Diagnostic value of 8-OHdG, 8-iso-PGF2α and TNF-α levels in blood for early carcinogenesis of erosive oral lichen planus.

BACKGROUND: Oral cancer has a high worldwide incidence and mortality rate showing an upward trend year by year, predominantly occurring in emerging countries. Oral squamous cell carcinoma (OSCC) is one of the main types of oral cancer, accounting for more than 90% of all cases in oral cancer. OBJECTIVE: To evaluate the diagnostic value of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-iso-Prostaglandin F2alpha (8-iso-PGF2α) and tumor necrosis factor (TNF)-α as biomarkers in the early carcinogenesis of erosive oral lichen planus (EOLP) by measuring their levels in the blood of patients with EOLP and oral squamous cell carcinoma (OSCC). METHODS: A total of 69 patients were enrolled in this case-control study [including an OSCC group (n= 23), an EOLP group (n= 23), and an age- and gender-matched healthy control group (n= 23)]. Blood levels of 8-OHdG, 8-iso-PGF2α and TNF-α were measured using enzyme-linked immunosorbent assay (ELISA). Statistical differences in these indicators among the three groups were analyzed. RESULTS: Plasma levels of 8-OHdG and 8-iso-PGF2α in the OSCC group were significantly higher than those in both the EOLP group and the control group (all P< 0.05); no significant statistical difference was found between the EOLP group and the control group. Serum levels of TNF-α in both the OSCC and EOLP groups were elevated compared with the control group, showing significant differences among all three groups (all P< 0.05). Receiver operating characteristic (ROC) curves revealed that plasma 8-OHdG and 8-iso-PGF2α levels and serum TNF-α levels had diagnostic effects on early carcinogenesis in EOLP patients. When these indicators were combined for diagnosis, the diagnostic effect was enhanced, with an area under the ROC curve (AUC) values of 0.819. CONCLUSION: 8-OHdG, 8-iso-PGF2α and TNF-α may serve as biological indicators for monitoring the early carcinogenesis of EOLP, and the diagnostic effect was augmented when these indicators were combined.

Pathogenic relevance of antibodies against desmoglein 3 in patients with oral lichen planus.

BACKGROUND AND OBJECTIVES: Oral lichen planus (OLP) is a T cell driven disorder that significantly impairs patients' quality of life. Previous reports suggest that both cellular and humoral activities against desmoglein (dsg) 1 and 3 may be involved in OLP pathogenesis. Here, we aim to analyze the frequency of occurrence and pathological significance of anti-dsg antibodies in a large cohort of OLP patients. MATERIALS AND METHODS: OLP patients were screened for anti-dsg antibodies by enzyme-linked immunosorbent assay in three tertiary referral centers. OLP sera with anti-dsg antibodies were further analyzed by Western blot and dispase-based keratinocyte dissociation assay (DDA) to identify the targeted dsg ectodomains and to assess their pathogenicity. RESULTS: Of 151-screened individuals with OLP, only four patients (2.6%) with erosive OLP showed serum IgG against dsg1/3. Western blot analysis with recombinant dsg3 ectodomains revealed preferential recognition of the extracellular domain 5. By DDA with spontaneously immortalized human keratinocytes, none of the sera from these four patients induced acantholysis. CONCLUSIONS: Activation of humoral immunity occurs prevalently in patients with erosive OLP, probably due to epitope spreading. OLP serum antibodies are unable to induce loss of intercellular adhesion in vitro, strongly suggesting that they are not disease causing but rather an epiphenomenon.

Comparative study of the efficacy of azathioprine, dapsone, and NB-UVB phototherapy as steroid-sparing modalities in generalised lichen planus.

Background Generalised lichen planus (GLP) is a chronic disease with an overall prevalence of 1% requiring longer treatment. Limited studies are available on GLP and its treatment in the literature, unlike oral lichen planus. Objective To determine the best steroid-sparing treatment modality for GLP by comparing the efficacy, response, safety, side effects, and remission with azathioprine, dapsone, and narrowband UV-B (NB-UVB) along with their impact on itching severity and life quality. Methodology Open-label, prospective, comparative, interventional study on generalised lichen planus patients treated with systemic steroids along with one of three steroid-sparing modalities. Totally 90 patients were studied including 30 patients each who received azathioprine (Group A), dapsone (Group B), and narrow band UVB (NB-UVB) (Group C), respectively, for 16 weeks. Itch severity index (ISI) and Dermatology life quality Index (DLQI) were assessed at baseline and week 24. All patients received oral prednisolone until there was no more active disease. Response was assessed in terms of occurrence of new lesions, flattening of lesions, post-inflammatory hyperpigmentation (PIH), and grading of lesions two weeks once for 6 months followed by six months of follow-up after treatment completion. Results Females outnumbered males in all 3 groups. Mean patient ages (34, 38, and 34) and the presence of one or more co-morbidities (50%, 42.3%, 37.5%) in Groups A, B, and C, respectively, were comparable. ISI and DLQI improvement at 24 weeks were greatest with NB-UVB, followed by azathioprine and dapsone in that order; the differences in improvement between groups showed high statistical significance. At week 24, occurrence of new lesions (0%, 0%, 3.8%), flattening (100% - all groups), PIH (100% - all groups), grade 3 lesions i.e. poor response, resolution of 20-50% of lesions (7.1%, 11.5%, 0%), grade 2 lesions i.e. partial response, resolution of 50-90% of lesions (35.7%, 76.9%, 8.3%) and grade 1 lesions i.e. complete response, resolution of >90% lesions (57.1%, 11.5%, 91.3%) were noted in Groups A, B and C, respectively; the differences in the extent of resolution of lesions between the groups were highly significant statistically. Remission was seen in 100%, 76.9%, and 87.5% in Groups A, B, and C, respectively, after six months. Limitations The sample size was small. Only 3 treatment options were compared in this study but many more options have been used for lichen planus. Long term follow-up is required. Conclusions NB-UVB with oral steroids showed a better response in terms of improvement in DLQI, ISI, disease control, and side effects than azathioprine and dapsone. Azathioprine showed a faster response and more prolonged remission. Dapsone showed poor response with multiple side effects.

Anogenital Erosive Lichen Sclerosus in a Male With Multiple Autoimmune Conditions.

Lichen sclerosus (LS) is a chronic inflammatory disorder primarily affecting the anogenital region, with a higher prevalence in females and often linked to autoimmunity. This association is not clearly elucidated in males, with LS commonly presenting in uncircumcised males. The most affected areas include the glans penis, prepuce, and coronal sulcus. In this report, we present an 11-year case of treatment-resistant LS in a male patient with an extensive history of autoimmune disorders, manifesting in the intergluteal cleft as a hypertrophic plaque, a rare location. The patient had a complex autoimmune history, including porphyria cutanea tarda, discoid lupus, and Sjogren's syndrome. Histopathological analysis confirmed a diagnosis of erosive LS. Despite numerous treatments, including intralesional corticosteroids and various topicals, the lesion persisted. This case highlights the challenges in managing LS, particularly in uncommon sites and in patients with extensive autoimmune backgrounds. Treatment goals for LS focus on symptom relief, cosmetic improvement, and disease prevention. Although topical corticosteroids are commonly used, systemic options like hydroxychloroquine may be beneficial in resistant cases, although clear guidelines are lacking. Our case underscores the importance of a multidisciplinary approach in addressing LS and its associated autoimmune conditions.

Elafin level in lichen planus.

Lichen planus (LP) is a chronic, inflammatory, autoimmune disease that affects the skin, oral mucosa and genital mucosa. Elafin is an epithelial host-defense protein that is absent in normal skin but highly expressed in inflamed skin keratinocytes. Overexpression of Elafin has been reported in various infective, inflammatory skin disorders, such as cellulitis, psoriasis, Behçet's syndrome, and graft versus host disease. The aim of this case- control study is to map the level of Elafin in LP in order to investigate its role in the pathogenesis of LP. This study included 30 LP patients and 30 healthy controls. 10 cc blood samples were withdrawn from study participants to evaluate the serum level of Elafin using enzyme-linked immunosorbent assay (ELISA) technique. Serum Elafin level was significantly higher in LP patients as compared to healthy controls; the mean values were (32.56 vs. 5.60) in LP cases and healthy controls respectively with a statistically significant p-value < 0.001. We conclude that Elafin could be part of the inflammatory autoimmune process in LP.

Idiopathic Eruptive Macular Pigmentation with Papillomatosis: A Common but Underdiagnosed Entity.

Idiopathic Eruptive Macular Pigmentation (IEMP) is an uncommon and possibly underdiagnosed dermatosis. It manifests as asymptomatic pigmented macules over the face, trunk and proximal extremities among children and adolescents. Degos et al. first documented this condition in 1978, unveiling its distinct characteristics. The macules, initially dark brown-black, naturally diminish over several months to years, with no lasting pigmentation or scarring. In this report, we highlight the case of a 14-year-old girl displaying all the distinctive traits of IEMP.

Estimation of depression, anxiety and serum cortisol in patients with oral lichen planus, leukoplakia and oral submucous fibrosis.

Stress and anxiety may be found in patients with oral submucous fibrosis (OSMF), oral leukoplakia (OL) and oral lichen planus (OLP). Cortisol, sometimes referred to as the "stress hormone," has been employed as a stress predictor. Therefore, it is of interest to estimate the levels of depression, anxiety and serum cortisol and establish correlation between them in patients with OL. OLP and OSMF. There were 240 patients, aged 20 years to 45 years, who were divided into four categories (OL, OSMF, OLP and control) of 60 patients apiece. In the supervision of a psychiatrist, the Hamilton Depression Rating Scale (HAM D) and Hamilton Anxiety Rating Scale (HAM (A) questionnaires were filled out. Five millilitres of venous blood were extracted using standard aseptic technique, and all of the samples were examined for serum cortisol level. Anxiety and depression was found in subjects of OL, OSMF and OLP at advanced stages. It was inferred that serum cortisol level was statistically correlated with depression and anxiety in patients with OL, OSMF and OLP.

Lichenoid Drug Eruption Secondary to Adalimumab: A Case Report.

Adalimumab, an anti-tumor necrosis factor-α (TNF-α), is widely prescribed for many autoimmune diseases and chronic inflammatory skin diseases such as hidradenitis suppurative, psoriasis, etc. We report a case of lichenoid drug eruption secondary to adalimumab, a rare side effect, in a 62-year-old female with ulcerative colitis. The skin eruption appeared two weeks after initiating adalimumab. A skin biopsy was taken, and the histopathological findings correlated with a lichenoid drug eruption. Although rare, drug-induced lichen planus has been associated with adalimumab. Early recognition and a high index of suspicion are key in the prompt management of these cases. The discontinuation of adalimumab must be carefully weighed against its therapeutic benefits, as the discontinuation might trigger a severe form of inflammation in the primary autoimmune disease being treated. Extreme caution, early intervention, and a multidisciplinary approach are best for the overall well-being and optimal care of the individual.

B Cells Infiltration Potentially Responded Better to Systemic Corticoids in Oral Lichen Planus and Oral Lichenoid Lesions.

Oral lichen planus (OLP) and oral lichenoid lesion (OLL) are chronic inflammatory diseases involving the oral mucosa. B cells infiltration in OLP and OLL, however, little is known about these cells in OLP and OLL. To analyze the function and infiltrating features of B lymphocytes in OLP and OLL, and to preliminarily evaluate their correlation with clinical outcomes. Tissue samples were collected from OLP, OLL, and healthy mucosa. The phenotypes and amounts of B cells in tissues were analyzed by single-cell sequencing. Their proportion and infiltrating features in tissues were examined by immunohistochemistry and immunofluorescence. With the systemic medication of corticoids, the correlation between B cells infiltrating characteristics and the clinical outcomes were evaluated. A quantified proportion increase of B cells was shown in both OLP and OLL. B cells in OLP demonstrated heightened activation and enhanced regulation in immune response. A cohort of 100 patients with OLP/OLL and 13 healthy controls were examined to investigate the B cells infiltration pattern. B cells were distributed in the superficial layer of lamina propria in 92.9% and 41.9% of OLP and OLL, respectively(P < 0.01); focally distributed in 25.0% and 62.9% of OLP and OLL, respectively(P < 0.01). With the systemic medication of corticoids, the cases with B cell infiltration (B+) in OLP and OLL groups showed a statistically significant reduction in REU scores before and after treatment (P < 0.01). B cells are widely present in OLP and OLL, and B cell infiltration in OLP and OLL are related to the better therapeutic effect of oral corticoids.

Widespread purplish-red plaques with plasma cell infiltrate: A rare type of lichen planus.

Diseases in which cutaneous plasma cell infiltrates predominate are rare and usually of unknown etiology, including those that transition from benign to malignant, such as cutaneous plasmacytosis, multicentric Castleman disease, and extramedullary plasmacytoma. These diseases may present as purplish, reddish-brown cutaneous plaques or nodules. Here, we report an exceptional case of lichen planus (LP) in which the patient had classic histopathological features, but the infiltrating inflammatory cells were plasma cells with restricted light chain expression. The patient presented with severe rashes, including purplish-red plaques and nodules, erythema, and erosions in the palmoplantar area, verrucous hyperplasia of the oral mucosa, and anonychia of the toes. These findings suggest a possible role of plasma cells with restricted light chain expression in the LP. Clinicians should closely follow patients for changes in their rash, perform repeat biopsies if necessary, and regularly conduct multisystemic evaluations.

A Molecular Hypothesis on Malignant Transformation of Oral Lichen Planus: A Systematic Review and Meta-Analysis of Cancer Hallmarks Expression in This Oral Potentially Malignant Disorder.

We aimed to qualitatively and quantitatively analyze, through a systematic review and meta-analysis, the current evidence on the differential expression of the hallmarks of cancer in oral lichen planus (OLP) samples, in order to know the earliest molecular mechanisms that could be involved in the malignant transformation of this oral potentially malignant disorder. We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2023. We evaluated the methodological quality of studies and carried out meta-analyses to fulfill our objectives. Inclusion criteria were met by 110 primary-level studies, with 7065 OLP samples, in which the expression of 104 biomarkers were analyzed through immunohistochemistry. Most OLP samples showed sustained cell proliferation signaling (65.48%, 95%CI = 51.87-78.02), anti-apoptotic pathways (55.93%, 95%CI = 35.99-75.0), genome instability (48.44%, 95%CI = 13.54-84.19), and tumor-promoting inflammation events (83.10%, 95%CI = 73.93-90.74). Concurrently, OLP samples also harbored tumor growth suppressor mechanisms (64.00%, 95%CI = 53.27-74.12). In conclusion, current evidence indicates that molecular mechanisms promoting hyperproliferative signaling, an antiapoptotic state with genomic instability, and an escape of epithelial cells from immune destruction, are developed in LP-affected oral mucosa. It is plausible that these events are due to the actions exerted by the chronic inflammatory infiltrate. Malignant transformation appears to be prevented by tumor suppressor genes, which showed consistent upregulation in OLP samples.

Development and validation of the Oral Lichen Planus-Disease Activity Scale: a novel tool for comprehensive clinical assessment.

OBJECTIVE: To develop and validate the Oral Lichen Planus-Disease Activity Scale (OLP-DAS) for assessing overall disease activity of OLP. METHODS: The OLP-DAS was created by refining the Thongprasom criteria, incorporating inputs from the literature and expert review, and integrating pain assessment. Content validity was evaluated in a virtual meeting with 8 Oral Medicine specialists. Reliability and validity of the final version were examined. Seventeen OLP subjects were assessed for disease activity by 10 investigators using the OLP-DAS, Oral Disease Severity Score (ODSS), OLP-Investigator Global Assessment (OLP-IGA), and Reticular-Erythema-Ulcerative (REU) scale. Convergent validity was assessed by rating 160 OLP subjects using the OLP-DAS, ODSS, and OLP-IGA. Inter-rater and intra-rater reliability, along with convergent validity, were analyzed using intraclass correlation coefficients (ICCs) and Spearman's rank correlation coefficients (rs). RESULTS: The final OLP-DAS achieved excellent content validity indices. Inter-rater and intra-rater ICCs for total OLP-DAS scores were 0.93 and 0.96, respectively. Total OLP-DAS scores exhibited strong positive correlations with the ODSS and OLP-IGA (rs = 0.94 and rs = 0.76; P < 0.001, respectively). The OLP Severity Index (OLP-SI), a component of the OLP-DAS, showed very strong positive correlations with OLP disease activity parameters of the ODSS (rs = 0.90; P < 0.001). CONCLUSIONS: The OLP-DAS is a valid and reliable clinician-reported outcome measure (CROM) for evaluating OLP disease activity. CLINICAL RELEVANCE: The OLP-DAS, as a standardized CROM for OLP, is valuable for both routine clinical assessments and research applications.

Improvements in Oral Lichen Planus Following Periodontal Treatment in a Patient With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Case Report.

Oral lichen planus (OLP), a chronic inflammatory mucocutaneous disease, is known to be associated with liver disease. Additionally, associations between periodontal disease and metabolic dysfunction-associated steatotic liver disease (MASLD), as well as cardiovascular disease, have been reported. Herein, we report a case of a 68-year-old male who presented at a dental clinic with OLP, which showed signs of improvement after treatment for periodontal disease. The patient had hepatic dysfunction and steatosis, which was complicated by angina pectoris. He was diagnosed with OLP and periodontal disease. Subsequent close examination of his liver led to a diagnosis of MASLD. Treatment for periodontal disease and enhanced oral self-care improved the OLP lesions and liver function values. This case demonstrates that collaboration between different medical disciplines can significantly impact patient health.

Coexistence of severe peripheral ulcerative keratitis and lichen planus: case report.

Introduction and importance: Ocular involvement in lichen planus is highly uncommon, primarily affecting the eyelids, conjunctiva, and less frequently, the cornea. Peripheral ulcerative keratitis (PUK), a rare subtype form of corneal lichen planus, has been reported only once in the literature. Case presentation: The authors report details of a 34-year-old man with confirmed cutaneous lichen planus who developed severe PUK, a rare ocular manifestation of lichen planus. Despite initial worsening with corticosteroids, successful resolution of PUK was achieved with topical Cyclosporin and azathioprine over 2 months but with a final visual acuity limited to light perception. Clinical discussion: To the best of our knowledge, very rare cases have been reported of the coexistence of severe PUK and lichen planus. Lichen planus should be considered in any case of PUKs associated with cutaneous-mucosal manifestations cyclosporin and azathioprine are crucial for effective management and favorable outcomes in such cases. Conclusion: This case aims to show the importance of dermatological examination in the presence of any peripheral ulcerative keratitis. It also sheds light on the therapeutic difficulties and the prognosis of this rare form of ocular lichen planus.

An overview of S100 proteins and their functions in skin homeostasis, interface dermatitis conditions and other skin pathologies.

S100 proteins comprise a family of structurally related proteins that are calcium-sensitive. S100 proteins have been found to play various roles in regulation of cell apoptosis, cell proliferation and differentiation, cell migration and invasion, energy metabolism, calcium homeostasis, protein phosphorylation, anti-microbial activity and inflammation in a variety of cell types. While the specific function of many S100 proteins remains unknown, some of the S100 proteins serve as disease biomarkers as well as possible therapeutic targets in skin diseases. Interface dermatitis (ID) is a histopathological term that covers many different skin conditions including cutaneous lupus erythematosus, lichen planus, and dermatomyositis. These pathologies share similar histological features, which include basal cell vacuolization and lymphocytic infiltration at the dermal-epidermal junction. In this review, we summarize how the S100 protein family contributes to both homeostatic and inflammatory processes in the skin. We also highlight the role of S100 proteins in neuronal signalling, describing how this might contribute to neuroimmune interactions in ID and other skin pathologies. Last, we discuss what is known about the S100 family proteins as both biomarkers and potential treatment targets in specific pathologies.

The impact of lipidome on five inflammatory skin diseases: a Mendelian randomization study.

OBJECTIVE: Two-sample Mendelian randomization (TSMR) was employed to examine the association between lipidome and five inflammatory skin diseases. METHOD: To evaluate the association between various molecular subtypes of lipidome and the risk of five inflammatory skin diseases, we analyzed a comprehensive GWAS dataset comprising 179 lipidome. The Two-Sample Mendelian Randomization (TSMR) method was employed to investigate causal relationships. Heterogeneity and pleiotropy were assessed using Cochran's Q test, MR-Egger intercept test, and MR-PRESSO global test. Additionally, a sensitivity analysis was conducted to evaluate the influence of individual single nucleotide polymorphisms on Mendelian Randomization study. RESULTS: Using 179 serum lipidome as exposures and five common inflammatory skin diseases as outcomes, we investigated their associations in this large-scale study. Our findings reveal significant impacts of glycerophospholipids, glycerolipids, and sphingomyelins on inflammatory skin diseases. Glycerophospholipids were protective against pemphigus but predominantly posed risks for other inflammatory skin diseases. Specifically, phosphatidylcholine (16:0_0:0) exhibited the most significant risk association with lichen planus (OR = 1.25, 95% CI 1.11-1.40, P < 0.001). Conversely, glycerolipids showed no effect on lichen planus but were protective against pemphigus while potentially posing risks for other conditions. Triacylglycerol (46:2) showed the most substantial risk association with vitiligo (OR = 1.99, 95% CI 1.35-2.93, P < 0.001). Furthermore, sphingomyelins had no effect on atopic dermatitis but posed potential risks for other inflammatory skin diseases. Sphingomyelin (d40:1) notably emerged as a significant risk factor for pemphigus (OR = 1.91, 95% CI 1.37-2.66, P < 0.001). CONCLUSIONS: This study has elucidated the potential harmful effects of glycerophospholipids, glycerolipids, and sphingomyelins on inflammatory skin diseases, while also providing valuable insights for future research into the pathophysiology, prevention and treatment of these conditions.

A Case of Oral Lichen Planus Preceding the Diagnosis of Good Syndrome.

Good syndrome (GS) is a rare condition characterized by thymoma and immune deficiency with a poorly understood mechanism in which patients have reduced immunoglobulin levels and circulating B-cells along with impaired T-cell function. GS is often accompanied by autoimmune and inflammatory conditions, and in this report, we present a case of refractory oral lichen planus (OLP) preceding the diagnosis of GS. In this case, a patient with a history of OLP was diagnosed with GS and common variable immunodeficiency (CVID) following thymectomy and was treated with intravenous immunoglobin (IVIG). Additionally, he was found to have pure red cell aplasia managed with cyclosporine. His oral symptoms worsened, and he presented to dermatology. Treatment was initiated with topical clobetasol and tacrolimus for his OLP, and fluconazole was started for concomitant oral candidiasis. His OLP has remained under satisfactory control with this regimen; however, he requires close surveillance for malignancy given his increased risk of oral squamous cell carcinoma (OSCC) with immunosuppression and active OLP. Although rare, clinicians should be aware of GS and its association with erosive OLP along with the heightened risk of infection in these patients.

Budesonide Orodispersible Tablet for the Treatment of Refractory Esophageal Lichen Planus.

Esophageal lichen planus is an uncommon but highly morbid condition where effective treatments are limited. Diagnosis may be challenging and requires a high degree of clinical suspicion considering endoscopic, histopathological, esophageal, and extraesophageal manifestations. We describe a severe case of esophageal lichen planus and recurrent esophageal stricture that was refractory to acid suppression, local and systemic steroid formulations, and dilatation. We present the first reported use of budesonide orodispersible tablet for this condition, including the excellent clinical, endoscopic, and histopathological response.