الفهرس 
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Abstract
Lichen planus (LP) is a chronic inflammatory mucocutaneous disorder with characteristic violaceous polygonal flat-topped papules and plaques. Skin lesions may be disfiguring, and involvement of the oral mucosa or genital mucosa in severe cases may be debilitating. The prevalence of lichen planus is unknown, but it is estimated to occur in less than 1 percent of the population.
Although its etiology and pathogenesis are not fully understood, LP has been associated with multiple diseases and etiopathological factors, including viral infection, autoimmune disease, medication, vaccination, and dental restorative materials. Lymphocytes, particularly T-cells, play a major role that represents T-cell mediated autoimmune damage to basal keratinocytes that express altered self- antigen on their surfaces. Both CD4+ and CD8+ T cells are found in lesional skin of lichen planus in the dermis, while CD8+ T cells infiltrate the epidermis. It has been proposed that CD8+ cytotoxic T cells recognize an antigen (currently unknown) associated with major histocompatibility complex (MHC) class I on lesional keratinocytes and lyse them. Mononuclear cells infiltrating the skin, the majority of which are CD8+as well as basal keratinocytes, express TNF-α and TNF-R1.
Cytokines are low molecular weight glycoproteins that are transiently produced and exert their biologic activities via specific cell-surface receptors. Cytokines regulate cell metabolism and functions: in addition, They exhibit immunoregulatory activities through a complex cytokine network consisting of paracrine and autocrine systems.
TNF-α, a 17 kDa protein, is a cytokine produced by a wide variety of cell types, including macrophages, T and B lymphocytes, Langerhans cells, endothelial cells and keratinocytes. TNF-α is a cytokine that plays an important role in host defense, including immunoregulatory responses implicated in the pathogenesis of many inflammatory and autoimmune diseases.
This work involved lesional and normal control skin specimens dividing into two groups; group (1) included 29 specimens from patients suffering from cutaneous lichen planus and group (2) included 29 subjects from normal individuals. The subjects were randomly collected from dermatology out patient clinic at Suez Canal University Hospital.
An immunohistochemical technique was applied in this study, using a mouse monoclonal IgG1 antibody, 100µg/ml raised against purified full length native TNF-α of human origin in order to study the expression pattern of TNF-α in lichen planus skin lesions and the normal skin.
This study included 12 male and 17 female with lichen planus with age range fom 21-73 years and disease duration range from 1 month to 12 years while the normal subjects are 20 male and 9 female with age range from 20-50 years. The results showed that all patients with lichen planus had different patterns of TNF-α expression in their tissue, The majority of the specimens (72.4%) in lichen planus group had moderate to strong TNF-α expression, while 18 (62.1%) specimens of the normal control skin had negative TNF-α expression and 11(37.9%) specimens had mild TNF-α expression in less than 5% of the resident cells (p<0.0001) which is highly significant and revealed that the expression of TNF-α in the lesional skin of patients with lichen planus is higher than the expression in the skin of the control group and this could explain that TNF-α had an important role in the pathogenesis of lichen planus.
In conclusion, the immunohistochemical detection of TNF-α in lichen planus skin lesion is indicative of the involvement of this cytokine in the immuopathogenesis of the disease. This may allow better understanding of the pathogenic mechanism of this disease and suggest new modalities for its treatment.
Consequently, the development of anti-TNF-α therapy has been proposed for the treatment of many inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. TNF-α production by the immune system is a double-edged sword. It has both a beneficial effect by initiation of the inflammatory response and promoting the reparative process as well as a devastating effect to the body. For example, excessive production of this cytokine during wound healing can result in tissue damage, cachexia, shock, and even death. Because TNF-α has many functions, the anti-TNF-α treatments can cause side effects in clinical trials such as the development of antinuclear antibodies (ANA) and double-stranded DNA (dsDNA) antibodies, as well as the infrequent development of systemic lupus erythematosus (SLE)-like disease. Hence, we should consider modulating the level of TNF-α and other related cytokines in the treatment of lichen planus by weighing the good it will do against the risk it may cause. Thus, understanding the biologic effects of TNF-α is important for dermatologists and oral medicine clinicians because the clinical application of this cytokine in the treatment of lichen planus will be safer and more effective.
Conclusion and Recommendations:
◘ It is speculated that Tumor necrosis factor alpha plays a certain role in the pathogenesis of lichen planus.
◘ Histopathological evaluation and TNF-α expression may be used as useful indicator for the disease severity.
◘ Further studies at biochemical and molecular levels should be done to understand the exact role of TNF-α in LP and clarify whether this cytokine modulates the expression of genes that affect the consequence of the disease.
◘ Anti-TNF-α therapy can be introduced as one of the successful modalities for the treatment of lichen planus but we should consider modulating the level of TNF-α and other related cytokines by weighing the good it will do against the risk it may cause.