Update on chronic-venous-insufficiency-induced inflammatory processes.
The causes of venous ulceration remain unclear. Twentieth-century hypotheses concentrated on the possibility that this problem was caused by failure of oxygen delivery to the skin. However, it has been difficult to substantiate these predictions in practice. Although the presence of tissue hypoxia has been suggested by studies in which transcutaneous oxygen tension has been assessed with transducers heated to unphysiological temperatures, when oxygen measurements are made at room temperature there is little evidence of tissue hypoxia. This has led to the assessment of alternative mechanisms of ulcer development. There has been considerable interest in recent years in the inflammatory processes that surround venous ulceration. A complex sequence of events appears to surround the development of leg ulceration. Increased leukocyte activation has been shown in patients with venous disease as well as increased expression of soluble endothelial adhesion molecules. Histologic studies of the skin in patients with chronic venous disease show a perivascular infiltration of the capillaries of the papillary plexus (the most superficial part of the dermis) with monocytes, macrophages, and connective tissue proteins including fibrin. Fibrosis of the skin and subcutaneous tissues may be initiated by increased gene expression and production of transforming growth factor-beta1. Vascular endothelial growth factor may be involved in the capillary proliferation that has been reported in the skin by a number of authors. Increased expression of several tissue metalloproteinases has been reported both in liposclerotic skin and periulcer skin. The tissue inhibitors of metalloproteinases are also increased and the net result is unclear. Treatment of venous disease using micronized purified flavonoid fraction moderates some of the inflammatory markers, including leukocyte ligand expression and endothelial adhesion molecule shedding. These compounds have also been shown to reduce leukocyte-endothelial adhesion in animal models of ischemia-reperfusion injury. Many inflammatory processes have now been shown to be involved in the development of the skin changes in patients with chronic venous disease. However, the precise sequence of events that leads to leg ulceration is still unclear. Pharmacologic treatments aimed at moderating some of these inflammatory processes are now under investigation as potential ways of treating patients with the more advanced stages of venous disease.
Smith
P D
PD
Department of Surgery, Royal Free and University College Medical School, The Middlesex Hospital, London, UK. p.coleridgesmith@ucl.ac.uk
D002908:Chronic Disease; D006801:Humans; D007249:Inflammation; D007871:Leg Ulcer / Q000209:etiology / Q000503:physiopathology; D007962:Leukocytes / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000502:physiology; D012867:Skin / Q000473:pathology; D012871:Skin Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D014689:Venous Insufficiency / Q000150:complications* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology
D020782:Matrix Metalloproteinases