الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 155 |  |  |
| | | from | 155 | | |
Abstract
Skin tags are benign connective tissue tumors of the dermis that present as small, soft, usually pedunculated, less commonly sessile skin protrusion sometimes with a long stalk, mainly on sides of the neck, axillae, and flexures. When they are profuse, they may occur on the face, chest, and back. Many synonyms were described for skin tags, such as acrochordons, cutaneous tags, soft fibromas, fibroepithelial polyps. Acrochordons are found in about 25% of adults, Skin tags show more incidence in females than males [2:1.3] with two peaks, one at pregnancy and the other at menopause. A family history of acrochordons sometimes exists. Acrochordons are usually asymptomatic, They are not painful unless inflamed or irritated Leptin is one of the most important adipose derived hormones, a 16-kDa protein,it has been shown that leptin has multiple biological functions. It plays a key role in regulation of food intake and body weight, regulation of immunity, hematopoiesis, coagulation, reproduction, lung development, thyroid function, thermogenesis, ovarian function , bone formation, angiogenesis and wound healing. These functions occur after binding of leptin to its receptors which are expressed primarily in the hypothalamus and also in other tissues as keratinocytes , fibroblasts, endothelial cells, and peripheral blood mononuclear cells. The current study aimed to investigate the possible role of leptin in skin tags pathogenesis through its immunohistochemical expression in these lesions. We aimed also to study the relationship between leptin expression and the clinico-pathological characters of studied cases. This prospective case-control study was carried out on 90 non obese subjects. These included 60 cases with skin tags and 30 age, sex and BMI matched normal subjects as a control group. Cases were selected from Dermatology Outpatient Clinic, Menoufiya University Hospital. Normal skin specimens were obtained from subjects attending Plastic Surgery Department, Menoufiya University Hospital. Every case was subjected to complete history taking, complete general and dermatologic examination. Nonobese subjects were selected based on BMI values {weight (Kg)/height (m2)}. The study included those with BMI between 19-25 Kg/m2. Overweight (BMI: >25-29 Kg/m2) and obese (BMI >30 Kg/m2) subjects were excluded from the study. Patients with type I and type II diabetes mellitus, patients with concomitant disorder(s) that may affect the outcome of the study, subjects taking any drug that affect leptin expression and/or glucose metabolism (insulin, glucocorticoids, estrogens, glucosamine, short chain fatty acids, catecholamines , thyroid hormones, androgen and adrenergic agonists), subjects with metabolic syndrome and with unsteady weight in the past three months were also excluded. Excisional skin biopsies were taken under local anesthesia. All biopsies were fixed in 10% neutral buffered formalin and sent to Pathology Department, Faculty of Medicine, Menoufyia University for routine processing. The specimens underwent dehydration in ascending grades of ethanol followed by xylene then impregnation in paraffin wax. Several 5 micron (5μ) thick sections from each block were obtained. One section was stained by haematoxylin and eosin (H&E) for the histopathological examination, one section was stained by Giemsa stain for mast cell identification and count and the other sections were mounted on positive charged slides and stored at room temperature until used for immunostaining with leptin. All cases of skin tags showed positive epidermal expression of leptin 100%, with whole thickness epidermal localization in 100%of cases. Epidermal intensity was mild in 30% of cases, moderate in 63.3% and strong in 6.7%. Pattern of leptin staining was cytoplasmic in 43.3% of cases, nuclear in 6.7% and nucleo-cytoplasmic in 50%. Regarding leptin dermal expression, all the studied skin tags cases showed positive staining 100%. Dermal intensity was mild in63.3% of cases, moderate in 30% and strong in 6.7%. Dermal pattern was cytoplasmic in 20% of cases, nuclear in 6.7% and nucleocytoplsmic in 73.3%. Immunohistochemical expression of leptin in epidermis of normal skin showed positive expression in all examined specimens 100%. Epidermal localization was basal in 30% of samples and occupied the whole thickness in 70% of samples. Epidermal intensity was mild in 63.3% and moderate in 36.7% of sections. Epidermal pattern of was cytoplasmic in 70% of sample and nucleo-cytoplasmic pattern in 30%. Dermis of all normal skin samples 100% showed positive staining of leptin. Dermal intensity was mild in 86.7% of samples and moderate in 13.3% of samples. Dermal pattern was cytoplamic in 86.7% and nucleo-cytoplasmic in 13.3% of samples. Skin tag cases showed significantly higher epidermal H score categories (P<0.001), epidermal H score (P<0.001), epidermal localization of leptin (P<0.001), epidermal pattern (P<0.04) and epidermal intensity (P=0.007) compared to normal skin. A highly significant difference was found between cases and controls regarding dermal pattern (P<0.001), where nuclear and nucleocytoplasmic patterns were significantly associated with cases. Epidermal leptin expression was significantly associated with large skin tags (P=0.006) and higher collagen % (P=0.001). High epidermal H score category was significantly associated with female gender (P=0.001), higher mast cells count (P=0.01) and higher collagen % (P=0.02). Higher epidermal leptin H score was significantly associated with female gender (P=0.004) and mixed collagen arrangment (P<0.03). Dermal leptin expression was significantly associated with multiple skin tags (P=0.02), dilated blood vessels (P=0.02), presence of mast cells (P=0.02) and loose collagen arrangement (P=0.003). Higher dermal leptin H score was significantly associated with smooth skin tags (P=0.01), presence of mast cells (P=0.002), presence of inflammatory cells (P=0.004) and mixed collagen arrangement (P<0.001). In conclusion, the results obtained in the current study indicate that leptin may share in the pathogenesis of skin tags through its direct proliferative and mitogenic effect on keratinocytes, stimulation of fibroblast proliferation, collagen synthesis and deposition. It also enhances angiogenesis, endothelial cell growth, vasodilatation and increased blood flow and tissue perfusion. In addition, it stimulates mast cell growth which inturn stimulate fibroblast growth, differentiation and collagen deposition. MC stimulate keratinocyte proliferation and epidermal acanthosis. This may open an avenue for research for new therapeutic modalities based on leptin inhibition.