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CHAPTER 116

Diabetic Foot Ulcers

AKSONE NOUVONG / DAVID G. ARMSTRONG

Based on a chapter in the seventh edition by George Andros and Lawrence A. Lavery

Diabetes is a global epidemic and a leading cause of death by disease. An estimated 366 million people worldwide had diabetes in 2011. This figure is expected to reach 552 million by 2030, corresponding to roughly 8.3% (2011) and 9.9% (2030) of the adult population.1 Diabetes is the most common underlying cause of foot ulcers, infection, and ischemia, which are among the most serious and costly complications of diabetes. Despite advances in the management of diabetes, the rising disease prevalence has resulted in an increased incidence of lower limb amputation due to diabetes.

EPIDEMIOLOGY

As the population ages, the incidence of diabetic foot ulcers (DFUs) and diabetic complications increases. A study of Medicare fee-for-service beneficiaries from 2006 to 2008 reported the incidence of DFUs to be 6.0% and that of lower extremity amputation to be about 0.5%. Among the same population, the prevalence of microvascular and macrovas-cular complications is approximately 46% and 65%, respec-tively. The annual mortality rate of patients with DFUs is 11%, and it is 22% in those with a history of lower extremity amputation.2 Patients who undergo a lower extremity ampu-tation have poor quality of life, and the 5-year adjusted mor-tality rate after a major limb amputation is 46%, which is higher than for many forms of cancer.3

DFUs pose a significant social and economic burden on society. The estimated cost for treatment of one foot ulcer has been calculated at approximately $28,000 during a 2-year period.4 Others have reported that the direct cost estimates (in 2010-adjusted U.S. dollars) range from U.S. $3,096 for a superficial ulcer5 to U.S. $107,900 for an ulcer resulting in amputation.6

Natural History

The natural history of diabetes-related lower extremity ampu-tation can be described as a stairway (Fig. 116-1). The first step is the diagnosis of diabetes, followed by the onset of neuropathy. If an ulcer occurs, it may be complicated by peripheral artery disease (PAD), which slows healing. The

coup de grâce is often an ascending infection leading to the urgent need for amputation. There are interventions to prevent each advancing “step” and, ultimately, to prevent a major amputation. It is imperative that the ulcerated diabetic foot be free from infection and receive adequate blood flow to heal in a timely fashion. If one can heal a DFU or at least prevent it from becoming infected, most amputations can be avoided. Interestingly, several reports state that up to 85% of complications, such as amputation, may be preventable.7,8

Incidence

Up to 25% of patients with diabetes will suffer from a foot ulcer during their lifetime.3 Ulceration is a pivotal factor in the causal pathway to infection and amputation. Approxi-mately 50% of DFUs become infected, and 20% of these require amputation.3 The incidence of DFU ranges from 2.0% to 6.8% per year in the general diabetes population.6,8-11 Those with diabetes and neuropathy with no other comor-bidities will develop an ulcer and represent 7% to 10% of cases annually. Individuals with additional risk factors, such as foot deformity, PAD, previous ulceration, and amputation, will have a 25% to 30% increased risk for ulceration. In more than 85% of lower extremity minor and major amputations, a foot ulcer that subsequently deteriorates to severe infection or gangrene is a critical aspect of the causal pathway.9

It is uncommon for an adult with diabetes to develop a limb infection without a wound as a precipitating factor. Hematogenous soft tissue and bone infections are distinctly unusual. Therefore, it is imperative that foot ulcers be identi-fied and managed promptly.8,12-14 Complications of foot ulcers are the leading cause of hospitalization and amputations. This added burden leads to a 20% to 40% increase of health care resources in diabetes care.9 The most significant cause of amputation after foot ulcers is infection. The presence of PAD increases the risk of this amputation’s being a proximal one.

Recurrence Rate

Reported recurrence rates have been variable but consistently high, ranging from 55% at 12 months to 60% at just 126

CHAPTER 116 Diabetic Foot Ulcers 1817 SE

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ipsilateral limb within 3 years after the first operation, and 46% died within 3 years.19

Diabetes-related foot complications and amputations are disproportionately more common among men and minorities. These rates are 150% higher in Hispanics and 170% to 240% higher in African Americans in the United States.2 In non-Hispanic whites, 56% of amputations occur in patients with diabetes, whereas 75% of amputations in African Americans and 86% of amputations in Hispanics are due to diabetes.5,8 Across all race and ethnic groups, the incidence of diabetes-related amputations is more than twice as high in men. The risk of amputation in diabetic patients also increases with age.21

ETIOLOGY AND PATHOMECHANICS

The etiology of DFU is complex and rarely unifactorial. In general, foot ulcers are the cumulative result of repetitive trauma that wears a hole in the skin.6,17,18 The triad of neu-ropathy, foot deformity, and minor trauma cannot be over-emphasized as the major contributing factors of ulcer development. Poor biomechanics causes shear stress and ver-tical stress to develop on the sole of the foot at the site of high pressures resulting from structural foot deformity and limited joint mobility.13,17,18 Structural deformities, such as claw or hammer toes, first metatarsal joint dislocation, bunion, and limited motion of the ankle and first metatarso-phalangeal joint, are often associated with foot ulcers. A combination of clawing of the toes and dislocation of the metatarsophalangeal joints causes retrograde buckling and dislocation. These forces cause the metatarsal head to be pushed in a plantar direction. Ulcers on the great toe often develop because of arthritis or limited motion of the first metatarsophalangeal joint, termed hallux limitus. The pres-ence of neuropathy and hallux limitus has an associated risk ratio of 4.6 for ulceration.22

Ulcers on the tips of clawed toes usually arise because of constant pressure and weight bearing. Ulcers on the metatar-sal heads (the “ball” of the foot) occur at sites of high pressure and shear forces that are exposed to repetitive injury during normal walking. Dorsiflexion of the ankle joint should be 10 degrees from neutral, and dorsiflexion of the first metatarso-phalangeal joint should be about 50 degrees from neutral. When the ankle motion does not exceed 10 degrees, the abnormality is termed equinus. In diabetic patients, tendons such as the Achilles tendon become glycosylated and less elastic, which can cause equinus leading to increased plantar pressure under the forefoot. A neuropathic patient with decreased ankle joint motion has a risk ratio of 2.3 for devel-opment of a forefoot ulcer.22-24 At toe-off in gait, the reduced motion causes more pressure and shear forces under the first metatarsal head (forefoot) or at the hallux interphalangeal joint.23,24

The importance of bone deformities that expose the overlying skin to trauma cannot be overemphasized. Bone prominences in the midfoot often result from Charcot’s neuro-osteoarthropathy, neuropathic fracture, or dysfunction

days.10,11 In the presence of diabetes, additional comorbidities appear to confer markedly increased risk. For example, the presence of sensory neuropathy or PAD15 increases the risk of these adverse outcomes from 3-fold to 50-fold.14-16

Amputation Rate

Lower extremity amputation may best exemplify the impact of diabetes because it is a measure of end-stage disease and, in many cases, treatment failure. Patients with diabetes are 15 to 30 times more likely to have an amputation than are patients without diabetes2,4,5; 70% to 80% of all nontraumatic amputations occur in people with diabetes.

In the past 15 years, the annual rate of extremity amputa-tion in people with diabetes in the United States has almost halved, to 4.6 per 1000, most of which have been above-the-ankle amputations.12 Although these data are promising, a study from the United Kingdom found that between 1996 and 2005, the number of amputations in people with type 1 diabetes decreased substantially. However, among type 2 dia-betic patients, the number of minor amputations almost doubled, and major amputation rates increased more than 40%.12,13 It is estimated that more than 1 million limb ampu-tations are performed on people with diabetes annually, which equates with the loss of limb every 20 seconds some-where in the world.14

In patients with DFUs, 5% to 8% will require a major amputation within 1 year.15,16 The survival rate in patients with above-the-knee or below-the-knee amputation is 62% at 1 year and 29% at 5 years.17 In patients with peripheral vascular disease or diabetes, progression of their underlying disease can lead to ipsilateral limb reamputation.18-20 Ream-putation rates have been noted to be 60% at 5 years. Among patients who underwent forefoot amputation, 79% had ream-putation in the first 6 months, 49% had reamputation of the

Figure 116-1 Common natural history of major lower extremity amputation. Each step in this “stairway to amputation” is a target for intervention to prevent the escalation to amputation. (From Armstrong DG, et al: Guest editorial: are diabetes-related wounds and amputations worse than cancer? Int Wound J 4:286-287, 2007.)

Diabetes

Neuropathy

Ulceration

Infection

Ischemia (+/–)

Amputation

1818 SECTION 18 Lower Extremity Arterial Disease

Loss of protective sensation does not necessarily mean com-plete absence of sensation or pain. So-called painful-painless ulcers may develop because of ischemia or deep sepsis; these require prompt attention and intervention. This scenario can also represent damage to both large myelinated nerves and small unmyelinated nerves, so the patient may have burning symptoms because of small-fiber damage and deep, gnawing pain and numbness because of large-fiber neuropathy.

Motor Neuropathy and Resultant Foot Deformity

Motor neuropathy often occurs later in the course of diabetic peripheral neuropathy and contributes to intrinsic muscle wasting of the feet and hands. Motor neuropathy affects the leg and intrinsic foot muscles and changes the biomechanics of the foot, directly contributing to increased shear and pres-sure under the ball of the foot, the most common site of neuropathic foot ulcers. Severe motor neuropathy contrib-utes to the development of the “intrinsic minus” foot, or the appearance of a high arch structure because of muscle wasting and weakness. Short, weak flexors and extensors that are overpowered by long, stronger flexors and extensors in the foot contribute to structural foot deformities such as hammer or claw toes, dislocated metatarsophalangeal joints, and ankle equinus (Fig. 116-2). Deformities like pes cavus and clawed toes can result in increased pressure at the tips of toes, dorsal aspect of the interphalangeal joints, plantar metatarsal heads, and heel. The increase in pressure during normal ambulation causes callus and ulceration. Neuropathic bone and joint disease (Charcot’s neuro-osteoarthropathy) often affects the midfoot or hindfoot, which can cause severe deformity and plantar ulceration.31

Autonomic Neuropathy

Autonomic neuropathy (sympathetic dysfunction) causes shunting of blood and loss of sweat and oil gland function. The result is dry skin that is prone to cracks and fissures. This is often first manifested as skin breakdown on the heel. The intrinsic “autosympathectomy” caused by autonomic neu-ropathy explains why surgical sympathectomy fails to improve skin blood flow or to benefit the ulcerated diabetic foot.

Sensory Neuropathy Testing

Even though testing criteria have been established and the tools and tests are inexpensive and noninvasive, neuropathy is often not evaluated. There are several methods to identify sensory neuropathy, including history, vibration perception testing, and pressure assessment. These simple noninvasive investigations have high sensitivity and specificity for the identification of persons with loss of protective sensation and can be performed by nurses or technicians in a few minutes. A simple history of neuropathic symptoms, such as numbness, tingling, burning, or the sensation of insects crawling on the feet (formication), can help identify patients at risk for foot ulcers.32

Patients sometimes mistake the symptoms of diabetic peripheral neuropathy for those of PAD. In addition to

of the tibialis posterior tendon; these areas may ultimately become sites of ulceration. In the presence of sensory neu-ropathy, a normally painful insult to soft tissues is not recog-nized until an ulcer develops and is detected by inspection or malodor. Ulcers on the dorsum or sides of the foot are usually due to ill-fitting shoes causing minor trauma. Because patients with diabetic neuropathy lack normal protective sensation, they may select shoes that are too small. Patients may sustain penetrating injuries such as lacerations and puncture wounds that are not recognized owing to the loss of protective sensation.

RISK ASSESSMENT

Screening Evaluation

The risk for DFU can be established by a structured screening evaluation. The essential elements of screening include history of foot ulcers, amputations, or lower extremity bypass surgery or angioplasty; inspection of all surfaces of the foot for ulcers or pre-ulcerative lesions; and evaluation for neu-ropathy, PAD, structural foot deformities, and mobility of the ankle and metatarsophalangeal joints. Screening to identify risk factors in the diabetic foot can be performed by a nurse or trained technician.12,14,17,19 All surfaces of the foot and ankle, including the spaces between all the toes, the soles, and the heels, must be inspected for fissuring, cracks, bullae, calluses, and ulcers. The shoes should also be inspected for sites of wear or pressure and palpated for foreign bodies and irregularities.

Diabetic Neuropathy

Neuropathy affects up to 50% of people with diabetes25,27 and consists of three components: sensory, motor, and auto-nomic.26,27 Neuropathy itself can also accelerate development of foot deformity,28,29 muscle dysfunction or atrophy, dynamic contracture, and paresis such as footdrop.30 The combined effect of this triad is a foot that cannot respond to pain and is biomechanically impaired, with increased foot pressures, limited joint mobility, and poorly hydrated skin that cannot appropriately respond to injury, predisposing the foot to ulceration. This complication, together with retinopathy, nephropathy, and diabetic arteriopathy, is due to the pro-longed effects of hyperglycemia.

Sensory Neuropathy

The damage from sensory neuropathy affects the large myelin-ated alpha fibers. Its distribution is usually symmetrical in a stocking pattern; as a result, patients are unable to perceive injury to their feet because the primary protective or warning systems are defective. This fundamental pathophysiologic impairment is referred to as loss of protective sensation. Affected patients sustain repetitive, unrecognized injuries to their feet that culminate in full-thickness ulcerations. An ulcer in an insensate foot is usually painless. However, neu-ropathy can have a wide range of severities and symptoms.


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Figure 116-2 Diabetic foot deformity due to motor neuropathy produces pressure points at specific bone prominences (A), which the patient often cannot feel because of sensory neuropathy and loss of protective sensation. Ulceration frequently develops at these sites of increased pressure or shear: hammer toes or claw toes (B), metatarsal head mal perforans ulcer (C), and midfoot collapse or Charcot’s foot (D).

A B C D

reporting numbness, tingling, burning, and formication, they may complain of cold feet despite strong peripheral pulses, an integument that is warm to touch, and no other signs of ischemia. Additional complaints may include a variety of sensations, such as a feeling of thick feet, the sensation that mud is caked on the bottom of the feet, or the feeling of walking in “cement shoes.”

Monofilament Testing

Semmes-Weinstein monofilament testing is one of the most common methods used in the United States to screen for sensory neuropathy.6,19,32 The 10-g monofilament measures pressure sensation and is inexpensive and easy to use. The test apparatus consists of a nylon monofilament attached to a handle; it is designed to provide 10 g of force when it is buckled perpendicular to the test surface of the skin. It is important to explain to the patient that this is not a needle, and a nurse or technician should demonstrate that the monofilament bends on the patient’s hand or arm (Fig. 116-3).

The monofilament is pushed perpendicular to the skin with enough pressure to bend the filament, forming a semi-circle on the patient’s hand; it is held for approximately 1 second and then removed. Approximately 10 sites on each foot are tested, and the patient is instructed to say yes every time he or she feels pressure or thinks he or she feels pressure. The test is performed with the patient’s eyes closed. Sites to be tested include the first, third, and fifth digits; first, third, and fifth metatarsal heads; base of the fifth metatarsal; heel; arch; and dorsum of the foot.32 Any site at which the patient does not accurately identify the presence of pressure is scored

as an abnormal response and is associated with neuropathy with loss of protective sensation.

Vibration Testing

Vibration perception testing, also an alpha myelinated fiber sensory modality, can be evaluated with a 128-Hz tuning fork or a vibration perception threshold testing device. The tuning fork is struck and placed on a bone prominence, such as the great toe or metatarsal head, and the patient is instructed to signify when the vibration stops. The examiner then makes a subjective judgment of whether the level of vibration per-ception is abnormal. The vibration perception threshold tester is designed to measure vibration sensation on a semi-quantitative scale from 0 to 100. The instrument consists of a handpiece with a testing probe on the end, motor, rheostat, and voltmeter. It is applied perpendicular to the distal tip of the erect hallux and is held gently so the weight of the probe is the only applied force (Fig. 116-4). The rheostat is slowly increased until the subject senses the vibration and informs the examiner. Before starting the test, the nurse or technician demonstrates the process on the patient’s hand. The level of perceived vibration is read in volts. Vibration sensation of less than 25 volts has been associated with an increased risk of foot ulceration.33

Peripheral Artery Disease

People with diabetes often have both vascular disease and neuropathy.34,35 PAD has been shown to be present in 20% to 58% of patients with diabetes.16,20,36-39 Therefore, assess-ment of the vascular supply is crucial.


Figure 116-3 A and B, Testing for sensory neuropathy with Semmes-Weinstein monofilament is performed in both feet in 3 to 10 sites, depending on the individual protocol.

A

B

Figure 116-4 Vibration testing tuning fork.

Anatomy of Peripheral Artery Disease in Patients with Diabetes

Previously, it was erroneously suggested that microangiopathy or small-vessel disease was the primary cause of DFUs. It is now understood that microvascular dysfunction contributes to poor ulcer healing in the neuroischemic diabetic foot36-38 but that macrovascular disease is an important and often treatable contributor.

Microangiopathy is an obstructive arteriolar process that in the past was thought to preclude successful revasculariza-tion in diabetic patients.39 Updated studies have now deter-mined that correction of infrapopliteal macrovascular disease often allows wounds to heal but also that microvascular dys-function is an important component of impaired perfusion in the diabetic foot.39,40 Microvascular dysfunction includes arteriovenous shunting, capillary leakage, precapillary sphinc-ter malfunction, venous pooling, hormonal activity in the vessel, and inflammation in the vessel wall. Impaired perfu-sion in the diabetic foot is thus complex, and atherosclerosis is not the only cause.39

In patients with diabetes, vascular disease is often localized to the femoropopliteal and tibial segments. The pattern of arterial involvement in diabetes differs from classic athero-sclerosis, being characterized by more distal distribution with long segmental occlusions and heavy calcification.33 Although medial calcinosis does not necessarily cause ischemia, it often interferes with indirect measurement of arterial blood pres-sure.41 In patients with diabetes, collateral formation of large arteries is impaired, causing tissue downstream to be more susceptible to ischemia.42

In many cases, the peroneal artery in the calf remains patent and is the last of the three crural arteries to occlude. It provides pedal circulation through its terminal branches, the anterior and posterior perforating arteries, to collaterals of the dorsal pedal and posterior tibial and plantar arteries. The primary pedal arch is frequently incomplete, but in most cases at least a segment of the plantar arch retains patency if not continuity with the anterior and posterior circulation. Consequently, bypass to a single tibial or pero-neal artery usually provides good blood flow to the foot. Infrequently, only a single infrapopliteal arterial segment remains patent, without direct communication to the pedal arteries. In this situation, bypass to the “isolated segment” is the only revascularization option but has a reasonable success rate.23-26 Reports that heel ulcers are slow to heal after bypass to the dorsal pedal artery27 and its collateral runoff suggest that the pedal circulation, somewhat analo-gous to the coronary circulation, is compartmentalized.23,28 If the ulcer is in the hindfoot, bypass to the posterior tibial–plantar artery axis is preferred. Forefoot and toe ulcers should preferentially receive dorsal pedal bypasses if pos-sible. Midfoot, plantar, and combined toe and heel ulcers can be treated with bifurcated grafts to both the dorsal pedal and posterior tibial branches if these arterial targets are available (Fig. 116-5).

It is usually agreed that revascularization is indicated to relieve symptoms of limb-threatening ischemia, including ischemic rest pain, ischemic ulcers, and gangrene. In addi-tion, the International Working Group on the Diabetic Foot


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Figure 116-5 If forefoot and hindfoot ulcerations occur in the absence of a patent primary pedal arch, healing may be enhanced by creating a bifurcated bypass to both the anterior and posterior tibial arteries when these are patent, as illustrated in this image. DPA, Dorsal pedal artery; PTA, posterior tibial artery.

Figure 116-6 Calcific iliofemoral arterial occlusions (arrows) are occurring more frequently and are often associated with “coral reef” exophytic plaques.

(IWGDF) recommends that if severe PAD impairs wound healing, revascularization (endovascular or bypass) should be considered for all ambulatory patients. Exceptions include patients who are severely frail and patients who have short life expectancy (<6-12 months), preexisting severe functional impairment, or a nonsalvageable limb.43

Peripheral Artery Disease Evaluation in the Diabetic Foot

Clinical symptoms are often not helpful in the diagnosis of ischemia in patients with diabetes. DFUs are less often fore-shadowed by claudication, a common symptom of PAD in atherosclerotic patients without diabetes. Only 25% of dia-betics with PAD report symptoms of intermittent claudica-tion. Either the patient has infrapopliteal arterial occlusions, which do not usually cause claudication, or the patient walks too little or too slowly to experience calf pain. Diabetic patients with ischemia also often lack typical symptoms of claudication or rest pain, probably because such symptoms are masked by underlying peripheral neuropathy.7,33,44,45

In the patient with diabetes, the aortoiliofemoral segment seldom develops occlusive lesions, so buttock and thigh symptoms are rare. The superficial femoral and popliteal arteries are more often affected in patients with diabetes than is the aortoiliac segment, so when claudication is present, it is usually experienced in the calf. Diabetic patients with foot ulcers and gangrene are often found to have a strong popliteal pulse and absent pedal pulses. This finding is due to a highly prevalent pattern of predominantly tibial artery occlusive

disease in diabetics; moreover, it portends a high likelihood that the patient is a suitable candidate for revascularization because the peroneal artery or the inframalleolar pedal arter-ies are usually spared. These general observations underscore the importance of the physical examination in the initial vascular assessment.

The increasing incidence of diabetic vascular disease has led to the emergence of new patterns of diabetic arteriopathy. These lesions include exophytic and “coral reef” plaques and stenoses involving the iliofemoral segment (Fig. 116-6). Arterial calcification, first noted by West46 to be a hallmark of diabetic arteriopathy in the tibial arteries, is now recog-nized as widespread throughout the arterial system. It fre-quently results in noncompressible arteries in major arterial segments.

The severity of ischemia in the lower limb has a strong predictive value in the outcome of infections,47 wound healing, and level of amputation healing. Optimal diagnostic modalities to accurately predict wound healing and to determine level of amputation are currently not available. Modalities studied to date include ankle-brachial index, segmental blood pressures, arteriography, skin blood flow, skin perfusion pressure, indocyanine green angiography, laser Doppler flowmetry, and transcutaneous oximetry.48,49 None of these tests, either singly or collectively, is completely accurate in the prediction of ulcer healing. Confounding


Table 116-1 Diabetic Foot Risk Classifications

Risk Group

Classification 0 1 2 3 4

International Working Group on the Diabetic Foot43

No neuropathyNo PAD

Peripheral neuropathyNo deformity or PAD

Peripheral neuropathy and deformity or PAD

History of ulcer or amputation

Modified International Working Group on the Diabetic Foot43

No neuropathyNo PAD

Peripheral neuropathyNo deformity or PAD

2A: Peripheral neuropathy and deformity

2B: PAD

3A: History of ulcer3B: History of

amputation

American Diabetes Association14,50

No neuropathyNo PAD

Neuropathy ± deformityNo PAD

PAD ± neuropathy History of ulcer or amputation

PAD, peripheral artery disease.

Table 116-2 Diabetic Foot Ulcer Classification: Wagner and University of Texas Systems

Wagner University of Texas

Grade Details (Depth/Penetration, Osteomyelitis, Gangrene/Necrosis) Grade Details (Depth/Penetration, Infection, Ischemia)

0 No open foot lesion 0 Presence of pre-ulcer or post-ulcer epithelialization

1 Presence of superficial ulcer, partial or full thickness 1 Superficial ulcer not penetrating tendon, bone, or joint

2 Ulcer extends to ligaments, tendon, joint capsule, or deep fascia without abscess or osteomyelitis

2 Ulcer penetrating through to tendon or capsule

3 Presence of deep ulcer with abscess, osteomyelitis, or joint sepsis 3 Ulcer penetrating to bone or joint

4 Gangrene localized to the forefoot or heel A Noninfected and nonischemic ulcer5 Extensive gangrene B Infection present

C Ischemia present

D Both infection and ischemia are present

factors such as comorbidities, wound severity, and infection may alter degree of perfusion that is required for healing to occur. A variety of cut points have been used for each of these tests in different study populations, often with different clinical endpoints, making the interpretation of data difficult.

Assessment of arterial perfusion is discussed in more detail elsewhere in this book. Initial evaluation should include inspection for clinical signs such as dependent rubor, pallor with elevation, atrophic integument, and absent hair growth, which are common manifestations of PAD. As people with diabetes and clinically significant PAD are often asymptomatic, guidelines recommend that diabetics have early noninvasive vascular evaluation to identify those who are at risk for poor healing and amputation.

Classification of Risk for Ulceration

Once screening evaluation has been performed for loss of protective sensation, PAD, foot deformity, and history of pre-vious complications, the patient can be placed into an appro-priate risk stratum. The classification most widely in use is the American Diabetes Association foot risk system, which involves elements of the IWGDF system as well as subsequent modifications (Table 116-1).14,50 Risk classification assists in the initial triage of the patient and suggests appropriate follow-up intervals, as described later.

DIABETIC FOOT ULCERS: ASSESSMENT, CLASSIFICATION, AND MANAGEMENT

Classification of Ulcer Severity

Once one has assessed the extremity for extent of tissue loss (depth), presence of and extent of ischemia, and foot infection, it is often useful to classify wounds to help direct therapy. There are multiple wound classification systems; the Wagner and University of Texas systems are most widely used (Table 116-2).

Meggitt-Wagner System

This system was initially described by Meggitt51 in 1976 and subsequently popularized by Wagner52 in 1981. It uses six wound grades that are mainly based on wound depth and takes into account the presence of osteomyelitis and gan-grene. The Wagner system is shown in Table 116-2. This system does not allow the classification of superficial wounds that are infected or wounds of different depths affected by PAD. The Meggitt-Wagner classification system also lacks a clinically relevant and objective measure of PAD.

University of Texas Health Science Center, San Antonio

Another widely used classification system is the University of Texas Health Science Center, San Antonio. This system assesses ulcer depth, presence of wound infection, and


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but no benefit was noted in healing at 12 weeks. Maggot (larval) débridement therapy is considered a biosurgical method.59 There are limited bench-top and cohort studies examining larval therapy as an adjunctive method to reduce the requirement for systemic antimicrobials as well as to improve quality of serial débridement.53,60-62

Dressings

Once an ulcer has been thoroughly débrided, granulation tissue is necessary before wound closure. This process, also called wound bed preparation, starts by achieving an appro-priate moisture balance in the wound. The principle of keeping wounds moist without maceration has been demon-strated to accelerate epithelialization.63 On the basis of current research, there is little evidence to support the prefer-ence for the use of any one specific dressing or wound applica-tion to promote healing of chronic foot ulcers.

Negative Pressure Wound Therapy

Few advances in wound healing have had as significant an impact as negative pressure wound therapy. This technology uses a piece of foam in contact with the wound bed, covered by an occlusive dressing and placed under subatmospheric pressure. The system produces granular tissue that has a char-acteristic rough appearance. The device can decrease the depth and area of large diabetic foot wounds into a shallow, smaller wound.64 A multicenter randomized controlled trial compared negative pressure wound therapy with advanced moist wound therapy for the treatment of DFUs. The study found reduced time to 90% granulation, wound closure, and amputation with increased incidence of healing by 16 weeks56 (Fig. 116-7).

presence of lower extremity ischemia. The University of Texas system is based on grades of the wound depth (horizon-tal axis) and stage of wounds determined by infection and ischemia (vertical axis). The four grades and stages are dem-onstrated in Table 116-2. Patients with wounds that pene-trate to bone with infection and PAD (grade 3D) were 90 times more likely to require amputation than were those with superficial wounds without infection or PAD.53 The rationale for including depth is based on the observation that wounds involving deep structures, such as tendons or joint capsules, are more likely to develop cellulitis, abscess, and osteomyeli-tis. The rationale for including infection and PAD is that these are two of the factors that most often lead to amputa-tion, poor wound healing, and hospitalization. A comparative study of DFUs by the Wagner and University of Texas clas-sification systems showed a slightly greater association with increased risk of amputation and prediction of ulcer healing with the University of Texas system, which can be used to predict clinical outcome.54,55

Management of Chronic Diabetic Foot Ulcers

The approach to ulcer healing, particularly in the face of a broad list of techniques and technologies, should be system-atic. Key elements involve débridement, pressure offloading (whether external by devices or internal by surgery), and wound simplification or closure.

Débridement

Débridement removes devitalized tissue, bioburden, and senescent cells and promotes healing through bleeding. By débridement, a chronic ulcer becomes more of an acute state.56 All necrotic and nonviable tissue should be removed, and there should not be concern about the residual defect caused by the débridement as removal of this tissue is impor-tant to attain closure. Most wounds require serial débride-ment. DFUs that are débrided at each visit have a significantly greater chance of healing in 12 weeks than with débridement less often.57

Several methods of wound débridement exist: mechanical, autolytic, enzymatic, surgical, and biosurgical. Mechanical débridement consists of applying wet gauze dressings, allow-ing them to dry, and then removing the dry gauze, thereby removing the surface layer (wet-to-dry dressing). This approach has fallen out of favor as a primary method. Auto-lytic débridement is completed by covering the wound with an occlusive dressing and allowing the ulcer’s proteolytic enzymes to lyse the fibrotic or necrotic tissue. This procedure is not often recommended as there is risk of infection, and more effective methods are available. Enzymatic débridement uses a topical vehicle to remove devitalized tissue. Weak research evidence supports the use of hydrogel. Surgical débridement is the most common and effective method.57 It can be performed with a scalpel, curet, or modalities such as a hydroscalpel or ultrasound with adjustable irrigation systems.58 Hydrotherapy using the Versajet system (Smith & Nephew, Largo, Fla) resulted in shorter débridement time,

Figure 116-7 Diabetic foot ulcers should be treated in an orderly fashion according to this pie algorithm. Each piece of the pie should be considered, beginning with infection management. Offloading is important throughout the life cycle of the wound and encircles the algorithm.

Infectionmanagement

Vascular diagnosisand management

Debridement

Offloading

1

2

3

4

5

Promotegranulation

Woundclosure


Figure 116-8 Toe filet flap of the hallux is lifted from the underlying bone. The incision is made laterally, and the soft tissue is lifted full thickness from the periosteum to ensure that the digital arteries are captured in the flap.

Platelet and Stem Cell Application

Recent research, including randomized controlled trials, has demonstrated 8- to 12-week full healing of DFUs of 79% to 100% in comparison with control groups ranging from 46% to 62%.65-67 Whereas these data appear promising, much more work is required to confirm or to refute these findings.

Bioengineered Skin and Skin Grafts

After a vascularized wound bed is prepared, wound closure should be performed as rapidly as possible to avoid complica-tions. The IWGDF previously reported improved healing associated with dermal fibroblast culture and fibroblast/keratinocyte co-culture for shallow wounds. Successful healing of DFUs has been seen in up to 51.5% of treated subjects versus 26.3% of standard therapy groups.68 Other types of bioengineered skin have been studied and have shown a higher healing rate and reduction of amputation rate compared with control.60,136

Split-thickness skin grafting is a viable, minimally inva-sive, and cost-effective method to cover large defects where granulation tissue predominates.58 These grafts perform best on non–weight-bearing surfaces of the foot, including the dorsal, medial, lateral, and arch areas. Although meshed grafting can reduce the rate of seroma and hematoma forma-tion, some have shown that unmeshed grafts perform equally well.62 A retrospective case series reported on the adherence and survival of meshed split-thickness skin grafts with the use of negative pressure wound therapy as a bolster dressing, which reduces seroma and hematoma formation of chronic leg ulcers. The results showed a 93% healing rate of grafts compared with a 67% healing rate in the control group without postoperative negative pressure wound therapy.69 As split-thickness grafts are less suitable for weight-bearing sur-faces, some have recommended donor glabrous skin grafts in these locations.70 In a recent review, the authors concluded that split-thickness skin grafts can be used successfully for primary closure of DFUs, despite noting that there is limited research on split-thickness skin grafting.63

In larger soft tissue defects and wounds with exposed deep structures such as bone, more aggressive measures to obtain closure are required. Multiple types of soft tissue flaps can be used to manage these defects. The flaps should be based on current vascular flow and not assumed anatomic flow because patients with diabetes may have segmental or regional arterial occlusions. With fasciocutaneous flaps, the fascia and super-ficial tissue are rotated into place to cover a defect. One of the more common fasciocutaneous flaps performed in the diabetic foot is a medial plantar artery flap, which can be rotated laterally to cover a subcuboid ulcer or proximally to cover a plantar calcaneal defect. Toe filet flaps can be used to cover submetatarsal head ulcers but require sacrifice of a digit64,71 (Fig. 116-8). Muscle flaps are used to cover exposed bone, such as the extensor digitorum brevis flap and the abductor hallucis or abductor digiti minimi flap. The exposed muscle can be covered with a split-thickness skin graft. Free flaps involve the autotransplantation of a vascularized

myocutaneous area to the recipient site and microvascular reanastomosis.72

Nonsurgical Pressure Offloading

Effective pressure reduction is the cornerstone of DFU treat-ment. Repetitive trauma and pressure on the wound bed are two of the primary reasons for ulcer persistence.73 The accepted “gold standard” treatment of neuropathic diabetic plantar ulcer is the total contact cast. Consistently good outcomes have been demonstrated in many studies.74 However, the device is not widely used because of several concerns, the most common of which is difficulty in applica-tion and removal.75 Healing success ranges from 83% to 91% when total contact casting is used.76-78 Compared with remov-able devices such as cast walkers and half shoes, the total contact cast seems to heal a higher proportion of wounds than the other two modalities do.79

Because increased time and potential cost of weekly cast changes along with a high learning curve may limit the clini-cal utility of the total contact cast, another option, the instant total contact cast, has been developed. With this method, a removable cast walker is rendered irremovable with the application of a cohesive bandage or cast tape (Fig. 116-9). The instant total contact cast has been shown to have healing rates and total healing similar to those of the total contact cast.78,80-82

In clinical practice, total contact casts and instant total contact casts are better at healing ulcers than removable devices are. This can be explained by the nature of removable devices, for which patient compliance is a factor. One study evaluated the compliance of patients by hiding pedometers inside removable cast walkers and also gave patients pedom-eters to wear on their hips.80 Subjects were instructed to use the removable cast walkers at all times while ambulating. The investigators found a significant discordance between the hip and removable cast walker pedometers, indicating that the patients were not compliant with instructions to wear their


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offloading devices at all times and suggesting that improved outcomes would be achieved with a nonremovable device.

Surgical Pressure Offloading

When offloading cannot be accomplished with standard or custom footwear, surgical offloading must be considered. This can be performed with ulcer resection, exostectomy, arthro-plasty, reconstruction, or Achilles tendon lengthening. These procedures can be elective, prophylactic, or curative,

Figure 116-9 The instant total contact cast is a removable cast walker rendered irremovable by a cohesive bandage or fiberglass.

Figure 116-10 Triple hemisection approach to Achilles tendon lengthening. The linear markings connote the outline of the left Achil-les tendon medially and laterally. Two transverse stab incisions are made medially and one is made laterally, all 1 cm apart, transecting slightly more than 50% of the tendon substance. The foot is then forc-ibly dorsiflexed to create a sliding effect of the tendon.

Figure 116-11 A, Preoperative view of limited mobility of the hallux (hallux limitus) with a distal hallux ulcer. B, Intraoperative view illustrating an improvement in dorsiflexion after resection of the base of the proximal phalanx. C, Hallux ulcer healed within 3 weeks of surgery.

A B C

depending on whether there is absence or presence of neu-ropathy or open wounds.83

Tendon Lengthening and Transfer. Several techniques are described in the literature to lengthen the Achilles tendon. The standard Achilles tendon lengthening is accomplished through three stab incisions, posing minimal surgical risk (Fig. 116-10). Although this “lengthening” might be consid-ered more of a “weakening” of the posterior muscle group, it results in muscle tendon balancing and reduces forefoot pres-sures.84-86 This pressure reduction can lead to ulcer healing and prevent recurrence (Fig. 116-11). In a foot that demon-strates both equinus and varus, in which the foot is inverted and pressure is placed on the plantar or lateral fifth metatarsal area, an additional tendon procedure might be of benefit. The


head resection is indicated, which can significantly reduce plantar forefoot pressures (Fig. 116-12). Multiple metatarsal head resection or panmetatarsal head resection may also be considered for nonhealing ulcers in the presence of abnormal parabola.94 Development and maintenance of a normal meta-tarsal parabola are important to avoid transfer lesions. The first to fifth metatarsal heads are removed through multiple dorsal longitudinal incisions or through one plantar trans-verse incision in the sulcus, distal to the metatarsal heads. Some surgeons prefer to perform a fusion of the first metatar-sophalangeal joint instead of resecting it. A case-control study of 92 subjects with multiple forefoot ulcers suggested that those in the panmetatarsal head resection group healed faster and had fewer recurrent ulcers at 1 year than did sub-jects in the nonsurgical group.95

tibialis anterior tendon transfer can be performed through three anterior incisions. The tendon is transected from its normal insertion on the medial cuneiform and transposed laterally into the lateral cuneiform or cuboid; it is usually secured with a bone anchor. This eliminates the forces that pull up on the medial midfoot, transferring pressure laterally. The new function of the tibialis anterior is a more central dorsiflexion action.43

Digital Surgery. Hammer toe deformities are common and can cause repetitive trauma at the distal tip of the toe or dorsal interphalangeal joint, which is difficult to offload with footwear.87 Ulceration or recurrence secondary to digital deformity is common.88 Percutaneous flexor digitorum longus tenotomy has been used to repair flexible deformities of the digits, whereas rigid deformity can be treated by osseous pro-cedures. Successful outcomes have been noted from both types of procedures.

One retrospective study showed 98% ulcer healing in 48 diabetic patients who had 58 tenotomies of the flexor digito-rum longus tendon, with a 12% recurrence at the same site in the mean time of 14 months.89 Similarly, another retro-spective study evaluated 28 percutaneous flexor tenotomies in 18 patients (11 lesser toes), all of which healed without recurrence. No infections, toe amputations, or other compli-cations were reported.90 On the basis of these findings, flexor tenotomies are effective in healing digital ulcers.

Modified resectional toe arthroplasty has resulted in a mean wound healing time of 26 days.91 Another case-control series compared morbidity and outcomes of elective single proximal interphalageal joint toe arthroplasties among 31 people with diabetes and 33 nondiabetics with isolated toe deformities with a mean follow-up of 3 years. Patients with history of ulceration remained 96% ulcer free at a mean of 3 years postoperatively.92

Metatarsal Head Resection. Plantar metatarsal head ulcer-ation is common and challenging to treat. Various procedures have been described, including metatarsal head osteotomy and resection.30,93 Isolated, specific metatarsal head osteotomy should be considered for a chronic, non-undermining, and non-tunneling ulceration. Metatarsal head resection should be considered when the ulcer penetrates to bone. The ulcer should be débrided and the metatarsal head can be resected to internally offload the ulcer. If there is evidence of equinus, an Achilles tendon lengthening procedure can be performed in conjunction with the metatarsal procedure.

A case-control study reviewed fifth metatarsal head resec-tions for uninfected, nonischemic ulcers compared with con-servative therapy. The charts were reviewed for 40 subjects, of whom 22 had metatarsal head resections and 18 nonsurgi-cal care. The mean time for healing was 5.8 versus 8.7 weeks in the resection and control groups, respectively. Ulcer recur-rence was significantly increased in the conservative group at 27.8% versus 4.5% in the surgical group.71

On occasion, when there are multiple foci of pressure or ulcerations under plantar metatarsal heads, a panmetatarsal

Figure 116-12 Clinical photograph (A) and peak plantar pressures (B, acquired with a pressure-sensitive mat) of a foot with ulcers under metatarsal heads 1 and 5. After panmetatarsal head resection, the ulcers have healed (C), and the peak plantar pressures have been reduced (D; red color connotes the zones of highest pressure, and the magnitude of this pressure is depicted by the height of the peaks).

A

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B


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Hallux ulceration is often secondary to limited range of motion at the first metatarsophalangeal joint (hallux limitus). Conservative therapy with an offloading device can be used, although it does not address the underlying cause. Should conservative therapy fail or the ulcer recur, surgical offloading with correction of the underlying deformity can be consid-ered. Outcome studies support the safety and efficacy of a first metatarsophalangeal joint arthroplasty to heal first metatarsal ulcers without significantly increased risk of infection or amputation.96

If the ulcer is more proximal at the first metatarsopha-langeal joint with underlying osteomyelitis, resection of the first metatarsophalangeal joint can be considered. The incision is placed dorsally to avoid the ulcer, or the inci-sion can incorporate and excise the ulcer. The incision is made directly to bone without undermining of the soft tissue. The metatarsal head is cut and beveled plantarly to reduce bone prominence. Resection of the base of the proximal phalanx can also be performed. The sesamoids should be removed to reduce possible prominence and source of infection, especially if the ulcer communicates with the joint.30

In the presence of open lesions, single-stage versus multiple-stage surgery is determined on a case-by-case basis. One retrospective study reported single-stage surgery for noninfected DFUs in 62 patients who underwent 67 pro-cedures with total ulcer excision, osseous reconstruction, and random local flap reconstruction; 97% of the wounds healed, with an ulcer recurrence rate of 10% during a follow-up of 6 years. All but one patient returned to previ-ous level of ambulation.97

Digital and Midfoot Amputations. Often, with a complex deformity or the presence of bone or soft tissue infection, a partial foot amputation may be a better alternative than either difficult foot reconstruction or high-level amputation.

Digital Amputation. Foot-sparing amputations include isolated toe, toe-metatarsal (partial ray), transmetatarsal, Lisfranc’s, and Chopart’s. The goal is to select an amputation level with adequate perfusion and soft tissue coverage to provide a durable and usable extremity. An amputation that requires no prosthesis is the optimal goal. Osteomyelitis, focal gangrene, or extensive soft tissue infection often necessitates amputation of a single toe. A common approach is to place two converging, elliptical incisions (“fish mouth”) over the base of the toe, with a linear incision extending over the metatarsophalangeal joint or the proximal interphalangeal joint on the dorsum of the foot, depending on the amount of viable tissue. The joint is disarticulated, and the toe is removed. If necessary, the head of the metatarsal can be resected to allow subsequent soft tissue closure.

Midfoot Amputation. When there is extensive soft tissue infection of the forefoot or when multiple toes are not viable, a transmetatarsal amputation can prove durable and highly functional. The plantar incision is made at the toe sulcus and extended medially and laterally just proximal to the first and fifth metatarsal heads. The dorsal incision is

then placed over the metatarsal necks, and the metatarsals are resected at this level following the normal metatarsal parabola. The first metatarsal should be resected shorter than the second. The third, fourth, and fifth metatarsals should be cut sequentially shorter than the adjacent meta-tarsal bone. A good-quality plantar fat pad is essential for a durable residual limb. If there is extensive soft tissue infec-tion or a thin, atrophied fat pad under the resected metatarsal bones, the risk of reulceration is high. Importantly, if there is ankle equinus, a percutaneous lengthening of the Achilles tendon can reduce forefoot pressures and reduce the risk of reinjury. Whenever possible, primary closure of a clean amputation is preferred because it provides the best chance of healing. Principles remain the same for more proximal foot amputation (Lisfranc’s, Chopart’s, Pirogoff’s, or Syme’s). However, the requirement for tendon balancing and more complex offfloading strategies becomes greater with these amputations.

Assessment and Classification of Infected Diabetic Foot Ulcers

More than 50% of diabetic ulcers will become infected, and diabetic foot infection is one of the most common related causes of hospitalization in the United States.98,99 Diabetic foot infection accounts for 20% of all hospital admissions and 40% of readmissions in patients with diabetes, and nearly one in six patients dies within 1 year of the infection.98,100 The risk ratio for death due to infection in people with diabetes versus without is 1.92.101 According to data from the Centers for Disease Control and Prevention, the annual number of hospitalizations for diabetic foot “ulcer/infection/inflamma-tion” has steadily risen from 1980 to 2003, exceeding 111,000 and surpassing PAD.13

Empirical antibiotics for clinically infected wounds should be based on available clinical and epidemiologic data. Defini-tive therapy should be based on cultures of infected tissue.13 Diabetic foot infections should be evaluated for underlying osteomyelitis, ischemia, venous insufficiency, presence of neuropathy, and biomechanical abnormalities.13 Predisposing factors for the development of diabetic foot infection are neuropathy, vasculopathy, and immunopathy. In a case-control study, PAD was independently associated with a 5.5-fold increased risk for diabetic foot infection,88 and patients with limb ischemia and osteomyelitis had more frequent amputations.102 This may be attributed to inadequate anti-bacterial concentration in deep foot tissue,103 which can lead to selection of resistant strains. Poor tissue penetration may also be due to microvascular disease.104

Risk factors for diabetic foot infection include wounds that are neuropathic; wounds that penetrate bone; wounds that are present for more than 30 days, recurrent, or due to trauma; and wounds that have concomitant PAD or history of ampu-tation. Socioeconomics, demographics, and other patient characteristics such as elevated body mass index and duration of diabetes are not significantly associated with diabetic foot infections.13,105


Radiographic imaging is often needed to confirm the diag-nosis, and working with a multidisciplinary team will improve outcomes.13

Patient Evaluation

Diabetic foot infections involving soft tissue and bone are often challenging and difficult to diagnose. Consensus docu-ments by the Infectious Diseases Society of America (IDSA) and the IWGDF have been published to help direct the assessment, classification, and treatment of infection.13,106

Clinical Evaluation

The clinical signs and symptoms of infection may be dimin-ished in persons with diabetes by sensory neuropathy, lack of pain, vascular disease, and impaired cellular immunity. The diagnosis of diabetic foot infection is based on clinical suspi-cion with a comprehensive history and physical examination that is confirmed by laboratory, microbiology, and other diag-nostic examinations. The IDSA guidelines state that infec-tion is present if there are two or more signs of inflammation including erythema, pain, tenderness, warmth, induration, and purulent secretion. Infection can be manifested by local or systemic symptoms. Systemic signs include fever, chills, nausea, anorexia, night sweats, vomiting, and change in mental status and glycemic control.55 Other objective signs, such as fever, hypotension, tachycardia, and tachypnea, are often noted in severe infection. However, sepsis may not be manifested in patients with diabetes who have an impaired neuroinflammatory response (Table 116-3); they are often afebrile, with only minimal or mild local signs of redness and swelling. There may be a subtle history of malaise or influenza-like symptoms. In diabetic patients admitted for osteomyeli-tis, one study noted that 82% were afebrile.107 Therefore, the absence of these findings should not exclude the possibility of serious infection. The only systemic evidence of a serious infection is often worsening glycemic control.107,108

Laboratory Studies

Laboratory tests that screen for systemic infection include a left-shifted leukocyte differential and elevated inflamma-tory markers (e.g., erythrocyte sedimentation rate and C-reactive protein). These values are important to establish a baseline and to assess the treatment response. In one report, a threshold C-reactive protein value of 32.1 mg/dL had a sensitivity of 29% and specificity of 100% for the diagnosis of diabetic foot infection. Corresponding values for an erythrocyte sedimentation rate of 40.5 mm/h were 77% and 77%, respectively.109 Elevated C-reactive protein level after 1 week of treatment for diabetic foot infection was an independent factor that predicted the need for lower extremity amputation.102

Another important laboratory marker in the treatment of diabetic foot infection is serum albumin. Higher morbidity and mortality were associated with protein-calorie malnutri-tion with serum albumin level below 3.5 g/dL and total lymphocyte count below 1500 mm2 in patients undergoing Syme’s amputations.110

Table 116-3 Infectious Diseases Society of America and International Working Group on the Diabetic Foot Classifications of Diabetic Foot Infection

Clinical Manifestation of InfectionPEDIS Grade

IDSA Infection Severity

No symptoms or signs of infectionInfection present, as defined by at least 2

of the following: Local swelling or induration Erythema Local tenderness or pain Local warmth Purulent discharge (thick, opaque to

white or sanguineous secretion)

1 Uninfected

Local infection involving only the skin and the subcutaneous tissue (without involvement of deeper tissues and without systemic signs as described below)

If erythema is present, it must be >0.5 cm to ≤2 cm around the ulcer

Exclude other causes of an inflammatory response of the skin (e.g., trauma, gout, acute Charcot’s neuro-osteoarthropathy, fracture, thrombosis, venous stasis)

2 Mild

Local infection (as described above) with erythema >2 cm or involving structures deeper than skin and subcutaneous tissues (e.g., abscess, osteomyelitis, septic arthritis, fasciitis), and

No systemic inflammatory response signs (as described below)

3 Moderate

Local infection (as described above) with the signs of systemic inflammatory response syndrome, as manifested by ≥2 of the following:

Temperature >38° C or <36° C Heart rate >90 beats/min Respiratory rate >20 breaths/min or

PaCO2 <32 mm Hg White blood cell count >12,000 or

<4000 cells/µL or ≥10% immature (band) forms

4 Severe*

IDSA, Infectious Diseases Society of America; PEDIS, perfusion, extent/size, depth/tissue loss, infection, and sensation.

*Ischemia may increase the severity of any infection, and the presence of critical ischemia often makes the infection severe. Systemic infection may sometimes be manifested with other clinical findings, such as hypotension, confusion, vomiting, and evidence of metabolic disturbances, such as acidosis, severe hyperglycemia, and new-onset azotemia.

Imaging Studies

Plain radiographs should be obtained to evaluate soft tissue and osseous structures in acute diabetic foot infection. Soft tissue emphysema represents severe infection and is consid-ered a surgical emergency. Radiographic changes may lag several weeks behind the clinical course. In the setting of acute osteomyelitis, typical findings include soft tissue swell-ing, periosteal reaction, and irregularity of the bone cortex after 30% to 50% loss of bone mineralization.111 Plain films


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Bacteriology

The organisms most frequently isolated from mild to moder-ate diabetic foot infections are gram-positive cocci, mainly Staphylococcus aureus, Staphylococcus epidermidis, and Strepto-coccus species. In a prospective observational study of diabetic patients admitted to 38 hospital centers in France, the micro-organisms most frequently isolated from infected foot ulcers were gram-positive cocci, particularly S. aureus.119 Anaerobes isolated from diabetic foot infection include Peptostreptococ-cus magnus and Bacteroides fragilis.120 In limb-threatening infections, isolates identified have included S. aureus, group B streptococci, enterococcus, and facultative gram-negative bacilli. Obligate anaerobes may be present in necrotic or gangrenous infections.116 Most puncture-related infections in persons with diabetes are due to Staphylococcus and Streptococ-cus species.54

Infection Classification

Classification systems developed by the IDSA and IWGDF that are now widely accepted include four progressive levels of infection based on severity of clinical findings. The two systems only slightly differ in the infection section (Table 116-3). The infected wounds are further divided into mild, moderate, or severe on the basis of size and depth of the infection and presence of systemic manifestations of infection or metabolic instability.121,122

The IDSA classification was later validated in an observa-tional study of patients with diabetic foot infection. There was a trend toward an increased risk for amputation, higher level amputation, and more frequent lower extremity–related hospitalizations with increasing infection severity based on the IDSA classification.122 Both the IDSA and the IWGDF systems provide some quantitative gradation for severity. The advantages of these classifications are clear definitions and relatively few categories, making them more user-friendly.13

Management of Acute Diabetic Foot Infections

Antimicrobial Therapy

On the basis of reviews of recently published clinical out-comes, the IDSA made the following recommendations for diabetic foot infection. Clinically uninfected wounds should not be treated with antibiotic therapy. Infected wounds should be treated with both antibiotics and appropriate wound care. Antibiotic choice should be based on severity of the infection and likely organisms. In patients who present with mild to moderate infection with no history of recent antibiotics, therapy should target gram-positive cocci. In cases with severe infection, broad-spectrum empirical antibi-otic therapy is recommended until culture and susceptibility data are available. Patients with severe infection and those with a history of methicillin-resistant S. aureus (MRSA) infection or in areas of local prevalence of MRSA should be treated empirically with therapy directed against MRSA. It is not usually necessary to empirically treat for Pseudomonas aeruginosa, except in patients with risk factors or proven

to diagnose osteomyelitis are 50% to 92% specific and 28% to 93% sensitive.112

The IDSA recommends that all patients with new diabetic foot infections have plain radiographs completed to evaluate for bone abnormalities, soft tissue gas, and foreign bodies. If further imaging is required to evaluate for tissue abscess or to support the diagnosis of osteomyelitis in equivocal cases, magnetic resonance imaging (MRI) can be used. MRI is the most specific and sensitive noninvasive test to evaluate osteo-myelitis, abscess, or sinus track formation at 75% to 100% sensitivity and 75% to 89% specificity.113

If MRI is unavailable or contraindicated, radionuclide bone scan and labeled white blood cell scans are reason-able alternatives. Indium In 111–labeled white blood cell, technetium Tc 99m HMPAO, and sulfur colloid marrow scans may help distinguish acute and chronic infection. By specifying bone marrow reactivation and neutrophil production, radionuclide scans may help distinguish between osteomyelitis and Charcot’s neuroarthropathy.55,114,115 Radio-nuclide tests have a sensitivity of 45% to 100% and a specificity of 0% to 100%. The reliability of both radio-graphs and bone scans is diminished in the presence of arterial disease or Charcot’s arthropathy and after recent surgery or trauma.24,49

Culture of Ulcer

DFUs are colonized with bacteria that may predispose immu-nocompromised patients to development of infection. The type and variety of bacterial pathogens in diabetic foot infection depend on host immunity, mechanism of injury, wound depth, and severity of infection. If possible, culture specimens of infected ulcers should be obtained and sent before empirical therapy is started. Noninfected ulcers should not be cultured, and superficial swabs are not reliable and can produce false-positive results.47,55,116 Community-acquired mild to moderate infections usually respond to empirical therapy, so cultures are not required. Deep tissue aerobic and anaerobic cultures are required in several scenarios: if the infection is not responding to empirical therapy; if the wound is deep; or if there is extensive tissue necrosis, a fetid odor, or crepitus. Ideally, tissue specimens for culture are obtained from the débrided base of the wound. Super-ficial swabs are less likely to grow anaerobes and fastidious aerobes. A systematic review comparing superficial wound cultures with deep cultures found poor overall sensitivity (49%) and specificity (62%) for superficial wound swabs.103 The use of polymerase chain reaction analysis to detect the presence of organisms in diabetic foot infections has been proposed to facilitate earlier diagnosis and implementation of targeted treatment.117,118

Deep tissue culture remains the standard approach for accurate identification of pathogens. Tissue sampling of the wound base can be achieved by several methods, such as dermal curettage or scalpel, and samples should be obtained after the wound has been cleansed and débrided. Specimens should be sent promptly in appropriate transport medium for both aerobic and anaerobic culture.


functional extremity. Initial incision and drainage should decompress the infection and facilitate drainage from all affected anatomic spaces. Wounds are left open, and drains may be placed. A second débridement in the operating room is often scheduled within 48 to 72 hours to remove remaining nonviable tissue. When there is extensive soft tissue damage and all or a major portion of the foot is nonviable, amputa-tion at the most functional level should be considered. In patients with a truly unsalvageable foot due to extensive gas or invasive infection with extensive pedal tissue necrosis, a two-stage approach—initial rapid ankle guillotine amputa-tion, followed by below-knee amputation and closure after the elimination of sepsis (generally 5 to 7 days)—is prudent.

Diabetic foot infection tends to follow the path of least resistance. It can travel up the foot along tendon sheaths and tissue planes and may not be clinically obvious by external inspection alone. Detailed knowledge of potential pathways of extension is therefore important for the surgeon who explores a diabetic foot infection. The evaluation of foot ulcers and infections should include insertion of a sterile probe to identify tunneling and tracks that penetrate to tendon sheaths or extend along fascial planes in the foot. Plantar space infections often have erythema extending from the ulcer toward the medial arch, with tenderness on palpa-tion of the arch or along the flexor tendons. However, in patients with severe neuropathy, even deep infection may be asymptomatic, and the patient’s poor inflammatory response may mask the clinical signs of infection. Deep plantar space infections are more likely to have a mixed bacterial flora that includes anaerobes and are thus more likely to have a fetid smell. In some cases, soft tissue emphysema can be appreci-ated with plain film radiographs.

Exploration and débridement of infection may require a step-by-step exploration of the plantar compartments of the foot, with a layered approach to dissection. The incision for plantar space infections begins at the ulcer site and extends along the course of the long flexor tendons in the direction of the porta pedis at the medial arch and proximally along the tarsal tunnel if necessary. Each fascial plane or muscle layer should be adequately evaluated and explored if abscess or necrotic tissue is identified.

Fascial Compartments. The first fascial layer in the foot involves the space from the skin to the plantar fascia. The plantar fascia attaches to the tuberosity on the plantar aspect of the calcaneus and extends distally to the toes. The second layer also originates from the calcaneal tuberosity and con-sists of three intrinsic foot muscles: abductor hallucis, flexor digitorum brevis, and abductor digiti minimi brevis. These muscles are just deep to the plantar fascia. The flexor digito-rum brevis muscle has tendons to the lateral four toes. The abductor digiti minimi brevis inserts into the lateral side of the base of the proximal phalanx of the fifth toe, and the abductor hallucis inserts into the medial side of the proximal phalanx of the great toe. The third fascial space contains the flexor hallucis longus, flexor digitorum longus, quadratus plantae, and lumbricals. The flexor hallucis longus originates

infection with this organism. MRSA and resistant P. aerugi-nosa have become an increasing problem in diabetic foot infections, so these infections require specifically targeted antibiotic therapy.13,123-127 Studies indicate that the preva-lence of MRSA in patients with an infected DFU is 15% to 30%.127 New strains of MRSA resistant to vancomycin (vancomycin-resistant S. aureus) and multidrug-resistant organisms including S. aureus and Enterobacteriaceae have been isolated from diabetic foot infections, which makes it important for clinicians to strategize preventive measures.127

The IDSA recommends that route of therapy be based on severity of infection. Most moderate and all severe infections should be treated with parenteral antibiotics. Once patients become systemically stable and culture results are available, the route can be switched to highly bioavailable oral antibiot-ics. Oral agents can be used for mild and some selected mod-erate infections. In very selected superficial mild infections, topical therapy may be appropriate. Antibiotics should be continued until the infection resolves, but it is not necessary to continue therapy until completion of wound healing. Duration of antibiotic therapy is usually 1 to 2 weeks for mild soft tissue infections and 2 to 3 weeks for moderate to severe infections.13

Comparison of Antibiotic Regimens

Skin and Soft Tissue Infection. The IWGDF reported that no study demonstrated a significant benefit of any specific anti-biotic agent, route of administration, or duration of treat-ment. These findings are similar to the IDSA’s conclusion. Clinical cure rate ranged from 48%128 to 90%86 in infections without osteomyelitis.

Osteomyelitis. The IWGDF concluded that no study demon-strated a significant advantage of any specific antibiotic agent or route of administration in diabetic foot osteomyelitis. Prior studies demonstrated lack of superiority of any particular route of delivery or duration of systemic antibiotic for soft tissue infection or osteomyelitis. Further, well-designed pro-spective studies with comparative trials are recommended.106

Surgical Treatment

Current recommendations suggest early surgical intervention for deep foot infection with and without osteomyelitis. Data from two studies suggest that early minor surgeries reduce major amputation, with significant reductions in major ampu-tations from 8% to 27.6% to 0% to 13.0%.129,130 Urgent surgi-cal intervention is recommended in the presence of gas in the deeper tissue, abscess, or necrotizing fasciitis.

Débridement and Drainage. When there is abscess or necrotic tissue, removal of the nidus of infection is impera-tive. The choice between aggressive surgical débridement with limited digit or ray amputation (and the prospect of limb salvage) and preemptive above-ankle (guillotine) amputa-tion hinges on the ability to remove nonviable tissue and to eliminate limb-threatening infection. These options should be weighed in the context of a long-term strategy to retain a


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are clinically stable with acceptable glycemic control and urgent surgical procedures have been completed, discharge plans can be considered. On discharge, appropriate anti-biotic, offloading, and wound care instructions should be provided.13

MANAGEMENT OF OSTEOMYELITIS

Osteomyelitis should be considered for any infected, deep, or large foot ulcer. The diagnosis of osteomyelitis is challenging; clinical assessment alone often provides insufficient evidence. The ulcer should be inspected thoroughly, and a probe-to-bone test should be performed in any diabetic foot infection. If bone is visible or palpable in the base of the ulcer, osteo-myelitis should be considered.

Diagnosis

The probe-to-bone test has been widely adopted for diagnosis of bone infections in the foot.45 Palpation with a sterile metallic probe can increase the accuracy of diagnosis of osteo-myelitis. The technique is simple and inexpensive. However, the positive and negative predictive values and sensitivity and specificity of this test are controversial and are dependent on the clinical setting. A landmark study used this technique in a group of patients admitted to the hospital for limb-threatening infections.131 As might be expected, there was a high prevalence of bone infection (66%) proven by bone biopsy, surgical exploration, or radiologic studies. The authors reported a very high positive predictive value (89%) and low negative predictive value (56%), with a sensitivity of 66% and a specificity of 85% if the bone was palpable with a sterile probe. Reported data from two outpatient studies demon-strated a much lower prevalence of osteomyelitis (20%),115,132 with a positive predictive value of 57% and 53% and negative predictive value of 97% and 85%. This indicates that a posi-tive probe-to-bone test result improves the pretest probability only slightly, but a negative test result most likely rules out a bone infection.

Confirmation or exclusion of osteomyelitis with plain radi-ography has a low sensitivity and specificity, but serial plain radiographs can be used to diagnose or to monitor suspected osteomyelitis. Although MRI is not always necessary to diag-nose diabetic foot osteomyelitis, MRI is recommended for confirmation. If MRI is unavailable or contraindicated, leu-kocyte or antigranulocyte scan combined with a three-phase bone scan is recommended. The most definitive method to diagnose osteomyelitis is with bone culture and histology, for which samples can be obtained during débridement. If débridement is not being performed, percutaneous bone biopsy can be considered.

In osteomyelitis, the erythrocyte sedimentation rate and C-reactive protein level are elevated in the acute phase. An erythrocyte sedimentation rate above 70 mm/h and C-reactive protein level above 3.2 mg/dL significantly increase the prob-ability of osteomyelitis.133,134 The use of leukocytosis for the diagnoses of osteomyelitis is limited as 54% of patients

from the posterior aspect of the fibula, and the flexor digito-rum longus originates from the posterior tibia. They both enter the foot through the tarsal tunnel along the medial arch and insert into the distal phalanx of the toes. The fourth plantar space includes the flexor hallucis brevis, adductor hallucis, and flexor digiti minimi. The deepest layer involves the interossei, peroneal longus, and tibialis posterior tendons.

The spaces in the foot can be further divided into medial, central, and lateral compartments on the basis of the medial and lateral intermuscular septa of the plantar fascia. Ulcers under the great toe or first metatarsal com-municate with the medial compartment. Ulcers of the middle three rays communicate with the central compart-ment, and fifth toe and metatarsal ulcers communicate with the lateral compartment.

Arterial Revascularization. After the initial control of sepsis, the vascular status is assessed as previously described. Before any formal amputation (either minor or major) is contem-plated, assessment of arterial hemodynamics is essential.20-23,61 Without it, a salvageable limb may be amputated because remediable arterial obstructions have been overlooked and left untreated. A course of initial “damage control” of gan-grene or sepsis, regular wound débridement, negative pressure wound therapy, skin grafting, or definitive amputation can succeed only if the foot has adequate arterial perfusion. What might have been sufficient circulation for an intact, unin-fected foot may be inadequate once ulceration, sepsis, and gangrene develop. Likewise, débridement of an ischemic, ulcerated foot will only exacerbate gangrene until the circula-tory insufficiency has been rectified. How much augmenta-tion of blood flow is required is usually proportional to the extent of gangrene and sepsis.

Once acute or infected ulceration is superimposed on chronic ischemia, therapy is initially, and appropriately, directed toward drainage and débridement, antibiotics, and offloading. This approach addresses the acute problem but ignores the fact that healing and limitation of amputation can occur only when the underlying chronic ischemia is treated. Therefore, underlying ischemia should be evaluated and addressed by open or endovascular means as soon as the infection has been controlled. Fortunately, the majority of arterial lesions accompanying DFUs are amenable to revas-cularization. In general, in the presence of major tissue necro-sis with recent infection, it is usually necessary to restore a pedal pulse if healing is to occur.

Inpatient versus Outpatient Therapy

Currently, there are no definitive evidence-based criteria for admission or discharge of patients with diabetic foot infections. The IDSA recommends that patients with severe diabetic foot infection be admitted for treatment. Patients with moderate infection and associated issues such as severe PAD, inability to comply with outpatient therapy, and lack of home support should also be initially hospitalized. Patients who do not meet these criteria but fail to improve with outpatient therapy should be admitted. Once patients


neuroarthropathy is most often unilateral (although it can be bilateral) and self-limited. In acute cases, the ability to mount an inflammatory response and to increase blood flow to the distal limb is required. The inability to increase blood flow as a result of vasomotor damage or occlusive arterial disease may explain its rarity.65,144

Charcot’s foot is associated with sensory neuropathy that is essential for the development of arthropathy. No cases have been reported in the absence of neuropathy. Risk factors for the development of Charcot’s neuroarthropathy include peripheral neuropathy, trauma, foot infection, transplant surgery, bypass surgery, osteopenia, glucocorticoid use, and renal failure.66-68,145 Other risk factors include age, sex, weight, and duration of diabetes.

Clinical Evaluation

Classically, Charcot’s neuroarthropathy initially is manifested with an erythematous, warm, and swollen foot that is often indistinguishable from infection and may be mistaken for other pathologic processes unless the treating physician has a high index of suspicion. The differential diagnosis includes infection, osteomyelitis, deep venous thrombosis, acute gouty arthropathy, posterior tibialis tendon dysfunction, and bone tumor. Others with Charcot’s neuroarthropathy may present with what initially seems to be a unilateral flatfoot deformity, with the arch of the foot “suddenly” collapsing. Although patients are insensate, 76% complain of pain on initial pre-sentation.146 Traumatic injury is thought to precede a signifi-cant proportion of cases. However, only 22% to 53% of patients recall a specific traumatic event.76,146

Diagnosis is primarily based on clinical examination, including evaluation of neurologic, vascular, musculoskeletal, and radiographic findings.136 A clinical presentation of edema with a temperature difference between the feet of several degrees and well-preserved or exaggerated arterial flow of the foot is often noted. Imaging studies should be obtained but may well be misleading, especially in early stages. Available classifications do not provide prognostic or direct treatment recommendations. The terms active and inactive (chronic) are used to describe the inflamed and stable stages, respectively, although there is no accepted measure to define the transition point.136

The diagnosis of active Charcot’s neuroarthropathy is mainly based on history and clinical findings and should be confirmed by imaging. Active Charcot’s neuroarthropathy is the occurrence of acute foot or ankle fractures or dislocations in neuropathic patents with or without concurrent foot defor-mity. Radiography should be the initial diagnostic test to evaluate for subtle fractures or subluxation. If these findings are not obvious, MRI or nuclear imaging can be performed to help confirm the clinical suspicion.136

Imaging Studies

Plain film radiographs often show periosteal elevation, mul-tiple fractures, and, in some instances, osteopenia that may

admitted for osteomyelitis had white blood cell counts within normal limits.107

Treatment

The treatment of osteomyelitis consists of surgical or medical therapy. In noncomparative studies, both approaches have successfully arrested infection in most patients.

If surgical débridement is performed and all infected tissues have been resected, antibiotics may be continued for a short duration of 2 to 5 days. If persistent infected or necrotic bone is present, antibiotics may be continued for a longer time of 4 weeks or more. In treatment of osteomyelitis, the IDSA does not support the use of adjunctive therapy, including hyperbaric oxygen therapy, growth factors, maggots, and topical negative pressure therapy.135

CHARCOT’S NEUROARTHROPATHY

Charcot’s neuroarthropathy, a condition affecting the bone, joints, and soft tissue of the foot and ankle, is characterized by inflammation in the earliest phase and leads to joint destruction in people with peripheral neuropathy. This process, also termed Charcot’s foot or Charcot’s joint, is clinically challenging for clinicians.136 The major morbidity of Charcot’s neuroarthropathy is deformity that can lead to either an osseous plantar prominence, termed rocker-bottom foot, or joint instability.130 The fracture and dislocation of the foot and ankle joint predispose patients to ulcerations, reulceration, infection, and amputation secondary to the deformity.29,137

Charcot’s neuroarthropathy affects 8.5 per 1000 people with diabetes annually.138 The prevalence varies from 0.08% to 13% in the general diabetic population and high-risk diabetic patients, respectively.139 However, the true preva-lence is unknown as it is often underdiagnosed.134 In a series of 68 patients treated for midfoot Charcot’s neuroarthropa-thy, 25% of the referrals had been misdiagnosed as infection, gout, arthritis, fracture, venous insufficiency, or tumor.137 It often affects persons younger than those with other foot disorders at 55 years versus 65 years of age. Charcot’s neu-roarthropathy is less likely to be associated with occlusive arterial disease, but this may be because affected patients tend to be younger.134,140,141

Etiology

The causes of Charcot’s neuroarthropathy are not well known but are thought to involve several mechanisms, and several theories exist to describe this process. Charcot’s neuroar-thropathy is unilateral, whereas neuropathy is symmetrical; Charcot’s neuroarthropathy is rare, whereas neuropathy is common; and Charcot’s neuroarthropathy is self-limited, but neuropathy is irreversible.141 Current research points to an exaggerated local inflammatory response, triggering cytokines that lead to increased osteoclast activity and subsequent bone destruction.68,141-143 This theory explains why Charcot’s


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Nuclear scintigraphy is usually not reliable for differentia-tion of bone infection, trauma, fracture, and postsurgical inflammation. The surgeon should have a clear diagnosis of bone infection before planning an amputation, especially in the absence of a wound.

MRI is not required for diagnosis when osseous changes are evident on radiographs but can be useful in making the diagnosis at the onset to detect subtle changes before they are noted on plain films.136

Bone Biopsy

Bone biopsy is considered the gold standard to diagnose bone infection and often to exclude Charcot’s neuroarthropathy. Diagnosis of Charcot’s neuroarthropathy can be made through a histologic specimen, which shows shards of bone and soft tissue embedded in the synovium.147 A Jamshidi needle, used under fluoroscopy, permits the surgeon to obtain a bone speci-men for a definitive diagnosis, and it minimizes the ambiguity associated with more expensive imaging techniques. However, pathologic assessment and imaging are still not entirely free from subjectivity.148

Treatment

Both medical and surgical primary treatment approaches are available, although evidence-based, accepted treatment pro-tocols are lacking.68,136

be misinterpreted as osteomyelitis by an inexperienced radi-ologist or surgeon. Many patients are treated for osteomyelitis even though they have never had a wound or injury. The midfoot is the most common site of Charcot’s fracture. The result is often a convex arch, with the head of the talus and navicular bones or the cuboid projecting through the bottom of the foot. In advanced stages, these midfoot bones may be destroyed, with the weight of the extremity borne by the malleoli. Overlying ulcers often develop because of the abnormal pressure and shear forces created by the collapse of the arch (Figs. 116-13 and 116-14).

Failure of these wounds to heal is usually not primarily due to ischemia. Rather, it is a combination of neuropathy, bone deformity, pressure, shear, and repetitive local trauma.

Figure 116-13 Radiographic appearance of midfoot collapse that produces rocker-bottom foot.

Figure 116-14 A, Plantar diabetic foot ulcer under a Charcot’s foot deformity. B, Healing of the ulcer 12 weeks after a midfoot reconstruction, medial plantar artery flap, and split-thickness skin grafting.

A B


Offloading

The conservative biomechanical treatment of Charcot’s neu-roarthropathy is cast immobilization. A cast is generally required for 3 to 6 months to reach a state of quiescence for acute Charcot’s arthropathy. Management after cast removal is focused on lifelong protection of the involved extremity. Patient education and specialized, regular foot care are inte-gral. After cast removal, a protective foot brace or accom-modative footwear should be prescribed, such as a modified ankle-foot orthosis, a Charcot-restraint orthotic walker, or a double metal upright ankle-foot orthosis. Custom footwear includes extra-deep shoes with rigid soles and a plastic or metal shank. If ulcers are present, a rocker-bottom sole can be used, with the addition of Plastazote inserts for those with insensate feet. Continued use of custom footwear in the post-acute phase is essential for foot protection and support. Ongoing vigilance by the patient and foot care specialist is mandatory to prevent recurrence.

Medical Therapy

Several pharmacologic interventions have been suggested to treat Charcot’s neuroarthropathy by targeting the reduced bone mineral density often found in the Charcot foot. The primary aim has been to inhibit excess osteoclast activation and to suppress the excess proinflammatory cytokine response. The two main groups of antiresorptive therapy for Charcot’s neuroarthropathy are intravenous and oral bisphosphonates and calcitonin.149-152 There is evidence that these therapies demonstrate a reduction of bone turnover, although there is no report of significant benefit with respect to fracture healing and resolution of the arthropathy.149-152 Other pharmacologic therapies currently under investigation include anabolic agents, human parathyroid hormone, and cytokine inhibi-tors, but no conclusive evidence of their effectiveness for the treatment of Charcot’s neuroarthropathy has been reported.153

Surgery

Surgical procedures for Charcot’s neuroarthropathy are uncommonly performed but are based on the location of the disease and the surgeon’s preference and experience. Indications for surgery include failure to provide effective management with conservative treatment, recurrent ulcer-ation, pain associated with malalignment, severe joint insta-bility, offending exostosis, skin complications from braces, and severe deformity not amenable to bracing alone.137,139,154 Today, surgical intervention is increasingly common, but because of the lack of robust data, specific surgical treat-ments are not well defined, and there is no established consensus as to the proper timing or optimal approach. Surgical techniques described in the literature include oste-otomy, exostosectomy of a bone prominence, reconstruction with internal and external fixation, realignment arthrodesis, Achilles tendon lengthening, autologous bone grafting, and, rarely, major amputation.30 The goals of surgery are to establish a stable, plantigrade foot and to reduce plantar prominence to decrease pressure and shearing forces that

cannot be accommodated with therapeutic footwear or custom orthoses alone. Because of the extension of disease across multiple joints, combinations of these procedures are often necessary.

PREVENTIVE CARE OF THE HIGH-RISK PATIENT IN REMISSION

Once a patient has either been risk screened or healed a wound, the patient should be placed in an appropriate risk stratum, as discussed earlier. Patients in risk category 0 (no neuropathy, no PAD) can be assessed on an annual basis by the primary care physician or podiatric surgeon. Risk category 1 patients may require appropriate shoe gear to accommodate any deformity that may be present in the face of loss of pro-tective sensation. They may also benefit from surgical correc-tion of deformity if it is difficult to accommodate a specific deformity. They may return every 4 to 6 months for follow-up. Patients in risk category 2 (PAD) will require referral to and monitoring by vascular specialists along with foot specialists, returning for podiatric care every 3 to 4 months, as needed. People in category 3 (history of ulcer or amputation) require the most intensive attention by foot specialists and vascular specialists, returning for foot care every 1 to 2 months or as required.

Patients with DFUs are complex and should be treated in multispecialty centers. Once the initial ulcer heals, one might suggest to the patient that he or she is “in remission.” This concept is easy for patients and other caregivers to under-stand. A patient in remission might be more likely to seek follow-up care than a patient who is “healed” and seeking preventive care visits, which might slip to the back of the mind, particularly in the face of neuropathy and the absence of other symptoms.155

Education

Patient education may play an important role in prevention. In one study, amputation rates in patients who did not receive comprehensive behavioral foot care education were three times higher than in those who received education, 12% versus 4%, respectively (P = .025). Education also was associ-ated with a threefold reduction in the ulceration rate.156 However, other studies have reported contradictory results and shown no long-term improvement in ulcer or amputation rates.156,157 Although the literature concerning the benefits of education is conflicting, it seems reasonable to educate patients, given the considerable morbidities of ulceration and amputation.

Therapeutic Footwear

Therapeutic footwear is commonly prescribed to patients with diabetes to prevent foot ulcers and amputation. The focus should include reducing pressure due to deformity and external forces to prevent traumatic injuries. This can be


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accomplished by reducing pressure internally through surgical intervention or externally with accommodative footwear or bracing.

A prospective randomized multicenter study evaluated the efficacy of specially manufactured shoes (Podiabetes by Buratto Italy) for diabetic patients to prevent relapse of foot ulcerations. Patients were assigned to wear either therapeutic shoes or their own shoes. At 1-year follow-up, ulcer relapses were significantly lower in the therapeutic shoe group (27.7% vs 58.3% in the control group; P = .009). The investigators concluded that the use of specially designed shoes is effective in preventing relapse of ulceration.158 Other studies have also demonstrated positive results with decreased reulceration rates in patients with severe deformity.158

Multidisciplinary Team Approach

A multidisciplinary team approach has been cited in several DFU studies as an important contributor to improved rates of ulcer healing and reductions in recurrent foot ulceration and major limb amputation. In one study, patients observed by a multidisciplinary team consisting of a physician, podia-trist, and nurse visit every 3 months were compared with patients in the control group, who were observed by a local clinic on a trimonthly basis. During the 2-year follow-up period, there were 30% fewer ulcer recurrences in the multi-disciplinary group compared with 58% in the standard group.159 Another study from Denmark also showed that a multidisciplinary team with broad knowledge and under-standing of wound problems had improved healing rates of leg ulcer and decreased rate of major amputations.160 Simi-larly, other studies have shown reductions in major amputa-tions by up to 37%.160,161 On the basis of the findings of these studies, we would agree that a multidisciplinary team approach appears to confer a significant, positive impact on reducing recurrent ulcerations and amputations.

SELECTED KEY REFERENCES

Boulton AJ, Armstrong DG, Albert SF, Frykberg RG, Hellman R, Kirkman MS, Lavery LA, Lemaster JW, Mills JL Sr, Mueller MJ, Sheehan P, Wukich DK; American Diabetes Association; American Association of Clinical Endocrinologists: Comprehensive foot examination and risk assessment: a report of the task force of the foot care interest group of the American Diabetes Association, with endorsement by the American

Association of Clinical Endocrinologists. Diabetes Care 31:1679–1685, 2008.A multidisciplinary task force assembled by the American Diabetes Association

reported a summary of recommendations on the preventive approach for diabetic foot care, including which screening test should be adopted in clinical practice to reduce the prevalence of lower extremity morbidity in this population.Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG,

Deery HG, Embil JM, Joseph WS, Karchmer AW, Pinzur MS, Senneville E: 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 54:e132–e173, 2012.Practice guideline developed by the Infectious Diseases Society of America based

on published evidence outlining diagnosis and treatment of foot infections.Peters EJ, Lipsky BA, Berendt AR, Embil JM, Lavery LA, Senneville E,

Urbančič-Rovan V, Bakker K, Jeffcoate WJ: A systematic review of the effectiveness of interventions in the management of infection in the diabetic foot. Diabetes Metab Res Rev 28(Suppl 1):142–162, 2012.Comprehensive systematic review by the International Working Group on the

Diabetic Foot of published evidence relating to the treatment of foot infection in patients with diabetes.Prompers L, Huijberts M, Apelqvist J, Jude E, Piaggesi A, Bakker K, Edmonds

M, Holstein P, Jirkovska A, Mauricio D, Ragnarson Tennvall G, Reike H, Spraul M, Uccioli L, Urbancic V, Van Acker K, van Baal J, van Merode F, Schaper N: High prevalence of ischaemia, infection and serious comor-bidity in patients with diabetic foot disease in Europe. Baseline results from the Eurodiale study. Diabetologia 50:18–25, 2007.Data analysis in a large prospective cohort study concluded that the severity of

foot ulcer is greater than previously reported as one third of these subjects had both peripheral arterial diseases and infection and patients with severe diseases had more nonplantar ulcers.Prompers L, Schaper N, Apelqvist J, Edmonds M, Jude E, Mauricio D,

Uccioli L, Urbancic V, Bakker K, Holstein P, Jirkovska A, Piaggesi A, Ragnarson-Tennvall G, Reike H, Spraul M, Van Acker K, Van Baal J, Van Merode F, Ferreira I, Huijberts M: Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with and without peripheral arterial disease. The EURODIALE Study. Diabetologia 51:747–755, 2008.Data analysis in a large prospective cohort study concluded that healing in

diabetic foot ulcers differs between patients with and without peripheral vascular diseases.Schaper NC, Andros G, Apelqvist J, Bakker K, Lammer J, Lepantalo M,

Mills JL, Reekers J, Shearman CP, Zierler RE, Hinchliffe RJ: Diagnosis and treatment of peripheral arterial disease in diabetic patients with a foot ulcer. A progress report of the International Working Group on the Diabetic Foot. Diabetes Metab Res Rev 28(Suppl 1):218–224, 2012.Practice guideline by the International Working Group on the Diabetic Foot for

the diagnosis and treatment of peripheral arterial disease in patients with foot ulcers and diabetes, taking both risks and benefits into consideration.

The reference list can be found on the companion Expert Consult website at www.expertconsult.com.

http://refhub.elsevier.com/B978-1-4557-5304-8.00116-3/sr0010



































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CHAPTER 116 Diabetic Foot Ulcers 1835.e1 SE

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1835.e2 SECTION 18 Lower Extremity Arterial Disease

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61. Armstrong DG, et al: Maggot therapy in “lower-extremity hospice” wound care: fewer amputations and more antibiotic-free days. J Am Podiatr Med Assoc 95:254–257, 2005.

62. Sherman RA: Maggot therapy for treating diabetic foot ulcers unre-sponsive to conventional therapy. Diabetes Care 26:446–451, 2003.

63. McCartan B, et al: The use of split-thickness skin grafts on diabetic foot ulcerations: a literature review. Plast Surg Int 2012:715273, 2012.

64. Kalbermatten DF, et al: Use of a combined pedicled toe fillet flap. Scand J Plast Reconstr Surg Hand Surg 38:301–305, 2004.

65. Shapiro SA, et al: Normal blood flow response and vasomotion in the diabetic Charcot foot. J Diabetes Complications 12:147–153, 1998.

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68. Dissanayake SU, et al: The diabetic Charcot foot. Curr Diabetes Rev 8:191–194, 2012.

69. Korber A, et al: Vacuum assisted closure device improves the take of mesh grafts in chronic leg ulcer patients. Dermatology 216:250–256, 2008.

70. Banis JC: Glabrous skin grafts for plantar defects. Foot Ankle Clin 6:827–837, viii, 2001.

71. Armstrong DG, et al: Efficacy of fifth metatarsal head resection for treatment of chronic diabetic foot ulceration. J Am Podiatr Med Assoc 95:353–356, 2005.

72. Ozkan O, et al: Reliability of free-flap coverage in diabetic foot ulcers. Microsurgery 25:107–112, 2005.

73. Lavery LA, et al: Predictive value of foot pressure assessment as part of a population-based diabetes disease management program. Diabetes Care 26:1069–1073, 2003.

74. Lewis J, et al: Pressure-relieving interventions for treating diabetic foot ulcers. Cochrane Database Syst Rev 1:CD002302, 2013.

75. Wu SC, et al: Use of pressure offloading devices in diabetic foot ulcers: do we practice what we preach? Diabetes Care 31:2118–2119, 2008.

76. Pinzur MS: Benchmark analysis of diabetic patients with neuropathic (Charcot) foot deformity. Foot Ankle Int 20:564–567, 1999.

77. Hunt DL. Diabetes: foot ulcers and amputations. Clin Evid (Online) 2011.

78. Katz IA, et al: A randomized trial of two irremovable off-loading devices in the management of plantar neuropathic diabetic foot ulcers. Diabetes Care 28(3):555–559, 2005.

79. Armstrong DG, et al: Off-loading the diabetic foot wound: a random-ized clinical trial. Diabetes Care 24(6):1019–1022, 2001.

80. Armstrong DG, et al: Evaluation of removable and irremovable cast walkers in the healing of diabetic foot wounds: a randomized controlled trial. Diabetes Care 28:551–554, 2005.

81. Van De Weg FB, et al: Wound healing: total contact cast vs. custom-made temporary footwear for patients with diabetic foot ulceration. Prosthet Orthot Int 32(1):3–11, 2008.

82. Caravaggi C, et al: Nonwindowed nonremovable fiberglass off-loading cast versus removable pneumatic cast (AircastXP Diabetic Walker) in the treatment of neuropathic noninfected plantar ulcers: a randomized prospective trial. Diabetes Care 30(10):2577–2578, 2007.

83. Armstrong DG, et al: Classifying diabetic foot surgery: toward a ratio-nal definition. Diabet Med 20:329–331, 2003.

84. Armstrong DG, et al: Lengthening of the Achilles tendon in diabetic patients who are at high risk for ulceration of the foot. J Bone Joint Surg Am 81:535–538, 1999.

85. Mueller MJ, et al: Effect of Achilles tendon lengthening on neuro-pathic plantar ulcers. A randomized clinical trial. J Bone Joint Surg Am 85:1436–1445, 2003.

86. Lipsky BA, et al: Topical versus systemic antimicrobial therapy for treating mildly infected diabetic foot ulcers: a randomized, controlled, double-blinded, multicenter trial of pexiganan cream. Clin Infect Dis 47:1537–1545, 2008.

87. Ashry HR, et al: Effectiveness of diabetic insoles to reduce foot pres-sures. J Foot Ankle Surg 36:268–271; discussion 328–329, 1997.

88. Peters EJ, et al: Risk factors for recurrent diabetic foot ulcers: site matters. Diabetes Care 30:2077–2079, 2007.

89. Kearney TP, et al: Safety and effectiveness of flexor tenotomies to heal toe ulcers in persons with diabetes. Diabetes Res Clin Pract 89(3):224–226, 2010.

90. Laborde JM: Neuropathic toe ulcers treated with toe flexor tenotomies. Foot Ankle Int 28:1160–1164, 2007.

91. Kim JY, et al: Modified resection arthroplasty for infected non-healing ulcers with toe deformity in diabetic patients. Foot Ankle Int 29:493–497, 2008.

92. Armstrong DG, et al: Is prophylactic diabetic foot surgery dangerous? J Foot Ankle Surg 35:585–589, 1996.

93. Sayner LR, et al: Elective surgery of the diabetic foot. Clin Podiatr Med Surg 20:783–792, 2003.

94. Giurini JM, et al: Panmetatarsal head resection in chronic neuropathic ulceration. J Foot Surg 26:249–252, 1987.

95. Armstrong DG, et al: Clinical efficacy of the pan metatarsal head resection as a curative procedure in patients with diabetes mellitus and neuropathic forefoot wounds. Foot Ankle Spec 5:235–240, 2012.

96. Armstrong DG, et al: Clinical efficacy of the first metatarsophalangeal joint arthroplasty as a curative procedure for hallux interphalangeal joint wounds in patients with diabetes. Diabetes Care 26(12):3284–3287, 2003.

97. Blume PA, et al: Single-stage surgical treatment of noninfected diabetic foot ulcers. Plast Reconstr Surg 109(2):601–609, 2002.

98. Frykberg RG, et al: Surgical management of diabetic foot infections and osteomyelitis. Clin Podiatr Med Surg 24:469–482, viii–ix, 2007.

99. Frykberg RG, et al: Diabetic foot disorders: a clinical practice guideline. American College of Foot and Ankle Surgeons. J Foot Ankle Surg 39(Suppl):S1–S60, 2000.

100. Fincke BG, et al: A classification of diabetic foot infections using ICD-9-CM codes: application to a large computerized medical database. BMC Health Serv Res 10:192, 2010.

101. Shah BR, et al: Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 26:510–513, 2003.









































































































































CHAPTER 116 Diabetic Foot Ulcers 1835.e3 SE

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ER EXTREM

ITY A

RTERIAL D

ISEASE

102. Akinci B, et al: Acute phase reactants predict the risk of amputation in diabetic foot infection. J Am Podiatr Med Assoc 101:1–6, 2011.

103. Raymakers JT, et al: The effect of diabetes and severe ischaemia on the penetration of ceftazidime into tissues of the limb. Diabet Med 18:229–234, 2001.

104. Boulton AJ: The diabetic foot: grand overview, epidemiology and pathogenesis. Diabetes Metab Res Rev 24(Suppl 1):S3–S6, 2008.

105. Lavery LA, et al: Risk factors for foot infections in individuals with diabetes. Diabetes Care 29:1288–1293, 2006.

106. Peters EJ, et al: A systematic review of the effectiveness of interven-tions in the management of infection in the diabetic foot. Diabetes Metab Res Rev 28(Suppl 1):142–162, 2012.

107. Armstrong DG, et al: Leukocytosis is a poor indicator of acute osteo-myelitis of the foot in diabetes mellitus. J Foot Ankle Surg 35:280–283, 1996.

108. Eneroth M, et al: Deep foot infections in patients with diabetes and foot ulcer: an entity with different characteristics, treatments, and prognosis. J Diabetes Complications 13:254–263, 1999.

109. Uzun G, et al: Procalcitonin as a diagnostic aid in diabetic foot infec-tions. Tohoku J Exp Med 213:305–312, 2007.

110. Dickhaut SC, et al: Nutritional status: importance in predicting wound-healing after amputation. J Bone Joint Surg Am 66:71–75, 1984.

111. Crim JR, et al: Imaging evaluation of osteomyelitis. Crit Rev Diagn Imaging 35:201–256, 1994.

112. Termaat MF, et al: The accuracy of diagnostic imaging for the assess-ment of chronic osteomyelitis: a systematic review and meta-analysis. J Bone Joint Surg Am 87:2464–2471, 2005.

113. Schwegler B, et al: Unsuspected osteomyelitis is frequent in persistent diabetic foot ulcer and better diagnosed by MRI than by 18F-FDG PET or 99mTc-MOAB. J Intern Med 263:99–106, 2008.

114. Palestro CJ, et al: Marrow versus infection in the Charcot joint: indium-111 leukocyte and technetium-99m sulfur colloid scintigraphy. J Nucl Med 39:346–350, 1998.

115. Lavery LA, et al: Probe-to-bone test for diagnosing diabetic foot osteo-myelitis: reliable or relic? Diabetes Care 30:270–274, 2007.

116. Lipsky BA: New developments in diagnosing and treating diabetic foot infections. Diabetes Metab Res Rev 24(Suppl 1):S66–S71, 2008.

117. Chakraborti C, et al: Sensitivity of superficial cultures in lower extrem-ity wounds. J Hosp Med 5:415–420, 2010.

118. Fisher TK, et al: Diabetic foot infections: a need for innovative assess-ments. Int J Low Extrem Wounds 9:31–36, 2010.

119. Richard JL, et al: Management of patients hospitalized for diabetic foot infection: results of the French OPIDIA study. Diabetes Metab 37:208–215, 2011.

120. Calhoun JH, et al: Diabetic foot ulcers and infections: current con-cepts. Adv Skin Wound Care 15:31–42, 2002.

121. Lipsky BA: A report from the international consensus on diagnosing and treating the infected diabetic foot. Diabetes Metab Res Rev 20(Suppl 1):S68–S77, 2004.

122. Lavery LA, et al: Validation of the Infectious Diseases Society of America’s diabetic foot infection classification system. Clin Infect Dis 44:562–565, 2007.

123. Dang CN, et al: Methicillin-resistant Staphylococcus aureus in the dia-betic foot clinic: a worsening problem. Diabet Med 20:159–161, 2003.

124. Stanaway S, et al: Methicillin-resistant Staphylococcus aureus (MRSA) isolation from diabetic foot ulcers correlates with nasal MRSA carriage. Diabetes Res Clin Pract 75:47–50, 2007.

125. Tascini C, et al: Clinical and microbiological efficacy of colistin therapy alone or in combination as treatment for multidrug resistant Pseudo-monas aeruginosa diabetic foot infections with or without osteomyeli-tis. J Chemother 18:648–651, 2006.

126. Richard JL, et al: Risk factors and healing impact of multidrug-resistant bacteria in diabetic foot ulcers. Diabetes Metab 34(Pt 1):363–369, 2008.

127. Eleftheriadou I, et al: Methicillin-resistant Staphylococcus aureus in diabetic foot infections. Drugs 70:1785–1797, 2010.

128. Siami G, et al: Clinafloxacin versus piperacillin-tazobactam in treat-ment of patients with severe skin and soft tissue infections. Antimicrob Agents Chemother 45:525–531, 2001.

129. Tan JS, et al: Can aggressive treatment of diabetic foot infections reduce the need for above-ankle amputation? Clin Infect Dis 23:286–291, 1996.

130. Armstrong DG, et al: Elevated peak plantar pressures in patients who have Charcot arthropathy. J Bone Joint Surg Am 80:365–369, 1998.

131. Grayson ML, et al: Probing to bone in infected pedal ulcers. A clinical sign of underlying osteomyelitis in diabetic patients. JAMA 273:721–723, 1995.

132. Shone A, et al: Probing the validity of the probe-to-bone test in the diagnosis of osteomyelitis of the foot in diabetes. Diabetes Care 29:945, 2006.

133. Butalia S, et al: Does this patient with diabetes have osteomyelitis of the lower extremity? JAMA 299:806–813, 2008.

134. Rajbhandari SM, et al: Charcot neuroarthropathy in diabetes mellitus. Diabetologia 45:1085–1096, 2002.

135. Lipsky BA, et al: Specific guidelines for the treatment of diabetic foot infections 2011. Diabetes Metab Res Rev 28(Suppl 1):234–235, 2012.

136. Rogers LC, et al: The Charcot foot in diabetes. Diabetes Care 34:2123–2129, 2011.

137. Wukich DK, et al: Charcot arthropathy of the foot and ankle: modern concepts and management review. J Diabetes Complications 23:409–426, 2009.

138. Lavery LA, et al: Diabetic foot syndrome: evaluating the prevalence and incidence of foot pathology in Mexican Americans and non-Hispanic whites from a diabetes disease management cohort. Diabetes Care 26:1435–1438, 2003.

139. Frykberg RG, et al: Epidemiology of the Charcot foot. Clin Podiatr Med Surg 25:17–28, v, 2008.

140. Jeffcoate W, et al: The Charcot foot. Diabet Med 17:253–258, 2000.141. Jeffcoate WJ: Charcot neuro-osteoarthropathy. Diabetes Metab Res Rev

24(Suppl 1):S62–S65, 2008.142. Molines L, et al: Charcot’s foot: newest findings on its pathophysiology,

diagnosis and treatment. Diabetes Metab 36(4):251–255, 2010.143. Jeffcoate WJ. Theories concerning the pathogenesis of the acute

charcot foot suggest future therapy. Curr Diab Rep 5(6):430–435, 2005.144. Veves A, et al: Endothelial dysfunction and the expression of endothe-

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145. Darst MT, et al: Charcot’s joint following Keller arthroplasty. A case report. J Am Podiatr Med Assoc 88:140–143, 1998.

146. Armstrong DG, et al: The natural history of acute Charcot’s arthropa-thy in a diabetic foot specialty clinic. Diabet Med 14:357–363, 1997.

147. Horwitz T: Bone and cartilage debris in the synovial membrane; its significance in the early diagnosis of neuro-arthropathy. J Bone Joint Surg Am 30:579–588, 1948.

148. Meyr AJ, et al: Statistical reliability of bone biopsy for the diagnosis of diabetic foot osteomyelitis. J Foot Ankle Surg 50:663–667, 2011.

149. Jude EB, et al: Bisphosphonates in the treatment of Charcot neuroar-thropathy: a double-blind randomised controlled trial. Diabetologia 44:2032–2037, 2001.

150. Pakarinen TK, et al: The effect of zoledronic acid on the clinical resolu-tion of Charcot neuroarthropathy: a pilot randomized controlled trial. Diabetes Care 34:1514–1516, 2011.

151. Bem R, et al: Intranasal calcitonin in the treatment of acute Charcot neuroosteoarthropathy: a randomized controlled trial. Diabetes Care 29:1392–1394, 2006.

152. Pitocco D, et al: Six-month treatment with alendronate in acute Charcot neuroarthropathy: a randomized controlled trial. Diabetes Care 28:1214–1215, 2005.

153. Petrova NL, et al: Medical management of Charcot arthropathy. Dia-betes Obes Metab 15:193–197, 2013.

154. Burns PR, et al: Surgical reconstruction of the Charcot rearfoot and ankle. Clin Podiatr Med Surg 25:95–120, vii–viii, 2007.

155. Armstrong DG, et al: Toward a change in syntax in diabetic foot care: prevention equals remission. J Am Podiatr Med Assoc 103:161–162, 2013.

156. Malone JM, et al: Prevention of amputation by diabetic education. Am J Surg 158(6):520–523; discussion 523–524, 1989.









































































































































1835.e4 SECTION 18 Lower Extremity Arterial Disease

157. Bloomgarden ZT, et al. Randomized, controlled trial of diabetic patient education: improved knowledge without improved metabolic status. Diabetes Care 10(3):263–272, 1987.

158. Uccioli L, et al: Manufactured shoes in the prevention of diabetic foot ulcers. Diabetes Care 18:1376–1378, 1995.

159. Dargis V, et al: Benefits of a multidisciplinary approach in the manage-ment of recurrent diabetic foot ulceration in Lithuania: a prospective study. Diabetes Care 22:1428–1431, 1999.

160. Gottrup F, et al: A new concept of a multidisciplinary wound healing center and a national expert function of wound healing. Arch Surg 136:765–772, 2001.

161. Trautner C, et al: Reduced incidence of lower-limb amputations in the diabetic population of a German city, 1990-2005: results of the Leverkusen Amputation Reduction Study (LARS). Diabetes Care 30(10):2633–2637, 2007.
















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Documents

major amputation

management of diabetes

diagnosis of diabetes

general diabetes population

major limb amputation

incidence of dfus

diabetic complications

ulcerated diabetic foot