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The role of leukocytes in tissue damage in the liposclerotic skin of venous disease has been investigated. Twenty-eight skin biopsy specimens were obtained from 23 patients with varicose veins of the lower limb, with a spectrum of skin injury ranging from normal to severe liposclerosis. In no patient was a venous ulcer present. Immunohistochemistry was used to determine the cell types present and provide an indication of their activity. The predominant infiltrating cell types present were T lymphocytes and macrophages. B cells and neutrophils were rarely seen. As described previously, the capillaries were greatly increased in number in the papillary dermis and exhibited grossly increased expression of factor VIII-related antigen and major histocompatibility complex class II. Surprisingly, expression of adhesion molecules endothelial leukocyte adhesion molecule-1 and vascular cell adhesion molecule were not elevated, but intercellular adhesion molecule-1 expression did increase in more severely diseased skin. Perivascular fibrin was seen occasionally, but there was no evidence of microvascular occlusion. Staining for the cytokine tumor necrosis factor-alpha was not increased in liposclerotic skin. Dermal staining for both interleukin (IL)-1 alpha and IL-1 beta was increased in severely liposclerotic skin, but this was not seen at an early stage. Epidermal staining for IL-1 alpha and IL-1 beta was not increased. All changes were confined to the subpapillary region of the skin. These findings demonstrate that accumulation of macrophages and T cells is an event associated with the development of liposclerotic skin changes that may lead to ulceration in venous disease.(ABSTRACT TRUNCATED AT 250 WORDS)

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