Update on chronic-venous-insufficiency-induced inflammatory processes

The causes of venous ulceration remain unclear. Twentieth-century hypothese s concentrated on the possibility that this problem was caused by failure o f oxygen delivery to the skin. However, it has been difficult to substantia te these predictions in practice. Although the presence of tissue hypoxia h as been suggested by studies in which transcutaneous oxygen tension has bee n assessed with transducers heated to unphysiological temperatures, when ox ygen 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 sequ ence of events appears to surround the development of leg ulceration. Increased leukocyte activation has been shown in patients with venous disea se as well as increased expression of soluble endothelial adhesion molecule s. Histologic studies of the skin in patients with chronic venous disease s how 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 subcu taneous tissues may be initiated by increased gene expression and productio n of transforming growth factor-V 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 metalloprot einases has been reported both in liposclerotic skin and periulcer skin. Th e tissue inhibitors of metalloproteinases are also increased and the net re sult is unclear. Treatment of venous disease using micronized purified flav onoid fraction moderates some of the inflammatory markers, including leukoc yte ligand expression and endothelial adhesion molecule shedding. These com pounds have also been shown to reduce leukocyte-endothelial adhesion in ani mal models of ischemia-reperfusion injury, Many inflammatory processes have now been shown to be involved in the development of the skin changes in pa tients with chronic venous disease. However, the precise sequence of events that leads to leg ulceration is still unclear. Pharmacologic treatments ai med at moderating some of these inflammatory processes are now under invest igation as potential ways of treating patients with the more advanced stage s of venous disease.