,13 cases of the 28 OLP pa-tients responding well with the sign score reducing from 7.0(4.5,9.0)to 5.0(3.0,6.3),pain score decreasing from 5.0(2.0,5.5)to 2.0(0.0,3.5),oral health impact profile lessening from 5.0(3.5,9.0)to 1.0(0.0,5.0)significantly(P＜0.01)were classified as effective group and 15 cases with poor response to the drug were sorted as ineffective group.There were no significant differences of demographic and baseline levels of clinical features,especially disease severity between these two groups.A total of 499 DEGs including 274 upregulated and 225 downregulated genes were identified between ef-fective group and ineffective group.KEGG enrichment analysis showed that upregulated genes in effective group compared with ineffective group including CLDN8,CTNNA3,MYL2 and MYLPF were associated with leukocyte transendothelial migration,while downregulated genes were significantly enriched in tumor necrosis factor(TNF),interleukin-17(IL-17),nuclear factor kappa B(NF-κB)signaling pathways,and cortisol synthesis and secretory.Conclusion:High expressions of CLDN8,CTNNA3,MYL2 and MYLPF genes in patients with oral lichen planus have a good clinical response to topical dexamethasone,while patients with high expression genes of inflammation pathway such as TNF,IL-17,NF-κB and corti-sol synthesis and secretion received poor effect.

Research progress on oral lichenoid drug reactions / 口腔疾病防治

@#Oral lichenoid drug reactions (OLDRs) are inflammatory reactions of the oral mucosa caused by the use of specific drugs in sensitive individuals and are classified as oral lichenoid lesions (OLLs). Its clinical and pathological manifestations do not have significant specificity compared to other types of OLL. Various types of drugs have been reported to induce OLDR, including antihypertensive drugs, nonsteroidal anti-inflammatory drugs, hypoglycemic drugs, antipsychotics, and immunosuppressants, among other drugs. Apart from local or systemic administrate glucocorticoids, the most effective treatment measure is to stop using suspicious drugs. Most patients can achieve significant relief from mucosal ulcers and erosion, but white lines may still remain. OLDR has been widely reported in the literature. However, due to a lack of systematic understanding, we do not have a recognized standard for the diagnosis and treatment of this disease. There are still doubts about the causal relationship between related drugs and oral lichen-like lesions. In response to the abovementioned problems, we searched the literature on drug-related oral lichen planus and lichen-like lesions at home and abroad over the past 20 years, most of which were case reports and only a few of which were case-control studies. This article describes the current research status of lichenoid lesions from four perspectives: concepts, suspicious drugs, clinical and pathological manifestations, and treatment prognosis. We hope to provide a theoretical reference for the prevention, diagnosis, and clinical treatment of related lichenoid lesions. A literature review demonstrated that there are still many unclear issues related to the etiology, pathogenesis, clinical diagnosis and treatment, treatment prognosis, and other aspects of this disease, and further clinical and basic research is needed for in-depth exploration.

Low dose oral glucocorticoid therapy in lichen planus: A retrospective cohort study

Background: There are various topical and systemic treatment options for the management of lichen planus. However, it is often difficult to achieve long-term disease control and many of the common therapies may be associated with unwanted side effects. Aims: To evaluate the effectiveness of 8 mg oral methylprednisolone administered daily in lichen planus by the analysis of medical records. Methods: In this retrospective cohort study, we compared the rates of improvement between two groups of patients. The first group received 8 mg oral methylprednisolone daily for at least one month. In the second group, patients with similar parameters to the first group (age, sex, disease manifestation) but without systemic glucocorticoid therapy were included. Fisher’s exact test was used to compare the rates of remission in the two groups. Results: In the daily oral methylprednisolone (n = 24) and no systemic corticosteroids (n = 16) groups, 23 (95.8%) and 6 (37.5%) patients achieved partial or complete remission, respectively. The frequency of improvement was significantly higher in patients who received oral methylprednisolone (P < 0.0001). Limitations: Limitations of this study include its retrospective design and the relatively small sample size. Conclusion: Low dose oral glucocorticoid therapy may be an effective option for the systemic treatment of lichen planus. Based on our results and previous studies, instead of higher doses, longer therapy duration with low doses should be considered.

Oral lichen planus: case series and experience in a tertiary dermatology service in Brazil

Abstract Background: Lichen planus is an inflammatory disease that can affect both the skin and mucous membranes, including the oral mucosa. There is very little original Brazilian dermatology literature about oral lichen planus. Objective: To describe the clinical, pathological, and treatment data of 201 patients diagnosed with oral lichen planus followed at the Stomatology Outpatient Clinic of Hospital das Clínicas, Universidade de São Paulo, from 2003 to 2021. Method: The patients demographic profile, the morpho-topographic features of the lesions, the treatment employed, and the possible presence of squamous cell carcinoma were analyzed. Results: The disease was more common in women over 50 years of age, tending to be chronic, with a large number of cases showing cicatricial sequelae in the mucosa. Topical treatment with potent corticosteroids was shown to be effective in the vast majority of cases. Squamous cell carcinoma in oral lichen planus cicatricial sequelae was observed in eight cases. Study limitations: Retrospective study of medical records, with gaps regarding the filling out of data; unequal observation time among the studied cases. Conclusions: This is the largest Brazilian dermatology series on oral lichen planus. The response to topical corticoid therapy was excellent in the vast majority of cases. The high prevalence of atrophic lesions, demonstrating the chronicity and tissue destruction potential of this disease, may explain the large number of cases of squamous cell carcinoma.

Desordens orais potencialmente malignas: o que o cirurgião-dentista precisa saber? / Oral potentially malignant disorders: what do dentists need to know?

Introdução:as desordens orais potencialmente malignas (DOPMs) são condições que podem preceder o aparecimento do câncer em cavidade bucal. Objetivo: descrever os principais aspectos clínicos, histológicos e tratamento da leucoplasia, eritroplasia, queilite actínica e líquen plano oral. Metodologia: trata-se de uma revisão da literatura atual, em que foram consultados artigos nas bases do MEDLINE/PUBMED e Biblioteca Virtual em Saúde, publicados nos últimos 10 anos. Os descritores foram localizados usando o vocabulário controlado do MeSH, sendo eles: Leukoplakia; Erythroplakia, Actinic cheilitis, Oral lichen planus, Diagnosis, Therapeutics. Resultados: asapresentações clínicas das DOPMs são diversas. A leucoplasia é a mais comum e deve ser distinguida da leucoplasia verrucosa proliferativa que tem uma apresentação clínica generalizada e uma tendência à recorrência após a excisão; a eritroplasia, embora rara, tem maior chance de malignização. A queilite actínica acomete com frequência o lábio inferior, tem forte relação com exposição solar e pode progredir para o carcinoma escamocelular labial; o líquen plano oral tem uma variedade de apresentações clínicas, sendo a forma reticular a mais comum. O tipo erosivo, atrófico ou bolhoso é acompanhado de sintomatologia dolorosa variável. A biópsia é essencial para confirmar a suspeita clínica das DOPMs e o encaminhamento oportuno para um especialista é indicado. Conclusão: as DOPMs podem ser encontradas durante o exame bucal, possibilitando assim, o diagnóstico precoce, e o correto encaminhamento a um especialista e a intervenção adequada, podendo reduzir a taxa de progressão dessas condições para câncer.

Introduction: Oral Potentially Malignant Disorders (OPMDs) are conditions that may precede the onset of cancer in the oral cavity. Objective: To describe the main clinical features, histological aspects and treatment of leukoplakia, erythroplakia, actinic cheilitis and oral lichen planus. Methodology: this is a review of the current literature, in which articles in the databases of MEDLINE/PUBMED and the Virtual Health Library, published in the last 10 years, were consulted. The descriptors were located using the MeSH controlled vocabulary, namely: Leukoplakia; Erythroplakia, Actinic cheilitis, Oral lichen planus, Diagnosis, Therapeutics. Results:the clinical presentations of OPMDs are diverse. Leukoplakia is the most common and must be distinguished from proliferative verrucous leukoplakia which has a generalized clinical presentation and a tendency to reoccur after excision; erythroplakia, although rare, has a greater chance of becoming malignant. Actinic cheilitis frequently affects the lower lip, is strongly related to sun exposure and can progress to labial squamous cell carcinoma; oral lichen planus has a variety of clinical presentations, with the reticular form being the most common. The erosive, atrophic or bullous type is accompanied by different levels of pain. Biopsy is essential to confirm the clinical suspicion of OPMDs and timely referral to a specialist is indicated. Conclusion: OPMDs can be found during oral examination, thus enabling early diagnosis, correct referral to a specialist and appropriate intervention, which may reduce the rate of progression of these conditions to cancer.

Senescence in oral lichen planus as assessed by the immunohistochemical evaluation of senescence marker protein-30 (Regucalcin)

Background: Oral lichen planus is a T-cell-mediated chronic inflammatory disease affecting approximately 1% to 2% of the population, the etiology of which is currently unknown. The objectives of this study were to observe if senescence occurs in oral lichen planus, through the assessment of the immunohistochemical expression of a novel marker for senescence called Senescence marker protein-30 or regucalcin, and compare the expression to that in oral lichenoid reaction and non-specific inflammation. Subjects and Methods: The study material consisted of 30 cases of oral lichen planus, 15 cases of oral lichenoid reaction and 15 cases of non-specific inflammation. The number of positive cells in ten randomly selected high power fields were counted in the epithelium and the connective tissue separately and the mean was determined. Results: Mann–Whitney U test was used to statistically analyze if there was any significant difference in the expression of Senescence marker protein-30 between oral lichen planus, oral lichenoid reaction and non-specific inflammation. Even though a greater expression was seen in the oral lichen planus cases than oral lichenoid reaction, the difference in both the epithelium and connective tissue was not statistically significant. Conclusion: This study shows that in addition to the already known mechanisms like apoptosis and increased cell proliferation rates, the activated T-lymphocytes may also trigger a senescent change in the cells of oral lichen planus. As with the other mechanisms, this is also seen only in a small proportion of the cases.

Research progress on T cell glycolytic metabolism in oral lichen planus / 口腔疾病防治

@#Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa. The pathogenesis of OLP is still unclear. Immune abnormalities mediated by T cells and related cytokines play a crucial role in the pathogenesis of OLP. In recent years, glycolytic metabolism-related transporters, enzymes and regulators, such as glucose transporter-1 (Glut1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase A (LDHA), mammalian target of rapamycin (mTOR) and hypoxia inducible factor-1α (HIF-1a), have attracted an increasing amount of attention in OLP by regulating the proliferation and differentiation of T cells and the secretion of inflammatory factors. It has been shown that 2-deoxy-D-glucose (2-DG) or rapamycin (RAPA) inhibits the glycolytic metabolism of T cells and then inhibits OLP. This article reviews the research progress of glycolytic metabolism-related transporters, enzymes and regulatory factors in OLP in recent years.

Co-expression of circRNA in oral leukoplakia and oral lichen planus / 口腔疾病防治

Objective@# To find any differentially expressed circRNAs in oral leukoplakia (OLK) and oral lichen planus (OLP), to investigate the possible role of circRNAs in the pathogenesis of these two diseases.@*Methods@# This study obtained hospital ethical approval. High-throughput sequencing was used to detect differentially expressed circRNAs in OLK, OLP, oral squamous cell carcinoma and normal oral mucosal tissues. CircRNAs were verified by qRT-PCR, enzyme tolerance assays and Sanger sequencing. GO functional analysis and KEGG pathway analysis were performed to predict the functions of circRNAs in OLP. TargetScan and miRanda were applied to predict targeted miRNAs and mRNAs of circRNAs, and ceRNA networks were mapped. @*Results@#A total of 49 circRNAs were differentially expressed in OLK and OLP together, including 30 upregulated and 19 downregulated circRNAs. The five circRNAs confirmed with RT-qPCR, including circHLA-C, circRNF13, circTTN, circSEPN2 and circALDH3A2, were all abnormally expressed in OLK and OLP, among which circHLA-C was a key circRNA with trans splice sites, which was validated by expanding the sample size. ROC curve analysis showed that the area under the circHLA-C curve for predicting OLK was 0.955, and the area under the circHLA-C curve for predicting OLP was 0.988. GO functional analysis showed enrichment of many biological processes related to the immune process. The KEGG pathway with the highest enrichment score was "Natural killer cell mediated cytotoxicity". HLA-C was significantly enriched in these processes/pathways. CeRNA network analysis showed that circHLA-C interacted with a variety of miRNAs, such as hsa-miR-26a-5p, hsa-miR-129-5p, and hsa-miR-29a-3p.@*Conclusion@#Many circRNAs were differentially expressed in both OLK and OLP, circHLA-C being the most elevated. CircHLA-C is valuable for the early diagnosis of OLK and OLP and may serve as a potential biomarker for the diagnosis and prognosis of OLK and OLP.

Clinical effect of compound phellodendron gargle with total glucosides of paeony capsule in the treatment of erosive oral lichen planus / 药学实践与服务

Objective To observe the short-term clinical effect of compound phellodendron gargle combined with the total glucosides of paeony (TGP) in the treatment of erosive oral lichen planus (OLP). Methods 62 patients were divided into observation group and control group through a designed parallel randomized controlled study. All the patients used the total glucosides of paeony capsule , the patients in the observation group also used the compound phellodendron gargle. The pain condition, the healing condition of face, and the treatment effective in both group were evaluated through physical signs and VAS scores evaluations by SPSS 22.0, which could further evaluate the short-term clinical efficacy of compound phellodendron. Results After 30 days, the scores of VAS and physical signs of each group are much better than before. And the scores of VAS and treatment effective of observation group were significantly better than those of the other control groups (P<0.05). Conclusion The application of phellodendron gargle with total glucosides of paeony capsule could improve the treatment effect of OLP patients and reduce the oral pain , which could be used widely in clinical practice.

Proliferative verrucous leukoplakia mimicking oral lichen planus: case report and literature review

This report presents the clinical, microscopic and immunohistochemical aspects of a case of proliferative verrucous leukoplakia (PVL) mimicking oral lichen planus (OLP) in a 66-year-old woman. We also review the literature reporting cases of PVL mimicking OLP, where we found a higher prevalence in women who do not consume tobacco or alcohol. The initial manifestation of lichenoid areas was around the age of 59, with the diagnosis of PVL being established on average 6 years later, while malignant transformation occurred in 8 of the 22 cases at an average of 3.7 years after the final diagnosis of PVL. We emphasize the need for a close follow-up of any patient presenting white lesions of the oral mucosa. Lesions that are clinically and microscopically compatible with lichenoid reactions or OLP must be investigated and differentiated from PVL, which has a worse prognosis.

Este relato apresenta os aspectos clínicos, microscópicos e imuno-histoquímicos de um caso de leucoplasia verrucosa proliferativa (LPV) mimetizando líquen plano oral (LPO) em uma paciente do sexo feminino de 66 anos. Também revisamos a literatura relatando casos de LPV mimetizando LPO, onde encontramos maior prevalência em mulheres que não consomem tabaco ou álcool, com manifestação inicial de áreas liquenoides por volta dos 59 anos, sendo estabelecido o diagnóstico de LPV em média 6 anos depois, enquanto a transformação maligna ocorreu em 8 dos 22 casos em média 3,7 anos após o diagnóstico final de LPV. Ressaltamos a necessidade de acompanhamento rigoroso de qualquer paciente que apresente lesões brancas da mucosa oral, devendo ser investigadas lesões clinicamente e microscopicamente compatíveis com reações liquenóides ou LPO e diferenciadas da LPV, que tem pior prognóstico

Este reporte presenta los aspectos clínicos, microscópicos e inmunohistoquímicos de un caso de leucoplasia verrugosa proliferativa (LVP) simulando liquen plano oral (LPO) en una paciente de 66 años. También revisamos la literatura reportando casos de LVP simulando LPO, donde encontramos una mayor prevalencia en mujeres que no consumen tabaco ni alcohol, con una manifestación inicial de áreas liquenoides alrededor de los 59 años, estableciéndose el diagnóstico de LVP en promedio 6 años después, mientras que la transformación maligna ocurrió en 8 de los 22 casos en un promedio de 3,7 años después del diagnóstico final de LVP. Resaltamos la necesidad de un seguimiento estrecho de todo paciente que presente lesiones blanquecinas de la mucosa oral, que las lesiones clínica y microscópicamente compatibles con reacciones liquenoides o LPO deben ser investigadas y diferenciadas de la LVP, que tienen peor pronóstico.

Estudio de los efectos de un microambiente hipóxico en queratinocitos humanos in vitro y su correlato con alteraciones del microambiente en la patología de liquen plano oral

La hipoxia es un factor fundamental en el proceso de génesis tumoral, así como en patologías precursoras de cáncer, como es el Liquen Plano Oral (LPO). Objetivo: Determinar si es posible establecer una correlación entre las alteraciones que sufren queratinocitos normales en un microambiente hipóxico in vitro y alteraciones que aparecen en los queratinocitos en el epitelio de la mucosa oral en el contexto de la patología LPO. Métodos: Se estudiaron los cambios morfológicos mediante microscopía de contraste de fases, y la detección de marcadores asociados a hipoxia de queratinocitos humanos (HaCaT), como modelo celular oral, en un microambiente hipóxico generado por la variante del método "Hipoxia inducida por cubreobjetos". Resultados: Mediante microscopía confocal se observó la presencia de los marcadores de hipoxia GLUT-1 y aductos de pimonidazol (Hipoxyprobe) en los cultivos celulares de HaCaT expuestos a un microambiente hipóxico. Además, se observó la presencia del marcador GLUT-1 mediante inmunohistoquímica en tejido epitelial humano derivado de biopsias de la patología LPO. Conclusiones: Se estableció una correlación entre las alteraciones detectadas en queratinocitos humanos inducidos a un microambiente hipóxico in vitro y las alteraciones detectadas in vivo en tejido epitelial de la mucosa oral.

A hipóxia é um fator fundamental no processo de gênese tumoral, bem como em patologias precursoras do câncer, como o Líquen Plano Oral (LPO). Objetivo: Determinar se é possível estabelecer uma correlação entre as alterações que os queratinócitos normais sofrem em um microambiente hipóxico in vitro e as alterações que aparecem nos queratinócitos no epitélio da mucosa oral no contexto da patologia do LPO. Métodos: As alterações morfológicas foram estudadas por microscopia de contraste de fase e a detecção de marcadores associados à hipóxia de queratinócitos humanos (HaCaT), como modelo de célula oral, em um microambiente hipóxico gerado pela variante do método "Hipóxia induzida por lamínulas". Resultados: Por microscopia confocal, observou-se a presença dos marcadores de hipóxia GLUT-1 e Hipoxyprobe em culturas de células HaCaT expostas a um microambiente hipóxico. Além disso, a presença do marcador GLUT-1 foi observada por imuno-histoquímica em tecido epitelial humano derivado de biópsias de patologia de LPO. Conclusões: Foi estabelecida uma correlação entre as alterações detectadas em queratinócitos humanos induzidas em um microambiente hipóxico in vitro e as alterações detectadas in vivo no tecido epitelial da mucosa oral.

Hypoxia is a fundamental factor in the process of tumor genesis, as well as in precursor pathologies of cancer, such as Oral Lichen Planus (OLP). Objective: To determine if it is possible to establish a correlation between the alterations that normal keratinocytes suffer in a hypoxic microenvironment in vitro and alterations that appear in the keratinocytes in the epithelium of the oral mucosa in the context of OLP pathology. Methods: Morphological changes were studied by phase contrast microscopy, and the detection of markers associated with hypoxia of human keratinocytes (HaCaT), as an oral cell model, in a hypoxic microenvironment generated by the variant of the method "Hypoxia induced by coverslips". Results: Using confocal microscopy, the presence of hypoxia markers GLUT-1 and Hipoxyprobe was observed in HaCaT cell cultures exposed to a hypoxic microenvironment. In addition, the presence of the GLUT-1 marker was observed by immunohistochemistry in human epithelial tissue derived from biopsies of OLP pathology. Conclusions: A correlation was established between the alterations detected in human keratinocytes induced in a hypoxic microenvironment in vitro and the alterations detected in vivo in epithelial tissue of the oral mucosa.

Consensus guidelines on management of oral potentially malignant disorders

Oral cancer is usually preceded by oral potentially malignant disorders (OPMDs) and early detection can downstage the disease. The majority of OPMDs are asymptomatic in early stages and can be detected on routine oral examination. Though only a proportion of OPMDs may transform to oral squamous cell carcinoma (OSCC), they may serve as a surrogate clinical lesion to identify individuals at risk of developing OSCC. Currently, there is a scarcity of scientific evidence on specific interventions and management of OPMDs and there is no consensus regarding their management. A consensus meeting with a panel of experts was convened to frame guidelines for clinical practices and recommendations for management strategies for OPMDs. A review of literature from medical databases was conducted to provide the best possible evidence and provide recommendations in management of OPMDs

Relación entre la Vitamina D y el Liquen Plano Oral. Revisión Sistemática Exploratoria

RESUMEN: Determinar el rol de la vitamina D (VD) en el desarrollo y tratamiento de liquen plano oral (LPO). Se realizó una revisión sistemática exploratoria durante el mes de Abril del 2021 utilizando Pubmed/Medline, Ebsco y Scopus/ Elsevier. Se utilizaron los términos "Oral lichen planus" y "Vitamin D". Se incluyeron sólo estudios en humanos y fueron excluidos aquellos de más de 5 años de antigüedad. Se obtuvieron 40 artículos, de los cuales 15 se descartaron por estar duplicados. Al seleccionar según título y resúmenes, 7 publicaciones cumplían con los criterios para ser incluidas en esta revisión. Diversas investigaciones han cuantificado niveles de VD en pacientes con LPO obteniendo mediciones significativamente más bajas que en pacientes sanos. Además, se describe una posible correlación entre la severidad del cuadro y la magnitud del déficit. Finalmente, la suplementación con VD como coadyuvante surge como alternativa para la disminución de síntomas dado su rol en procesos inmunes y a reportes de mejoras en cuadros de LPO a partir de su uso. Pacientes diagnosticados con LPO tienen niveles insuficientes de VD sérica en comparación con pacientes sanos. La deficiencia del micronutriente se relaciona con una respuesta inflamatoria exagerada y alteraciones del sistema inmune. La suplementación de VD en pacientes con LPO sería beneficiosa como coadyuvante al tratamiento con corticosteroides en casos severos. Sin embargo, la escasa evidencia hace necesario realizar más estudios clínicos que reafirmen la efectividad de la VD como tratamiento complementario de LPO.

ABSTRACT: To determine the role of vitamin D (VD) in the development and treatment of oral lichen planus (OLP). An exploratory systematic review was carried out during April of 2021 using the databases Pubmed / Medline, Ebsco and Scopus / Elsevier. The terms "Oral lichen planus" and "Vitamin D" were used. Only human studies were included and those publications older than 5 years old were excluded. 40 articles were obtained, of which 15 were discarded because they were duplicated. When selecting according to title and abstract, publications met the criteria to be included in this review. Various investigations have quantified VD levels in patients with OLP: obtaining significantly lower measurements than in healthy patients. In addition, a possible correlation between the severity of the condition and the magnitude of the deficit is described. Finally, supplementation with VD as an adjuvant arises as an alternative for the reduction of symptoms, given the role of VD in immune processes and reports of improvements in OLP symptoms with its use. Patients diagnosed with OLP have insufficient levels of serum VD compared to healthy patients. Micronutrient deficiency is related to an exaggerated inflammatory response and alterations in the immune system. VD supplementation in patients with OLP would be beneficial as an adjunct to corticosteroid treatment in severe cases. However, the limited evidence makes it necessary to carry out more clinical studies to reaffirm the effectiveness of VD as a complementary treatment for OLP.

Diode laser – A cure for obstinate oral lichen planus: A case series and review of the literature

Oral lichen planus (OLP) is a chronic T-cell mediated inflammatory disease of unknown etiology. Hence, no gold standard treatment modalities are available. Due to therapeutic challenges offered by conventional therapy, there is a need for effective alternate treatment with minimal side effects. The development of lasers has brought light to the treatment of obstinate OLP. Three cases of male patients in the age group 30–40 years complaining of a burning sensation in the mouth have been mentioned. Clinical and histopathological investigations showed typical findings of OLP. The treatment was started with conventional therapy of corticosteroids. The symptoms were assessed on the visual analog scale (VAS) and showed marked reduction but without complete alleviation. Hence, ablation of the lesion using a 980 nm soft-tissue diode laser was planned. The outcome of the treatment was successful, VAS 0 and no recurrence occurred in 11 months follow-up. The results of a 980 nm diode laser for the treatment of OLP are satisfactory and should be considered as a treatment alternative to conventional remedies

Immunohistochemical expression of cyclooxygenase-2 in oral lichen planus and normal oral mucosa

Background: Oral lichen planus (OLP) is a chronic inflammatory disease for which the pathogenesis is complex and not fully understood; autoimmunity has been suggested as a causative factor. World health organization (WHO) has classified OLP as a potentially malignant lesion. Cyclooxygenase-2 (COX-2) is an inducible key enzyme that generates prostanoids which play a critical role in inflammation, immunopathology; also considered as a malignant potential marker. Aims: The present study was conducted to analyze and compare epithelial COX-2 expression in OLP clinical subtypes and normal oral mucosa to evaluate its role in the pathophysiology of the disease process. Methods: This retrospective immunohistochemistry (IHC) study was performed on tissue sections of 30 OLP and 10 normal oral mucosae for COX-2 expression. Statistical Analysis Used: Descriptive and comparative statistical methods were done using 'one-way Analysis of Variance (ANOVA), 't' and Chi-square tests. Results: All the OLP showed epithelial COX-2 expression; strong expression was noted in 80% of the OLP while normal oral mucosa sections showed no expression. Cox-2 expression was significantly higher in erosive lichen planus compared to reticular lichen planus. Conclusions: Strong expression of COX-2 in OLP suggested its important role in pathogenesis. Although COX-2 has been connected to malignant development and autoimmunity, as the malignant development in OLP is quite rare, this study suggests that increased levels of COX-2 seen here may support an autoimmune cause of the disease process.

Transcriptome analysis of primary human oral keratinocytes stimulated with Prevotella melaninogenica / 口腔疾病防治

Objective@# To investigate the transcriptomic changes in primary human oral keratinocytes (pHOKs) after coculture with Prevotella melaninogenica (P.m) and to verify the changes in human oral keratinocyte (HOK) cell lines.@*Methods@# pHOK was isolated and cocultured with P.m for 0, 4 and 24 h. Total RNA was extracted, a gene library was constructed, transcriptional sequencing was performed, differentially expressed genes (DEGs) were analyzed, gene ontology (GO) pathway analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed, and the validation of DEGs was performed by qRT-PCR and Western Blot in the HOK and P.m coculture cell model. @*Results @#1 788 DEGs were detected between the 4 h group and control group, including upregulated DEGs such as lymphocyte cytosolic protein 1(LCP1), keratin 7 (KRT7) and Cilia and flagella associated protein 251(CFAP251) and downregulated DEGs such as FERM, ARH/RhoGEF and Pleckstrin domain protein 1 (FARP1), WW domain containing transcription regulator 1(WWTR1) and Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2). 1 832 DEGs were detected between the 24 h group and control group, including upregulated DEGs such as LCP1, complement C1s(C1S), kynureninase (KYNU) and downregulated DEGs such as phosphoserine aminotransferase 1 (PSAT1), FARP1 and FKBP prolyl isomerase 10 (FKBP10). There were 1 090 common differentially expressed genes (cDEGs) in the 4 h and 24 h groups, including LCP1, KYNU and long intergenic nonprotein coding RNA 958 (LINC00958). The GO pathways were mainly enriched in response to lipopolysaccharide and the molecules of bacterial origin and apical part of the cell. KEGG pathway analysis revealed enrichment in the interleukin-17 (IL-17) signaling pathway, tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) pathway, etc. We verified the expression of a cDEG, Myosin1B (MYO1B), and qRT-PCR and Western Blot analysis showed that MYO1B expression was significantly upregulated between the control group and the P.m cocultured group (P<0.001), and its expression followed a time-dependent and concentration-dependent manner. @*Conclusion@#P.m played an important role in the transcriptome of oral keratinocytes.

Research progress on OX40/OX40L axis mediated T cell immunity in the course of oral lichen planus / 口腔疾病防治

@#Oral lichen planus (OLP) is a common chronic disease of the oral mucosa with unclear pathogenesis. Local infiltration of T cells plays a key role in the pathological process of OLP. Increased evidence supports the notion that the imbalance of helper T cells (Th) 1/Th2 and Th17/regulatory T cells (Treg) and their related cytokines is closely related to the pathogenesis and progression of OLP. In recent years, studies have shown that OX40 (CD134) and its ligand OX40L (CD252) play an important role in the process of the T-cell immune response. They participate in the balance regulation of Th1/Th2 and Th17/Treg, mediate the imbalance of pro-inflammatory and anti-inflammatory, and affect the occurrence and development of a variety of autoimmune diseases. However, there is no direct evidence that the OX40/OX40L axis mediates the imbalance of T-cell subsets in the pathogenesis of OLP. Therefore, large sample clinical as well as in vitro and in vivo experimental studies on the mechanism by which the OX40/OX40L axis regulates the balance of T-cell subsets in OLP are still needed in the future.

Does oral lichen planus aggravate the state of periodontal disease? A systematic review and meta-analysis

OBJETIVO: O objetivo desta revisão sistemática e metanálise (SRM) foi avaliar as evidências entre a associação de líquen plano oral (OLP) e doença periodontal, avaliando os parâmetros clínicos periodontais e os níveis de biomarcadores. MATERIAIS E MÉTODOS: Esta revisão sistemática e meta-análise seguiu PRISMA e foi registrada no PROSPERO (CRD42020181513). Foram realizadas buscas em bases de dados de artigos publicados até junho de 2021. A metanálise foi realizada com as variáveis: índice de placa (PI), índice gengival (GI), profundidade de sondagem (PD) e perda de inserção clínica (CAL). A diferença média foi aplicada com intervalo de confiança de 95%. RESULTADOS: 6 artigos foram incluídos. A análise qualitativa mostrou que os níveis de biomarcadores (metaloproteinases de matriz, interleucinas e perfil microbiológico periodontal) estão aumentados em indivíduos com doença periodontal e líquen plano oral. Na metanálise, esses indivíduos também apresentaram aumentos em todos os parâmetros clínicos periodontais avaliados: GI­ gengivite 0,22 [0,14, 0,31] p< 0,0001 e periodontite 0,12 [0,06, 0,19] p=0,0003; PI­ gengivite 0,22 [0,12, 0,31] p< 0,0001 e periodontite 0,15 [0,08, 0,23] p< 0,0001; PD­ gengivite 0,27 [0,06; 0,48] p=0,0107 e periodontite 0,11 [0,01; 0,21] p=0,0299; e CA ­ periodontite 0,06 [0,01, 0,12] p=0,0176. CONCLUSÕES: Evidências sugerem uma relação significativa entre a gravidade da doença periodontal e a presença de líquen plano oral. RELEVÂNCIA CLÍNICA: Este SRM fornece informações sobre a interação entre OLP e a doença periodontal e orienta os médicos a tomar decisões baseadas em evidências e sugere recomendações para estudos adicionais de alta qualidade(AU)

BACKGROUND: The objective of this systematic review and meta-analysis (SRM) was to assess the evidence between the association of oral lichen planus (OLP) and periodontal disease, evaluating the periodontal clinical parameters and biomarkers levels. METHODS: This systematic review and meta-analysis followed PRISMA and was registered in PROSPERO (CRD42020181513). Searches were accomplished in databases for articles published until June 2021. The meta-analysis was performed with the variables: plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment loss (CAL). The mean difference was applied with a 95% confidence interval. RESULTS: 6 articles were included. Qualitative analysis showed the levels of biomarkers (matrix metalloproteinases, interleukins, and periodontal microbiological profile) are increased in subjects with periodontal disease and oral lichen planus. In the meta-analysis, these subjects also presented increases in all periodontal clinical parameters evaluated: GI­ gingivitis 0.22 [0.14, 0.31] p < 0.0001 and periodontitis 0.12 [0.06, 0.19] p =0.0003; PI­ gingivitis 0.22 [0.12, 0.31] p < 0.0001 and periodontitis 0.15 [0.08, 0.23] p < 0.0001; PD­ gingivitis 0.27 [0.06; 0.48] p=0.0107 and periodontitis 0.11 [0.01; 0.21] p=0.0299; and CA ­ periodontitis 0.06 [0.01, 0.12] p=0.0176. CONCLUSIONS: Evidence suggests a significant relationship between the severity of periodontal disease and the presence of oral lichen planus. CLINICAL RELEVANCE: This SRM provides information on the interaction between OLP and periodontal disease and guides clinicians to make evidence-based decisions and suggests recommendations for further high-quality studies(AU)