Majid Ebrahimi

Mucosal lichen planus, a systemic disease requiring multidisciplinary care : a cross-sectional clinical review from a multidisciplinary perspective

Objective This study aimed to emphasize the importance of seeing mucosal lichen planus (LP) as a systemic disease and not an isolated oral or genital disease and to analyze the proportion of thyroid antibodies among patients with multimucosal LP. Materials and Methods All patients examined by the authors and diagnosed with mucosal LP within 1 year were consecutively included. Full medical histories were collected with special emphasis on autoimmune and thyroid diseases. Sera were analyzed for thyroid antibodies and underwent serologic test for herpes virus. The control group comprised 83 healthy volunteers matched regarding sex and age. Results Of the patients, 120 were included, 89 (74%) of whom were women and 31 (26%) were men. The vast majority of the patients had multifocal lesions, whereas oral lesions solely were found in 28% of women and 36% of men. Of the patients, 28% had at least 1 additional autoimmune disease. Approximately half of the women were treated with levothyroxine owing to thyroid disease. Antibodies against herpes simplex virus were found in 60% of the patients and 44% of the controls (p < .03). Conclusions Lichen planus with mucosal involvement should be considered and taken care of as a systemic disease and not as an isolated oral and/or genital lichen. Contradictory to many former reports, most of our patients have a multimucosal disease that emphasizes the need for a multidisciplinary clinic to get optimal care and treatment.

Oral lichen planus and the p53 family: what do we know?

Oral lichen planus (OLP) is a relatively common chronic disease of the oral mucosa for which the aetiopathogenesis is not fully understood. It mainly affects middle aged and elderly. The finding of autoantibodies against p63, a member of the p53 family, is a strong indication of autoimmunity as a causative or contributing factor. The WHO classified OLP as a potentially malignant disorder, but still there is an ongoing debate in the literature on this subject. The TP53 gene encodes a tumour suppressor protein that is involved in induction of cell-cycle arrest or apoptosis of DNA-damaged cells. The p63 gene encodes six different proteins that are crucial for formation of the oral mucosa and skin. The coordinated stabilization of p53 and decreased expression of p63 seen in OLP cause induction of apoptosis enabling removal of DNA-damaged cells. In view of the complexity of cancerogenesis, no firm statement can at present be made about the relevance of the observed relationship between p53 and p63 and the possible malignant transformation of OLP.

The use of a novel ELISA method for detection of antibodies against p63 in sera from patients diagnosed with oral and/or genital and skin lichen planus.

Lichen planus is a chronic inflammatory disease of mucosa and skin affecting approximately 1-2% of the adult population. Autoimmunity has been implicated in the etiology of this disease, and recently we detected antibodies directed against all six p63 isoforms in sera from 2 out of 20 patients diagnosed with oral lichen planus (OLP) using Western blot analysis. Here we have developed an ELISA method for screening sera for presence of autoantibodies directed against p63. Using the same sera as previously analysed, we show that the optical density ratios for sera from the two patients with known autoantibodies was considerably higher compared to mean optical density ratios for all samples as well as controls analysed. Applying this novel ELISA technique for screening of sera from an additional group of 46 patients with oral and/or genital or skin lichen and 43 matched controls, we detected another three patients with autoantibodies against the p63 proteins. These data are discussed together with the observation that all five patients with detectable p63 autoantibodies from our two studies had clinically severe disease symptoms.

Autoantibodies and decreased expression of the transcription factor ELF-3 together with increased chemokine pathways support an autoimmune phenotype and altered differentiation in lichen planus located in oral mucosa

Background  The pathogenesis of oral lichen planus (OLP), a chronic inflammatory disease, is not fully understood. It is known that OLP has autoimmune features, and it is suggested to be an autoimmune disease. ELF‐3 is involved in differentiation of keratinocytes and deregulated in different tumours and inflammatory diseases. CXCR‐3 and its ligands CXCL‐10 and CXCL‐11 are increased in autoimmune diseases and linked to Th‐1 immune response.

Genes involved in epithelial differentiation and development are differentially expressed in oral and genital lichen planus epithelium compared to normal epithelium.

Lichen planus (LP) is a chronic mucocutaneous disease with unknown cause. Patients with LP often have both oral and genital lesions, but these conditions are often considered as separate diseases and treated accordingly. To find out which genes are differently expressed in mucosal LP compared to normal mucosa and establish whether oral and genital LP are in fact the same disease, whole genome expression analysis was performed on epithelium from 13 patients diagnosed with oral and/or genital LP and normal controls. For confirmation of keratin 4 and corneodesmosin expression, quantitative reverse-transcription PCR and immunohistochemistry were used. Many genes involved in epithelial development and differentiation are differently expressed in epithelium from LP compared to normal epithelium. Several of the differentially expressed genes are common for oral and genital LP and the same biological processes are altered which supports the fact that oral and genital LP are manifestations of the same disease. The change in gene expression indicates that differentiation is altered leading to changes in the epithelial barrier.

Alterations in factors involved in differentiation and barrier function in the epithelium in oral and genital lichen planus

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

Epstein-Barr virus is not detected in mucosal lichen planus

Background Lichen planus (LP) is a chronic inflammatory, immunological, mucocutaneous disease can affect skin, genital and oral mucosa. Oral lichen planus (OLP) is the most common noninfectious, chronic inflammatory oral disease affecting 1-2% of the general adult population. World Health Organization (WHO) classifies OLP as a potentially malignant disorder. Epstein Barr virus or human herpesvirus-4, is a member of the herpes virus family and one of the most ubiquitous viruses known to human, infecting approximately 90% of the world’s adult population. The virus often infects B lymphocytes resulting in a wide spectrum of mucocutaneous and systemic diseases, ranging from mild lesions to aggressive malignancies. The aim of this study was to investigate expression of the EBV encoded RNAs EBER1 and EBER2 in oral and genital lichen planus and compare results with normal tissues in situ hybridization which is considered the golden standard for detection of EBER. Material and Methods A total of 68 biopsies, 25 oral LP, 26 genital LP, 10 oral controls and finally 7 genital controls were analysed using situ hybridization. Results All samples had RNA as shown by the control slide, whereas no case contained neither EBER1 nor EBER2. Conclusions Based on results from our study EBV is not involved in aetiology of lichen planus. Key words:Mucosal lichen planus, Epstein - Barr virus.

Increased expression of p16 in both oral and genital lichen planus

Background Lichen Planus, LP, is an inflammatory disease of possible autoimmune origin affecting mainly oral and genital mucosa and skin. According to the WHO oral LP is considered a potentially malignant disorders. The p16 tumour suppressor protein can act as an inhibitor of cyclin dependent kinases 4 and 6 and thus down regulate cell cycle progression. Since the discovery of p16 several studies have evaluated its expression in various forms of human cancers. The aim of this study was to evaluate and compare the expression of p16 in oral and genital LP and corresponding healthy mucosa. Material and Methods A total of 76 cases of oral LP (OLP), 34 cases of genital LP (GLP), 12 cases of healthy oral and 9 cases of healthy genital mucosa were analysed by the use of immunohistochemistry. Results Data showed p16 to be highly expressed in both oral and genital LP, higher than in oral (p=0.000), and genital controls (p=0.002). Conclusions Results suggest that the over-expression of p16 seen in LP play a part in the histopathology of the disease. Key words:p16, inflammation, oral, genital, lichen planus, malignant risk.