About four of 1,000 people will develop a leg ulcer during their lives, but the prevalence of leg ulcers rises dramatically with age, increasing to about 1 percent in people over the age of 60 and 2 percent in people over the age of 80. In the U.S., about 3 million people suffer from leg ulceration, costing an annual $4 billion in treatment costs and losses of over 2 million days from work.
In general, diagnosing the cause of leg and foot wounds requires examining the wound, the extremity and the patient. Let’s start by taking a look at venous problems.
Any disease state that leads to venous insufficiency or venous hypertension can lead to venous stasis disease. Such pathologies include varicose veins, deep venous thrombosis and congestive heart failure. The common denominator of these divergent conditions is that venous valves become incompetent.
Primary venous valvular incompetence manifests as the gradual onset of superficial varicosities. Venous ulcers are three times more common in women than men because varicosities, the most common cause of venous insufficiency, are that much more common in females. Interestingly, because the left iliac vein is somewhat more prone to develop venous valvular incompetence than the right iliac vein, varicosities are about 10 percent more common in the left lower extremity. In the case of deep vein thrombosis, valvular incompetence results from valve damage during the acute thrombotic phase. As the thrombus recannalizes, the now incompetent valves become exposed.
In the case of congestive heart failure, elevated pressures on the right side of the heart are transmitted to the iliac veins and distend these veins to the point that the valve leaflets fail to coapt and hence become functionally incompetent. With incompetence of the proximal valves comes a cascade effect to cause distension and incompetence of more and more distal valves. When venous valves become incompetent, venous blood flow becomes bidirectional, causing venous hypertension in the distal leg and foot.
Venous hypertension enlarges the capillary bed in the skin, increases permeability of the capillary wall and allows large molecules such as fibrinogen to extrude. Fibrinogen forms a fibrin cuff around the capillary bed and interferes with oxygen diffusion. Thus, an area of skin becomes relatively ischemic and ulceration-prone. At the same time, leukocytes become trapped in the capillaries, discharging proteolytic enzymes and free radicals that cause tissue necrosis.
How Do You Know An Ulcer Is Due To Venous Disease?
The usual clinical findings in venous stasis ulceration follow from this pathophysiology. First, as I noted above, these ulcers often occur in patients with a history of one of these inciting factors—prior deep vein thrombosis (which may have occurred decades prior), varicose veins or chronic congestive heart failure.
Second, venous stasis ulcers tend to be chronic and recurrent, as the underlying etiology is longstanding and often uncorrectable. Third, these ulcers tend to occur where the venous pressure remains highest, in the so-called “gaiter” area that is the distal ankle, especially around the medial malleolus.
The limb harboring venous ulcers also will have findings that follow from the pathophysiology. Therefore, you can expect chronic edema, varicose veins, hyperpigmentation (hemosiderin deposits), induration (lipodermatosclerosis) and dermatitis. When examining the patient with venous ulceration, we attempt to identify underlying factors pointing to the usual etiologies.
Beware of masqueraders such as lymphedema and acute deep vein thrombosis. Lymphedema is, of course, characterized by edema but is not associated with the other findings characteristic of venous stasis disease. Early on in lymphedema, a protein-rich fluid accumulation causes soft extremity swelling which easily pits, involves distal extremity including the dorsal foot and responds to limb elevation and compression. But in the late stage of lymphedema, inflammatory fibrosis supervenes, causing woody, firm, non-pitting edema (brawny edema), thickened and hyperkeratotic skin, and becomes refractory to limb elevation and compression.
Acute deep vein thrombosis is even easier to distinguish. It also is characterized by edema, but there are no chronic findings—no induration, hemosiderosis, dermatitis or ulceration. There is instead pitting edema, calf tenderness and pain upon dorsiflexion of the ankle (Homan’s sign). A more difficult differential diagnosis is acute deep vein thrombosis occurring in a limb which has known chronic venous insufficiency. The clinical tipoff may be calf muscle pain or tenderness or an unexplained increase in preexisting edema.
What You Should Know About Systemic And Topical Agents
The management of venous stasis ulcers also follows from the pathophysiology. Most heal without surgical intervention, requiring only control of the underlying venous hypertension and the wound itself. In general, treatment focuses on maintaining an optimal wound bed, controlling infection, managing pain and minimizing edema.
Although no drug is a panacea in managing venous disease, there is at least anecdotal evidence on the efficacy of several medications in alleviating some of the symptoms. Since activated free radicals seem to comprise an important part of the inciting etiology, antioxidants (such as vitamins C and E), nonsteriodal antiinflammatory drugs and pycnogenol would seem to have potential utility. In one controlled clinical study, horse chestnut seed extract had some salutary effects.
But only one drug, pentoxifylline, has been shown to change the course of venous disease significantly. By interfering with leukocyte activation, pentoxifylline may prevent or reduce skin changes such as lipodermatosclerosis. When pentoxifylline is administered for this indication, usually give 800 mg three times daily with food. (This is twice the usual dose of 400 mg typically administered for claudication.) This dosage is reduced for patients with renal insufficiency. Be sure to warn patients that the most common side effects are gastrointestinal.
Initial treatment of the venous ulcer is often surgical debridement, followed by wet to moist saline dressings. If the wound appears superficially infected, use an antibiotic ointment (silvadene, bactroban) or a debriding agent (hypertonic saline gel, collagenase, papain-urea). For annoying pruritis, try a topical steroid cream or ointment. The surrounding skin is often dry and flaky, and requires frequent application of an emollient. Excessive clean exudate may be absorbed with an alginate dressing.
Finally, when the wound is clean and beginning to heal, it is important to provide a moist wound bed to promote epithelialization. In this stage of healing, use a hydrocolloid gel. Note that patients with stasis dermatitis tend to be very sensitive to some topical agents. Such sensitizers include benzocaine, lanolin, neomycin and parabens, and may complicate matters by inducing a contact dermatitis.
How To Facilitate Edema Control
The underlying edema requires control both during the ulcer healing phase as well as subsequently to prevent the all too common recurrences. Recommend leg elevation (above the level of the heart) while sitting and at night. To reduce edema and improve venous return to the heart, sustained external pressure is important. Therefore, you should prescribe external compressive therapy (not TED stockings) or elastic bandages for patients to use when they are standing.
Gradient compression stockings are available with different grades of pressure. The choice will depend upon patient tolerance and systemic factors, such as congestive heart failure, that may contraindicate heavy compression as this overloads the circulatory system or coexisting arterial insufficiency. For otherwise healthy patients, prescribe 30-40 mm stockings (e.g., Jobst or Sigvaris). These need to be replaced every six months or so to maintain efficacy. Refractory cases may require pneumatic compressive boots.
Another option is Unna’s boot (e.g., Unna-Flex from ConvaTec), a zinc oxide impregnated inelastic bandage that becomes rigid as it dries. When the calf muscles contract against the inelastic bandage, they pump more effectively, improving proximal venous blood flow and consequently reducing edema. Because the bandage loses efficacy over time, has limited absorptive capability and becomes malodorous, it requires more frequent (perhaps weekly) replacement. Be aware, though, that maceration of surrounding skin from prolonged contact with wound exudate is sometimes problematic.
Elastic wraps are an inexpensive alternative. New wraps tend to maintain an average pressure of about 20 mm Hg but lose significant compressive power after being washed and require an underlying absorptive wrap. A multilayer compressive wrap such as Profore (Smith & Nephew) provides an inner absorptive layer and can sustain therapeutic pressure for seven days or so.
With any elastic wrap, you must beware of leg geometry and application tension. The dressing will be ineffective if applied too loosely but can potentially induce tissue necrosis if applied too tightly. In rare cases, elastic wrap dressings were applied too tightly to patients with associated underlying arterial disease and led to subsequent amputation. Controlled pressure elastic bandages have a geometrical design printed at intervals. This pattern changes shape when the bandage tension is at a predetermined level. For example, with Setopress (ConvaTec) 30-40 mm Hg graduated compression hose, green rectangles become squares at 70 percent extension and brown rectangles become squares at complete extension.
A Few Thoughts On Surgical Treatment Of Venous Ulcers
Surgical intervention is rarely required to heal venous ulcers. Occasionally, excising the ulcer and applying an autologous split thickness skin graft may help. An alternative to harvesting the patient’s own skin for the graft is to use a dermal graft (Dermagraft) or bilayered skin prosthesis (Apligraf). Intractable ulcers due to varicose veins may respond to removal of the offending varicose veins and ligation of incompetent perforating veins (open or endoscopic, SEPS). A relatively new procedure, VNUS, involves radio frequency ablation of superficial veins.
Understanding Arterial Problems
The garden-variety type of arterial disease is atherosclerosis, “hardening of the arteries,” in which cholesterol plaque gradually—over decades—narrows and eventually obstructs blood flow in large and medium sized arteries. Patients with diabetes are particularly prone to developing atherosclerotic disease. Other less common causes of wounds, in which the common denominator is arterial insufficiency, include Buerger’s disease, vasospastic disease (e.g., Raynaud’s), collagen vascular disease, sickle cell anemia and radiation-induced ulcers. While the pathophysiology of venous ulcers may seem somewhat difficult to understand, the pathophysiology of arterial ulcers is rather straightforward. These ulcers stem from a lack of oxygen and nutrients, especially at the locations most remote from the left side of the heart.
From the above pathophysiology, you can predict the characteristics of wounds due to arterial disease:
• a deep, pale or gangrenous wound bed;
• distal locations such as between the toes, tips of the toes and lateral malleolar;
• often precipitated by minor trauma where tissue poor vascularity precludes the usual healing process;
• often quite painful; and
• commonly associated with infection such as cellulitis or lymphangitis.
Likewise, the ischemic extremity harboring an arterial wound often demonstrates the following findings characteristic of arterial disease: pulse deficit, prolonged venous and capillary refill time, hair loss, skin atrophy, pallor, cyanosis and dependent rubor. Be aware that 10 percent of the healthy population do not have a dorsalis pedis pulse. Although you should be suspicious of arterial disease if either pedal pulse is absent, absence of both the dorsalis pedis and posterior tibial pulse is a more specific finding signaling the presence of arterial insufficiency.
Assessing The Diagnostic Testing Measures
Palpation of pedal pulses may be somewhat difficult, especially in patients who have coexisting extremity edema. In these cases, use the handheld Doppler to identify arterial flow signals and then direct palpation to that location. A weak Doppler signal and non-palpable pulses are highly suggestive of arterial inflow obstruction.
Another parameter that is only sometimes useful is the ankle-brachial pressure index (ABI). You can calculate the ABI by measuring the pressure at which Doppler flow ceases and dividing it by the upper extremity systolic blood pressure. A very low ABI of
Arterial flow can be measured noninvasively. Arterial evaluation pulse volume recording (plethysmography) provides an accurate physiologic qualitative measurement of the significance of arterial obstruction. This noninvasive study involves computer measurement using sequential extremity pneumatic cuffs of the cyclic fluctuation of the circumference of the extremity with each heartbeat. Duplex scan provides ultrasound imaging as well as Doppler flow characterization of accessible arteries, especially the aorta, femoral and popliteal vessels. While it is the gold standard in detecting and measuring aneurysmal disease, it is not terribly accurate in assessing actual flow to the lower extremity.
Arterial anatomy often requires mapping. Contrast angiography provides a definitive “road map” of the arterial lumina. However, because the contrast agent may be nephrotoxic, you must exercise caution in using contrast angiography (if you use it all) for patients with renal insufficiency. Acetylcysteine (Mucomyst) is an antioxidant that has been shown to be somewhat protective of the kidneys if administered prior to angiography.
Magnetic resonance angiography (MRA) is a reasonable alternative for patients with renal insufficiency (or those allergic to iodine dye). Unfortunately, the resolution of MRA is often inadequate to plan vascular procedures below the knee. You also can’t use MRA on patients who have a cardiac pacemaker and it may be problematic for claustrophobic patients.
Essential Treatment Tips For Arterial Disease
Patients with arterial disease of the lower extremity commonly have diffuse atherosclerosis, which may involve the carotid, coronary, mesenteric and renal arteries. Therefore, these patients always carry the risk of stroke, myocardial infarction, intestinal angina and renal failure. Cigarette smoking, obesity and diabetes may be contributing factors. To try to optimize the patient’s status will require control of hypertension, diabetes, coronary insufficiency, renal insufficiency, blood lipids, anemia, pulmonary function, obesity and smoking cessation. As far as the treatment options go …
1. Consider pharmacotherapy. Two drugs are approved for treating the symptoms of intermittent claudication. These are pentoxifylline (Trental) and cilostazol (Pletal). Pentoxifylline and its metabolites improve the flow properties of blood by decreasing its viscosity and enhancing tissue oxygenation. Cilostazol, a phosphodiesterase III inhibitor, increases pain-free walking distance by a mechanism that seems to involve vasodilatation and inhibition of platelet aggregation. The major side effect of pentoxyfilline is gastrointestinal upset that can be severe enough to cause the patient to discontinue this drug after the first dose. Cilostazol is less likely to cause gastrointestinal upset and is possibly more likely to improve walking distance. However, as a phosphodiesterase inhibitor, Cliostazol can theoretically cause sudden cardiac death in patients with underlying congestive heart failure.
2. Manage the arterial wound. As with treating venous wounds, you need to direct care to the wound as well as to the underlying cause. However, unlike the management of venous wounds, wound care and revascularization usually go hand-in-hand with arterial ulcers. Regarding the wound, surgical debridement is often the first intervention. This may include amputation of gangrenous toes. Toes with wet gangrene require open amputation with closure as a second stage when infection has cleared. After surgical debridement, chemical debridement with wet to moist saline dressings or enzymatic debridement using topical agents (hypertonic saline gel, collagenase or papain-urea) is continued daily until the wound appears relatively clean.
At this point, you can maintain a moist wound environment with a saline gel or hydrocolloid. The underlying arterial disease requires comprehensive assessment noninvasively and usually invasively as well (as described above). If revascularization is possible, the timing of this intervention is the next issue you need to consider. With wet gangrene, you would first initiate surgical debridement and antibiotic therapy, following with revascularization. With dry gangrene or intractable but uninfected wounds, revascularization may precede or be performed concurrently with toe amputations.
A Primer On Endovascular And Vascular Surgical Procedures
3. Consider revascularization of the ischemic leg. There are numerous, varied methods of revascularization. Personal experience and clinical judgment will dictate the precise choice of treatment. The basic choices are classified as endovascular and vascular surgical. Endovascular procedures include angioplasty and stenting. Vascular surgical procedures include removal of plaque (endarterectomy) and bypass surgery.
As far as the endovascular options go, high-grade strictures or short segment occlusions of the aorta or iliac arteries are commonly treated by balloon angioplasty and stenting. Intravascular stents are devices made of metallic mesh that are introduced into the artery through a delivery catheter in a collapsed form. After the stent is placed at the desired location under fluoroscopic control, it is expanded to a larger diameter and deployed within the lumen of the artery.
The main function of an intravascular stent is to overcome the flow limiting effect of elastic recoil and intimal dissection induced by balloon angioplasty. Endovascular reconstruction of these retroperitoneal vessels avoids the risks associated with transabdominal and retroperitoneal surgery. Furthermore, the success rate is high and patency tends to be preserved reliably for quite a long time. Antiplatelet therapy with aspirin, dipiridamole (Persantine), ticlopidine (Ticlid) or clopidogrel (Plavix) is often given for 10 to 30 days post-procedure to prevent early stent occlusion during the period when neointima is forming within the stent.
The method of vascular surgical intervention depends upon the location and degree of disease. With the increasing success of stenting for aortoiliac disease, vascular surgical intervention for aortoiliac disease is becoming less common. However, endovascular treatment of infrainguinal disease is much less successful. Therefore, vascular surgeons tend to spend most of their operating time on reconstructing occlusions of the femoral, popliteal and infrapopliteal arterial segments.
How do we address a superficial femoral artery occlusion? We bypass the occlusion by jumping a graft from above the disease to below the disease. “Above” usually means the common femoral artery. “Below” varies depending on runoff and accounts for the variability of bypasses. The vascular surgeon can achieve a durable bypass to the popliteal artery by using a variety of conduits including the patient’s own saphenous vein, preserved cadaveric vein and expanded polytetrafluorethylene grafts. In contrast, bypasses to the infrapopliteal vessels require autologous vein to achieve any hope of long-term patency. Arguably the best such conduit is the in situ saphenous vein bypass.
In this somewhat complex procedure, the ipsilateral saphenous vein remains mostly intact in its natural bed. It is taken down from the femoral vein, anastomosed to the common femoral artery and then—after the valves have been destroyed using a special valvulotome— transected distally and anastomosed to the outflow vessel. Communicating veins are then identified and ligated.
The usual bread-and-butter reversed saphenous vein bypass involves harvesting the ipsilateral or contralateral saphenous vein and reversing it prior to doing the anastomoses. This method avoids the complexity of vein valve lysis and tributary ligation but has a disadvantage in that the smaller end of the vein is anastomosed to the larger artery. Because coronary disease is common in patients with peripheral arterial disease, many of these patients have already had the greater saphenous veins harvested for use in coronary bypass surgery. In such cases, alternative conduits are the lesser saphenous veins or upper extremity veins, which unfortunately turn out, more often than not, to be unsuitable.
In the absence of an adequate length of autologous vein and the need to bypass to the distal infrapopliteal vessels, a composite graft (part vein and part synthetic) or a synthetic graft anastomosed to a specially-fashioned vein cuff (Miller cuff) distally may be the only reasonable options if surgery is contemplated.
Finally, hyperbaric oxygen therapy is an option to keep in mind when vascular surgical reconstruction is not possible due to prohibitive medical risk factors, lack of suitable vein or lack of suitable outflow artery and where the extent of gangrene does not already preclude salvage of a usable limb. In such cases, however, below or above knee amputation is often inevitable.
Venous and arterial diseases often contribute to the stubbornness of intractable extremity wounds. Each has its own characteristic findings as a result of its unique pathophysiology. Each requires care of the wound, the extremity and the patient. Venous wounds often resolve with mechanical measures while arterial wounds commonly require revascularization.
Dr. Stillman is the Medical Director of the Wound Healing Center as well as Chief of Staff of Northwest Medical Center in Margate, Fla. He has published approximately 100 research papers and textbook chapters, and authored or edited a half-dozen surgical textbooks. Dr. Stillman is also a senior member of the Society of University Surgeons and the Association for Academic Surgery.
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