Inflammatory mechanisms play a significant role in the pathogenesis of venous disease but the exact mechanisms producing venous ulceration remain to be elucidated.

BACKGROUND. Articles were identified from a literature search based on Index Medicus from 1983 onwards with additional, as yet, unpublished data obtained directly from ongoing research at The Middlesex Hospital Vascular Laborato y. Original scientific articles were selected if they addressed the mechanisms causing venous ulceration in relation to the events in the microcirculation. OBJECTIVE. To review the mechanisms proposed recently to explain the pathogenesis of venous Ulceration. RESULTS. Recent data suggest that there is a systemic inflammato y response associated with the presence of venous disease in the lower limb, as indicated by measuring plasma neutrophil elastase and lactoferrin. In volunteers without venous disease white cell activation may be produced by experimental venous hypertension lasting 30 minutes, produced by applying a venous tourniquet to the lower limb or by standing without moving for 30 minutes. CONCLUSION. Inflammato y mechanisms play a significant role in the pathogenesis of venous disease but the exact mechanisms producing venous ulceration remain to be elucidated. J Dermatol Surg Oncol 1994;20:474-480.'enous valvular incompetence is present in up to 10% of the population of Western countries, and 0.2% have venous ulceration as a con~equence.'-~ It is generally agreed that sustained venous hypertension is an essential prerequisite to the development of ulcers, but the precise pathophysiological mechanism remains o b s c~r e .~,~ Various theories of the etiology of venous ulceration have been put forward, of which the two currently most popular are the fibrin cuff theory of Browse and Burnand6 and the white cell trapping theory of Coleridge Smith et al.' Research has failed to show that fibrin cuffs present a dffusion barrier to the passage of oxygen "and other nutrients,"8 and cutaneous oxygen tension is actually higher in patients with venous d i~e a s e .~The white cell trapping hypothesis suggests that increased venous pressure causes a reduction in capillary blood flow, resulting in trapping of the white blood cells in the leg. These cells may plug the capillaries, resulting in areas of localized ischemia, and become activated, releasing toxic oxygen metabolites (free radicals), proteolytic enzymes, and chemotactic substances. White cell margination has been shown to occur in the postcapillary venules when blood flow is reduced,I0 and increased numbers of white cells have been demonstrated in the skin of patients with lipodermatosclerosis (LDS)." We have recently obtained di-