LEUKOCYTES - THEIR ROLE IN THE ETIOPATHOGENESIS OF SKIN DAMAGE IN VENOUS DISEASE

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-I 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)-1alpha and IL-1beta was increased in severely liposclerotic skin, but this was not seen at an early stage. Epidermal staining for IL-1alpha and IL-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. However, no evidence was found to suggest that hypoxia caused by occlusion of vessels by leukocytes or other mechanisms of microvascular insufficiency contribute. No evidence was found to implicate either tumor necrosis factor-alpha or epidermal IL-1 in the initiation of leukocyte infiltration, but an increase in dermal IL-1 may be involved in later stages of the process.