Management of leg ulcer.pdf

8/10/2019 Management of leg ulcer.pdf

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REVIEWS

Management of leg ulcers

P K Sarkar, S Ballantyne

Abstract

Leg ulcer is a leading cause of morbidity

among older subjects, especially women in

the Western world. About 400 years BC,

Hippocrates wrote, In case of an ulcer, it

is not expedient to stand, especially if the

ulcer be situated on the leg. Hippocrates

himself had a leg ulcer. The best treatment

of any leg ulcer depends upon the accurate

diagnosis and the underlying aetiology.

The majority of leg ulcers are due to

venous disease and/or arterial disease, but

the treatment of the underlying cause is

far more important than the choice of

dressing. The aetiology, pathogenesis,treatment, and the future trends in the

management of the leg ulcers are dis-

cussed in this review.(Postgrad Med J2000;76:674682)

Keywords: leg ulcers; compression bandages; skin graft-

ing

There are about 400 000 patients with leg ulcerdisease in the UK and at any one time 100 000have open leg ulcers requiring treatment. Thiscosts about 600 million/year.1 Venous ulcera-tion of the lower leg is the result of increasedvenous pressure and its secondary eVects onthe microvascular system.2 In patients withvenous leg ulcers, nearly half have evidence of apast venous thrombosis while the remainderresults from incompetence of valves of thesuperficial or communicating veins. The ve-nous leg ulcer is an age related disease in theelderly population, especially women. It may beassociated with lipodermatosclerosis and ec-zema. Whereas the venous leg ulcer is usuallyoriginated by external trauma, the course isoften chronic and/or relapsing.

Epidemiology

INCIDENCE

Community surveys in Lothian, north westLondon, and Southampton all suggest an over-all incidence of about 0.2%.3

PREVALENCE

The prevalence of leg ulcers in Europe is welldocumented, varying between 0.18% and 1%in diVerent countries.47 In the UK two majorstudies demonstrated the prevalence of activeulcers at 0.15% to 0.18% in contrast to 1% inthe Scandinavian countries. Leg ulcers occurmore commonly in elderly people and theirprevalence is likely to increase as the averageage of the population increases.8 9

AetiologyIn the Western world, leg ulcers are mainlycaused by venous insuYciency, arterial insuY-ciency, neuropathy, diabetes, or a combinationof these factors (table 1). Venous ulcers are themost common type of leg ulcers, accountingfor approximately 70% of cases (fig 1).10 11

Arterial disease accounts for another 5% to10% of leg ulcers; most of the others are due toeither neuropathy (usually diabetic) or a com-bination of those diseases.12 13

Pathogenesis of venous leg ulcersThe association between ulceration at the ankleand venous disorders of the lower limbs hasbeen known for more than 2000 years. 14 15 Thisconnection between deep vein damage andulceration was noted by Gay16 and later by

Table 1 Causes of leg ulcers

Vascular Neuropathic Metabolic Haematological TraumaVenous Diabetes Diabetes Sickle cell disease PressureArterial Tabes Gout Cryoglobulinaemia InjuryMixed* Syringomyelia Prolidase deficiency BurnsTumours Infection Panniculitis Pyoderma SpecialBasal cell carcinoma Bacter ial Necrob iosis lipo idi ca Gang renosum Hyper tensive ulcerSarcoma Fungal Fat necrosisSquamous cell carcinoma Protozoal

*Mixed = venous and arterial ulcers.

Figure 1 Causes of leg ulcers in the UK (see MoVatt andFranks10 and Morrison and MoVatt11).

Venous

(70.0%)

Others

(5.0%)

Mixed

venous

and arterial

(20.0%)

Arterial

(5.0%)

Postgrad Med J2000;76:674682674

City Hospital NHSTrust, Dudley Road,BirminghamB18 7QH, UKP K SarkarS Ballantyne

Correspondence to:Dr Sarkar

Submitted 17 September1999Accepted 6 March 2000

www.postgradmedj.com


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Homans,17 who also noticed that venous ulcersoften had few visible varicose veins.

The concept of venous stasis suggested thatstagnant blood lying within tortuous anddilated veins close to the skin can cause tissueanoxia and cell death. Recently, it has beenproposed that the preceding stage of venousulceration represents a scleroderma-like skincalled lipodermatosclerosis.18 There is a grow-ing recognition that an excessive proteolytic

activity by proteases, especially that of matrixmetalloproteinases (MMP1, MMP2, MMP8,and MMP9)19 and fibrinolytic factors of theplasminogen activation system may be a keyfeature in the pathogenesis of venous legulceration. Elevated expression on mRNA andprotein level of MMPs and fibrinolytic factorshave been detected in liposclerotic skinlesions.18 Furthermore, MMP2 was imbal-anced by locally reduced expression of tissueinhibitors of metalloproteinases (TIMP2) inthe basement membrane zone of skin lesions.19

MMP8 is the predominant collagenase in heal-ing wounds and non-healing ulcers.20 But indiabetic foot ulcers, increased nitric oxide syn-

thase activity may be responsible for theimpaired healing.21 Furthermore, the increasedactivity of arginase could account for the char-acteristic callus formation around the ulcers. Inaddition, the lower concentrations of trans-forming growth factor-1 in diabetic ulcersmay explain the raised concentrations of nitricoxide in this condition.21

Loots and colleagues demonstrated theimportant diVerances in cellular infiltrates andextracellular matrix of chronic diabetic andvenous ulcers compared with acute wounds.22

The CD4/CD8 ratio in chronic ulcers was sig-nificantly lower (p


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Pathogenesis of arterial (ischaemic)ulcerationArterial or arteriolar occlusion due to anycause can result in ischaemia of the skin andsubcutaneous tissues which might lead toulceration. Peripheral vascular disease due toatherosclerosis, diabetes with microvascular ormacrovascular disease and/or vasculitis couldlead to ischaemic leg resulting in ulceration.35

There are three mechanisms involved in the

pathophysiology of ischaemic leg ulcer35:(1) Extramural strangulation(2) Mural thickening or accretion(3) Intramural restriction of blood flow

Extramural strangulation is usually due to scartissue and radiodermatitis causing fibroticbands around the arterioles which may give riseto small but persistent ischaemic ulceration.Mural thickening or accretion of intimalplaques as for example in atherosclerosis, mayproceed with an impaired blood flow untilatherothrombosis, embolism, or superimposedinfection may precipitate complete occlusion,resulting in ulceration. Intramural changescould occlude the small vessels by changes in

blood viscosity, platelet adhesiveness and/orfibrinogenesis as in vasculitis, which might leadto leg ulceration.

There is often considerable overlap and theexact pathogenesis cannot be always welldefined. Most acute forms of vasculitis andsome subacute and chronic forms are likely tocause leg ulceration due to tissue hypoxia andexudation of fibrin-like substances.35

Diabetic foot ulcerThere is usually small vessel disease whichinterferes with peripheral circulation leading totissue hypoxia, which may result in ulcerationafter minor or major trauma. Peripheralgangrene may occur as a large single ulcer

characteristically situated at the side or at theback of the ankle due to atherosclerosis.Peripheral neuropathy may coexist, with cold,swollen, and dry feet. Trivial trauma or blisterdue to any cause may lead to ulceration.36

Haematological disordersIndolent, non-healing ulcers are a feature ofsickle cell disease,37 thalassaemia, and otherhaemolytic anaemias. These are usually due toblockage of microcirculation. Thrombotic andocclusive diseasesfor example, antiphos-pholipid syndrome, protein C and protein Sdeficiency, cryoglobulinaemia, etc, lead torapid skin necrosis and gangrene.26

Familial leg ulcers caused by genetic disor-ders of coagulation, causing recurrent familialvenous thrombosis, may occur as a result of

mutations in protein C, protein S, anti-thrombin III, fibrinogen, and factor Vgenes.38 39

InfectionsInfections may lead to ulceration that is oftenslow in healing because of associated oedema,cellulitis, thrombophlebitis, or underlying vas-cular disease or diabetes. Bacterial synergisticgangrene (Meleneys ulcer) extends rapidly

and usually has a burrowing, bluish, andundermined edge.35 Primary uncomplicatedstreptococcal ulcer is rare, but Streptococcus

pyogenes or Staphylococcus aureus may compli-cate existing ulceration. Tuberculous cutane-ous ulcer might occur in erythema induratumor Bazins disease, situated usually on the backof the calves.35

Hypertensive ulcer SynonymousMartorells ulcer)In hypertension, the density of the capillarybeds in the middle and deep dermis of the skinparticularly of its lateral aspect is muchreduced, which may predispose to ischaemic

necrosis when the sparse arterioles are sub-jected to severe hypertension.35 Hypertensionproduces superficial ulceration,26 when periph-eral pulses are always present, distinguishingthe condition from peripheral vascular disease.

Rheumatoid arthritis/vasculitisThe leg ulcer usually develops on the shin orankle after trauma, is related to vasculitis, andoften diYcult to heal. Delayed healing is alsodue to impaired mobility which contributes topoor muscle pump.35 The oedema is often dif-ficult to control. Ulceration of rheumatoidnodules is not common except at pressurepoints.40

Trophic ulcersThese ulcers may occur as a result of pressureor friction on areas which have become anaes-thetic due to peripheral neuropathy. Some-times they may be associated with underlyingvascular abnormalitiesfor example, diabetescausing small vessel disease.35

Ulceration due to dermatitis artefactaUlceration secondary to artefact may bediYcult to diagnose. Clinical suspicion mightbe raised by the following: unusual appearance,unusual site, after trauma at work with possiblecompensation issues, angulate shape or theapparent indiVerence of the patient to their

ulcer and its implication to their life.

26

If theulcer tends to come and go, a skin biopsy maybe necessary to show up out-side-in damage,that is, disproportionate damage to the epider-mis compared with the dermis.26

Pyoderma gangrenosumPyoderma gangrenosum is a relatively commondestructive non-infective ulceration of the skinwith sloughy base and ragged underminededge. It may be associated with chronic condi-tions such as inflammatory bowel disease,inflammatory arthropathies, or myeloprolifera-tive disorders.26 A skin biopsy may be helpful

Table 2 Factors which may prevent healing of leg ulcers

Oe de ma Co ng es ti ve c ar di ac f ai lu rePostural/gravitional oedema

Ar thr itis Reduced mob ilityIncreased risk of lymphoedema

Ski n disease EczemaSystemic disease Diabetes mellitusNutritional Vitamin C deficiencyDrugs Cortico steroids/immunosuppressivesE xe rc is e La ck o f p hy si ca l a ct iv it yPsychosocial Depression/loss of interest in healing

676 Sarkar,Ballantyne



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but the histological features of pyoderma gan-grenosum are not diagnostic.

Treatment of leg ulcersINITIAL ASSESSMENT

Assessment of a patient with leg ulcer consistsof the following:x Comprehensive clinical history and physical

examination in order to determine theaetiology of the ulcer.

x Doppler measurement of the pressure at theankle (dorsalis pedis or posterior tibialartery) and brachial artery to determineankle:brachial pressure index (if 1.0 =venous insuYciency, and if 59 mm Hg/>7.9 kPa). Lightcompression hosiery is indicated for treatingmild varicosis; medium compression for pro-nounced varicosis with oedema, after healing ofminor leg ulcer and after thrombophlebitis;strong compression for late complications ofconstitutional or post-thrombotic venous in-suYciency, atrophie blanche, dermatosclerosisand after healing of severe or recurrent ulcers;very strong for lymphoedema and elephantia-sis. The ideal is made to measure for thepatient and to receive assistance with dressing.There are many aids availablefor example,

Management of leg ulcers 677



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Medivalet with short handles, Medi-Exportvalet with long handles, Medivalet with vari-able handles, Medi-Hospital valet with adjust-able diameter, and Medi-Magnum valet, espe-cially for larger stocking sizes. The dressing aidsolves the often diYcult problem of putting oncompression hosier y.

Patients should stop smoking, if there isassociated arterial disease. Factors causingdelay in healing leg ulcers include poor control

of leg oedema because of inadequate compres-sion, unrecognised arterial disease, continuedsmoking, secondary infection (S aureus), anae-mia, and/or heart failure. Adequate analgesicsshould be prescribed if the leg ulcers arepainful.35 The Cadexomer Iodine Study Groupdemonstrated that cadexomer iodine paste isan eYcient, cost eVective, and safe alternativeto hydrocolloid dressing and paraYn gauzedressing for the treatment of venous legulcers.54

INTERMITTENT PNEUMATIC COMPRESSION

Pneumatic compression device may be used forthe relief of oedema.31 55 It may promote

healing in patients with venous ulcers

31

and isalso useful in the treatment of lymphoedema. Itconsists of a sleeve that fits over the leg,attached to a pump device with a variety ofpneumatic pumps with diVerent specificationsbeing available.55 56 The response usually de-pends upon the absolute pressure generatedwithin the compression cycle and the sequenceand duration of compression.57 This method oftreatment is generally useful in diYcult venousulcers which have not responded to compres-sive dressings.

HYPERBARIC OXYGEN

Hyperbaric oxygen is of no value in treatingvenous stasis ulcers or ulcers due to incompe-

tent perforators.58 However, 18 of 27 arterialulcers healed in 621 days. The aVected legwas covered by a disposable polythene bagthrough which oxygen flowed (15 litres/min, sixhours/day, four days/week). Pressure was moni-tored and kept at 2530 mm Hg (3.34.0 kPa),using a Y tube connected to a sphygmoma-nometer. Interspersed periods of tissue hypoxiahelp to stimulate formation of granulationtissue, so that continuous oxygen therapy is notdesirable.58 It is diYcult to assess the value ofthe hyperbaric oxygen independently of theperiod of enforced rest in the chamber. 35

OTHER MEASURES

Diuretics are widely used in general practiceeven for postural oedema, which are bestrelieved by elevation and/or compression.35 Inthe past, diVerent types of dressing withDebrisan, DuoDerm, benzoyl peroxide,choles-tyramine powder, etc were used with somesuccess, but are historically redundant. Otherdrugs might be helpfulfor example,oxpentifylline,59 venruton,60 etc, but to datethere is no substantial evidence to support this.A proteolytic ointment such as Elase (a combi-nation of DNAase and fibrinolysin) providesno long term benefit in reducing exudate, pain,erythema, necrotic tissue, or overall condition

of chronic leg ulcers when compared witheither of its two components or placebo.61

Treatment of arterial ulcersThe most important aim in the treatment ofarterial ulcers is to increase the blood supply tothe aVected area.35 The patient must stopsmoking and diabetes or hypertension shouldbe well controlled. Regular graded exercisesshould be encouraged to promote development

of collateral circulation. Pressure areas may beprotected by sheepskin or a special cushionwith bony prominences, for example heel,malleoli, etc, being the vulnerable areas for legulcers. The head of the patients bed should beraised by 46 inches to encourage gravitydependent arterial flow and the limbs shouldbe kept warm. Regular use of analgesics shouldbe encouraged for the relief of pain, but if restpain or acute infection is present, the patientshould be referred to a vascular surgeon. Arte-rial reconstruction surgery may be performedto salvage the limb. After angiographic studies,endarterectomy to remove the clot or athero-matous plaques and/or reconstruction to by-

pass occluded artery may be performed.

29

Bal-loon angioplasty may be the intervention ofchoice for ischaemic rest pain, ulceration, andgangrene of the leg. If angioplasty fails,femoropopliteal bypass graft may be tried.62

Cellulitis with or without lymphangitis needsto be treated with systemic antibiotics.

Management of diabetic and neuropathiculcersThe following instructions should be given tothe patient:x Stop smokingx Regularly inspect the legs/feet for scratch

marks, blisters, etcx Wash the feet with warm water daily

followed by careful drying between the toesx Apply emolients, for example, Vaseline on

the dry skin but not between the toesx Inspect shoes regularlyx Wear properly fitting shoesx It is useful to see a chiropodist regularlyx Avoid sandals and pointed shoes which may

lead to foot traumax Never walk bare footedx See your doctor regularly if there is any

injury or blister of the leg/feetNeuropathic ulcers are most commonly seen indiabetic patients. In diabetics, the feet shouldbe examined regularly for tinea, deformities,and onychogryphosis. It is important to remove

crusted areas,and to inspect and probe thewounds to determine the depth and the extentof tissue destruction.6365 In case of infectionwith cellulitis the wound should be culturedand debrided.66 Oral broad spectrum antibiot-ics should be started and changed according tothe sensitivity results. If there is no significantimprovement within 48 hours, the patientshould be hospitalised. Bacteroides, coliforms,and streptococci are frequently cultured. Non-weight bearing is essential until healing is inprogress. Insulin is usually required to ensuregood diabetic control and broad spectrumintravenous antibiotics are indicated.67 Re-




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cently, new growth factor gel and licenced skingrafting (Apligraf) may be useful in quick heal-ing of the ulcers.68 69 Recently, it was claimedthat topically applied granulocyte-macrophagecolony stimulating factor healed chronic legulcers of necrobiosis lipoidica diabeticorumand may be a valuable drug for chronicnon-healing ulcers in patients with diabetes.70

Radiography of the aVected areasfor ex-ample, spiral computed tomography and/or

magnetic resonance imaging should be per-formed to exclude osteomyelitis and also airwithin the soft tissues should be looked for toconfirm the presence of gas forming organisms.Radionucleide bone scan, gallium scan, andbone biopsy may be necessary to confirm adiagnosis of osteomyelitis.

Once infection is controlled a decision canbe made as to whether the patient needs vascu-lar surgical treatment. Biopsy should be donefor chronic non-healing ulcers. Biopsy of theulcer edge certainly seems to be a procedurewhich can be performed at no risk to thepatient. It has been suggested that biopsy of theulcers that have not improved after three

months of treatment should be performed toexclude squamous cell carcinoma, basal cellcarcinoma, or vasculitis. If squamous cellcarcinoma is suspected, a wedge rather than astandard punch biopsy should be performed.71

Systemic treatmentANTIBIOTICS

Bacteria from the wound can be variable, butSaureus is a common pathogen together withGram negative bacilli and other organisms.32 72

In the patients with venous ulcers, culturesfrom the wound swabs correlate with culturesfrom biopsy specimens.72 Systemic antibioticsin uncomplicated venous ulcers are often notuseful unless cellulitis or sepsis intervenes.

FIBRINOLYTICS

It has been demonstated that the patients withlipodermatosclerosis have depressed fibrino-lytic activity.63 Stanozolol, an anabolic steroidand fibrinolytic enhancing agent, was found toimprove liposclerosis but not venous ulcerationin 14 patients treated in a preliminary trial.64 Asubsequent double blind crossover trial in 23patients did not shown any significant diVer-ence between the group who used only elasticcompression stockings and the group who alsoreceived stanozolol.65 To date, there are noconvincing data that suggests any benefit fromthe use of stanozolol in patients with dermato-

sclerosis or leg ulcers.

VasodilatorsPROSTAGLANDINS

Prostaglandins PGE1 and PGI2 are potentvasodilators and also inhibit platelet aggrega-tion. Initial uncontrolled trials suggest successof intravenous infusions of PGE1 and PGI2 inpatients with severe peripheral vascular diseasewith ulceration.73 A subsequent large multicen-tre trial demonstrated no diVerence betweenthe placebo and the treatment group.74 There-fore, it should not be prescribed as its role intreating leg ulcers is not evidence based.

CALCIUM CHANNEL BLOCKERS

Nifedipine is a potent vasodilator with its modeof action, believed to be due to increased bloodflow in the leg and foot in peripheral vasculardisease. But the results of its use in the trials areconflicting.75 76 To date there is no convincingevidence of its value in the healing of leg ulcersdue to peripheral arterial insuYency. There-fore, from a practical point of view, it is usuallynot recommended.

Serotonin antagonistsKetanserin, a serotonin antagonist, reducesperipheral vascular resistance and may improveperipheral haemodynamics in patients withintermittent claudication.41 Initial trials withketanserin in treating patients with impendinggangrene and peripheral ulceration arepromising,42 but further data are necessary.Topical 2% ketanserin ointment appears toimprove granulation tissue formation in skinulcers.77 In practice, it is hardly used to treat legulcers.

Skin graftingPINCH GRAFTS

The simple type of split thickness skin graftsare safe and easy to perform. These proceduresare particularly advisable in patients with mul-tiple medical problems, taking drugs interfer-ing with the healing of leg ulcers. It can be per-formed as an outpatient basis and in primarycare.78

SPLIT THICKNESS SKIN GRAFT

This method is used for large ulcers undergeneral, spinal, or extensive local anaesthesia.These grafts are usually successful, but thegrafts may contract after harvesting and need alarge donor site, which may be slow to heal andcause a lot of pain. In grafting large leg ulcers,

graft failure may occur because of build-up ofexudate underneath the graft; this is bestavoided by the use of a meshed graft. 79

Future trends in leg ulcer treatmentORAL ZINC TREATMENT

To determine whether oral zinc treatment wasuseful for venous leg ulcer, the search strategyof the Cochrane Wounds Group was used toidentify the relevant randomised controlledtrials. There were six such trials, which weresmall double blind, randomised, median size33 (range 1040 patients). At present there isno evidence to support the use of oral zinc inthe treatment of patients with leg ulcers due to

venous or arterial disease.

80

There is limitedevidence that zinc may be beneficial in thetreatment of venous leg ulcers when there is alow serum zinc but recommendations for thedose and duration of treatment cannot bemade on the available information.81

ORAL ASPIRIN

Randomised trial of oral aspirin for chronicvenous leg ulcer revealed reduction in ulcersurface area which was significantly better inthe aspirin treated group at two months andfour months compared with that in the placebogroup.82




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ULTRASOUND FOR CUTANEOUS WOUND HEALING

Five controlled trials from the Cochrane Cuta-neous Wound Healing Group demonstratedthat low dose ultrasound is an eVectivecomplementary therapy for wound healing.Further experimental and clinical investiga-tions should test its eVectiveness more rigor-ously and elucidate the mechanisms that mightbe involved.83 84

LASER THERAPY FOR THE TREATMENT OF VENOUS

LEG ULCERS

To assess the eVectiveness of low level lasertherapy in the treatment of venous leg ulcersthe Cochrane Wounds Group search strategyidentified four eligible randomised controlledtrials which demonstrated no evidence of anybenefit associated with low level therapy onvenous leg ulcer healing. One small studysuggests that a combination of HeNe lasertherapy and infrared light may promote thehealing of venous ulcers, however more re-search is needed.85

Compression treatment of leg ulcers: a

systematic reviewTo estimate the clinical and cost eVectivenessof compression systems for treating venous legulcers, 19 electronic databases includingMedline, CINAHL, Embase, relevant journals,and conference proceedings included 24 ran-domised controlled trials which demonstratedthat compression systems improve healing ofvenous leg ulcers and should be routinely usedin uncomplicated venous ulcers. High com-pression is more eVective than lowcompression,49 but should only be used in theabsence of significant arterial disease. Thereare no clear diVerences in the eVectiveness ofdiVerent types of compression systems (multi-layer and short stretch bandages and Unnas

boot) have been shown. Intermittent pneu-matic compression appears to be a usefuladjunct to bandaging. Rather than advocateone particular system, the increased use of anycorrectly applied high compression treatmentshould be performed.86 Compression bandagesand stockings in the treatment of venous legulcers as reviewed by Cochrane WoundsReview Group,87 demonstrated that multilayerhigh compression bandages were significantlymore eVective than a single layer bandage. Thedirect comparisons of the healing rates weredescribed in the two observational studies as40% (of leg ulcers) in 12 weeks88 and 42% (oflimbs) of people attending a leg ulcer clinic.89

The limitations for use of four layer bandagingin a community clinic include the fact thatsome people are unable to leave their home dueto immobility and cannot tolerate or do not likethe treatment.90

Cultured epidermal graftingAUTOGRAFT

The treatment of venous stasis ulcer can bedone by the use of cultured epidermal cells(keratinocytes) as a skin graft. Keratinocytelayers cultured from the patients own skin(autografts) have been successfully used forseveral years in the USA and Europe to cover

large burn wounds.91 Other investigaters haveused cultured autografts for chronic legulcers.92 One group reported healing of chronicleg ulcers within 35 days of application of cul-tured epithelial autografts.82

ALLOGRAFTS

Cultured epidermal allografts can be used inenhancing the healing rate of chronic legulcers. Previous trials have demonstrated that

more than two thirds of chronic ulcers healedcompletely within eight weeks of grafting with amean healing time of 3.3 weeks.93 94 Howevercultured allografts should be reserved for thetreatment of non-healing leg ulcers as cultiva-tion procedure is very complex, labour inten-sive, and expensive.

Apligraf: a biomaterial for woundhealing/human skin equivalent68

Apligraf (Organogenesis, Canton, MA; No-vartis, East Hanover, NJ, USA) is a new tissueengineered skin product cultured from humandermal fibroblasts and keratinocytes. Histo-logically it resembles a simplified version of

skin. When applied, Apligraf seems to react tofactors in the wound and may interact with thepatients own cells to stimulate the productionof growth factors. It is being extensively studiedin diabetic ulcers, clean excision wounds, andburns.95 Human skin equivalent appeared topromote wound healing in three ways: (1)apparent graft take, (2) temporary woundclosure, and (3) stimulation of host healing byacting as a biological dressing. The eYcacy ofhuman skin equivalent suggests that it willprove useful for promoting the healing ofvenous ulcers.69

Electrical stimulationElectrical stimulation has been demonstrated

to enhance wound healing.96 97 The mechanismby which healing occurs remains unknown.They may include inhibition of bacterialgrowth, eVects on fibroblasts motility, orincreased expression of transforming growthfactor-on fibroblasts.98 99

Growth factorsIn animal models epidermal growth factor pro-motes granulation tissue formation and woundhealing. A variety of growth factorsfor exam-ple, tumour necrosis factors, fibroblast growthfactor, transforming growth factors, and ,epidermal growth factor, and platelet derivedgrowth factors promote wound healing by ang-

iogenic properties.

95 97 98 100

Perhaps in thefuture combination of growth factors andcompression dressings may have a role in thequick healing of the ulcers. Therapeutic angio-genesis may be one of the treatment strategiesin the future.

ConclusionLeg ulcers seem to have a cycle of healing fol-lowed by reulceration and rehealing. Recur-rence rates of venous ulcers after treatment arehigh.98 Once the leg ulcer is healed careful skincare, continuous vigilance, and strict use ofcompression hosiery must be emphasised.




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We thank the staV of the day hospital, especially Sue Walsh,Pamela Sarkar, and the junior medical staV of City HospitalNHS Trust for their help in preparing the manuscript.

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Key points

x Treatment with compression bandages(three or four layers) hastens the healingof venous leg ulcers compared with nocompression

x High compression is more eVective thanlow compression provided there is noarterial insuYciency

xIntermittent pneumatic compression is auseful adjunct to compression bandaging

x Cultured epidermal autograft or allograftmay be useful for chronic mixed ulcers




9/9

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