Deleterious effects of white cells in the course of skin damage in CVI.
Venous ulceration remains a common problem and a significant challenge to the physicians treating it. Many theories have been advanced in the past to explain its causes but there is little evidence to support tissue hypoxia as the main factor, as was once thought. In recent years attention has focussed on the inflammatory events which attend venous disease and the development of venous ulceration. It has been proposed that these form a major contribution to the development of venous leg ulcers. In the arterial system an analogous series of events appears to cause damage following severe ischemia. Massive neutrophil activation in the microcirculation following reperfusion of a tissue results in severe, ischemic damage to that tissue. A similar series of events is proposed to explain venous disease. During venous hypertension leukocytes are sequestrated in the microcirculation of the lower limb. It has been shown that these undergo activation whilst they are in the leg. The exact location of leukocyte sequestration is unclear but it is suggested that this may occur in the skin. The damage caused to the lower limb skin components can be identified by measuring plasma levels of endothelial adhesion molecules, which are shed into the circulation following a period of venous hypertension. In the long term this leads to a chronic inflammatory state in the skin in some patients where venous hypertension is sustained or there is susceptibility to venous hypertension. The resulting inflammatory process is referred to as "lipodermatosclerosis" and has a number of well known clinical features. There is proliferation of the dermal capillaries eventually leading to a "glomerulus" like appearance. In the skin and subcutaneous tissues there is fibrosis. The microcirculation in the papillary dermis is surrounded by an inflammatory cellular infiltrate. The importance of understanding the mechanisms of the development of venous ulceration is in creating new treatments for this problem. Compression treatment has been effective in healing leg ulcers for thousands of years. Surgical treatment offers a possible cure in patients where superficial venous reflux is the main problem. Deep vein reconstruction is only suitable for a few patients. Many venous ulcers can be healed by compression, only to recur within a few months. Pharmacological treatments may offer the possibility of more rapid ulcer healing and the maintenance of an ulcer-free state if the correct pathophysiological mechanisms can be identified and addressed.
Coleridge Smith
P D
PD
Department of Surgery, Royal Free and University College Medical School, The Middlesex Hospital, London, UK. p.coleridgesmith@ucl.ac.uk
D000527:Alprostadil / Q000627:therapeutic use; D015815:Cell Adhesion Molecules; D002908:Chronic Disease; D006801:Humans; D016285:Iloprost / Q000627:therapeutic use; D007871:Leg Ulcer / Q000097:blood*; D007962:Leukocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D010431:Pentoxifylline / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000627:therapeutic use; D014689:Venous Insufficiency / Q000097:blood* / Q000188:drug therapy
D015815:Cell Adhesion Molecules; D014665:Vasodilator Agents; D000527:Alprostadil; D016285:Iloprost; D010431:Pentoxifylline