674 Postgrad Med J 2000;76:674–682

REVIEWS

Management of leg

P K Sarkar, S Ballantyne

Abstract Others Leg is a leading cause of morbidity (5.0%) among older subjects, especially women in Mixed the Western world. About 400 years BC, venous Hippocrates wrote, “In case of an ulcer, it and arterial (20.0%) is not expedient to stand, especially if the ulcer be situated on the leg”. Hippocrates himself had a leg ulcer. The best treatment Venous of any leg ulcer depends upon the accurate Arterial (70.0%) diagnosis and the underlying aetiology. (5.0%) The majority of leg ulcers are due to venous and/or arterial disease, but the treatment of the underlying cause is far more important than the choice of dressing. The aetiology, pathogenesis, Figure 1 Causes of leg ulcers in the UK (see MoVatt and treatment, and the future trends in the Franks10 and Morrison and MoVatt11). management of the leg ulcers are dis- cussed in this review. (Postgrad Med J 2000;76:674–682) PREVALENCE The prevalence of leg ulcers in Europe is well Keywords: leg ulcers; compression bandages; graft- documented, varying between 0.18% and 1% ing in diVerent countries.4–7 In the UK two major studies demonstrated the prevalence of active ulcers at 0.15% to 0.18% in contrast to 1% in There are about 400 000 patients with leg ulcer the Scandinavian countries. Leg ulcers occur disease in the UK and at any one time 100 000 more commonly in elderly people and their have open leg ulcers requiring treatment. This prevalence is likely to increase as the average 1 costs about £600 million/year. Venous ulcera- age of the population increases.89 tion of the lower leg is the result of increased venous pressure and its secondary eVects on Aetiology 2 the microvascular system. In patients with In the Western world, leg ulcers are mainly venous leg ulcers, nearly half have evidence of a caused by venous insuYciency, arterial insuY- past venous thrombosis while the remainder ciency, neuropathy, , or a combination results from incompetence of valves of the of these factors (table 1). Venous ulcers are the superficial or communicating veins. The ve- most common type of leg ulcers, accounting nous leg ulcer is an age related disease in the for approximately 70% of cases (fig 1).10 11 elderly population, especially women. It may be Arterial disease accounts for another 5% to associated with and ec- 10% of leg ulcers; most of the others are due to zema. Whereas the venous leg ulcer is usually either neuropathy (usually diabetic) or a com- originated by external trauma, the course is bination of those .12 13 often chronic and/or relapsing. Pathogenesis of venous leg ulcers Epidemiology The association between ulceration at the INCIDENCE and venous disorders of the lower limbs has Community surveys in Lothian, north west been known for more than 2000 years.14 15 This London, and Southampton all suggest an over- connection between deep vein damage and all incidence of about 0.2%.3 ulceration was noted by Gay16 and later by City Hospital NHS Trust, Dudley Road, Birmingham Table 1 Causes of leg ulcers B18 7QH, UK P K Sarkar Vascular Neuropathic Metabolic Haematological Trauma S Ballantyne Venous Diabetes Diabetes Sickle cell disease Pressure Arterial Tabes Gout Cryoglobulinaemia Injury Mixed* Syringomyelia Prolidase deficiency Burns Correspondence to: Tumours Panniculitis Pyoderma Special Dr Sarkar Basal cell carcinoma Bacterial lipoidica Gangrenosum Hypertensive ulcer Sarcoma Fungal Submitted 17 September Protozoal 1999 Accepted 6 March 2000 *Mixed = venous and arterial ulcers.

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Homans,17 who also noticed that venous ulcers circulation in the skin and subcutaneous often had few visible varicose veins. tissues of the .15 They hypothesised that the The concept of venous stasis suggested that distended local capillary bed widened the stagnant blood lying within tortuous and endothelial pores, allowing fibrinogen mol- dilated veins close to the skin can cause tissue ecules to escape into the extracellular fluid, anoxia and cell death. Recently, it has been where they form fibrin complexes around the proposed that the preceding stage of venous capillaries.27 Pericapillary fibrin has been ulceration represents a -like skin shown to impede oxygen diVusion in the 18 called lipodermatosclerosis. There is a grow- patients with venous disease.28 ing recognition that an excessive proteolytic Various theories have been put forward—for activity by proteases, especially that of matrix example, venous stagnation, fibrin cuV, white metalloproteinases (MMP1, MMP2, MMP8, 19 cell trapping, and growth factor trapping theo- and MMP9) and fibrinolytic factors of the ries. In the “venous stagnation” theory, blood plasminogen activation system may be a key stagnates within the veins leading to local feature in the pathogenesis of venous leg ischaemia and ulceration. The “fibrin cuV” ulceration. Elevated expression on mRNA and theory states that increased venous pressure protein level of MMPs and fibrinolytic factors have been detected in liposclerotic skin causes leakage of macromolecules from plasma .18 Furthermore, MMP2 was imbal- into perivascular space when fibrinogen changed to fibrin and this acts as a barrier to anced by locally reduced expression of tissue 26 inhibitors of metalloproteinases (TIMP2) in diVusion of oxygen and nutrients. It is now the basement membrane zone of skin lesions.19 recognised that the fibrin cuV is seen as an MMP8 is the predominant collagenase in heal- eVect but not a cause of the disease, as these ing wounds and non-healing ulcers.20 But in lesions are seen in many other diabetic ulcers, increased nitric oxide syn- situations. Pericapillary fibrin cuVs remain a thase activity may be responsible for the prominent feature, whether they act as a impaired healing.21 Furthermore, the increased barrier, a marker for endothelial cell damage, activity of arginase could account for the char- or as part of an overall mechanism of acteristic formation around the ulcers. In macromolecular leakage and trapping.29 addition, the lower concentrations of trans- A recent hypothesis proposed that in venous forming growth factor-â1 in diabetic ulcers ulceration, trapped leucocytes occlude capillar- may explain the raised concentrations of nitric ies, thereby resulting in cutaneous ischaemia.30 oxide in this condition.21 White cells are normally trapped within the Loots and colleagues demonstrated the cutaneous microcirculation when legs are important diVerances in cellular infiltrates and dependent. In venous hypertension, these extracellular matrix of chronic diabetic and white cells are activated leading to damage and venous ulcers compared with acute wounds.22 destruction of the capillaries.31 Falanga and The CD4/CD8 ratio in chronic ulcers was sig- Eaglstein have proposed that macromolecules nificantly lower (p<0.0027) due to a relatively leaking into the “trap” growth factors lower number of CD4+T cells. There was a and matrix material leading to inadequate significantly higher number of macrophages in tissue repair, which eventually causes 22 the edges of both types of ulcers. ulceration.32 Hahn et al found that the upregulation of The skin may break down, due to three endothelial adhesion molecules (ICAM-1) and mechanisms: (a) damage to blood vessels lead- dermal infiltration by T-lymphocytes and mac- ing to ischaemia, (b) inflammation, and/or (c) rophages in chronic venous insuYciency pa- infiltration. In many instances, it is the inability tients is limited to the region of the ulcer, or at of the damaged skin to repair itself normally least to skin areas with a severe microangiopa- that results in ulceration.26 thy, and is part of a secondary elimination of Similar to fibrin cuV theory, growth factors necrotic tissue (an “injury and repair” and cytokines are held in the fibrin cuV process).23 preventing the maintenance of the normal In patients with venous disease, there is homoeostatic environment. incompetence of the valves within the perforat- More recently, Birgette Maessen-Visch and ing veins connecting the superficial to the deep venous systems in the leg. In normal subjects, colleagues claimed that factor V Leiden muta- venous pressure decreases during exercise. In tion is more frequent in patients with venous patients with venous incompetence, pressure leg ulceration than in the control group and the remains high during exertion.24 High venous general population. Patients with factor V Lei- pressure is associated with capillary prolifera- den mutation have an increased risk of tion and increased permeability of large developing deep vein thrombosis and recurrent 33 molecules into the skin.24 25 It is not clear how leg ulceration. venous hypertension is transmitted into skin Danielsen et al demonstrated that the ulceration, but it is apparent that venous ulcers exotoxin A serum antibodies in patients with represent a disease of the cutaneous microcir- chronic leg ulcers, infected with Pseudomonas culation as there is rarefaction and dilatation of aeruginosa, may provide a marker for ulcer the skin capillaries (atrophie blanche) together deterioration, and may support the decision for with the changes in the microlymphatics.26 In skin grafting.34 1982, Browse and Burnand proposed that the There are many predisposing factors, which high ambulatory venous pressure within the may prevent healing of leg ulcers, shown in calf muscle is transmitted to the capillary table 2.

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Pathogenesis of arterial (ischaemic) mutations in protein C, protein S, anti- ulceration thrombin III, fibrinogen, and factor V Arterial or arteriolar occlusion due to any genes.38 39 cause can result in ischaemia of the skin and subcutaneous tissues which might lead to ulceration. Peripheral vascular disease due to Infections may lead to ulceration that is often atherosclerosis, diabetes with microvascular or slow in healing because of associated oedema, macrovascular disease and/or could , thrombophlebitis, or underlying vas- lead to ischaemic leg resulting in ulceration.35 cular disease or diabetes. Bacterial synergistic There are three mechanisms involved in the (Meleney’s ulcer) extends rapidly pathophysiology of ischaemic leg ulcer35: and usually has a burrowing, bluish, and (1) Extramural strangulation undermined edge.35 Primary uncomplicated (2) Mural thickening or accretion streptococcal ulcer is rare, but Streptococcus (3) Intramural restriction of blood flow pyogenes or Staphylococcus aureus may compli- Extramural strangulation is usually due to cate existing ulceration. Tuberculous cutane- tissue and radiodermatitis causing fibrotic ous ulcer might occur in induratum bands around the arterioles which may give rise or Bazin’s disease, situated usually on the back to small but persistent ischaemic ulceration. of the calves.35 Mural thickening or accretion of intimal plaques as for example in atherosclerosis, may Hypertensive ulcer Synonymous proceed with an impaired blood flow until Martorell’s ulcer) atherothrombosis, embolism, or superimposed In hypertension, the density of the capillary infection may precipitate complete occlusion, beds in the middle and deep dermis of the skin resulting in ulceration. Intramural changes particularly of its lateral aspect is much could occlude the small vessels by changes in reduced, which may predispose to ischaemic blood viscosity, platelet adhesiveness and/or necrosis when the sparse arterioles are sub- fibrinogenesis as in vasculitis, which might lead jected to severe hypertension.35 Hypertension to leg ulceration. produces superficial ulceration,26 when periph- There is often considerable overlap and the eral pulses are always present, distinguishing exact pathogenesis cannot be always well the condition from peripheral vascular disease. defined. Most acute forms of vasculitis and some subacute and chronic forms are likely to Rheumatoid /vasculitis cause leg ulceration due to tissue hypoxia and The leg ulcer usually develops on the shin or exudation of fibrin-like substances.35 ankle after trauma, is related to vasculitis, and often diYcult to heal. Delayed healing is also due to impaired mobility which contributes to There is usually small vessel disease which poor muscle pump.35 The oedema is often dif- interferes with peripheral circulation leading to ficult to control. Ulceration of rheumatoid tissue hypoxia, which may result in ulceration nodules is not common except at pressure after minor or major trauma. Peripheral points.40 gangrene may occur as a large single ulcer characteristically situated at the side or at the Trophic ulcers back of the ankle due to atherosclerosis. These ulcers may occur as a result of pressure may coexist, with cold, or friction on areas which have become anaes- swollen, and dry feet. Trivial trauma or thetic due to peripheral neuropathy. Some- due to any cause may lead to ulceration.36 times they may be associated with underlying vascular abnormalities—for example, diabetes Haematological disorders causing small vessel disease.35 Indolent, non-healing ulcers are a feature of sickle cell disease,37 thalassaemia, and other Ulceration due to dermatitis artefacta haemolytic anaemias. These are usually due to Ulceration secondary to artefact may be blockage of microcirculation. Thrombotic and diYcult to diagnose. Clinical suspicion might occlusive diseases—for example, antiphos- be raised by the following: unusual appearance, pholipid syndrome, protein C and protein S unusual site, after trauma at work with possible deficiency, cryoglobulinaemia, etc, lead to compensation issues, angulate shape or the rapid skin necrosis and gangrene.26 apparent indiVerence of the patient to their Familial leg ulcers caused by genetic disor- ulcer and its implication to their life.26 If the ders of coagulation, causing recurrent familial ulcer tends to come and go, a skin may venous thrombosis, may occur as a result of be necessary to show up “out-side-in” damage, that is, disproportionate damage to the epider- Table 2 Factors which may prevent healing of leg ulcers mis compared with the dermis.26

Oedema Congestive cardiac failure Postural/gravitional oedema Arthritis Reduced mobility Pyoderma gangrenosum is a relatively common Increased risk of lymphoedema destructive non-infective ulceration of the skin Skin disease Eczema with sloughy base and ragged undermined Systemic disease Diabetes mellitus Nutritional Vitamin C deficiency edge. It may be associated with chronic condi- Drugs Corticosteroids/immunosuppressives tions such as inflammatory bowel disease, Exercise Lack of physical activity inflammatory arthropathies, or myeloprolifera- Psychosocial Depression/loss of interest in healing tive disorders.26 A skin biopsy may be helpful

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but the histological features of pyoderma gan- into the wound, sealing the site with an grenosum are not diagnostic. adhesive drape, and applying subatmospheric pressure (125 mm Hg (16.7 kPa) below ambi- Treatment of leg ulcers ent) that is transmitted to the wound in a con- INITIAL ASSESSMENT trolled manner. Blood flow levels increased Assessment of a patient with leg ulcer consists about fourfold when 125 mm Hg subatmos- of the following: pheric pressure was applied.45 The VAC device x Comprehensive clinical history and physical is used to provide evacuation of wound fluid, examination in order to determine the stimulation of granulation tissue, decrease in aetiology of the ulcer. bacterial colonisation, improvement of local x Doppler measurement of the pressure at the oxygenation and promotion of angiogenesis, ankle (dorsalis pedis or posterior tibial thereby enhancing wound healing.46 The Food artery) and brachial artery to determine and Drug Administration has recently ap- ankle:brachial pressure index (if <0.8 = proved the VAC device for closure of chronic presence of arterial insuYciency, if >1.0 = wounds.46 The preferential indications of the venous insuYciency, and if <0.5 = need for VAC device include leg ulcers, pressure sores, urgent reVeral to a vascular surgeon). burns, wounds with skin defects, complications x The wound size and shape must be docu- of surgical wounds, and delayed healing.47 mented either by measuring the length and width of the ulcer by tracing onto an acetate SECONDARY DRESSING sheet or by photographic record. Secondary dressing with diVerent types of x The ulcer should be swabbed for microbiol- compression bandages48 (three layers, four lay- ogy. ers of bandages, for example, Charing Cross x Full blood count, random blood sugar, method) is crucial to the healing of venous chemical profile, and plasma viscosity should ulcers (these bandages must not be used if be done. there is arterial insuYciency).49 Community x Ulcers of unusual appearance should be based leg ulcer clinics with trained nurses using biopsied. a four layer bandage is more eVective than tra- x Deep ulcers should have plain ditional home based treatment and this is cost of the aVected areas and computed tomogra- eVective.50 A survey of the management of leg phy, magnetic resonance imaging, etc to ulcers in primary care settings in Scotland exclude , especially in chronic revealed that compression bandages were rou- non-healing ulcers. tinely used by 64% of nurses.51 x Patch tests may be indicated if there is an extensive eczema or local allergy. GENERAL MEASURES These consist of avoidance of prolonged stand- SPECIFIC TREATMENT ing or sitting with the feet dependent. Periods Primary dressing depends on the conditions of of rest with the legs elevated1 and graded exer- the ulcer base. Simple non-adherent gauze cises to improve the leg muscles pump should should be used for shallow, non-exudating be practised. Once the ulcer is healed, the ulcer.35 Absorbent foam or alginate dressings patient should wear elastic support hosiery.35 should be used for exudating ulcers, and The severity of the venous insuYciency and hydrocolloids reserved for sloughy, smelly the type of lifestyle ultimately determine the ulcers. dressing is often used type of hosiery. There are three categories of for sloughy, necrotic ulcers. compression hosiery conforming to the British It is often necessary to treat S aureus or S Standard Instituition standard52 53: light pres- pyogenes (haemolytic streptococci) if signs of sure at ankle (12 mm Hg/1.6 kPa); medium (20 inflammation are present. Larval (maggot) mm Hg/2.7 kPa) and strong (30 mm Hg/4.0 therapy is now available for debriding resistant kPa). Light compression is mostly inadequate sloughy ulcers.41 Indications of biosurgery (lar- whereas strong compression is eVective, but val therapy) include necrotic or sloughy uncomfortable and diYcult for many elderly wounds—for example, leg ulcers, unsuitability people. European standard compression ho- for surgical , and/or ineVective sieries are increasingly used. There are four previous treatment.41 42 classes of compression: light compression at Surrounding skin should be protected with the ankle (18.4–21.1 mm Hg/2.5–2.8 kPa); simple water based emollients. Eczema may medium (25.2–32.3 mm Hg/3.3–4.3 kPa); require treatment with potassium permanga- strong (36.5–46.6 mm Hg/4.9–6.2 kPa); and nate, and wet compress and topical cortico- very strong (>59 mm Hg/>7.9 kPa). Light steroid. Topical should be avoided, compression hosiery is indicated for treating because they can sensitise the skin.35 The most mild varicosis; medium compression for pro- important allergens in 1994–95 were fragrance nounced varicosis with oedema, after healing of mix, colophony, excipients wool alcohol, amer- minor leg ulcer and after thrombophlebitis; chol, neomycin, and gentamycin. The changing strong compression for late complications of trends in contact allergens over the last 20 years constitutional or post-thrombotic venous in- may be explained by changes in the compo- suYciency, atrophie blanche, dermatosclerosis nents of topical agents used for treatment.43 and after healing of severe or recurrent ulcers; Vacuum assisted closure (VAC), a non-invasive very strong for lymphoedema and elephantia- negative pressure healing device, is a wound sis. The ideal is “made to measure” for the care technology for the new millennium.44 The patient and to receive assistance with dressing. technique entails placing an open cell foam There are many aids available—for example,

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Medivalet with short handles, Medi-Export of chronic leg ulcers when compared with valet with long handles, Medivalet with vari- either of its two components or placebo.61 able handles, Medi-Hospital valet with adjust- able diameter, and Medi-Magnum valet, espe- Treatment of arterial ulcers cially for larger stocking sizes. The dressing aid The most important aim in the treatment of solves the often diYcult problem of putting on arterial ulcers is to increase the blood supply to compression hosiery. the aVected area.35 The patient must stop Patients should stop , if there is smoking and diabetes or hypertension should associated arterial disease. Factors causing be well controlled. Regular graded exercises delay in healing leg ulcers include poor control should be encouraged to promote development of leg oedema because of inadequate compres- of collateral circulation. Pressure areas may be sion, unrecognised arterial disease, continued protected by sheepskin or a special cushion smoking, secondary infection (S aureus), anae- with bony prominences, for example , mia, and/or heart failure. Adequate analgesics malleoli, etc, being the vulnerable areas for leg should be prescribed if the leg ulcers are ulcers. The head of the patient’s bed should be painful.35 The Cadexomer Iodine Study Group raised by 4–6 inches to encourage gravity demonstrated that cadexomer iodine paste is dependent arterial flow and the limbs should an eYcient, cost eVective, and safe alternative be kept warm. Regular use of analgesics should to hydrocolloid dressing and paraYn gauze be encouraged for the relief of , but if rest dressing for the treatment of venous leg pain or acute infection is present, the patient ulcers.54 should be referred to a vascular surgeon. Arte- rial reconstruction surgery may be performed INTERMITTENT PNEUMATIC COMPRESSION to salvage the limb. After angiographic studies, Pneumatic compression device may be used for endarterectomy to remove the clot or athero- the relief of oedema.31 55 It may promote matous plaques and/or reconstruction to by- healing in patients with venous ulcers31 and is pass occluded artery may be performed.29 Bal- also useful in the treatment of lymphoedema. It loon angioplasty may be the intervention of consists of a sleeve that fits over the leg, choice for ischaemic rest pain, ulceration, and attached to a pump device with a variety of gangrene of the leg. If angioplasty fails, pneumatic pumps with diVerent specifications femoropopliteal bypass graft may be tried.62 being available.55 56 The response usually de- Cellulitis with or without lymphangitis needs pends upon the absolute pressure generated to be treated with systemic antibiotics. within the compression cycle and the sequence and duration of compression.57 This method of Management of diabetic and neuropathic treatment is generally useful in diYcult venous ulcers ulcers which have not responded to compres- The following instructions should be given to sive dressings. the patient: x Stop smoking HYPERBARIC OXYGEN x Regularly inspect the legs/feet for scratch Hyperbaric oxygen is of no value in treating marks, , etc venous stasis ulcers or ulcers due to incompe- x Wash the feet with warm water daily tent perforators.58 However, 18 of 27 arterial followed by careful drying between the toes ulcers healed in 6–21 days. The aVected leg x Apply emolients, for example, Vaseline on was covered by a disposable polythene bag the dry skin but not between the toes through which oxygen flowed (15 litres/min, six x Inspect regularly hours/day, four days/week). Pressure was moni- x Wear properly fitting shoes tored and kept at 25–30 mm Hg (3.3–4.0 kPa), x It is useful to see a chiropodist regularly using a Y tube connected to a sphygmoma- x Avoid sandals and pointed shoes which may nometer. Interspersed periods of tissue hypoxia lead to foot trauma help to stimulate formation of granulation x Never walk bare footed tissue, so that continuous oxygen therapy is not x See your doctor regularly if there is any desirable.58 It is diYcult to assess the value of injury or blister of the leg/feet the hyperbaric oxygen independently of the Neuropathic ulcers are most commonly seen in period of enforced rest in the chamber.35 diabetic patients. In diabetics, the feet should be examined regularly for tinea, deformities, OTHER MEASURES and onychogryphosis. It is important to remove Diuretics are widely used in general practice crusted areas,and to inspect and probe the even for postural oedema, which are best wounds to determine the depth and the extent relieved by elevation and/or compression.35 In of tissue destruction.63–65 In case of infection the past, diVerent types of dressing with with cellulitis the wound should be cultured Debrisan, DuoDerm, benzoyl peroxide, choles- and debrided.66 Oral broad spectrum antibiot- tyramine powder, etc were used with some ics should be started and changed according to success, but are historically redundant. Other the sensitivity results. If there is no significant drugs might be helpful—for example, improvement within 48 hours, the patient oxpentifylline,59 venruton,60 etc, but to date should be hospitalised. Bacteroides, coliforms, there is no substantial evidence to support this. and streptococci are frequently cultured. Non- A proteolytic ointment such as Elase (a combi- weight bearing is essential until healing is in nation of DNAase and fibrinolysin) provides progress. Insulin is usually required to ensure no long term benefit in reducing exudate, pain, good diabetic control and broad spectrum erythema, necrotic tissue, or overall condition intravenous antibiotics are indicated.67 Re-

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cently, new growth factor gel and licenced skin CALCIUM CHANNEL BLOCKERS grafting (Apligraf) may be useful in quick heal- Nifedipine is a potent vasodilator with its mode ing of the ulcers.68 69 Recently, it was claimed of action, believed to be due to increased blood that topically applied granulocyte-macrophage flow in the leg and foot in peripheral vascular colony stimulating factor healed chronic leg disease. But the results of its use in the trials are ulcers of diabeticorum conflicting.75 76 To date there is no convincing and may be a valuable drug for chronic evidence of its value in the healing of leg ulcers non-healing ulcers in patients with diabetes.70 due to peripheral arterial insuYency. There- Radiography of the aVected areas—for ex- fore, from a practical point of view, it is usually ample, spiral computed tomography and/or not recommended. magnetic resonance imaging should be per- formed to exclude osteomyelitis and also air Serotonin antagonists within the soft tissues should be looked for to Ketanserin, a serotonin antagonist, reduces confirm the presence of gas forming organisms. peripheral vascular resistance and may improve Radionucleide scan, gallium scan, and peripheral haemodynamics in patients with bone biopsy may be necessary to confirm a intermittent claudication.41 Initial trials with diagnosis of osteomyelitis. ketanserin in treating patients with impending Once infection is controlled a decision can gangrene and peripheral ulceration are be made as to whether the patient needs vascu- promising,42 but further data are necessary. lar surgical treatment. Biopsy should be done Topical 2% ketanserin ointment appears to for chronic non-healing ulcers. Biopsy of the improve granulation tissue formation in skin ulcer edge certainly seems to be a procedure ulcers.77 In practice, it is hardly used to treat leg which can be performed at no risk to the ulcers. patient. It has been suggested that biopsy of the ulcers that have not improved after three Skin grafting months of treatment should be performed to PINCH GRAFTS exclude squamous cell carcinoma, basal cell The simple type of split thickness skin grafts carcinoma, or vasculitis. If squamous cell are safe and easy to perform. These procedures carcinoma is suspected, a wedge rather than a are particularly advisable in patients with mul- standard punch biopsy should be performed.71 tiple medical problems, taking drugs interfer- ing with the healing of leg ulcers. It can be per- Systemic treatment formed as an outpatient basis and in primary 78 ANTIBIOTICS care. Bacteria from the wound can be variable, but S aureus is a common pathogen together with SPLIT THICKNESS SKIN GRAFT Gram negative bacilli and other organisms.32 72 This method is used for large ulcers under In the patients with venous ulcers, cultures general, spinal, or extensive local anaesthesia. from the wound swabs correlate with cultures These grafts are usually successful, but the from biopsy specimens.72 Systemic antibiotics grafts may contract after harvesting and need a in uncomplicated venous ulcers are often not large donor site, which may be slow to heal and useful unless cellulitis or intervenes. cause a lot of pain. In grafting large leg ulcers, graft failure may occur because of build-up of FIBRINOLYTICS exudate underneath the graft; this is best It has been demonstated that the patients with avoided by the use of a meshed graft.79 lipodermatosclerosis have depressed fibrino- lytic activity.63 Stanozolol, an anabolic steroid Future trends in leg ulcer treatment and fibrinolytic enhancing agent, was found to ORAL ZINC TREATMENT improve liposclerosis but not venous ulceration To determine whether oral zinc treatment was in 14 patients treated in a preliminary trial.64 A useful for venous leg ulcer, the search strategy subsequent double blind crossover trial in 23 of the Cochrane Wounds Group was used to patients did not shown any significant diVer- identify the relevant randomised controlled ence between the group who used only elastic trials. There were six such trials, which were compression stockings and the group who also small double blind, randomised, median size received stanozolol.65 To date, there are no 33 (range 10–40 patients). At present there is convincing data that suggests any benefit from no evidence to support the use of oral zinc in the use of stanozolol in patients with dermato- the treatment of patients with leg ulcers due to sclerosis or leg ulcers. venous or arterial disease.80 There is limited evidence that zinc may be beneficial in the Vasodilators treatment of venous leg ulcers when there is a PROSTAGLANDINS low serum zinc but recommendations for the Prostaglandins PGE1 and PGI2 are potent dose and duration of treatment cannot be vasodilators and also inhibit platelet aggrega- made on the available information.81 tion. Initial uncontrolled trials suggest success of intravenous infusions of PGE1 and PGI2 in ORAL ASPIRIN patients with severe peripheral vascular disease Randomised trial of oral aspirin for chronic with ulceration.73 A subsequent large multicen- venous leg ulcer revealed reduction in ulcer tre trial demonstrated no diVerence between surface area which was significantly better in the placebo and the treatment group.74 There- the aspirin treated group at two months and fore, it should not be prescribed as its role in four months compared with that in the placebo treating leg ulcers is not evidence based. group.82

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91 ULTRASOUND FOR CUTANEOUS WOUND HEALING large burn wounds. Other investigaters have Five controlled trials from the Cochrane Cuta- used cultured autografts for chronic leg neous Wound Healing Group demonstrated ulcers.92 One group reported healing of chronic that low dose ultrasound is an eVective leg ulcers within 35 days of application of cul- complementary therapy for wound healing. tured epithelial autografts.82 Further experimental and clinical investiga- tions should test its eVectiveness more rigor- ALLOGRAFTS ously and elucidate the mechanisms that might Cultured epidermal allografts can be used in be involved.83 84 enhancing the healing rate of chronic leg ulcers. Previous trials have demonstrated that LASER THERAPY FOR THE TREATMENT OF VENOUS more than two thirds of chronic ulcers healed LEG ULCERS completely within eight weeks of grafting with a To assess the eVectiveness of low level laser mean healing time of 3.3 weeks.93 94 However therapy in the treatment of venous leg ulcers cultured allografts should be reserved for the the Cochrane Wounds Group search strategy treatment of non-healing leg ulcers as cultiva- identified four eligible randomised controlled tion procedure is very complex, labour inten- trials which demonstrated no evidence of any sive, and expensive. benefit associated with low level therapy on venous leg ulcer healing. One small study Apligraf: a biomaterial for wound suggests that a combination of HeNe laser healing/ equivalent68 therapy and infrared light may promote the Apligraf (Organogenesis, Canton, MA; No- healing of venous ulcers, however more re- vartis, East Hanover, NJ, USA) is a new tissue search is needed.85 engineered skin product cultured from human dermal fibroblasts and . Histo- Compression treatment of leg ulcers: a logically it resembles a simplified version of systematic review skin. When applied, Apligraf seems to react to To estimate the clinical and cost eVectiveness factors in the wound and may interact with the of compression systems for treating venous leg patient’s own cells to stimulate the production ulcers, 19 electronic databases including of growth factors. It is being extensively studied Medline, CINAHL, Embase, relevant journals, in diabetic ulcers, clean excision wounds, and and conference proceedings included 24 ran- burns.95 Human skin equivalent appeared to domised controlled trials which demonstrated promote wound healing in three ways: (1) that compression systems improve healing of apparent graft “take”, (2) temporary wound venous leg ulcers and should be routinely used closure, and (3) stimulation of host healing by in uncomplicated venous ulcers. High com- acting as a biological dressing. The eYcacy of pression is more eVective than low human skin equivalent suggests that it will compression,49 but should only be used in the prove useful for promoting the healing of absence of significant arterial disease. There venous ulcers.69 are no clear diVerences in the eVectiveness of diVerent types of compression systems (multi- Electrical stimulation layer and short stretch bandages and Unna’s Electrical stimulation has been demonstrated boot) have been shown. Intermittent pneu- to enhance wound healing.96 97 The mechanism matic compression appears to be a useful by which healing occurs remains unknown. adjunct to bandaging. Rather than advocate They may include inhibition of bacterial one particular system, the increased use of any growth, eVects on fibroblasts motility, or correctly applied high compression treatment increased expression of transforming growth should be performed.86 Compression bandages factor-â on fibroblasts.98 99 and stockings in the treatment of venous leg ulcers as reviewed by Cochrane Wounds Growth factors Review Group,87 demonstrated that multilayer In animal models epidermal growth factor pro- high compression bandages were significantly motes granulation tissue formation and wound more eVective than a single layer bandage. The healing. A variety of growth factors—for exam- direct comparisons of the healing rates were ple, tumour necrosis factors, fibroblast growth described in the two observational studies as factor, transforming growth factors, á and â, 40% (of leg ulcers) in 12 weeks88 and 42% (of epidermal growth factor, and platelet derived limbs) of people attending a leg ulcer clinic.89 growth factors promote wound healing by ang- The limitations for use of four layer bandaging iogenic properties.95 97 98 100 Perhaps in the in a community clinic include the fact that future combination of growth factors and some people are unable to leave their home due compression dressings may have a role in the to immobility and cannot tolerate or do not like quick healing of the ulcers. Therapeutic angio- the treatment.90 genesis may be one of the treatment strategies in the future. Cultured epidermal grafting AUTOGRAFT Conclusion The treatment of venous stasis ulcer can be Leg ulcers seem to have a cycle of healing fol- done by the use of cultured epidermal cells lowed by reulceration and rehealing. Recur- (keratinocytes) as a skin graft. rence rates of venous ulcers after treatment are layers cultured from the patient’s own skin high.98 Once the leg ulcer is healed careful skin (autografts) have been successfully used for care, continuous vigilance, and strict use of several years in the USA and Europe to cover compression hosiery must be emphasised.

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