Assessment of interleukin-18 gene polymorphism and serum levels in cutaneous lichen planus.

BACKGROUND: Lichen planus (LP) is a chronic inflammatory disease with uncertain etiology. Interleukin-18 (IL-18) is an interferon gamma (INFγ) inducing agent. It is a pro-inflammatory cytokine that was found to play a role in the pathogenesis of some autoimmune disorders. MATERIAL AND METHODS: This study included 50 patients with classic cutaneous lichen planus (CLP) and 50 healthy volunteers serving as controls. Venous blood samples were withdrawn from the study subjects under complete aseptic precautions. Blood samples were examined for single nucleotide polymorphisms (SNPs) of IL-18 gene at promoter -137(G/C) and -656 (G/T) using polymerase chain reaction (PCR) and IL-18 level was assessed using enzyme linked immunosorbent assay (ELISA). RESULTS: The mean level of IL-18 was significantly higher in CLP patients (31.63 ± 4.90) compared to control subjects (13.95 ± 6.82). Significantly high levels of IL-18 were found among patients with diabetes, hypertension (p < 0.01 in both). HCV positive patients and patients with both OLP and CLP also expressed higher levels of IL-18. Genotypic and allelic distribution at position -137(G/C) showed that the genotype GG was present at significantly higher frequency in cases (58%) compared to controls (28.0%). On the other hand the CC genotype at position -137 was significantly higher in the controls (28%) as compared to CLP cases (6%). Polymorphism of IL-18 at position -656(G/T) showed no significant difference between cases and controls. No significant difference could be detected in IL-18 level between different genotypic variants at position -137(G/C) and -656(G/T). CONCLUSION: IL-18 may play important role in pathogenesis of LP. Elevated IL-18 levels could be part of the pro-inflammatory autoimmune process in LP. The presence of OLP, HCV, diabetes and hypertension is associated with higher production of IL-18. IL-18 promotor region -137(G/C) polymorphism might be a factor that increase the risk of development of lichen planus in Egyptian patients.

Evaluation of correlation between transcription factors and IL-17 in oral and cutaneous lichen planus lesions and Leukocytes.

BACKGROUND: Lichen planus (LP) is a chronic autoimmune disease with different clinical subtypes including cutaneous LP (CLP) and oral LP (OLP). We aimed to compare mRNA expression of RORγt and IL-17 in paraffin-embedded blocks of OLP and CLP lesions with normal oral mucosa (NOM), and also its correlation with hematologic parameters. MATERIALS & METHODS: This study included 89 paraffin-embedded blocks contain OLP (44 cases), CLP (45 cases) and NOM from the archive of Mashhad University of Medical Sciences, Mashhad, Iran. The expression of RORγt and IL-17 was evaluated by Real-time RT-PCR method. The result was compared to Leukocyte counts and the other hematological parameters of studied patients. RESULTS: The results of our study showed IL-17 and RORγt expression in OLP lesions were significantly higher than CLP and NOM groups (P = 0.001). Although we found high expression of RORγt and IL-17 in erosive OLP in compared to classic OLP lesion, but this increment was not significant for IL-17 (P = 0.26) and RORγt (P = 0.14). Further, Leukocyte and monocyte counts were substantially high in OLP group in compared to the CLP and NOM groups (P < 0.05). CONCLUSIONS: We concluded that increased expression of RORγt and IL-17 in LP lesions could play role in the pathogenesis of LP. As well, higher expression of RORγt and IL-17 in oral LP more than cutaneous LP might be associated with difference in clinical behavior of the two types of disease and role of these factors in premalignant behavior of OLP lesions.

New markers of oxidative stress in lichen planus and the influence of hepatitis C virus infection - a pilot study.

Introduction. Lichen planus (LP) is a mucocutaneous T-cell mediated disorder of unknown etiology. There is growing evidence that oxidative stress is an important player in the pathogenesis of LP. Therefore, we have investigated oxidative stress markers in LP and the influence of hepatitis C virus (HCV) infection, a frequently associated condition, on oxidative stress in LP patients. Method. We have determined the serum levels of 4- hydroxynonenal (4-HNE) and symmetric dimethylarginine (SDMA), as markers of oxidative stress, and total antioxidant capacity (TAC), as a marker of the antioxidant defence, in 4 groups: group A - HCV positive patients with LP (n=12), group B - HCV positive patients without LP (n=12), group C - HCV negative patients with LP (n=31) and group D - control group (n=26). Results. In LP patients, we have identified an increased level of lipid peroxidation (4-HNE - group A - 8.41±1.11 µg/mL, group B - 7.97±2.17 µg/mL, group C - 7.81±1.96 µg/mL and group D - 6.15±1.17 µg/mL) and alterations in arginine methylation (SDMA - group A - 1.10±0.24 µmol/L, group B - 1.03±0.16 µmol/L, group C - 0.84±0.19 µmol/L and group D - 0.50±0.06 µmol/L) associated with a diminished antioxidant defence (TAC - group A - 234.50±49.96, µmol/L group B - 255.83±41.41 µmol/L, group C - 269.83±43.33 µmol/L and group D - 316.46 ±29.33 µmol/L), processes augmented by the association with HCV infection. Conclusion. There is an imbalance between oxidants and antioxidants in patients with LP, an imbalance that is augmented by the presence of HCV infection. SDMA could be regarded as a novel biomarker of oxidative stress among these patients. To the best of our knowledge this is the first study to investigate the influence of HCV infection on oxidative stress in LP patients.

No evidence for association between cutaneous lichen planus and hepatitis B and C virus infection in south Poland - a case-control study.

BACKGROUND: The incidence of hepatitis C virus (HCV) infection among patients with lichen planus (LP) varies considerably. Currently, there is more evidence for the association between hepatitic C and oral LP (OLP) than cutaneous LP (CLP). There is also lack of data on the Polish population. The study aimed at assessing the prevalence of HCV infection and liver test abnormalities among patients with CLP in south Poland. METHODS: Eighty-four patients with CLP and 130 patients with other dermatoses (controls) were included in this retrospective case-control study. Medical records were reviewed for the presence of anti-HCV antibodies and hepatitis B surface antigen (HBsAg) and serum levels of liver function tests: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glumatyltranspeptidase (GGT). RESULTS: Anti-HCV antibodies were not found in any of the patients in the study or control group. HBsAg was detected in one (1.19%) patient with CLP and none of the controls. Considering the prevalence of abnormal liver function parameters, there were no statistically significant differences in the frequencies of AST (P = 0.87), ALT (P = 0.9), and GGT (P = 0.81) above the upper limit between patients with CLP and patients with other dermatoses. CONCLUSIONS: Currently, there is no evidence confirming the relationship between HCV infection and CLP in southern Poland. There is also no increased incidence of liver function abnormalities compared to patients with other dermatoses. However, there is a need for further research on larger groups of patients.

Increased regulatory T cells and eosinophils characterize atopic dermatitis-like graft-versus-host disease compared with lichen planus-like graft-versus-host disease.

BACKGROUND: Graft-versus-host disease (GVHD) has various cutaneous manifestations. Little is known about the mechanisms of cutaneous GVHD with different clinical features. OBJECTIVE: To characterize the immunologic features and skin barrier functions of cutaneous GVHD. METHODS: The study included 19 patients with atopic dermatitis (AD)-like GVHD, 8 with lichen planus (LP)-like GVHD, 24 with AD, and 15 healthy controls. The subpopulation of T cells in peripheral blood and skin lesions was measured by flow cytometry and immunofluorescence, respectively. Filaggrin expression in skin lesions was measured by Western blot and immunohistochemistry. Transepidermal water loss was also measured using Tewameter TM 300 (Courage & Khazaka Electronic GmbH, Köln, Germany). RESULTS: The number of peripheral blood eosinophils in AD-like GVHD was significantly higher than that in LP-like GVHD. Type 2 helper T cells in peripheral blood and skin lesions were increased in AD-like GVHD and LP-like GVHD. Regulatory T cells in peripheral blood and skin lesions were increased in AD-like GVHD. Filaggrin expression and transepidermal water loss were increased in skin lesions of AD-like GVHD and LP-like GVHD. LIMITATIONS: The number of patients is limited. CONCLUSION: Although AD-like GVHD and LP-like GVHD both had elevated type 2 helper T cells and impaired skin barrier, increased eosinophils and regulatory T cells were found only in AD-like GVHD.

Chitinase-3-like protein 1 (YKL-40): novel biomarker of lichen planus.

BACKGROUND: Lichen planus (LP) is an inflammatory skin disorder of unknown etiology. Chitinase-3-like protein 1 (YKL-40) is a multifunctional proinflammatory protein, which has an important role not only in immunity and inflammation, but also in the regulation of cell proliferation, differentiation, and apoptosis. AIM OF THE WORK: The present study was designed to investigate the serum level of YKL-40 in patients with different clinical presentations of LP in comparison to healthy participants in order to study its possible role in the pathogenesis of LP. PATIENTS AND METHODS: A total of 60 consecutive subjects were enrolled in this prospective case-control study including 30 patients with different clinical variants of LP (16 male and 14 female patients) in addition to 30 healthy controls matched for age and gender. The serum level of serum YKL-40 was evaluated by means of ELISA method in both patients and controls. RESULTS: The serum YKL-40 level was significantly higher (P < 0.001) in patients than in controls. Also, significantly higher levels were found in patients with oral type than in patients with cutaneous type who do not have oral lesions (P < 0.05). The sensitivity and specificity of serum YKL-40 were 62.5 and 81.8%, respectively, (cut off value of 151 pg/ml) for the diagnosis of oral lesions in LP. CONCLUSION: The findings in our study support the role of YKL-40 in the pathogenic process of LP and may help in treatment of lichen planus.

Subclinical atherosclerosis and cardiovascular markers in patients with lichen planus: A case-control study.

BACKGROUND: Lichen planus is an idiopathic and chronic inflammatory disease that affects the skin and the mucous membranes, and has been associated with an increased risk for cardiovascular diseases. Hyperhomocysteinemia has been regarded as a risk factor for atherosclerosis and cardiovascular diseases. Increased plasma fibrinogen levels are also associated with increased risk of myocardial infarction. OBJECTIVE: The main aim of this study is the evaluation of common carotid artery mean intima media wall thickness, serum fibrinogen and homocysteine levels in patients with lichen planus. METHODS: Forty-three patients with lichen planus and 43 age, gender and body mass index (BMI) matched healthy controls (from general population without the disease) were included in this study. RESULTS: Compared to the healthy controls, patients had statistically significant greater mean intima media wall thickness of the common carotid artery. Moreover, a positive correlation was observed between lichen planus and increased serum homocysteine and c-reactive protein levels. LIMITATIONS: The main limitation of this study is the small sample size due to the time limitation and financial constraints. CONCLUSION: Early diagnosis of atherosclerosis in patients with lichen planus might afford better prophylaxis, including weight control and/or lipid profile monitoring. Measurement of the mean intima media wall thickness of the common carotid artery by duplex high-resolution B-mode ultrasound scanning could be beneficial as a valuable method for early diagnosis of atherosclerosis in lichen planus.

Dynamic thiol/disulfide homeostasis in patients with lichen planus.

OBJECTIVE: Lichen planus (LP) is an autoimmune inflammatory disease of the mucocutaneous tissue, whose exact pathological course remains unclear. Abnormal thiol/disulfide homeostasis has been postulated to be responsible for a number of diseases predominated by chronic inflammation. To be able to contribute complicated and unclear pathogenesis of LP, we aimed to investigate dynamic thiol/disulfide homeostasis in patients with LP, using an original automated method developed by Erel and Neselioglu in this study. METHODS: The study group consisted of 81 unrelated patients with LP and 80 unrelated healthy controls with no LP lesions in their personal history or on clinical examination. Thiol/disulphide homeostasis tests have been measured with a novel automatic spectrophotometric method developed and the results have been compared statistically. RESULTS: Native thiol and total thiol levels were found as significantly higher in patients with LP than the control group (P = 0.026 and 0.035, respectively). There was no significant difference between the disulfide levels of the patients with LP and the control group. CONCLUSIONS: We provide evidence that that thiol/disulphide homeostasis impaired in favor of thiol levels in LP patients compared to the control group based on the data of our study. To the best of our knowledge, the present study is the first examination on the correlation between thiol and disulfide homeostasis in patients with LP.

Analysis of Immunologic Function Changes in Lichen Planus After Clinical Treatment.

BACKGROUND Lichen planus (LP) is a common chronic superficial skin lesion that causes chronic or sub-acute inflammatory disorders. LP can affect the oral cavity, skin, mucous membrane, and other body parts, and features include repeat attacks and long duration, leading to lower quality of life. This study aimed to analyze the changes of immunologic function before and after treatment of LP. MATERIAL AND METHODS Thirty cutaneous LP patients were selected. Peripheral blood was collected in the morning before and after treatment. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient method. Flow cytometry was used to detect T cell subpopulation CD4⁺ T cells and CD8⁺ T to calculate CD4⁺ T/CD8⁺ T ratio. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the helper T-cell (Th) factor IL-2, IFN-γ, IL-4, IL-6, IL-17, and IL-22 levels. RESULTS Compared with before treatment, the expressions of CD4⁺ T cells and CD8⁺ T cells were decreased, while the proportion of CD4⁺ T/CD8⁺ T were significantly elevated after treatment. IL-2 and IFN-γ secretion were markedly increased, whereas IL-4, IL-6, IL-17, and IL-22 were significantly reduced after treatment (P<0.05). CONCLUSIONS LP treatment reduces the distribution of CD4⁺ T cells and CD8⁺ T cells, and promotes the changes of Th1, Th2, and Th17 cytokines secretion.

A study of prevalence of autoantibodies in patients with lichen planus from Mumbai, India.

BACKGROUND: Lichen planus is a common chronically relapsing autoimmune skin condition with poorly understood etiology. Apart from cellular immunity, presence of various antibodies has been hypothesized. Various studies have found the presence of serum anti-nuclear antibody, anti-mitochondrial antibody, anti-desmoglein 1 and 3 antibodies, anti-keratinocyte antibody and anti-thyroglobulin antibody in patients of cutaneous and oral lichen planus. AIM: To study the prevalence of autoantibodies and the clinical spectrum of disease in an Indian patient subpopulation with lichen planus. METHODS: A cross-sectional epidemiological study comprising 100 lichen planus patients was conducted in the dermatology outpatient department of Seth G.S Medical College and King Edward Memorial Hospital, Mumbai, Maharashtra, India. Serum concentrations of circulating anti-nuclear antibodies, anti-desmoglein 1 antibody, anti-desmoglein 3 antibody, anti-keratinocyte antibodies, anti-mitochondrial antibodies and anti-thyroglobulin antibodies were determined by indirect immunofluorescence. Pairs of groups were compared using "Student's t-test" for normally distributed continuous data. The "χ2-test" was used for the categorical variables as needed. Statistical significance was set at P < 0.05. RESULTS: It was found that 65 (65%) patients showed the presence of at least one of the six autoantibodies that we studied, while 35 (35%) tested negative for all six of them. Positivity of anti-keratinocyte antibody in 26 (26%), anti-nuclear antibody in 22 (22%), anti-desmoglein 1 antibody in 19 (19%), anti-desmoglein 3 antibody in 16 (16%), anti-mitochondrial antibody in 9 (9%) and anti-thyroglobulin antibody in 6 (6%) patients was detected. It was observed that 55 (71.4%) patients of cutaneous lichen planus, 6 (46.1%) patients of mucosal lichen planus and 4 (40%) patients of cutaneous and mucosal lichen planus overlap showed presence of at least one autoantibody. CONCLUSION: This study provides the serological parameters of a population of lichen planus from western India. Presence of autoantibodies in lichen planus suggests the possible role of humoral immunity in lichen planus. Identifying antibodies linked to lichen planus may help in identifying suitable diagnostic tests and therapeutic targets. Well-controlled studies with larger sample size are the need of the hour to confirm the role of humoral immunity in lichen planus. LIMITATIONS: Studies with a larger number of patients as well as controls should be undertaken to further evaluate the role of autoantibodies in lichen planus.

Up-regulation of HMGB1 and TLR4 in skin lesions of lichen planus.

Lichen planus (LP) is a chronic, mucocutaneous inflammatory disease of an unknown aetiology. The disease has been associated with certain viruses, and the factors such as DAMPs (damage-associated molecular patterns) and PAMPs (pathogen-associated molecular patterns) may also contribute to the inflammatory response in LP. HMGB1 (high mobility group box 1 protein) is one of the major DAMPs that induces inflammation and could trigger LP disease. The present study was aimed to examine TLR4, RAGE and HMGB1 production in epidermis or dermis by immunohistochemistry and the respective expression of these targets in the skin lesions of patients with LP. Moreover, we measured HMGB1 serum levels by ELISA. The results showed similar profile of expression by HMGB1 and TLR4, which are decreased at epidermis and up-regulated at dermis of skin lesions of LP patients that was sustained by intense cellular infiltration. RAGE expression was also increased in dermis of LP. Although there is increased RAGE protein levels, a decreased RAGE transcript levels was detected. Similar HMGB1 serum levels were detected in the LP and control groups. This study demonstrates that HMGB1 and TLR4 could contribute to the inflammatory LP process in skin.

Seven-year itch: a perplexing case of lichen planus-lupus erythematosus overlap syndrome.

Lichen planus-lupus erythematosus overlap syndrome is a rare disorder characterized by clinical and histopathological features of both lichen planus (LP) and lupus erythematosus (LE). Cutaneous lesions commonly affect the distal arms, legs, face, and trunk and these plaques are often large, scaly, painful, and atrophic, often exhibiting hypopigmentation or a red to blue-violet color. We report a case of LP-LE overlap syndrome diagnosed in a man previously believed to have atypical lichen planus who presented with an exacerbation of exuberant pruritic erythematous scaly plaques. The patient had six separate skin biopsies all of which displayed features of LP. Because the clinical symptoms did not correlate to the histopathological picture, a seventh skin biopsy with direct immunofluorescence (DIF) was performed and immunologic markers measured. The DIF demonstrated early lupus bands; serologic testing exhibited elevated ANA and anti-SSA. These findings established the diagnosis of LP-LE overlap syndrome. The patient was started on hydroxychloroquine with short-term trials of oral prednisone during disease flares, which took place in the first three months of treatment.

Studying the association between methylenetetrahydrofolate reductase (MTHFR) 677 gene polymorphism, cardiovascular risk and lichen planus.

BACKGROUND: There is a reported relation between hyperhomocysteinemia and lichen planus (LP). An increase in homocysteine (Hcy) and the risk of cardiovascular disease (CVD) in patients with methylenetetrahydrofolate reductase (MTHFR) mutation has been described. OBJECTIVE: To detect MTHFR (C677T) gene polymorphism, and to find its association with CVD risk, Hcy and folic acid levels in patients with LP. METHODS: This hospital-based case-control study included 110 patients with LP: 70 with cutaneous LP (CLP) and 40 with oral LP (OLP). A total of 120 age- and sex-matched healthy subjects were used as controls. Three millilitre venous blood sample was taken for detection of MTHFR gene polymorphism by PCR-RFLP technique and for measurement of the lipid profile. Hcy and folic acid were measured by ELISA. Hypertension was evaluated. RESULTS: There were significantly higher prevalence of hypertension with higher Hcy, triglycerides and cholesterol levels and lower folic acid and HDL levels among patients' groups. Hypertension with higher Hcy and cholesterol levels together with lower folic acid and HDL levels have been found in OLP when compared to CLP. Patients showed a significant higher percentage of the MTHFR 677 TT genotype (P=.003) and of the MTHFR 677 T allele (P=.042) compared to controls. Moreover, there was a higher prevalence of MTHFR 677 T allele in patients with CLP. CONCLUSION: MTHFR 677 gene polymorphism may be a risk factor for the development of the LP, and to predispose these patients to higher risk of CVD.

Evaluation of Cardiovascular Risk Factors, Haematological and Biochemical Parameters, and Serum Endocan Levels in Patients with Lichen Planus.

BACKGROUND AND OBJECTIVE: The current study aimed to evaluate cardiovascular risk factors, haematological and biochemical parameters, and serum endocan concentrations in lichen planus (LP) patients. METHODS: This study was conducted with 86 cases, including 43 LP patients and 43 healthy controls. Cardiovascular risk factors, haematological and biochemical parameters, and endocan levels were evaluated. RESULTS: The serum endocan concentrations of LP patients were not significantly different from those of the healthy controls (p > 0.05). There were no significant differences in the serum endocan levels according to classification by cardiovascular risk factors and smoking history (p > 0.05). In the LP group, white blood cell count, platelet distribution width and monocyte count/high-density lipoprotein cholesterol ratios were significantly higher when compared to the healthy controls (p < 0.05). The LP group had a lower mean platelet volume than the healthy controls (p < 0.05). CONCLUSIONS: Serum endocan levels did not change significantly in patients with LP, and there were significant differences in haematological and biochemical parameters.