British Journa/ ofSurgery 1994,81,1404-1405

Venous ulcerAn editorial in this Journal 4 years agoccconsidered the problem of venousulceration. More than 2000 articles on the subject of varicose veins and venousulcers have been cited in the pages of lndex Medicus since then. A number ofimportant advanceshave been made in the investigation of the venous system andunderstanding of the pathological processes that result in ulceration but,as yet,only modest progress has been made in the treatment of this condition.~ Venous ulceration is a éommon problem in patients With chronic venous disease.

The prevaIence of venous disease severe enough to lead to ulceration in Westerncountiies is 1-2 per cent and approximately one-fifth of those affected suffer anulcer of the leg at any one time!. The cost to health services is considerable.A venous ulcer costs 1:2000-4000 per year to manage, much of this spent in fuecommunity on nursing services2; an estimated 150000 patients in the UK withactiveleg ulceration result in an annual bill of 1:300-600 million. In comparison,20000 patients per year receive treatment for critical ischaemia of the lower limbin the vascular surgical units of fue UK 3.

Between 10 and 50 per cent of patients with venous ulcer have ulcerationattributable to superficial venous incompetence alone. Such patients cannot easilybe identified clinically and hand-held Doppler ultrasonography is of limitedaccuracy,especially in the popliteal fossa. While venography has been widely used,colour duplex ultrasonographic imaging has seen vast technological improvementsin the past 4 years and is more effective at assessing the competence of venousvalves, particularly in the popliteal vein4. AlI patients p.resenting with venousulceration who are fit enough to undergo treatment of superficial venous diseaseshould be evaluated by this technique. The cost of ultrasonographic imaging is halfthat of venography; the results provide anatomical and functionál information andthe test is non-invasive. At present, few radiologists and vascular surgeons in theUK are familiar with the methods required to perform ultrasonographic scanningfor venous valvular incompetence. However, there is growing interest in this fieldand the provision of suitable equipment in inany district general hospital s will soonpermit vascular surgeons access to this invaluable investigation.

The events in the microcirculation that lead to skin ulceratiqn have not beenfully resolved. Browse and Burnand suggested that perivascular fibrin cuffingmight prevent oxygen reaching the tissues but theoretical considerations indica tethat it is unlikely such cuffs present a barrier to the diffusion of oxygen or othersmall molecules5. Direct needle electrode measurements of skin oxygen tension inpatients with venous disease have shown only modest reductions of skin oxygena-tion compared with normal values6, The finding of fibrin cuffs in other patho-logical processes and the failure of fibrinolytic treatments to heal venous ulcershave led some authors to conclude that these are not the main mechanism behindtissue injury7.

In a small number of studies the changes in liposclerotic skin and ulcers of theleg have been investigated by electron microscopy and modero immunohisto-chemical techniques. These have shown that the perivascular cuff of skincapillaries is much more complex than previously suspected, containing collagentype IV, laminin, fibronectin, tenascin, macrophages and some T lymphocytes, aswell as fibrin. The endothelium of ihese capillaries is, very prolific and is'perturbed', expressing intercellular and endothelium-leucocyte adhesionmolecules, which participate in the mechanism of neutrophil adhesion. In addition,expression of factor VIlI-related antigen is upregulated.The presence of thecytokine interleukin 1 has been reported in two studies, and tumour necrosis factora in one8. These observations confirm that lipodermatosclerosis is a chronicinflammatory condition but do not indicate the causal factors. Systemic neutrophilactivation has been observed in a number of studies in patients with chronicvenous disease, ranging from uncomplicated varicose veins to ac,tiye ulceration,compared with that in age-matched control subjects9. This maysimply reflect a' ,cc. .response to the presence of venous dlsease. To understand the events leadrng totheseend-stage findings it is nece~sary to study the earliest events after the onset ofvenous hypertension.

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LEADING ARTICLES 1405

In 1988 I suggested that white cell sequestration ('trapping') in the legs oípatients with venous disease might be the main cause oí tissue damage. Trappingoccurs within 30 min oí raising the venous pressure in control subjects and isgreater in extent in patients with venous disease. It has since been reported thatvenous hypertension lasting 30 min produced by standin~ leads to increasedneutrophil degranulation and adhesion molecule express ion 1 in the legs oí controlsubjects. Laser Doppler fluxmetry measurement oí postischaemic reactivehyperaemia alter a period oí venous hypertension shows a reduced responsecompared with that beíore venous hypertension in control subjects. This suggeststhat microcirculatory injury occurs in association with neutrophil degranulation. Inindividuals with calí muscle pump íailure venous hypertension will occur wheneverthe patient stands, presumably leading to neutrophil activation. Repeatedendothelial injury may result in the changes seen in liposclerotic skin. Variabilitybetween individuals in susceptibility to venous disease may be the result oíalterations in any oí the complex mechanisms involved in neutrophil adhesion,activation or endothelial repair.

The mechanism oí white cell-endothelial cell interaction and the metabolismoíneutrophils are the subject oí intense study as these are crucial in the developmentoí tissue ischaemia. Adhesion oí white cells to endothelium, activation oíneutrophils and release oí free radicals all cause tissue damage during ischaemia.Drugs that influence these events are under development and might be used toprevent or heal venous ulcers. A preliminary study oí one such drug, oxpentiíylline,has reported encouraging results.

Venous ulceration remains a common, expensive, though unspectacular clinicalproblem in Western countries. The investigation oí patients with leg ulcer byduplex ultrasoQographic imaging will ensure that all those in whom superficialvenous incompetence is the cause oí ulceration will receive the correct surgicaltreatment. In the future, adjunctive pharmacological methods may be employed toassist and maintain the healing oí venous ulcers. The selection oí the best drugs willdepend on a betterunderstanding oí the processes causing venous ulceration.

P. D. Coleridge SmithUniversity College London Medical SchoolThe Middlesex HospitalLondon W1N 8AAUK

physiological examinations in lipodermato-sclerosis. In: Raymond-Martimbeau P,Prescott R, Zummo M, eds. Phlebologie '92.Montrouge: John Libbey, 1992: 172-4.

7 Falanga V, Kirsner R, Katz MH, Gould E,Eaglstein WH, McFalls S. Pericapillaryfibrin cuffs in venous ulceration.Persistence with treatment and during ulcerhealing. J Dermalol Surg Oncol 1992; 18:409-14.

8 Wilkinson LS, Bunker C, Edwards JC,Scurr JH, Smith PD. Leukocytes: their Tolein lhe eliopathogcnesis of skin damage in

yenous disease.' J Vasc Surg 1993; 17:669-75.

9 Shields DA, Andaz S, Timothy-AntoineCA, Porter JB, Scurr JH, Coleridge SmithPD. Plasma elastase in venous disease.BrJSurg 1994; 81: 1496-9.

1 OShields DA, Andaz S, Timothy-AntoineCA,Porter JB, Scurr JH, Coleridge SmithPD. CD11b/CDI8 and neutrophilactiyatiq~ in yenous hypertension.J Dermalol Surg Onco11994; 20: 72.

1 Callam MJ, Ruckley CV, Harper DR, DaleJJ. Chronic u.lceration of the leg: extent ofthe problem and provision of careo BMJ1985;290:1855-6.

2 Bosanquet N. Costs of venous utcers: frommaintenance therapy to investmentprogrammes. Ph/eb%gy 1992; l(Suppl):44-6.

3 Vascular Surgical Society of Great Britainand Iretand. Critica/ lschaemia: Mana,¡¡e-ment Report o/ a Nationa/ ¿"urvey. London:VSS, 1994: 12.

4 Baker SR, Bumand KG, Sommcrville KM,Thomas ML, W1tson NM, Browse NL.Comparison of venous reflux assessedby duptex scanning and descendingphlebography in chronic venous di sea se.Lancet 1993; 341: 400-3.

5 Michel i,,'CC¡,'1cC Oxygen ,'diffusionc "1noedematous tissue and throughperi-capillary cuffs. Ph/eb%gy 1990; 5:223-30.

6 Schmeller W, Roszinski S, Tronnier M,Gmelin'E..Combined morphotogical and

Brilísh Journal ofSurgery 1994,81, 1404-1405