PHARMACOLOGICAL TREATMENT OF VENOUS LEG ULCERS

In terms of prevalence, total cost and morbidity, venous leg ulcers ar e probably by far the most important type of ulcerations in the leg. T he macrocirculatory defect leading to a raised ambulatory venous press ure is now accepted as a common initial pathologic pathway. Most curre nt treatment modalities, such as surgery or external compression, are designed to control the macrovascular defect. However, it is the micro circulatory consequences of the venous hypertension that give rise to the trophic skin changes and ultimately to ulceration. At this microci rculatory level, pharmacotherapy may be a useful adjunct in the treatm ent of venous leg ulcers. The microcirculatory pathophysiologic change s include decreased fibrinolytic activity, elevated plasma fibrinogen, microcirculatory thrombi, and inappropriate activation of the white b lood cells. The oxidative burst from the activated white cells probabl y plays a key role by releasing locally leukocyte-derived free radical s, proteolytic enzymes, cytokines, platelet-activating factor, and a n umber of other noxious mediators. An important additional component in recalcitrant venous ulcers is coexisting arterial disease, which is p robably present in 15-20% of cases. Decreased arterial perfusion press ure will further aggravate the ischemic changes caused by the venous h ypertension. Pentoxifylline downregulates leukocyte activation, reduce s leukocyte adhesion, and also has fibrinolytic effects. A number of c linical studies have therefore been carried out to examine the clinica l efficacy of pentoxifylline in treatment of venous leg ulcers. Probab ly the largest published placebo-controlled, double-blind, randomized study was reported in 1990. In this study, 80 patients received either pentoxifylline 400 mg three times a day orally or matching placebo fo r 6 months or until their reference ulcer healed if this occurred soon er. Complete healing of the reference ulcer occurred in 23 of the 38 p atients treated with pentoxifylline compared to 12 of the 42 patients treated with placebo. The odds ratio in favor of pentoxifylline was 1. 81 (95 confidence intervals 1.20-2.71).