Lichen Planus Research Articles

CXCL9, CXCL10, and CCL19 synergistically recruit T lymphocytes to skin in lichen planus.

Lichen planus (LP) is a chronic, debilitating, inflammatory disease of the skin and mucous membranes that affects 1%-2% of Americans. Its molecular pathogenesis remains poorly understood, and there are no FDA-approved treatments. We performed single-cell RNA sequencing on paired blood and skin samples (lesional and nonlesional tissue) from 7 patients with LP. We discovered that LP keratinocytes and fibroblasts specifically secrete a combination of CXCL9, CXCL10, and CCL19 cytokines. Using an in vitro migration assay with primary human T cells, we demonstrated that CCL19 in combination with either of the other 2 cytokines synergistically enhanced recruitment of CD8+ T cells more than any individual cytokine. Moreover, exhausted T cells in lesional LP skin secreted CXCL13, which, along with CCL19, also enhanced recruitment of T cells, suggesting a feed-forward loop in LP. Finally, LP blood revealed decreased circulating naive CD8+ T cells compared with that in healthy volunteers, consistent with recruitment to skin. Molecular analysis of LP skin and blood samples increased our understanding of disease pathogenesis and identified CCL19 as a new therapeutic target for treatment.

Lichen planus following Covid-19 vaccination: a narrative review.

Lichen planus (LP) is an inflammatory disease that afflicts skin, mucous membranes, cutaneous appendages. Moreover, LP represents a prototype of lichenoid dermatosis, being characterized by the presence of a dense dermal cell infiltrate. Although most cases of LP are idiopathic, infectious and drug-related factors must also be considered in the etiology. In this context, the occurrence of LP and lichenoid drug eruption following different types of vaccination is a possible event. Therefore, the aim of our review is to provide a broad perspective to clinicians by analyzing the current literature cases of LP and lichenoid eruptions following COVID-19 vaccination, also investigating the possible pathogenetic mechanisms underlying this phenomenon. A total of 61 cases of LP and lichenoid eruption following COVID-19 vaccination have been collected. However, the number of cases of LP and lichenoid drug eruption is extremely low if compared to the number of vaccines administered overall, suggesting that the risk of LP and lichenoid eruption following COVID-19 vaccination is extremely low. Certainly, further studies are desirable to identify the population most at risk and the possibility of taking preventive measures.

Altered Tissue Factor Activity and Disrupted Oxidant-Antioxidant Status in Saliva of Patients with Oral Lichen Planus

Altered Tissue Factor Activity and Disrupted Oxidant-Antioxidant Status in Saliva of Patients with Oral Lichen Planus

Evaluation of the Effect of Low-Level Laser Therapy Versus Photodynamic Therapy on the Level of Serum IL-17 and Salivary IL-4 in Patients Suffering from Erosive/Atrophic Oral Lichen Planus: A Case Control Study

Evaluation of the Effect of Low-Level Laser Therapy Versus Photodynamic Therapy on the Level of Serum IL-17 and Salivary IL-4 in Patients Suffering from Erosive/Atrophic Oral Lichen Planus: A Case Control Study

Malignant transformation of post‐radiation induced erosive lichen planus to squamous cell carcinoma

Malignant transformation of post‐radiation induced erosive lichen planus to squamous cell carcinoma

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

Two-sample Mendelian randomization (TSMR) was employed to examine the association between lipidome and five inflammatory skin diseases. 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. 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). 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.

Clinical and Biological Perspectives on Noncanonical Esophageal Squamous Cell Carcinoma in Rare Subtypes.

Esophageal squamous cell carcinoma (ESCC) remains the most common malignancy of the esophagus worldwide. Environmental and lifestyle exposures such as alcohol and tobacco have been well defined in the pathogenesis of ESCC, acting in concert with cell intrinsic epigenomic, genomic and transcriptomic changes. However, a variety of nonenvironmental etiologies including Fanconi anemia, lichen planus, chronic mucocutaneous candidiasis, esophageal epidermoid metaplasia, epidermolysis bullosa, tylosis, esophageal atresia, and achalasia receive minimal attention despite a high risk of ESCC in these diseases. The goal of this review was to promote clinical recognition and suggest a diagnostic framework for earlier detection of ESCC in patients with these rare diseases. In all the discussed conditions, a change in symptoms should trigger a prompt endoscopic evaluation, and endoscopic surveillance programs with advanced imaging techniques and chromoendoscopy should be considered. Moreover, we leverage the convergence of these diseases on ESCC to identify common mechanisms underlying malignant transformation including aberrant proliferation, mucosal barrier dysfunction, increased inflammation, and genome instability. In this study, we summarize the clinical presentation, pathologic findings, potential screening strategies, and common mechanisms of malignant transformation associated with these rare diseases that drive ESCC.

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. 10cc 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.

Photobiomodulation therapy for oral lesions: a bibliometric analysis

Photobiomodulation therapy is a nonthermal light therapy with therapeutic properties for pain and inflammation relief, immune modulation, and tissue regeneration. Our goal was to provide a comprehensive overview of photobiomodulation therapy for oral lesions using visual mapping techniques. We used VOSViewer to analyze publications in the “photobiomodulation” and “oral lesion” categories from PubMed, Scopus, and Dimension AI databases, allowing us to track author contributions, journal, institutional affiliations, and contributions by country. A total of 373 publications from 1991 to 2022 were gathered. Notably, Brazil, the United States, and France emerged as major contributors in this field. The College of Dentistry at the University of Florida (US) ranked first with 515 citations. Jan Magnus Bjordal was the most prolific author, receiving 207 total citations. Supportive Care in Cancer and Photomedicine and Laser Surgery were identified as the two most promising journals. The intellectual structure was divided into four clusters: cluster one for ‘lllt’, cluster two for ‘head and neck cancer’, cluster three for ‘olp’, and cluster four for ‘inflammatory mediators’. Overall, there has been a significant increase in research on photobiomodulation, particularly over the last decade. The study identified four distinct research clusters: low-level light therapy, head and neck cancer, oral lichen planus, and inflammatory mediators. These findings highlight the need for further research into photobiomodulation in the treatment of various oral diseases. This trend may indicate an increase in the use of low-level light therapy to treat oral lesions in the population, as well as the potential for alternative treatments.

Pembrolizumab-induced hypertrophic lichenoid dermatitis with involvement of an old tattoo.

We present the case of a 58-year-old male who developed hypertrophic lichenoid dermatitis secondary to pembrolizumab, with involvement of normal skin as well as the red-ink areas of an old tattoo site. Lichenoid dermatitis is a well-recognised immune-related adverse event to immune checkpoint inhibitors, but the hypertrophic variant secondary to pembrolizumab has been reported infrequently in the literature. Successful management of the cutaneous eruption in this case enabled the patient to resume life-prolonging adjuvant immunotherapy for clear cell renal cell carcinoma.

Role of Vitamin D in Oral Lichen Planus: A Case Control Study.

It has been reported that vitamin D deficiency may be associated with the development of oral lichen planus (OLP). Given the high prevalence of vitamin D deficiency in many countries, we sought to determine whether it constitutes a comorbidity of OLP. One hundred and twenty patients clinically and histologically diagnosed with OLP were evaluated for their serum vitamin D levels. The results were compared to results from a control series of the same number of subjects matched for age and sex. Vitamin D deficiency was diagnosed in 45% (n = 54) of OLP patients and in 26.7% (n = 32) of the control group. Vitamin D supplements were being taken by 32 (26.7%) OLP patients and 15 (12.5%) subjects in the control group. A multivariate logistic regression model showed that OLP was associated with vitamin D deficiency [OR: 2.24 (1.28-3.98, p = 0.005)] and vitamin D supplementation [OR: 2.51 (1.25-5.22, p = 0.011)], even after controlling for confounding variables such as sex, age ≤60>, tobacco, and alcohol. The association between OLP patients and vitamin D deficiency or vitamin D supplementation suggests that further research might explore the benefits of vitamin D supplements in managing OLP patients.

Solitary verrucous plaque on a leg.

We present the case of a female in her 70s who presented with a solitary verrucous plaque on her left leg accompanied by painful oral erosions. Various differential diagnoses were considered, like lichen simplex chronicus, hypertrophic lichen planus, and chromoblastomycosis. We diagnosed pemphigus vegetans (PVeg) on a nonintertriginous site through comprehensive clinical examination and histopathological and immunopathological evaluations. This case highlights the importance of considering PVeg in the differential diagnosis of solitary verrucous plaques, even in atypical extra-flexural anatomical locations.

Network pharmacology and molecular docking analysis predict the mechanisms of Huangbai liniment in treating oral lichen planus.

This study explored the mechanism of Huangbai liniment (HB) for the treatment of oral lichen planus (OLP) through network pharmacology and molecular docking techniques. The study identified HB' active ingredients, therapeutic targets for OLP, and associated signaling pathways. The chemical composition of HB was screened using the HERB database. The disease targets of OLP were obtained through the GeneCards and OMIM databases. A protein-protein interactions network was constructed with the String platform. Topological analysis was performed using Cytoscape software to identify core targets. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using the Hiplot database, and the active ingredients and core targets were verified by molecular docking. Date analysis showed that the active composition of HB in the treatment of OLP were quercetin, wogonin, kaempferol, and luteolin. This survey identified 10 potential therapeutic targets, including TNF, CXCL8, IL-6, IL1B, PIK3R1, ESR1, JUN, AKT1, PIK3CA, and CTNNB1. Molecular docking revealed stable interactions between OLP' key targets and HB. These key targets were predominantly involved in the PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway. HB plays a crucial role in the treatment of OLP, acting on multiple targets and pathways, particularly the PI3K-Akt signaling pathway. It regulated biological processes like the proliferation of epithelial cells and lymphocytes and mediates the expression of transcription factors, cytokines, and chemokines. Therefore, this study provides a theoretical basis for the clinical trial and application of HB in the therapy of OLP.

Squamous Cell Carcinoma In Situ-The Importance of Early Diagnosis in Bowen Disease, Vulvar Intraepithelial Neoplasia, Penile Intraepithelial Neoplasia, and Erythroplasia of Queyrat.

Cutaneous squamous cell carcinoma (cSCC) is the second-most-prevalent malignancy in humans. A delayed diagnosis of cSCC leads to heightened invasiveness and positive surgical margins. Bowen's disease (BD) represents an early form of cSCC and presents as a small erythematous, photo-distributed, psoriasiform plaque. Although certain dermoscopy features in BD are quite characteristic, histopathology remains the gold standard for diagnosis and provides a severity-scoring system that assists in guiding appropriate treatment strategies. The classification of precancerous lesions of the vulva and penis has undergone multifarious transformations due to variations in clinical and histopathological characteristics. Presently, erythroplasia of Queyrat is categorized as a clinical variant of penile intraepithelial neoplasia (PeIN). The diagnoses of vulvar intraepithelial neoplasia (VIN) and PeIN present significant challenges and typically necessitate one or more biopsies, potentially guided by dermoscopy. Aceto-white testing demonstrates a notably high negative predictive value for genital precancerous lesions. Histopathological examination represents the gold-standard diagnosis in VIN and PeIN, while p16 and p53 immunostainings alongside HPV testing provide crucial diagnostic clues. The histopathologic features, degree of differentiation, and associations with lichen planus, lichen sclerosus, and HPV guide the selection of conservative treatments or surgical excision.

Comparison of Ophthalmologists versus Dermatologists for the Diagnosis and Management of Periorbital Atypical Pigmented Skin Lesions.

Background/Objectives: Lentigo maligna (LM) and lentigo maligna melanoma (LMM) are significant subtypes of melanoma, with an annual incidence of 1.37 per 100,000 people in the U.S. These skin tumors, often found in photo-exposed areas such as the face, are frequently misdiagnosed, leading to delayed treatment or unnecessary excisions, especially in the elderly. Facial melanocytic skin tumors (lentigo maligna-LM/lentigo maligna melanoma-LMM) and their simulators (solar lentigo, pigmented actinic keratosis, seborrheic keratosis and lichen planus-like keratosis) often affect the periocular region. Thus, their diagnosis and management can involve different medical figures, mainly dermatologists and ophthalmologists. This study aimed to evaluate the ability of ophthalmologists to diagnose and manage pigmented skin lesions of the periorbital area. Methods: A multicentric, retrospective, cross-sectional study on a dataset of 79 periorbital pigmented skin lesions with both clinical and dermoscopic images was selected. The images were reviewed by six ophthalmologists and two dermatologists. Descriptive statistics were carried out, and the accuracy, sensitivity, and specificity, with their 95% confidence interval (95% CI), were estimated. Results: Ophthalmologists achieved a diagnostic accuracy of 63.50% (95% CI: 58.99-67.85%), while dermatologists achieved 66.50% (95% CI: 58.5-73.8). The sensitivity was lower for ophthalmologists in respect to dermatologists, 33.3% vs. 46.9%, respectively. Concerning the case difficulty rating, ophthalmologists rated as "difficult" 84% of cases, while for dermatologists, it was about 30%. Management was also consistently different, with a "biopsy" decision being suggested in 25.5% of malignant lesions by ophthalmologists compared with 50% of dermatologists. Conclusions: Ophthalmologists revealed a good diagnostic potential in the identification of periorbital LMs/LMMs. Given progressive population ageing and the parallel increase in facial/periorbital skin tumors, the opportunity to train new generations of ophthalmologists in the early diagnosis of these neoformations should be considered in the next future, also taking into account the surgical difficulty/complexity of this peculiar facial area.

Assessment of Quality of Life in Patients with Chronic Oral Mucosal Diseases Using the Indonesian Version of the Chronic Oral Mucosal Disease Questionnaire-15 (COMDQ-15).

Chronic oral mucosal diseases (COMDs) can significantly impair the quality of life (QoL) of affected individuals. Monitoring the overall disease's impact and the efficacy of treatments requires the use of the Chronic Oral Mucosal Diseases Questionnaire-15 (COMDQ-15) as a standardized instrument for measuring QoL in these patients. This study aimed to assess QoL in patients with COMDs using an Indonesian version of the COMDQ-15. Seventy patients diagnosed with recurrent aphthous stomatitis (RAS), oral lichen planus, autoimmune blistering diseases (ABD), and cheilitis were included. Levels of QoL among different groups of disease were compared. Various potential factors influencing QoL were evaluated. Bivariate analysis was performed to identify factors associated with overall and specific aspects of QoL. The mean total COMDQ-15 score was 20.83 ± 10.07. The highest scores were in the physical discomfort domain (8.76 ± 4.65), while the lowest was in the medication and treatment domain (2.13 ± 1.99). Physical discomfort was significantly associated with gender, major RAS, and cheilitis. Social and emotional aspects were significantly associated with age and ABD, while patient support was linked to employment status, RAS types, and cheilitis. The Indonesian version of the COMDQ-15 is a valid and reliable tool for assessing QoL in patients with COMDs.

Successful treatment of recalcitrant follicular lichen planus (lichen planopilaris) with the topical JAK 1/2 inhibitor ruxolitinib

AbstractWe report the successful treatment of a patient with refractory follicular lichen planus (LP) with topical ruxolitinib, a Janus kinase (JAK) 1/2 inhibitor, which resulted in significant improvement of lesional skin within 1 month of daily use.

Nonsclerotic Lichen Sclerosus of Vulva: A Clinicopathologic Analysis.

The International Society of the Study of Vulvovaginal Diseases (ISSVD) recently defined nonsclerotic lichen sclerosus (NSLS) as a scenario wherein the clinical findings are consistent with lichen sclerosus (LS), but no microscopic evidence of dermal sclerosis is found and recognized 4 histologic subcategories. Herein, we present an institutional experience with NSLS, with an emphasis on frequency, application of the ISSVD categories in routine practice, and clinicopathologic correlation. The authors reviewed clinical and pathologic findings for consecutive vulvar biopsies in which LS was a clinical and/or pathologic consideration. Cases were classified as classical/sclerotic LS (CLS), NSLS (per ISSVD criteria), and "unclassified," the latter of which were cases not classifiable as NSLS or CLS, despite a clinical impression or LS or LS being a significant clinical consideration (ie, "clinical LS"). In clinical LS cases, CLS and NSLS were diagnosed histologically in 61% (182/298) and 15% (44/298), respectively, whereas the remainder were histologically unclassified. The latter group was microscopically heterogeneous, devoid of a consistent pathologic profile, and generally showed absence, focality, minimality, ambiguity, or infrequency of features that would have allowed their categorization into one of the NSLS categories. Among the 4 categories for the categorizable NSLS cases, the "lichenoid dermatitis" pattern (61.4%) was the commonest, followed by dermal fibrosis with acanthosis (22.7%), dermal fibrosis without acanthosis (9.1%), and hypertrophic lichenoid dermatitis (6.8%). The clinical response rates to topical therapies for the NSLS and unclassified groups were 71% and 62%, respectively (P=0.4). Our findings highlight the significance of clinicopathologic correlation in the diagnosis of NSLS. In the setting of clinical LS, some histologic evidence to support that impression is found in most cases when the ISSVD system for diagnosis and classification of biopsies is applied. However, a subset of clinical LS cases are not pathologically classifiable as either CLS or any of the NSLS categories; these display nonspecific histologic features and require future study.

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.

An unusual presentation of childhood lichen planus successfully treated with 308-nm excimer laser.

An unusual presentation of childhood lichen planus successfully treated with 308-nm excimer laser.