Published: August 2010
An ulcer is defined as a breakdown in the skin that may extend to involve the subcutaneous tissue or even to the level of muscle or bone. These lesions are common, particularly on the lower extremities. Leg and foot ulcers have many causes that may further define their character.
The prevalence of leg ulceration is approximately 1% to 2%, and is slightly higher in the older adult population.1 Venous ulcers are the most common form of leg ulcers, accounting for almost 80% of all lower extremity ulcerations.2 Peak prevalence is between 60 and 80 years.3 Approximately one third of patients with chronic venous insufficiency will develop venous ulceration before the age of 40 years.2 In addition, venous ulcers may have a prolonged duration and are associated with a high rate of recurrence, which contributes to their prevalence.
Ulcerations associated with diabetes are the most common cause of foot ulcers. Most of these ulcers are a direct result of loss of sensation secondary to peripheral neuropathy.
Arterial ulcers account for 10% to 20% of lower extremity ulcerations. Other causes of lower extremity ulceration are uncommon. Many ulcers may be of mixed cause, with two or more contributing factors leading to ulceration present in the same patient. We focus on the most common causes of ulceration.
The development of neurotrophic foot ulcers in patients with diabetes mellitus has several components, including neuropathy, biomechanical pressure, and vascular supply. Peripheral neuropathy is clearly the dominant factor in the pathogenesis of diabetic foot ulcers.
The neuropathy associated with diabetes is a distal symmetrical sensorimotor polyneuropathy. There is a clear correlation between the presence of hyperglycemia and the development of neuropathy. The mechanism by which this occurs, although extensively studied, continues to be investigated. Much attention has been focused on the polyol pathway. This pathway may result in the deposition of sorbitol within peripheral nerves. In addition, oxygen radicals may be produced, which may contribute to nerve damage. Vascular disease of nerve-supplying vessels may contribute to neuropathy. More recently, increased susceptibility to compression in diabetic patients as a contributor to the development of neuropathy has been postulated.6
The sensory component of the neuropathy results in a decreased ability to perceive pain from foreign bodies, trauma, or areas of increased pressure on the foot. Loss of sensation accompanied by trauma or increased pressure contributes to skin breakdown, often accompanied by ulcer formation at the site of pressure.
The motor component of neuropathy can lead to atrophy of the intrinsic musculature of the foot, resulting in digital contractures and areas of elevated pressure on the plantar foot. In addition, weakness of the anterior leg musculature may contribute to equinus deformity with lack of adequate dorsiflexion at the ankle joint, leading to elevated plantar pressures in the forefoot.
Autonomic neuropathy may occur, with loss of sympathetic tone and arteriovenous shunting of blood in the foot. Sweat glands may also be affected; the resultant anhidrosis leads to dry, cracked skin and predisposes the skin to breakdown.
There is a well-established association between diabetes and increased risks for the development of atherosclerosis and peripheral arterial disease. This is more likely to occur in smokers. This is not microvascular but macrovascular disease, predominantly of the infragenicular (tibial and peroneal arteries) vessels, with sparing of the vessels in the foot. Ischemia may therefore contribute at least in part to the development or persistence of foot ulcers in diabetic patients.
Venous ulceration is the eventual result of venous hypertension. This has multiple causes, but the most common cause is venous valvular incompetence or insufficiency, which may be congenital or acquired. Failure of the venous or muscle pump or venous obstruction may also contribute to venous hypertension. The end result is transmission of elevated venous pressure from the deep to superficial system of the veins, with local effects leading to ulceration. Although it is accepted that venous hypertension plays a dominant role in the development of ulceration, there are multiple hypotheses attempting to explain the direct cause of ulceration.
The fibrin cuff theory, proposed by Browse and colleagues,7 has asserted that as a result of increased venous pressure, fibrinogen is leaked from capillaries. This results in the formation of pericapillary fibrin cuffs that serve as a barrier to the diffusion of oxygen and nutrients. This theory has lost favor as the sole cause, because fibrin is probably not as significant a barrier to diffusion as previously believed.
The trapping of white cells to capillary endothelium is another hypothesis. Venous hypertension results in decreased flow in the capillaries, resulting in the accumulation of white cells. These white cells may then release proteolytic enzymes, as well as interfere with tissue oxygenation.8
A different trap hypothesis has been proposed. This suggests that venous hypertension causes various macromolecules to leak into the dermis and trap growth factors. These growth factors are then unavailable for repair of damaged tissue.9
Atherosclerosis is the most common cause of peripheral arterial occlusive disease. This predominantly affects the superficial femoral and popliteal vessels, reducing blood flow to the lower extremities. When the ischemia is severe enough, ulceration will develop.
Thromboangiitis obliterans (Buerger's disease) is an inflammatory segmental thrombotic disease of the medium and small vessels of the extremities usually associated with smoking. This is a cause of peripheral arterial disease and ulceration.
Atheroembolism may cause peripheral arterial occlusion when proximal plaques break off and travel distally. This is referred to as cholesterol emboli or blue toe syndrome.
Patients with venous ulcers may complain of tired, swollen, aching legs. These ulcers may be painful but not as severe as those seen with ischemic ulcers. The legs will typically be edematous, often with hyperpigmentation of the lower legs from chronic venous stasis. The skin around the ulcer is hyperpigmented. These ulcers are usually on or near the malleoli, usually the distal medial leg. The margins of the ulcers are irregular, with a shallow base. Lipodermatosclerosis may be present, a condition of the skin whereby it becomes indurated and fibrotic in a circumferential pattern, resembling an inverted champagne bottle.
With neuropathy being the underlying cause of ulceration, many patients complain of burning, tingling, or numbness of the feet on presentation. The ulcer is usually on the plantar foot, most commonly under the great toe or first metatarsal head. Because of pressure, it is often surrounded by a rim of hyperkeratotic tissue, which may even cover the ulcer and give the illusion that the ulcer has healed, when it in fact has not. Infected ulcers may be associated with cellulitis, lymphangitis, adenopathy, calor, edema, foul odor, and purulent drainage. Systemic signs such as fever and chills may be related, but are often absent, even in the presence of severe infection. There may be foot deformity or prominent areas of pressure associated with the ulcer.
Arterial ulcers are almost always painful. Patients may relate intermittent claudication, pain in the extremities or buttocks with activity that is relieved with rest. If occlusion is severe enough, there may be pain even at rest. A familiar complaint is pain in the legs when lying in bed at night that is relieved by dangling the legs off the side of the bed. Physical examination reveals diminished or absent lower extremity pulses, trophic changes in the skin, decreased hair growth, and nails that may be thickened or ridged. The skin may be shiny, smooth, cool, and demonstrate pallor or a reddish-blue discoloration. The ulcers have a predilection for the lateral aspect of the leg, posterior heel, distal aspects of the digits, medial aspect of the first metatarsal head, and lateral aspect of the fifth metatarsal. The ulcer itself will often have a dry, dark base of eschar. Gangrene may be present. The lesions are often punched out, with a well-demarcated border.
Accurate diagnosis is the foundation of ulcer care. Misdiagnosis may result in mismanagement, with failure to heal, and may even have devastating consequences. For example, venous ulcers are treated with compression. If an ischemic ulcer is mistakenly diagnosed as a venous ulcer and treated with compression, there may be a further progression of ischemia in the affected limb.
Usually, the history and physical examination are the primary means of obtaining the correct diagnosis. The signs and symptoms previously described will allow clinicians to make the correct diagnosis for the most common types of ulcers. Those with an atypical appearance may require further investigation or referral to a specialist. Long-standing ulcers may require biopsy to rule out malignancy.
Diabetics should be tested for neuropathy. Vibratory testing may be performed with a 128-Hz tuning fork on the dorsum of the great toe. Achilles tendon and patellar reflexes should be examined. The response on these tests is diminished with neuropathy. However, the simplest and most effective means of detecting neuropathy is examination with a 10-g monofilament. An inability to detect the monofilament when applied under the metatarsal heads or digits is indicative of neuropathy. A patient with a history of neuropathy who complains of new-onset pain in the extremity should raise concern for a pathologic process, such as infection or Charcot's neuropathic arthropathy.
A proper vascular assessment is critical to the evaluation of the diabetic foot. Vascular examination, including palpation of the dorsalis pedis and posterior tibial pulses, as well as general inspection of the extremities, should be performed. Patients with evidence of ischemia should be further investigated with vascular studies. An excellent tool is the ankle-brachial index (ABI), which is determined by dividing the higher systolic pressure of the anterior tibial or posterior tibial vessels by the highest systolic brachial pressure. Ankle pressure is determined with the assistance of a Doppler probe; a result of 1.0 to 1.1 is normal. Values less than 1.0 are abnormal and reflect decreased perfusion to the lower extremity. Medial calcification of the tibial vessels, which is common in diabetics, may falsely elevate the ankle pressure. Toe pressures in such patients more accurately reflect perfusion. Segmental pressure determination, pulse volume recordings, duplex scanning, transcutaneous oxygen diffusion, contrast angiography, and magnetic resonance angiography are other vascular studies that may assess perfusion.
All ulcers should be assessed for potential infection. Infected ulcers may be limb- and even life threatening. In addition to the signs previously noted, the ulcer base should be inspected. Diabetic foot ulcers should be probed, because they often reveal a tract under the skin that may harbor an abscess. In addition, probing may assess the depth of the ulcer. Grayson and associates10 have found a positive predictive value of 89% when an ulcer probes to the depth of bone. Leukocytosis may be present, but is often absent in diabetic patients. The erythrocyte sedimentation rate is frequently elevated in infected ulcers, and values higher than 70 mm/hr should heighten suspicion for osteomyelitis. Deep culture of tissue or purulence is helpful in establishing the microbiology of the infection. Superficial swabbing of sinus tracts is unreliable. Bone culture is the definitive method to diagnose osteomyelitis.
When bone infection is suspected, radiographs should be obtained. Films should be inspected for gas in the tissues. Signs of osteomyelitis include periosteal reaction, osteopenia, and cortical erosion. Unfortunately, these signs are delayed because approximately 50% of bone must be destroyed before osteomyelitis is evident radiographically. Bone scanning and magnetic resonance imaging (MRI) are other useful means for establishing the diagnosis of bone infection.
When speaking of any lower extremity ulceration, the best treatment is prevention. Management of edema should be instituted before the development of ulceration. Mechanical therapy is the gold standard for treatment of venous insufficiency. Elevation of the legs above the level of the heart for 30 minutes three or four times daily may reduce edema and improve the cutaneous microcirculation.11 Elevation of the legs while sleeping at night also reduces swelling.
Compression stockings are the primary method of edema management, particularly in the active patient. These methods are also the mainstay of treatment once a venous ulcer develops. Compression stocking use in compliant patients increases the ulcer healing rate and reduces the rate of recurrence.12 Compression therapy is believed to exert its positive effect on venous ulcers by increasing fibrinolysis, reducing venous hypertension, and improving the cutaneous microcirculation. Stockings exerting a pressure of 30 to 40 mm Hg are typically used in the setting of venous ulceration. Multilayered compression bandages are also effective at reducing edema. Compression should generally not be used in the setting of peripheral arterial disease or uncompensated congestive heart failure.
Although compression therapy is the key to venous ulcer treatment, some patients require adjunctive therapy to attain ulcer healing. In addition, some patients have venous ulcers combined with arterial occlusive disease, making excessive compression therapy a hazardous intervention. Pharmacologic therapy is sometimes used in these cases.
Pentoxifylline has been shown to improve venous ulcer healing, with and without compression therapy.13 A double-blind, randomized, clinical trial of 20 patients treated with enteric-coated aspirin, 300 mg daily, found that the aspirin-treated group had a significantly better reduction in ulcer size.14
Diuretics may be used for a short time in cases of severe edema. Venous edema is difficult to mobilize with diuretic therapy, so volume depletion may occur with prolonged use.
Neuropathy is the gateway to the development of foot ulceration in diabetic patients. Intensive treatment of blood glucose concentration has been shown to delay the onset and slow the progression of peripheral neuropathy.15 It is therefore critical that patients with or at risk for foot ulceration receive appropriate glucose concentration management from their primary care physician or endocrinologist. Regular screening for the development of neuropathy, intensive podiatric care, and custom footwear may all reduce the risk of foot ulceration.16 Once ulceration develops, treatment should focus on pressure relief, débridement, and treatment of infection.
Total contact casting is the gold standard for off-loading the diabetic foot. The cast cannot be removed, reducing the risk of patient noncompliance with pressure relief. The cast application is technically demanding and should only be applied with care and expertise. It should not be used in the presence of infection or excessive drainage. Removable cast walkers are commonly used to off-load the diabetic foot in place of the total contact cast. Because the device is removable, the wound may be monitored daily and can be used in the presence of infection. It also allows the patient to remove the device during sleep and bathing. However, because this device is removable, its success is dependent on patient compliance.
Wound débridement removes nonviable tissue that if left in the wound might promote infection. Hyperkeratotic tissue that increases plantar pressures is also removed. Débridement may serve to promote healing by converting a chronic wound to an acute wound. Platelets aggregate in the débrided wound, initiating the inflammatory phase of wound healing.
Management of infection is the most critical aspect of treating the diabetic foot. Infected foot ulcers are commonly limb- or even life threatening. Infections should be treated empirically until test results are available. Cefazolin and beta-lactamase inhibitor agents are effective empirical agents for such infections. Definitive therapy may then be instituted when culture and sensitivity results have been obtained. Incision and drainage should be performed when deep infection or abscess is present. When osteomyelitis is present, antibiotic therapy combined with surgical débridement, with removal of infected bone, is generally necessary.
In regard to arterial ulcers, a vascular medicine or surgery specialist should be consulted. It should be determined whether the patient is a candidate for a peripheral revascularization procedure. Interventional radiologists also perform less invasive vascular procedures, which may increase peripheral blood flow. Without sufficient tissue oxygenation, these wounds will not heal. Tissue that is infected or gangrenous must be removed, often requiring partial amputation. Vascular consultation is needed to determine the appropriate level of amputation when necessary.
In general, wounds should be kept clean and moist to promote granulation and prevent infection. There is a vast array of wound care products and dressings available that are beyond the scope of this discussion. Clinicians often erroneously rely on a topical therapy alone to heal a wound. It must be stressed that, in most cases, it is adherence to the principles outlined earlier and not what is put on a wound that will lead to a successful result. Wounds resistant to healing, however, may benefit from the many wound care modalities available. Topical growth factors, negative pressure wound therapy, living skin equivalents, and silver-impregnated dressings are among the many adjunctive therapies available for ulcer care, particularly for the specialist.
The evaluation and treatment of the most common types of leg and foot ulcers have been discussed. The general principles presented may be used to successfully treat most leg and foot ulcers. However, when presented with a wound that is atypical in presentation or fails to respond to conventional therapy, clinicians should have a low threshold for referral to a specialist.