Managing and Preventing Diabetic Foot Ulcers

Emerg Med 36(8):14-23, 2004

The authors explain in detail how to identify, quantify, and address the factors that determine ulcer healing rate, potential progression to lower extremity amputation, and likelihood of recurrence in a given patient.

By Thomas Miller, MD, Scott A. Clark, DPM, and Barry Stults, MD

A 64-year-old man with a 15-year history of type 2 diabetes presented to a clinic with a left heel ulcer that had developed several weeks earlier, after he began wearing a new pair of shoes. He also reported a three-month history of claudication in his left calf after walking approximately 25 yards. His other medical problems included hypertension, dyslipidemia, coronary artery disease, and depression.

The ulcer (see photo) proved to be populated with maggots, which may have minimized purulent drainage from the lesion. The patient was admitted to the hospital.

Runaway infection. This ulcer began with a new pair of shoes and ended in amputation.

The ulcer was explored with a sterile probe that easily reached bone and also revealed an extensive subcutaneous abscess. Magnetic resonance imaging (MRI) of the left heel demonstrated osteomyelitis of the calcaneus. Pedal pulses were not palpable in the left foot, and a subsequent ankle-brachial index (ABI) on the foot measured by Doppler ultrasound was 0.3 (normal, ›0.9).

Angiography of the left lower extremity confirmed severe infrapopliteal obstruction at multiple levels; vascular surgery and radiologic consultants felt that surgical and percutaneous revascularization were not feasible. The patient was managed with repeated surgical drainage and broad-spectrum parenteral antibiotics. However, local infection in the foot continued to progress, and a below-the-knee amputation was necessary.
 

LOWER EXTREMITY AMPUTATION AND FOOT ULCER

The above case scenario continues to be all too common. Lower extremity amputations (LEAs) in persons with diabetes now exceed 100,000 per year in the United States. They increased in incidence by 26% between 1990 and 2000; 50%, 10%, and 40% of these amputations involve the leg, foot, or toe(s), respectively. Males and ethnic minorities—especially Native Americans and, to a lesser degree, African Americans and Hispanic Americans—are at greatest risk. About 50% of patients will need a second LEA within five years.

Foot ulcers are the proximate cause of about 85% of diabetic LEAs. Diabetic patients have a 2% annual incidence, 5% prevalence, and 15% lifetime risk of foot ulceration. The three-year recurrence rate of diabetic foot ulcers, once healed, is nearly 70%. Unfortunately, about 15% of persons with a diabetic foot ulcer eventually require LEA because of uncontrolled infection, gangrene, or failure to heal.

Distal symmetric polyneuropathy, with peripheral arterial disease as a contributing factor in some patients, is the primary pathogenetic factor leading to diabetic foot ulcer and LEA. Distal sensory neuropathy, present in 20% to 50% of adult patients with type 2 diabetes, diminishes protective sensation in the feet, resulting in abnormal distribution of foot pressure and shear stresses with subsequent callus formation. It also reduces the patient's ability to recognize minor trauma to the foot.

Distal motor neuropathy leads to atrophy of the intrinsic and extrinsic musculature of the foot, with consequent deformities such as hammer toes, claw toes, prominent metatarsal heads on the plantar surfaces of the feet, and bunions on the first and fifth metatarsal-phalangeal joints. In turn, these deformities result in increased foot pressures, especially over bony prominences, again leading to callus formation. Calluses further increase local subcutaneous pressure, eventually causing hemorrhage under the callus, a lesion referred to as a "pre-ulcer" (see photo). With continued pressure the overlying skin breaks down to form an ulcer. Callus and subsequent ulcer formation commonly develop on the plantar surface of the foot overlying the first and fifth metatarsal heads (20%), tops of the toes (25%), plantar hallux (20%), and plantar surface of the heel (10%).

Early stage. Underneath the foot calluses commonly seen in patients with diabetes, hemorrhage may occur, forming a "pre-ulcer."

Distal autonomic neuropathy can also lead directly to plantar ulcers by reducing sweating in the feet, with subsequent drying and fissuring of the skin. Secondary bacterial infection and ulceration may follow. Peripheral arterial ischemia occasionally produces ischemic ulcers, but these are less common (1% to 2% incidence) than neuropathic ulcers (65%) or combined neuroischemic ulcers (25%).

Minor foot trauma, often not recognized by the patient because of sensory neuropathy, is the most common acute precipitant of diabetic foot ulcers. Mechanical trauma predominates, especially from ill-fitting shoes and less often from foreign bodies or self-trauma induced by cutting nails or calluses. Thermal trauma (from hot water or a hot pavement or sand, for example) and chemical trauma (from corn plasters, for example) may also precipitate ulcers in feet that are insensate because of neuropathy. About 6% to 10% of diabetic foot ulcers develop between the toes due to maceration from excessive moisture and fungal infection.

Without prompt and effective treatment, diabetic foot ulcers often develop a secondary bacterial infection. Superficial infections of the wound may progress to cellulitis, abscess and sinus tract formation, fasciitis, or osteomyelitis. Severe soft-tissue infection of the distal forefoot can abruptly precipitate in situ thrombosis of digital end-arteries and arterioles with subsequent gangrene of the toes. In the presence of peripheral arterial insufficiency, infection may be difficult to control, and ulcers may not heal unless revascularization can be accomplished.

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EXTENT AND DEPTH OF THE ULCER

Appropriate assessment of diabetic foot ulcers should identify and quantify those factors that determine ulcer healing rate, potential progression to LEA, and likelihood of recurrence. These factors are the extent and depth of the ulcer, the presence and severity of infection, the presence and severity of vascular insufficiency, and pathogenetic factors and patient self-care behaviors that may have contributed to ulcer formation and that may facilitate ulcer recurrence. Deeper, more extensive ulcers associated with concurrent infection or vascular ischemia, or especially with both, are at greatest risk for failure to heal and progression to LEA.

Comprehensive assessment should be accomplished urgently in the ambulatory or hospital setting and requires a multidisciplinary team approach, with possible input from podiatry, infectious disease specialists, vascular surgery, and orthopedic surgery. Unfortunately, appropriate multidisciplinary assessment is often delayed by the patient or primary care clinician, or both, and this may result in deterioration of the ulcer wound, increasing the likelihood of LEA.

The first key factor to assess is the extent and depth of the ulcer. Diabetic foot ulcers are frequently more extensive than they appear to be on superficial examination. Ulcer depth is an important predictor of healing rate, likelihood of concurrent osteomyelitis, and risk for amputation. An experienced clinician should carefully explore the wound with a sterile blunt probe to determine if it penetrates to the tendon or joint capsule or even to bone or into the joint space, and whether subcutaneous abscess or sinus tract formation is present. The likelihood of osteomyelitis is 90% or higher if the probe contacts bone.

The baseline length and width of the ulcer should be measured. Failure of the ulcer area to decrease 50% or more after one month of appropriate treatment is a strong predictor that the ulcer is unlikely to heal after three months. This may help to identify patients who require more aggressive therapy.
 

PRESENCE AND SEVERITY OF INFECTION

Infection is an important determinant of the need for hospitalization as well as ulcer healing rate and progression to LEA. About 50% or more of patients with severe diabetic foot infections have no signs of systemic toxicity such as fever, tachycardia, or an increased or left-shifted white blood cell count. Comprehensive assessment with a physical examination, laboratory testing, and radiographic studies is therefore necessary to classify infection as absent, mild, or severe. This classification system guides the use and selection of initial antibiotics and the decision as to whether to hospitalize patients. Bacterial cultures from the wound, bone, or blood, or from all three, depending on the clinical setting, may facilitate the decision to adjust initial antibiotic therapy.

Physical examination for signs of infection focuses on the presence or absence of fever, tachycardia, or hypotension and on the appearance of the wound and adjacent tissues. Infection of the wound is demonstrated by the presence of purulent drainage or two or more signs of inflammation (such as tenderness, warmth, induration, or erythema) around the ulcer. Infection should be considered severe if any of the following conditions are present: abnormal vital signs; a rim of erythema around the ulcer that is 2 cm or more in diameter; lymphangitic streaking or signs of fasciitis (such as crepitance or bullae); or if the wound probe reaches tendon, joint capsule, or bone or reveals a sinus tract or abscess.

Laboratory testing for evidence of infection should include a white blood cell count and differential, erythrocyte sedimentation rate (ESR), and glucose, bicarbonate, and creatinine levels. Leukocytosis or a shift to the left (or both), elevated ESR (above 40 mm/hr), severe hyperglycemia (glucose level of 300 mg/dl or higher), metabolic acidosis, or azotemia from dehydration strongly suggest the presence of severe infection. An ESR above 40 mm/hr increases the likelihood of concurrent osteomyelitis 12-fold, while an ESR above 70 mm/hr makes this diagnosis nearly certain. However, lower ESR values do not rule out osteomyelitis.

A plain foot x-ray should be obtained promptly to check for the presence of air produced by gas-forming bacteria, unexpected foreign objects or fractures, or signs of osteomyelitis. Plain films must be interpreted cautiously; changes caused by neuropathic osteoarthropathy (Charcot foot) may mimic osteomyelitis. Conversely, a normal plain foot x-ray does not rule out osteomyelitis, and repeat x-rays should be considered in two weeks to exclude occult osteomyelitis. If the initial plain x-rays are negative but clinical suspicion of osteomyelitis remains high, MRI or possibly leukocyte scanning should be performed. False-positive and false-negative results are still possible with these tests, and bone biopsy through noninfected tissue with specimens for culture and histology may be necessary to confirm the diagnosis.

Patients with Charcot foot may clinically as well as radiographically mimic an acute infection, with diffuse erythema, swelling, and warmth of the affected foot. However, in these patients a foot ulcer is generally absent, erythema and edema partially resolve with elevation of the foot for 10 minutes, and systemic manifestations of inflammation are not present.

In the absence of any of the above signs of infection, cultures of the ulcer are not indicated. However, when such signs are present, cultures may help guide antibiotic therapy if there is an inadequate response to the initial empiric antibiotics. Superficial cotton swab cultures are inadequate. The ulcer must first be thoroughly debrided and then cleansed with nonbacteriostatic saline, followed by tissue curettage or scraping of the base of the ulcer. The specimen should be submitted for both aerobic and anaerobic cultures.

Blood cultures are indicated in patients with apparent systemic toxicity. Bone biopsy through uninfected tissue may be necessary to confirm the diagnosis and microbiology of suspected osteomyelitis.
 

PRESENCE AND SEVERITY OF VASCULAR INSUFFICIENCY

Severe peripheral arterial insufficiency may delay or prevent ulcer healing. It may also interact with severe distal forefoot infection to cause abrupt digital artery thrombosis and gangrene of the toes. Persons with diabetes frequently have infrapopliteal atherosclerotic obstruction with relative sparing of the more proximal arteries and the arteries of the foot. Prompt vascular assessment is therefore essential in all patients, followed by early revascularization if critical ischemia is present.

The patient's ABI should be determined by Doppler ultrasonography in the presence of any of the following clinical findings: absence of both the dorsalis pedis and posterior tibial pulses; claudication symptoms in the calf, thigh, or buttock after walking one block or less or foot pain suggestive of ischemic rest pain; and a history of peripheral arterial disease. Interpretation of the ABI is summarized in the table.

A vascular surgeon should be consulted if the ABI is below 0.4, or if there is concern about a falsely normal or elevated ABI due to medial calcification of the infrapopliteal arteries. Measurements of toe systolic blood pressure, transcutaneous oxygen saturation, pulse volume recording, or further arterial imaging with duplex ultrasound or MRI or conventional angiography may be necessary to determine the presence and severity of ischemia.
 

PATHOGENETIC FACTORS AND SELF-CARE BEHAVIORS

Clinicians must identify the key pathophysiologic pathways contributing to ulcer formation in individual patients, so that these factors can be eliminated or modified, if possible, to reduce the likelihood of ulcer recurrence. Peripheral somatic sensory neuropathy contributes to 90% or more of diabetic foot ulcers. It is optimally detected in the clinical setting using the 5.07/10 g Semmes-Weinstein monofilament applied to four sites on the plantar surface of the foot. Failure of the patient to sense the monofilament at any of the sites indicates that the foot is insensate and at increased risk for ulceration. The previously described foot deformities caused by diabetic motor neuropathy or of developmental origin further increase the risk of diabetic foot ulcer.

Patients with diabetes complicated by sensory neuropathy, foot deformities, or ischemia must consistently practice multiple self-care activities to protect their feet. Clinicians need to identify which of these activities the patient is not performing regularly. They must also determine if there are barriers that inhibit these activities. Depression, which is present in 15% to 25% of diabetic patients and often unrecognized, and alcoholism, for example, may seriously reduce motivation. Social isolation combined with the patient's inability to reach or see his or her feet may prevent daily foot inspection. Also, financial constraints may make it difficult for patients to purchase needed therapeutic footwear.
 

PATIENT MANAGEMENT

The critical first step in the management of patients with diabetic foot ulcers is consultation with one or more specialists from podiatry, orthopedic surgery, vascular surgery, the infectious diseases service, and the diabetic education service. This multidisciplinary approach has been demonstrated in clinical trials to reduce the likelihood of major amputation.

Any infection must be properly treated; patients with severe ischemia must be revascularized, if possible. The wound must be immediately relieved of all pressure to prevent further damage, and effective local wound care must be administered. Finally, a comprehensive program to prevent recurrence of diabetic foot ulcer and LEA is essential.

Patients should be hospitalized if their infection is classified as severe by the clinical, laboratory, or radiographic criteria discussed earlier. Patients with clinical evidence of peripheral arterial insufficiency, those who are unlikely to take prescribed antibiotics or to relieve pressure on the ulcer, and those who are not available for prompt office follow-up within 24 to 72 hours should also be hospitalized, even if infection is mild or absent. Reliable patients with mild or no infection can be treated as outpatients, but they must be reassessed in the office within 24 to 72 hours.

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TREATMENT OF INFECTION

Superficial wounds with no purulent drainage, no more than one associated sign of local inflammation, and no evidence of systemic infection are not likely to be infected. Both vigorous debridement and antibiotic therapy are indicated for infected wounds. Repeated sharp debridement of callus and necrotic tissue by a trained professional, and sometimes deep surgical debridement of soft tissue abscesses, sinus tracts, or necrotic tissue or bone are essential to control infection and subsequently heal the wound.

The severity of infection and the expected spectrum of infecting bacteria guide the initial antibiotic selection (see table below). Antibiotic therapy can subsequently be tailored according to culture results and the patient's response to initial therapy. Recent studies using tissue curettage in diabetic foot ulcers with mild infections show polymicrobial recovery in 75% of patients, an average of 2.4 bacterial species per wound. Gram-positive aerobic bacteria—especially Staphylococcus aureus and species of Enterococcus, Streptococcus, and S. epidermidis—comprise 70% of isolates; group A Streptococcus species are found much less often. Gram-negative aerobic bacteria (24% of isolates) and occasionally anaerobic bacteria (6% of isolates) are also found. Despite the broad spectrum of isolates, focusing treatment on gram-positive aerobes with the oral antibiotics listed in the table for a course of one to two weeks appears effective for most mild infections.

Severe limb- or life-threatening infections are more likely to involve gram-negative aerobic and anaerobic bacteria in addition to gram-positive aerobes. Methicillin-resistant S. aureus (MRSA) organisms have been recovered with increasing frequency from diabetic foot ulcers. Accordingly, one of the parenteral antibiotic regimens listed in the table should be utilized initially for severe infections; patients with life-threatening infections should be treated initially with a combination of imipenem/ cilastin and, to cover MRSA, vancomycin. Antibiotic therapy may be required for two or more weeks.

For osteomyelitis, antibiotic therapy should be based on bone biopsy microbiology and administered for six weeks or longer. Shorter courses of antibiotic treatment may be possible if all infected bone is surgically removed. Some patients with diabetic foot osteomyelitis may be effectively treated with prolonged antibiotic therapy without bone resection.

If it is anatomically feasible, patients with diabetic foot ulcers and severe ischemia should undergo revascularization with angioplasty or vascular bypass procedures. Even with infrapopliteal obstruction, successful revascularization may be accomplished in many patients. If revascularization is not possible or in cases of severe progressive infection or extensive necrosis, amputation at some level may be required.
 

RELIEVING PRESSURE ON THE ULCER

From the time of diagnosis until the foot ulcer has been healed for two or more weeks, further damaging pressure and mechanical stress on the ulcer must be eliminated or at least minimized at all times. This may be accomplished for the first few days with crutches or a wheelchair. Subsequently, patients can use custom-made shoes (such as wedged sandals or half-shoes), orthotic devices (such as removable cast walkers), or total-contact casts to reduce plantar pressures on the ulcer while still allowing some mobility.

After the wound has been debrided of all callus and necrotic tissue, a warm, moist environment should be maintained thereafter using saline damp-to-dry dressings or other dressings such as hydrogels, hydrocolloids, or alginates. More absorbent dressings may be used if significant exudate is present. There is no evidence to support the use of topical enzymes, and hydrotherapy should be avoided. Peripheral edema should be eliminated or minimized.

For chronic diabetic foot ulcers of six or more weeks' duration, healing rates may be improved by applying topical growth factors (such as recombinant platelet-derived growth factor) or bioengineered skin or skin substitutes. Initial randomized trials have demonstrated a measurable benefit for these expensive therapies, but they should probably be limited to patients whose ulcers have not improved substantially after four to six weeks of standard therapy.
 

PREVENTING RECURRENCE AND AMPUTATION

Recurrence rates with diabetic foot ulcers and LEA are as high as 50% to 70% over three to five years. Comprehensive intervention programs customized to individual patients can lower these rates by 50% to 80%. Control of macrovascular and microvascular risk factors is obviously important. The key intervention may be regular and frequent follow-up every one to two months with a diabetic foot care program, if available, or with a podiatrist and primary care clinician attentive to foot care. The feet must be thoroughly inspected at every primary care office visit, with prompt referral to podiatry for treatment and preventive care of any nonulcerative pathology.

Patients must be educated, re-educated, and motivated to perform foot self-care activities. They should also be encouraged to make lifestyle modifications such as smoking cessation and avoidance of alcohol. In addition, primary care physicians should intensify patients' diabetes regimens and strive to achieve A₁c levels below 7%, blood pressure below 130/80 mm Hg, and a low-density lipoprotein level below 100 mg/dl (using a statin drug, if necessary), as recommended by the American Diabetes Association.

Clinicians should pay special attention to patient footwear; ill-fitting shoes may initiate the pathway to LEA in up to 50% of patients. At a minimum, patients should utilize appropriate off-the-shelf footwear, such as shoes with broad, round toes and adjustable laces, buckles, or velcro, or athletic or walking shoes made from leather or canvas and of lighter colors. They should wear protective house slippers in the home when they are not wearing shoes. Patients with more severe neuropathy and especially those with severe foot deformities may require extra-depth and extra-width therapeutic shoes, with cushioned off-the-shelf or custom-made insoles. Medicare pays 80% of the payment amount allowed for one pair of therapeutic shoes and two to three pairs of insoles per year if the appropriate forms are completed by the physicians caring for the patient.

Finally, some patients with major foot deformities may benefit from reconstructive surgery to prevent recurrent foot ulceration. Surgery may be particularly useful in patients who are unable to wear therapeutic footwear.
 

PATIENT OUTCOMES

Rates and speed of ulcer healing vary considerably among patients. Patients with concomitant deep infections or peripheral arterial ischemia or who require surgery have lower healing rates and heal more slowly. Overall, 50% to 80% of patients with diabetic foot ulcers will heal within six months with optimal management from a multidisciplinary team.

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