title: The causes of skin damage and leg ulceration in chronic venous disease.
abstract: Chronic venous disease with skin changes of the leg is a common condition affecting up to 1 in 20 people in westernized countries. The causes of this problem are not fully understood, although research in recent years has revealed a number of important mechanisms that contribute to the disease process. Patients with chronic venous disease suffer persistently raised pressures in their deep and superficial veins in the lower limb. Leucocytes become "trapped" in the circulation of the leg during periods of venous hyper-tension produced by sitting or standing. Studies of the plasma levels of neutrophil granule enzymes shows that these are increased during periods of venous hypertension, suggesting that this causes activation of the neutrophils. Investigation of the leucocyte surface ligands CD11b and CD62L shows that the more activated neutrophils and monocytes are sequestered during venous hypertension. Measurement of plasma levels of the soluble parts of the endothelial adhesion molecules VCAM, ICAM, and ELAM show that these are all elevated in patients with chronic venous disease compared to controls. Following 30 minutes of venous hypertension produced by standing, these levels are further increased. These data suggest that venous hypertension causes neutrophil and monocyte activation, which in turn causes injury to the endothelium. Chronic injury to the endothelium leads to a chronic inflammatory condition of the skin that we know clinically as lipodermatosclerosis. This is mediated by perivascular inflammatory cells, principally macrophages, in the skin microcirculation. These stimulate fibroblasts in the skin leading to tissue remodeling and laying down of fibrous tissue. Vascular endothelial growth factor stimulates proliferation of capillaries within the skin. Skin in this state has the potential to ulcerate in response to minor injury.
authors.affiliation: UCL Medical School, London, UK. p.coleridgesmith@ucl.ac.uk
authors.forename: Philip Coleridge
authors.initials: PC
authors.lastname: Smith
mesh_terms: D002908:Chronic Disease; D006801:Humans; D007871:Leg Ulcer / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D008833:Microcirculation / Q000502:physiology; D012867:Skin / Q000098:blood supply / Q000473:pathology*; D014689:Venous Insufficiency / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D014945:Wound Healing