ROLE OF TUMOR NECROSIS FACTOR ALPHA AND BASIC FIBROBLAST GROWTH FACTOR IN THE PATHOGENESIS OF VITILIGO:AN IMMUNOHISTOCHEMICAL STUDY BEFORE AND AFTER MELANOCYTE TRANSFER BY SANDPAPER TECHNIQUE

Abstract

Background: Vitiligo is an acquired depigmentation of skin and mucous membranes. Many theories explain its pathogenesis. Keratinocyte dysfunction in vitiligo may be a possible link between the various pathological changes occurring in vitiliginous skin. Keratinocytes produce several mediators, cytokines and growth factors that support or inhibit the growth and/or melanization of surrounding melanocytes. Basic fibroblastic growth factor (bFGF) is proposed to be a paracrine mitogen for human melanocytes.Tumor necrosis factor α (TNFα), is suggested to be as an early paracrine inhibitors of melanocyte.In this study,we evaluated the keratinocyte 's TNFα and b-FGF in vitiligo patients before and after treatment with melanocyte transfer by sandpaper technique. Methods: This study was carried out on two groups, 17 vitiligo patients ,and 17 healthy persons as control. Skin biopsies were taken from the patients before and after treatment with melanocyte transfer from the lesional and perilesional skin .Skin biopsies were taken also from skin of the normal control individuals. These biopsies were prepared for histological evaluation and immunohistochemical(IHC) staining forTNFα b-FGF.Evaluation of IHC slides was done by a subjective method(i.e. eyes of an expert pathologist) and an objective method(Image analyser) before and after 3 months of treatment with melanocyte transfer by sandpaper technique. Results: There was a statistically highly significant increase of b-FGF staining in lesional and perilesional skin of the patient's group in comparison with their staining in normal control. Regarding TNFα staining of lesional and perilesional skin,there were a statistically significant increase and a statistically highly significant increase respectively with its staining in the normal control. The clinical results of the melanocyte transfer by sandpaper technique,after 3 months of follow up, were as follow,47.1%of patients showed mild improvement,35.3%of patients showed good improvement,and 17.6% of patients showed no improvement.TNFα staining of lesional and perilesional skin,evaluated subjectively, showed a statistically highly significant increase after treatment with melanocyte transfer in comparison with their staining before treatment.Regarding b-FGF staining ,subjectively evaluated,there was a statistically highly significant increase after treatment in lesional skin and a statistically highly significant decrease after treatment in perilesional skin.Using image analyser as an objective method of evaluation,there was a statistically significant increase of TNFα staining of lesional and perilesional skin after melanocyte transfer in comparison with their staining before treatment.On comparing b-FGF stainings after treatment with their corresponders before treatment by image analyser,there was a statistically significant decrease of b-FGF staining in lesional skin after treatment and there was no significant change in perilesional skin before and after treatment. Conclusion:change in the microenvironment of vitiliginous skin is evident .These changes in the cytokines,growth factors affecting the melanocytes may be a joint step in the pathogenesis of vitiligo between an intial step (supposed to be oxidative stress and apoptosis in keratinocytes) and an eventual step marked by destruction of the melanocytes.