diabetic foot disorders - pdfs.semanticscholar.org · work in progress and will require future...

DIABETIC FOOT DISORDERSA Clinical Practice Guideline

Robert G. Frykberg, DPM, MPH, David G. Armstrong, DPM, JohnGiurini, DPM, Annemarie Edwards, DPM, Marc Kravette, DPM,Steven Kravitz, DPM, Charles Ross, DPM, James Stavosky, DPM,Rodney Stuck, DPM, and John Vanore, DPM

For the American College of Foot and Ankle Surgeons and the AmericanCollege of Foot and Ankle Orthopedics and Medicine

ABSTRACT

Foot ulcerations, infections, and Charcot neuropathic osteoarthropathy are three serious footcomplications of diabetes mellitus that can too frequently lead to gangrene and lower limbamputation. Consequently, foot disorders are one of the leading causes of hospitalization forpersons with diabetes and can account for expenditures in the billions of dollars annually inthe U.S. alone. Although not all foot complications can be prevented, dramatic reductionsin their frequency have been obtained through the implementation of a multidisciplinaryteam approach to patient management. Using this concept, the authors present a ClinicalPractice Guideline for diabetic foot disorders based on currently available evidence. Theunderlying pathophysiology and treatment of diabetic foot ulcers, infections, and the diabeticCharcot foot are thoroughly reviewed. Although these guidelines cannot and should notdictate the standard of care for all affected patients, they are intended to provide evidence-based guidance for general patterns of practice. The goal of a major reduction in diabeticlimb amputations is certainly possible if these concepts are embraced and incorporated intopatient management protocols.

INTRODUCTION

Foot disorders are a major source of morbidity and a leading cause of hospitalizationfor persons with diabetes mellitus. Ulceration, infection, gangrene, and amputationare significant complications of the disease. Costs of management are estimatedat several billion dollars annually. Another serious complication of long-standingdiabetes, neuropathic osteoarthropathy (Charcot foot), can lead to the developmentof other limb-threatening disorders. Although the underlying pathophysiology ofdiabetic foot complications has been elucidated to a great extent, much research isyet needed to determine which of our treatments are most effective. Furthermore,we must determine how to more effectively prevent those ulcerations which arenow known to be leading precursors to lower extremity amputation in patients withdiabetes.

Although not all diabetic foot disorders can be prevented, it is possible toeffect dramatic reductions in their incidence and morbidity through appropriateevidence-based prevention and management protocols. Utilizing a multidisciplinaryapproach, consistent improvement has been noted in rates of limb salvage fromcenters around the world. With this premise as our central theme, the authors presentthis Clinical Practice Guideline to diabetic foot disorders based on currently availableevidence. Three major pedal complications of diabetes are thoroughly reviewed:diabetic foot ulcers, diabetic foot infections, and the diabetic Charcot foot. Theseguidelines are intended to provide evidence-based guidance for general patterns ofpractice and not to necessarily dictate the care of a particular patient. Although ourintent is to be as comprehensive as possible, we realize that this work is, in fact, a

Copyright 2000, Second Printing, by the American College of Foot and Ankle Surgeons, 515Busse Highway, Park Ridge, IL 60068-3150, and is published by Data Trace Publishing Company,PO Box 1239, Brooklandville, MD 21022-9978. All rights reserved. Printed in the United States ofAmerica. May not be reprinted or reproduced without permission from the American College of Footand Ankle Surgeons.

Address correspondence to: Robert G. Frykberg, DPM, MPH, Assistant Professor of PodiatricMedicine, Des Moines University, 3200 Grand Ave., Des Moines, IA 50312;E-mail:[email protected]

S2 Diabetic Foot Disorders: A Clinical Practice Guideline

work in progress and will require future modification as new knowledge becomesavailable.

Entities

Diabetic foot complications are considered under ICD-9-CM classifications:

250.0x Diabetes without Complications250.4x Diabetes with Renal Complications

Note: You are also required to use one of these additional codes to identify themanifestation, as:

Diabetic:nephropathy NOS (583.81)nephrosis (581.81)intercapillary glomerulosclerosis (581.81)Kimmelstiel-Wilson syndrome (581.81)

250.5x Diabetic Retinopathy


Diabetic:background diabetic retinopathy (362.01)proliferative diabetic retinopathy (362.02)

250.6x Diabetes with Neurologic Manifestations


Diabetic:amyotrophy (358.1)mononeuropathy (354.0-355.9)neurogenic arthropathy (713.5)peripheral autonomic neuropathy (337.1)polyneuropathy (357.2)

250.7x Diabetes with Peripheral Vascular Disease


Diabetic:gangrene (785.4)peripheral angiopathy (443.81)

250.8x Diabetes with Other Special Manifestations


Diabetic:diabetic bone changes (731.8)

All codes in category 250 have to be reported as five-digit subclassificationcodes, as follows:

0 — Type 2: non-insulin-dependent (NIDDM) or (adult-onset) or unspecified type,not stated as uncontrolled. Fifth-digit 0 is for use with type 2, adult-onset diabetic patients, even if the patient requires insulin.

1 — Type 1: insulin-dependent (IDDM) or juvenile-onset, not stated as controlled.

The Journal of Foot & Ankle Surgery, Volume 39, Number 5, Supplement 2000 S3

2 — Type 2: non-insulin-dependent (NIDDM) or adult-onset or unspecified type,uncontrolled. Fifth-digit 2 is for use with type 2, adult-onset diabeticpatients, even if the patient requires insulin.

3 — Type 1: insulin-dependent (IDDM) or juvenile-onset, uncontrolled.

When applicable, the following diagnosis codes also should be reported:

040.0 Gas gangrene357.2 Polyneuropathy in Diabetes

(Report code 357.2 as secondary to 250.6x)440.23 Atherosclerosis of the Extremities with Ulceration

(Report code 440.23 as a secondary code to 250.7x)681.11 Cellulitis/Abscess, Toe682.6 Cellulitis/Abscess, Leg (including ankle)682.7 Cellulitis/Abscess, Foot (except toes)707.1 Ulcer of lower limbs, except Decubitis

(Both codes 707.1 and 785.4 should be used toreport an ulcer with gangrene)

713.5 Arthropathy Associated with Neurological Disorders (Charcot’s)(Report code 713.5 as a secondary code to 250.6x)

730.06 Osteomyelitis/Acute/Lower Leg(Report code 730.06 as a secondary code to 250.8x)

730.07 Osteomyelitis/Acute/Ankle and Foot(Report code 730.07 as a secondary code to 250.8x)

730.16 Osteomyelitis/Chronic/Lower Leg(Report code 730.16 as a secondary code to 250.8x)

730.17 Osteomyelitis/Chronic/Ankle and Foot(Report code 730.17 as a secondary code to 250.8x)

785.4 Gangrene (any site)V49.71 Status Post Amputation, Great ToeV49.72 Status Post Amputation, Other Toe(s)V49.73 Status Post Amputation, FootV49.74 Status Post Amputation, AnkleV49.75 Status Post Amputation, Below KneeV49.76 Status Post Amputation, Above Knee

Definitions

Amputation: The complete or partial removal of a limb or body appendage bysurgical or traumatic means.

Charcot Foot: (arthropathy, osteoarthropathy, neuroarthropathy): Noninfectious de-struction of bone and joint associated with neuropathy.

Diabetic Foot: The foot of a diabetic patient that has the potential risk of pathologicconsequences, including infection, ulceration, and/or destruction of deep tissuesassociated with neurologic abnormalities, various degrees of peripheral vasculardisease, and/or metabolic complications of diabetes in the lower limb. (Basedupon the World Health Organization [WHO] definition.)

Diabetes Type 1: Formerly called insulin-dependent diabetes mellitus (IDDM),describes an autoimmune disease of younger patients with a lack of insulinproduction causing hyperglycemia and a tendency toward ketosis.

Diabetes Type 2: A metabolic disorder resulting from the body’s inability to produceenough or properly utilize insulin. Formerly called non-insulin-dependentdiabetes mellitus (NIDDM), these patients also have hyperglycemia but areketosis resistant.


Epidemiology: The study of occurrence and distribution of disease.Gangrene: The death or necrosis of a part of the body secondary to injury, infection,

and/or lack of blood supply. This indicates irreversible damage where healingcannot be anticipated without loss of some part of the extremity.

Incidence: The rate at which new cases of disease occur within a specified timeperiod.

Infection: Invasion and multiplication within body tissues by organisms such asbacteria, fungi, or yeast, with or without the clinical manifestation of disease.

Intrinsic Minus Foot: A neuropathic foot with intrinsic muscle wasting andassociated clawtoe deformities.

Ischemia: The impairment of blood flow secondary to an obstruction or constrictionof arterial inflow.

LEAP: Lower Extremity Amputation Prevention program.Limited Joint Mobility: The stiffness or restricted range of motion of a joint

(cheiroarthropathy) due to protein glycosylation.LOPS: Loss of Protective Sensation describes the progression of neuropathy in the

diabetic foot to the point that the foot is at risk for ulceration.Neuropathy: Nerve dysfunction affecting sensory, motor, and/or autonomic fibers

with varying degrees of impairment, symptoms, and signs. Diabetic peripheralneuropathy is the presence of symptoms and/or signs of peripheral nervedysfunction in people with diabetes after exclusion of other causes.

Prevalence: A measure of frequency describing the percent of persons in a givenpopulation with a stated disease or characteristic at a point in time.

Ulceration (Ulcer): A partial- or full-thickness defect in the skin that may extendto subcuticular tissue, tendon, muscle, bone, or joint.

Goals and Objectives of Diagnosis and Treatment

The objectives of diagnosis and treatment of diabetic foot sequelae center aroundmaintaining the patient as an ambulatory, productive member of society or returningthe patient to that state as quickly and safely as possible. This may at any time requirethe expertise of a number of different generalists and specialists on the diabetic footcare team.

ž Primary Goalsž Prevent limb lossž Maintain quality of life

ž Objectivesž Appropriate screening and examinationž Patient and provider educationž Prevention of ulceration and recurrencež Early recognition and treatment of diabetic foot complications

Provider

The podiatric physician, by virtue of his or her training, is uniquely suited to serveas a primary member of a multidisciplinary team for the management of diabeticfoot disorders. The evaluation, diagnosis, and the conservative treatment of thesedisorders are skills attained at the professional degree level.

The podiatrist as part of a multidisciplinary team should be able to recognizeimpending diabetic foot complications, the need for advanced diagnostic studies,and the need for appropriate referral as indicated. Surgical management of theseconditions should be undertaken only by those individuals who, by virtue of


specialized training and/or experience in foot and ankle surgery, are able to managethe perioperative and intraoperative treatment.

BACKGROUND

Epidemiology of Diabetic Foot

The incidence of diabetes in the United States is estimated at 798,000 new casesannually with an overall prevalence of approximately 6% of the population (1–3).An estimated 10.3 million persons are currently diagnosed with the disease, while anadditional 5.4 million people who have diabetes remain undiagnosed. This representsa sixfold increase in the number of persons with diabetes over the past fourdecades (3). Furthermore, there is a higher incidence of diabetes among non-Hispanicblacks, Hispanic/Latino Americans, and Native Americans as compared to non-hispanic whites (4). Diagnosed diabetes is most prevalent in the middle-aged andelderly populations, with rates estimated at 11% for those persons aged 65 years andolder (5,6). The seventh leading cause of death (sixth-leading cause by disease) inthe United States, diabetes contributes to more than 193,000 deaths per year (1,3).

Several types of diabetes are recognized: Type 1, formerly insulin-dependentdiabetes mellitus-(IDDM), is an autoimmune disease affecting the pancreas in whichthe individuals are ketosis prone and are unable to produce endogenous insulin.Type 2, formerly non-insulin-dependent diabetes mellitus (NIDDM), accounts for90–95% of cases diagnosed. Persons with Type 2 diabetes mellitus are character-ized by hyperglycemia in the presence of hyperinsulinemia due to peripheral insulinresistance. Gestational and other types such as drug or surgically induced are alsorecognized (5). Numerous complications of diabetes can be related to microvascular,macrovascular, and metabolic etiologies. These include cerebrovascular, cardiovas-cular, and peripheral vascular disease, retinopathy, neuropathy, and nephropathy.Currently, cardiovascular complications are the most common cause of prematuredeath among patients with diabetes (1,4,6,7).

One of the most common complications of diabetes in the lower extremity isthe diabetic foot ulcer. It is estimated that 15% of patients with diabetes will developa lower extremity ulcer during the course of their disease (8–10). Several reportsfrom population-based studies indicate an annual cumulative incidence for diabeticfoot ulcers of 2–3% (11,12). In one British study of a large cohort of neuropathicpatients, there was a 7% one year incidence of first foot ulcer (13). Reported footulcer prevalence in a variety of populations has ranged between 2% and 10%(9,11,13,14). The cumulative effects of neuropathy, deformity, high plantar pressure ,poor glucose control, duration of diabetes, and gender are all contributory factors forfoot ulceration that are fully discussed in the next section (15–17). While most ulcerscan be successfully treated in the office or outpatient setting, infected and/or ischemicfoot ulcers are a major cause for diabetes-related hospitalization (18,19). Nationalhospital discharge data indicate that the average hospital length of stay in diabeticpatients with ulcer diagnoses was 59% longer than in those diabetes dischargeswithout them (9). While 14–20% of patients with foot ulcers will subsequentlyrequire an amputation, foot ulceration is the precursor to approximately 85% oflower extremity of amputations in persons with diabetes (20-22).

Diabetes continues to be the most common underlying cause of lower extremityamputation (LEA) in the United States and Europe. More than 50% of all nontrau-matic LEAs in the United States occur in people with diabetes, averaging 56,000per year (1,3,4,7,9,23). In 1994 there were 67,000 diabetes-related LEA discharges,accounting for 984,000 days of hospital stay with an average length of stay (LOS)


of 15 days (4). The age-adjusted rate of amputation for that year was 82 per 10,000persons with diabetes. Generally, the rate of LEA in the diabetic population is 15–40times higher than that found in nondiabetic individuals, with males having rates atleast 50% greater than diabetic women. (1,6,23).

There are several striking differences in the frequency of diabetes-relatedamputations between ethnic groups in the United States and abroad. Mexican(Hispanic) Americans, Native Americans, and African Americans each have at leasta 1.5- to 2-fold increased risk for diabetes-related amputation compared to age-matched diabetic Caucasians (4,7,9,10,24,25). When risks for LEA are comparedbetween diabetic and nondiabetic populations worldwide, it becomes clearly apparentthat both diabetes and ethnicity have profound implications on rates of lower limbamputation (10).

Survival rates after diabetes-related lower extremity amputation are significantlylower than those in age-matched nondiabetic individuals as well as in persons withdiabetes without history of amputation (9,10,21). The 3-year and 5-year survivalrates are about 50% and 40%, respectively, with the major cause of death beingcardiovascular disease (7). One study reported a 5-year mortality rate of 68% afterlower limb amputation, with lower survival rates in those patients with higher levelsof amputation (21). Following one lower extremity amputation, there is a 50%incidence of serious contralateral foot lesion and a 50% incidence of contralateralamputation within 2–5 years (9,21).

The total costs for both direct and indirect health care for the persons withdiabetes in 1997 has been estimated at $98 billion. Of this total, direct medical costsincluding hospitalization, medical care, and supplies, accounts for $44.1 billion (26).Costs for ulcer care in the United States have been estimated in the range of $4,595per ulcer episode to nearly $28,000 for the 2 years after diagnosis (12,27). One reportestimates 800,000 prevalent ulcer cases in the United States with costs averaging$5,457 per year per patient or total national annual costs of $5 billion (28). Over thepast few decades the length of hospitalizations for lower extremity amputations in theUnited States has decreased, but the overall direct costs have remained high (4,9).Direct and indirect costs of LEA vary greatly by year, payor, level of amputation,length of stay, or attendant comorbidities and can range from $20,000 to $40,000 (9).If the lower figure is applied to the 67,000 amputations performed in 1994, thetotal direct and indirect costs of LEA might be estimated at greater than $1 billionannually. In addition to the costs for ulcer care that preceded these amputations,the estimated overall total costs in the United States for diabetic foot disease canapproach or exceed $6 billion annually.

Etiology/Risk Factors

Risk for Ulceration

Foot ulceration is the most common single precursor to lower extremity amputationsamong persons with diabetes (20–22). Treatment of infected foot wounds accountsfor up to one-quarter of all diabetic admissions in the United States and Britain.This staggering figure makes it the single most common reason for diabetes-relatedhospital admission in these nations (9,18,19,29,30). The multifactorial nature ofdiabetic foot ulceration has been elucidated by numerous observational studies(9,13,15,17,31–35). Risk factors identified include peripheral neuropathy, vasculardisease, limited joint mobility, foot deformities, abnormal foot pressures, minortrauma, a history of ulceration or amputation, and impaired visual acuity. Theseand other putative causative factors are listed in Table 1.


TABLE 1 Risk factors for ulceration

ž Peripheral sensory neuropathyž Structural foot deformityž Trauma and improperly fitted shoesž Callusž History prior ulcers/amputationsž Prolonged, elevated pressuresž Limited joint mobilityž Uncontrolled hyperglycemiaž Duration of diabetesž Blindness/partial sightž Chronic renal diseasež Older age

Peripheral sensory neuropathy in the absence of perceived trauma is the primaryfactor leading to diabetic foot ulcerations (13,15–17). Approximately 45–60% of alldiabetic ulcerations are purely neuropathic, while up to 45% have neuropathic andischemic components (15,36). A recent prospective multicenter study of diabeticpatients revealed that sensory neuropathy was the most frequent component causein the causal sequence to ulceration (15).

Other forms of neuropathy may also play a role in foot ulcerations. Motorneuropathy resulting in anterior crural muscle atrophy or intrinsic muscle wastingcan lead to foot deformities such as foot drop, equinus, hammertoes, and promi-nent plantar metatarsal heads (16,29,30,37). Autonomic neuropathy may commonlyresult in dry skin with cracking and fissuring, thus creating a portal of entry forbacteria (29,38). Autosympathectomy with attendant sympathetic failure, arterio-venous shunting, and microvascular thermoregulatory dysfunction impairs normaltissue perfusion and microvascular responses to injury. These alterations can subse-quently be implicated in the pathogenesis of ulceration. (39–41).

Foot deformities resulting from neuropathy, abnormal biomechanics, congen-ital disorders, or prior surgical intervention may result in high focal foot pres-sures (15,16,34,42–44). This may lead to vulnerable areas on the foot predisposingto ulcerations. These areas are primarily located plantarly, although medial anddorsal ulcerations may occur from footwear irritation. Such deformities might includeprior partial foot amputations, prominent metatarsal heads, hammertoes, Charcotarthropathy, or hallux valgus.

Trauma to the foot in the presence of peripheral sensory neuropathy is animportant component cause of ulcerations (15). While trauma may include puncturewounds and blunt injury, a common injury leading to ulceration is moderate repeti-tive stress resulting from walking or day to day activity (45). This is often manifestedby callus formation under the metatarsal heads (15,34,46,47). Shoe-related traumahas been identified as a frequent precursor to foot ulceration (15,20,36,48).

Peripheral vascular disease rarely leads to foot ulcerations directly. However,once an ulceration develops, arterial insufficiency will result in prolonged healing andimparts an elevated risk for amputation (20,49). Attempts to resolve any infectionwill be impaired due to lack of oxygenation and difficulty in delivering antibiotics tothe site of infection. Early recognition and aggressive treatment of lower extremityischemia is therefore vital to lower limb salvage (22,34,37,50–52).

Limited joint mobility has recently been described as a potential risk factorfor ulcerations (34,53–56). Glycosylation of collagen as a result of long-standingdiabetes may lead to stiffening of capsular structures and ligaments (cheiroar-thropathy). The subsequent reduction in ankle, subtalar, and first metatarsophalangeal


(MTP) joint mobility has been shown to result in high focal plantar pressures withincreased risk of ulceration (54).

Other factors often associated with heightened risk for ulceration include:nephropathy, poor diabetes control, blindness, advanced age, and poor nutrition(16,29,34,38,53).

Mechanisms of Injury

The multifactorial etiology of diabetic foot ulcers is evidenced by the numerouspathophysiological pathways which can potentially lead to this disorder (15,30,37,38).Notwithstanding, there are two common mechanisms by which foot deformity andneuropathy may bring about skin breakdown in persons with diabetes: injuries due tocontinuous low pressure, typically from ill-fitting shoes, and injuries due to chronicrepetitive trauma from walking (45).

The first mechanism of injury refers to prolonged low pressure over a bonyprominence (i.e., bunion or hammertoe deformity). This generally causes woundsover the medial, lateral, and dorsal aspects of the forefoot and is associated withtight or ill-fitting shoes. Studies have shown that shoe trauma, in concert with loss ofprotective sensation and concomitant foot deformity, are major precipitating eventsleading to foot ulceration in persons with diabetes (15,20,48).

Regions of high pedal pressure are directly associated with foot deformity(34,37,43,50,57). When an abnormal focus of pressure is coupled with lack ofprotective sensation, the result can be the development of a callus, blister, andulcer. The other common mechanism of ulceration involves prolonged repetitivemoderate stress (45). This normally occurs on the sole of the foot and is relatedto prominent metatarsal heads, atrophied or anteriorly displaced fat pads, structuraldeformity of the lower extremity, and prolonged walking. Rigid deformities such ashallux valgus, hallux rigidus, hammertoes, and limited range of motion of the ankle,subtalar, and metatarsophalangeal joints have been associated with the developmentof diabetic foot ulcers (55,56). Other biomechanical perturbations, including partialfoot amputations, will have the same adverse effects (42,43,58). Sensory neuropathyis the predisposing factor which allows progression to ulceration in each of thesemechanisms of injury.

Figure 1 summarizes the various pathways and contributing factors leading todiabetic foot ulceration.

Risk for Amputation

(See Color Plate 1 on page 29.) The reported risk of lower extremity amputations(LEA) in diabetic patients ranges from 2% to 16% depending on study design andthe population(s) under investigation (10–12,59–61). Rates of LEA in persons withdiabetes can be 15–40 times higher than those found in persons without diabetes(7,9,10,23–25). The same risk factors which predispose to ulceration can alsogenerally be considered as contributing causes for amputation, albeit with severalmodifications (Table 2).

Whereas peripheral vascular disease (PVD) may not always be an independentrisk factor for ulceration when controlling for neuropathy, it can be a significant riskfactor for amputation (9,15–17,20,29,59). PVD affecting the feet and legs is presentin 8% of adult diabetic patients at diagnosis and in 45% after 20 years (62,63).The incidence in diabetic men and women is four to seven times greater thantheir nondiabetic counterparts. Since this impairment of arterial perfusion can be anisolated cause for amputation as well as a predisposing factor leading to gangrene,arterial insufficiency must be diagnosed early and managed by revascularizationprocedures to avoid limb loss (22,50).


Diabetes Mellitus

Trauma

Neuropathy

MOTOR

WeaknessAtrophy

Deformity

Abnormal Stress

High plantar pressure

Callus formation

SENSORY

Loss of protectivesensation

AUTONOMIC

AnhidrosisDry skin, FissuresDecreased sympathetic tone(Altered blood flow

regulation)

Osteoarthropathy

Vascular Disease

MICROVASCULAR

Structural: Capillary BM thickeningFunctional: A-V shunting Increased blood flow Neuropathic edema

MACROVASCULAR

Atherosclerosis

Ischemia

Reduced nutrientcapillary blood flow

Impaired Response to Infection

Amputation DIABETIC FOOT ULCERATION Amputati

FIGURE 1 Contributing factors in the pathogenesis of ulceration.

TABLE 2 Risk factors for amputation

ž Peripheral sensory neuropathyž Vascular insufficiencyž Infectionž History foot ulcer/amputationž Structural foot deformityž Traumaž Charcot deformityž Impaired visionž Poor glycemic controlž Poor footwearž Older Agež Male sexž Ethnicity

Infection is a significant risk factor in the causal pathway to amputation,while it is not often implicated in the pathway leading to ulceration (9,15). Lackof wound healing, systemic sepsis, or unresolved infection can lead to extensivetissue necrosis and gangrene requiring amputation to prevent more proximal limbloss. This includes soft-tissue infection with severe tissue destruction, deep spaceabscess, or osteomyelitis. Adequate debridement may require amputation at somelevel as a means of removing all infected material (16,22,50).

Another frequently described risk factor for amputation is chronic hyper-glycemia. Results of the Diabetes Control and Complications Trial (DCCT) and theUnited Kingdom Prospective Diabetes Study (UKPDS) have supported the long-held


theory that chronically poor control is associated with a host of systemic complica-tions (64,65). The association between degree of glucose control and incidence orprogression of numerous diabetic complications has consequently been well estab-lished by these and other studies (7,66,67). Such complications include peripheralneuropathy, microangiopathy, impaired leukocyte phagocytosis, and glycosylationof tissue proteins. Each has adverse effects on the diabetic foot, can contributeto the etiology of foot ulceration, delay normal wound healing, and subsequentlylead to amputation (34,38,53). Several studies have reported significant associationsbetween elevated glucose and lower extremity amputation (11,60,68–73). Ampu-tation has also been associated with other diabetes-related co-morbidities such asnephropathy, retinopathy, and cardiovascular disease (6,34,53). Aggressive glucosecontrol, management of associated comorbidities, and appropriate lower extremitycare coordinated in a team environment may indeed lower overall risk for amputation(9,22,34,37,51,74,75).

The best predictor of amputation is a history of previous amputation. A pasthistory of a lower extremity ulceration or amputation increases the risk for furtherulceration, infection, and subsequent amputation (6,21,31,59). It may also be inferredthat patients with a past history of ulceration possess all the requisite risk factorsnecessary to produce another ulceration, having demonstrated that they alreadyhave the component elements in the causal pathway (15,20,35). These data aresubstantiated by the fact that up to 34% of patients develop another ulcer within1 year after healing an index wound, while the 5-year rate of developing a newulcer is 70% (75,76). The rate of recurrence is always higher in those patientswho have previously undergone amputation. Recurrence of pedal ulceration is dueto abnormal distribution of plantar pressures, and changed osseous architecturefollowing amputation. The cumulative identified risks of neuropathy, deformity, highplantar pressure, poor glucose control, and male gender are all additive factors forpedal ulceration in these diabetic patients (15,17,20,31,35,59,60). Re-amputationcan be attributed to progression of the disease process, nonhealing wounds, and thedevelopment of additional risk factors for limb loss that develop as a result of thefirst amputation. Tragically, the 5-year survival rate after a diabetes-related lowerextremity amputation has been reported as low as 28% (77).

Risk for Charcot Joint Disease

It is estimated that 1 in 680 diabetic patients (0.15%) will develop Charcot jointdisease (78). The data concerning the true incidence of osteoarthropathy in diabetesare limited by the small number of prospective or population-based studies currentlyavailable. Much of the data we rely upon is based upon retrospective studies of smallsingle-center cohorts. Nonetheless, the incidence of Charcot cases reported is verylikely an underestimation since many cases go undetected, especially in the earlystages (79–81).

The primary risk factors for this potentially limb-threatening deformity are thepresence of dense peripheral sensory neuropathy, normal circulation, and a history ofpreceding trauma, often minor in nature (81–84). Trauma is not limited to injuriessuch as sprains or contusions. Foot deformities, prior amputations, joint infections,or surgical trauma may result in sufficient stress that can lead to Charcot jointdisease (80).

Risk for Infection

Infections in patients with diabetes are not only common but are often moresevere than those found in nondiabetic persons. It is well documented that diabetic


foot infections are polymicrobial in nature (22,50,85–88). Hyperglycemia, impairedimmunological responses, neuropathy, and peripheral vascular disease are the mainpredisposing factors leading to limb-threatening diabetic foot infections. Uncon-trolled diabetes results in impaired ability of host leukocytes to fight bacterialpathogens, while ischemia will also affect the ability to fight infections sincedelivery of antibiotics to the site of infection will be impaired. Consequently,infections can develop and spread rapidly and produce significant and irreversibletissue damage (50). Even in the presence of adequate arterial perfusion, underlyingperipheral sensory neuropathy will often allow the progression of infection throughcontinued walking or delay in recognition (8).

PROCESS OF CARE

The pedal manifestations of diabetes are well documented and potentially limb-threatening when left untreated. Recognition of potential problems and treatment offoot disorders in a diabetic patient requires the skill of a specialized practitionerto diagnose, manage, treat, and counsel the patient. The integration of knowledgeand experience, afforded by a multidisciplinary team, promotes more effectivetreatment thereby improving outcomes and limiting the risk of lower extremityamputation (22).

Diagnosis and Evaluation

The evaluation of the diabetic foot involves careful assimilation of the patient’shistorical and physical findings and the results of necessary diagnostic procedures.Screening tools may be valuable in patient evaluation and determining levels of risk(see Appendix 1).

History

A thorough medical and foot history should be obtained from the patient. Thefollowing chart provides guidelines of specific diabetic foot issues that should beaddressed.

Global History Foot-Specific History Wound/Ulcer History

Diabetes disease duration GeneralGlycemic management/control Daily activity LocationCardiovascular, renal, and Footwear Duration

opthalmic evaluations Chemical exposures Inciting event or traumaOther comorbidities Callus formation RecurrencesCurrent treating physicians Deformities InfectionsSocial habits — Previous foot surgery Hospitalizations

Alcohol/tobacco Neuropathy symptoms Wound care/off-loading methodsCurrent medications Ischemic symptoms Patient’s compliance/wound responseAllergies Interference with wound care/Previous hospitalizations/ surgeries family or social problems for patient

Previous foot trauma or surgeryEdema-unilateral vs. bilateralPrevious or active Charcot joint

treatment to date


Physical Examination

Recognizing important risk factors and making a logical, treatment-oriented assess-ment of the diabetic foot requires a consistent and thorough diagnostic approachusing a common language. Without such a method, the practitioner is more likely tooverlook vital information and to pay inordinate attention to less critical points inthe evaluation. A useful examination will involve identification of key risk factorsand assignment into an appropriate foot risk category. Only then can an effectivetreatment plan be designed and implemented.

Clinical Examination

All patients with diabetes presenting to any health care practitioner require apedal inspection and should receive a thorough foot examination at least onceeach year (89). Patients with diabetic foot-related complaints will require detailedevaluations more frequently. The examination should be performed systematicallyso that important aspects are not overlooked. First, one should grossly evaluate thepatient and his or her extremities. Any obvious problem can then receive closerscrutiny with examination. For clarity, the key components of the foot examinationare presented below in a bulleted format. Each bulleted item represents an importantcomponent of the pedal examination or a significant finding to be noted based onevidence which indicates likely predictors for ulceration. Although not specificallymentioned in this section, it is assumed that a general medical assessment will bedetermined including measurements of vital signs.

Vascular Examinationž Palpation of pulses

(dorsalis pedis, posterior tibial, popliteal, femoral)ž Subpapillary venous plexus filling time (normal �3 seconds)ž Venous filling time (normal �20 seconds)ž Color changes:

CyanosisDependent ruborErythema

ž Presence of edemaž Temperature gradientž Dermal thermometryž Integumentary changes consistent with ischemia:

Skin atrophyNail atrophyAbnormal wrinklingDiminished pedal hair

Neurologic Examinationž Vibration perception:

Tuning fork 128 cpsMeasurement of vibration perception threshold (Biothesiometer)

ž Light pressure: Semmes–Weinstein 10-gram monofilamentž Light touch: cotton woolž Two-point discriminationž Pain: pinprickž Temperature perception: hot and coldž Deep tendon reflexes: ankle, knee


ž Clonus testingž Babinski testž Rhomberg’s test

Musculoskeletal Examinationž Biomechanical abnormalities:

Orthopedic deformitiesHammertoesBunion(s) or Tailor’s bunion(s)Flat or high-arched feetCharcot deformitiesIatrogenic deformities (e.g., amputations)

Limited joint mobilityTendo-Achilles contractures/equinus

ž Gait evaluationž Muscle group strength testing:

Passive and active, nonweightbearing and weightbearingFoot dropAtrophy — intrinsic muscle atrophy

ž Plantar pressure assessment:Computerized devicesHarris ink mat

Dermatologic Examinationž Skin appearance:

Color, texture, turgor, qualityDry skin

ž Calluses: Discoloration/subcallus hemorrhagež Fissures (especially posterior heels)ž Nail appearance:

Onychomycosis, dystrophicAtrophyHypertrophyParonychia

ž Presence of hairž Ulceration, gangrene, infection (Note location, size, depth, infection status, etc.)ž Interdigital lesionsž Tinea pedisž Markers of diabetes:

Shin spots — diabetic dermopathyNecrobiosis lipoidica diabeticorumBullosum diabeticorumGranuloma annulare

Footwear Examinationž Type of shoež Fitž Shoewear, patterns of wearž Lining wearž Foreign bodiesž Insoles, orthoses


Communicating and Classifying Cumulative Risk

Following a detailed diabetic foot examination, the patient may be classifiedaccording to a cumulative risk category. This enables the physician to design atreatment plan which may possibly reduce lower extremity amputations and reducethe patient from a high-risk category to the lowest risk level possible for that patient.Several risk stratification schemes have been proposed, assigning different weightsto important risk factors for ulceration including peripheral neuropathy, arterialinsufficiency, deformity, high plantar pressures, and prior history of ulcerationor amputation (34,35,37,38,90–92). Although no one system has been universallyadopted which can predict ulceration, the following simplified risk stratification hasbeen accepted by the International Working Group (37):

Risk Categorization System

Category Risk Profile Evaluation Frequency

0 No neuropathy Annual1 Neuropathy Semi-annual2 Neuropathy, PVD, and/or deformity Quarterly3 Previous ulcer or amputation Monthly to quarterly

Diagnostic Procedures

Diagnostic procedures may be indicated in the assessment and care of the diabeticfoot. Consideration should be given to the following tests in concert with membersof the consulting team. It should be noted that many of the following tests lack theability to give a definitive diagnosis and clinical correlation is required.

Laboratory Testing

Clinical laboratory tests that may be necessary in the appropriate clinical situations mayinclude: fasting or random blood glucose, glycohemoglobin (HbA1C), complete bloodcount (CBC) with or without differential, erythrocyte sedimentation rate (ESR), serumchemistries, wound and blood cultures, and urinalysis. Caution must be exercisedin the interpretation of laboratory tests in these patients, since several reports havedocumented the absence of leukocytosis or fever in the presence of severe footinfections (87,88,93–97). Frequently, the most prognostic sign of infection severity isrecalcitrant hyperglycemia despite normal antihyperglycemic regimens.

Imaging Studies

The diabetic foot may be predisposed to developing both common and unusualinfectious or noninfectious processes. This is due in part to the complex natureof the disease and its associated vascular and neuropathic complications. As aresult, imaging presentations will vary due to lack of specificity in complex clinicalcircumstances (88,96,98). This will create a challenge in the interpretation of theimaging studies. Studies should only be conducted to establish or confirm a suspecteddiagnosis and/or direct patient management.

Plain radiographs should be the initial imaging study in diabetic patients withsigns and symptoms of a diabetic foot disorder (96,99). X-ray findings in a diabeticfoot infection, such as osteomyelitis, may not demonstrate any osseous changes onradiographs for up to 14 days. Plain radiographs may be indicated in the detection


of osteomyelitis, osteolysis, fractures, dislocations seen in neuropathic arthropathy,medial arterial calcification, and soft-tissue gas (100).

Computed tomography (CT) scans may be indicated in the assessment ofsuspected bone and joint pathology not evident on plain radiographs (96,100). Thisstudy offers high anatomic detail and resolution of bone with osseous fragmentationand joint subluxation being well visualized (101).

Technetium bone scans are often used in diabetic foot infections although thismodality lacks specificity, especially in the neuropathic patient (102). Three-phasebone scans may be indicated in the early detection of osseous pathology such asosteomyelitis, fractures, and Charcot arthropathy. However, such imaging tests arebest utilized to confirm clinical suspicion and have higher specificity when combinedwith other scintigraphic techniques such as white blood cell scans (98,103,104).

Gallium 67 citrate is another nuclear medicine technique that is not used asfrequently today due to more accurate alternative imaging studies. This study can beused in concert with technetium bone scans to aid in the diagnosis of osteomyelitisand also may be of value in the presence of acute osteoarthropathy (98,100,104).

Indium-111 leukocyte scans, TcGG-labeled white-cell scan (HMPO), or othervariations of white blood cell scintigraphy are useful in differentiating betweenosteomyelitis and neuropathic arthropathy due to their relatively high sensitivity andspecificity. These tests are expensive and time consuming, but are available at mosthospitals when early identification of bone infection is required (96,100,103,105– 108).

Magnetic resonance imaging (MRI) is often used in evaluating soft-tissue andbone pathologies. This scan may be indicated to aid in the diagnosis of osteomyelitis,deep abscess, septic joint, and tendon rupture. It is a readily available modality whichhas a very high sensitivity for bone infection and can also be used for surgicalplanning (96,100,109). Despite its high cost, MRI has gained wide acceptance in themanagement of patients with diabetic foot infection.

Vascular Procedures

When the history and physical examination suggest ischemia or the presence of anonhealing ulcer with absent pedal pulses, further noninvasive testing is warranted.Noninvasive arterial studies (NIAS) should be performed to determine lower extremityperfusion. Such studies may include Doppler segmental arterial pressures, and wave-form analysis, ankle-brachial indices (ABI), toe pressures, and transcutaneous oxygentension (TcPO2) (34,110,111). Ankle-brachial indices may be misleading since anklepressures can be falsely elevated due to medial arterial calcinosis and noncompress-ibility of affected arteries (112,113). A growing body of evidence suggests that toeblood pressures may have a role in predicting those diabetic patients at risk for footulceration as well as in the prediction of successful wound healing (34,114–116). Tran-scutaneous oxygen tension measurements have received similar support in the literature(33,49,117). Although not consistently predictive of wound healing outcomes, thesephysiologic measures of tissue oxygenation are highly predictive of wound healingfailure at levels below 25 mm Hg. (49,117,118). Both of these tests can be performeddistally on the foot, regardless of arterial calcification in the major pedal arteries, andare favorable at pressures in the range of 40 mm Hg (37,115).

Laser Doppler velocimetry and measurement of skin perfusion pressure (SPP)with this modality has been used primarily in research settings, but can accuratelyassess blood flow velocity in the superficial arterioles and capillaries of the skin(118–121). Several recent reports indicate that laser Doppler measurement of SPPcan be highly predictive of critical limb ischemia and wound healing failure at levelsless than 30 mm Hg (120,121).


Vascular consultation should be considered in the presence of abnormalnoninvasive arterial studies and a nonhealing ulceration (22,50). Arteriographywith clearly visualized distal runoff allows appropriate assessment for potentialrevascularization (122,123). Digital subtraction angiography (DSA) or magneticresonance angiography (MRA) are alternatives for evaluation of distal arterial perfu-sion (122,124).

Neurologic Procedures

Peripheral sensory neuropathy is the major independent risk factor for diabetic footulcerations (15,17,31,33,53). The patient history and physical examination utilizingthe 5.07 Semmes-Weinstein monofilament (10 g) wire is sufficient to identifythose individuals at risk for ulceration (17,125–127). Vibration perception thresholdassessment with the Biothesiometer is also useful in predicting those patients at highrisk for ulceration (32,35). More sophisticated studies, such as nerve conductionstudies, are rarely necessary to diagnose peripheral sensory neuropathy. Patientswith neuropathic ulcerations will usually have such profound sensory neuropathythat these studies add little to the management of these patients.

Plantar Foot Pressure Assessment

High plantar foot pressures have been identified as a significant risk factor for ulcer-ations (15,17,32,35,127). Measurement of these foot pressures is possible utilizinga variety of modalities. Several computerized systems can provide quantitativemeasurement of plantar foot pressure (128–131). These measurements may beimportant in identifying areas of the foot at risk for ulceration and possibly inthe evaluation of orthotic adjustments. Their primary usage, however, has beenin the area of diabetic foot research. The Harris mat, while not as sophisticated,can provide a qualitative measurement of plantar foot pressures and can identifypotentially vulnerable areas for ulceration (132).

ASSESSMENT AND TREATMENT OF PATHOLOGIC ENTITIES (FOOT ULCER, INFECTION,AND CHARCOT)

Effective management of diabetic foot disorders requires knowledge of the potentialpathologies, the associated classification systems and the principal tenets of inter-vention. Ulceration, infection, and Charcot arthropathy, are the most significant ofthese pathologies and classification systems have been developed for each entity.While the conditions may be seen either as an isolated event or coexisting in thesame extremity, each entity is discussed independently.

Diabetic Foot Ulcers: Assessment

(See Color Plate 2 on page 29.)

Extremity Assessment

The lower extremity must be assessed for vascular and neuropathic risk factors. Theacceptable evaluation parameters are listed in Table 3. Although positive findingsin the neurologic examination rarely require further evaluation, positive findings ofvascular insufficiency may require further consultation. The indications for vascularconsultation include an ankle brachial index of less than 0.7, toe blood pressures<40 mm Hg or TcPO2 levels of less than 30 mm Hg, since these measures of arterialperfusion are associated with impaired wound healing (33,37,49,115,117).


TABLE 3 Vascular and neurologic examination of the lower extremity

Evaluation Parameters Normal Values

VascularPalpation of pulses ž PresentDependent rubor ž AbsentVenous filling time ž <20 sCapillary refill ž <3 sArterial Doppler exam for ankle-brachial index (ABI) ž 1.1Toe pressures ž >40 mm HgTranscutaneous oxygen tension (TcPO2) ž >40 mm Hg

NeurologicSemmes-Weinstein 5.07 monofilament (10 g) ž DetectedBiothesiometer (vibration perception threshold) ž <25 VVibration perception — 128 cps tuning fork ž DetectedDeep tendon reflexes ž Present

Ulcer Evaluation

Description of the ulcer characteristics on presentation is critical for the mapping ofits progress during treatment (22,30). While some characteristics are more importantthan others, they all have a prognostic value during management. The presumedetiology of the ulcer needs to be determined (i.e., chemical vs. mechanical) as wellas ascertaining whether the lesion is neuropathic, ischemic, or neuroischemic incharacter (37). The evaluation should include the size and depth of the ulcer, aswell as a description of the margins, base, and geographic location on the extremityor foot. All but the most superficial ulcers should be examined with a blunt, sterileprobe. The description should note whether or not the sterile probe detects sinus tractformation, undermining of the ulcer margins, or extension of the ulcer into tendonsheaths, bone, or joints. A positive probe to bone finding has a high predictivevalue for osteomyelitis (133). The existence of odor or exudate and the characterof each should be noted. Cultures may be necessary when signs of inflammationare present. Current recommendations for culture and sensitivity include thoroughsurgical preparation of the wound site with curettage of the wound base for specimenor with aspiration of abscess material (22).

Classification of Ulcers

Appropriate classification of the foot wound is predicated upon its thorough assess-ment, should facilitate its treatment, and be generally predictive of expectedoutcomes (22). Several systems of ulcer classification are currently in use in thisnation and abroad in an attempt to meaningfully describe these lesions and to commu-nicate severity (16,22,37,38,134–137). Perhaps the easiest system is to simplyclassify the lesions as neuropathic, ischemic, or neuroischemic with descriptors ofwound size, depth, and infection (37). Regardless of which system is ultimatelyused, the clinician must be able to easily categorize the wound and, once classified,the ensuing treatment should be directed by the underlying severity of pathology.

Although no single system has been universally adopted, the classificationsystem most often used was described and popularized by Wagner (137). Sincethis system fails to consider the important roles of infection, ischemia and othercomorbid factors, subsequent authors have modified the classification systems byincluding descriptors for these considerations (135,136).


In the Wagner classification system, foot lesions are divided into six gradesbased on the depth of the wound and the extent of tissue necrosis (137):

ž Grade 0 — Preulcer. No open lesions, skin intact; may have deformities,erythematous areas of pressure or hyperkeratoses.

ž Grade 1 — Superficial ulcer. Disruption of skin without penetration of thesubcutaneous fat layer. Superficial infection with or without cellulitis maybe present.

ž Grade 2 — Full-thickness ulcer. Penetrates through fat to tendon, or jointcapsule without deep abscess or osteomyelitis.

ž Grade 3 — Deep ulcer which may or may not probe to bone, with abscess,osteomyelitis, or joint sepsis. Includes deep plantar space infections orabscesses, necrotizing fasciitis, and tendon sheath infections.

ž Grade 4 — Denotes gangrene of a geographical portion of the foot such astoes, forefoot or heel. The remainder of the foot is salvageable though it maybe infected. (See Color Plate 3 on page 29.)

ž Grade 5 — Gangrene or necrosis to the extent that the foot is beyond salvageand will require a major limb- or life-sparing amputation.

Failure of the Wagner classification to specifically address infection andischemia within each grade (30) has been recognized and hybrid schemes have beendeveloped to account for these important attributes of foot ulcers (16,134). A simpli-fied system which only attaches modifiers for ischemia (A) and infection (B) to thewell-known Wagner system is presented (Table 4), recognizing that grades 3 through5 usually have some degree of infection inherent within these lesions.

Another hybrid method for classifying diabetic foot lesions has been popularizedby the University of Texas and has been retrospectively validated within thatcenter (135,136). This scheme employs four grades of depth with four associatedstages based on ischemia, infection, or both (Table 5). This system is also generally

TABLE 4 Modified Wagner Classification System

Grade Lesion

0 No open lesions: may have deformity or cellulitisA IschemicB Infected

1 Superficial ulcerA IschemicB Infected

2 Deep ulcer to tendon, or joint capsuleA IschemicB Infected

3 Deep ulcer with abscess, osteomyelitis, or joint sepsisA IschemicB Infected

4 Localized gangrene — forefoot or heelA IschemicB Infected

5 Gangrene of entire footA IschemicB Infected


TABLE 5 University of Texas Wound Classification System

Stage Grade

0 I II III

A Pre- or postul-cerativelesioncompletelyepithelialized

Superficial wound,not involvingtendon, capsule,or bone

Woundpenetratingto tendonor capsule

Woundpenetrating tobone or joint

B Infected Infected Infected InfectedC Ischemic Ischemic Ischemic IschemicD Infected and

ischemicInfected and



ischemic

predictive of outcome since increasing grade and stage of wounds are less likely toheal without revascularization or amputation (136).

Imaging studies play an important role in the assessment and evaluation ofthe diabetic foot ulcer (96,98,100). Plain X-rays are indicated based on the extentand nature of the ulcer. Clinical change in the appearance of the ulcer or failure toheal with appropriate treatment may dictate repeating the radiograph periodically tomonitor for osseous involvement (22). Additional imaging modalities such as nuclearmedicine scans, ultrasonography, MRI, and CT may be indicated predicated on theclinical picture. Recommendations for these modalities are discussed elsewhere.

Table 6 summarizes the important elements of the overall assessment of thepatient with a diabetic foot ulcer based upon the underlying pathophysiology,possible causal factors, and important predictors of outcome (16,38,74).

TABLE 6 Assessment objectives for foot ulcerations

Classification: grade, depth, site, clinical descriptors of woundEtiology: mechanical, thermal, chemical traumaNeuropathy: vibration perception, light touch (10-gram monofilament), deep tendon

reflexesVascular: pulses, ankle-brachial index, toe pressures, TcPO2

Infection: cultures, radiographs, probe, scans, MRIDeformity/High Pressure: callus, hammertoes, bunion, Charcot, amputation

Diabetic Foot Ulcers: Treatment

Goals and General Principles of Treatment

The primary goal in the treatment of diabetic foot ulcers is to obtain wound closureas expeditiously as possible. The resolution of foot ulcers and decreasing the rate ofrecurrence can lower the probability of lower extremity amputation in the diabeticpatient (16,30,50,51,76).

The essential therapeutic objectives include:

ž Debridementž Pressure relief (off-loading)ž Appropriate wound managementž Management of infectionž Management of ischemia


ž Medical management of comorbiditiesž Surgical management

Frequent re-evaluation with response-directed treatment is essential. Once healed,the management consists of decreasing the probability of recurrence.

Debridement

Debridement of necrotic tissue is an integral component in the treatment of chronicwounds since they will not heal in the presence of nonviable tissue and debris.Adequate debridement must always precede the application of topical wound healingagents, dressings, or wound closure procedures (22,138–140). Types of debridementinclude: autolytic, enzymatic, mechanical, and surgical. Autolytic dedridementoccurs naturally in a healthy, moist wound environment when arterial perfusionand venous drainage are maintained. The efficacy of enzymatic debridement (usingtopical, proteolytic enzymes) has been questioned in the literature and suffersfrom a lack of randomized, controlled clinical trials (22,38,141). However, it iscommonly used as an adjunctive therapy in the management of chronic wounds.Mechanical debridement, including sharp debridement, wet-to-dry dressings, andhigh pressure irrigation or pulsed lavage, are well accepted therapeutic measures(18,22,38,141,142). The only method which has been proven efficacious in clinicaltrials is surgical debridement (140).

Surgical debridement is a key component and a cornerstone in the managementof diabetic foot ulcers. Thorough sharp debridement of all nonviable soft tissue andbone from the open wound is accomplished primarily with a scalpel, tissue nippers,and/or curettes. Excision of necrotic tissue extends as deeply and proximally asnecessary until healthy, bleeding soft tissue and bone are encountered. Any callustissue surrounding the ulcer must also be removed. A diabetic ulcer associated with adeep abscess requires hospital admission and immediate incision and drainage. Jointresection or partial amputation of the foot is needed in the presence of osteomyelitis,joint infection, or gangrene (50,87,88,96).

Necrotic tissue removed on a regular basis can expedite the rate at which awound heals and has been shown in a recent study to increase the probability ofattaining full secondary closure (140,143). Less frequent surgical debridement canimpact negatively on the rate of wound healing and secondarily increase the risk ofinfection. Surgical debridement is repeated as often as needed if new necrotic tissuecontinues to form. Weekly debridement is commonly required.

Off-loading

Reducing pressure to the diabetic foot ulcer is an essential component of treatment(22,34,50,128,144). Without proper off-loading and pressure reduction, ulcers willcontinually be traumatized to the point that they cannot heal. A study reported in1999 supports the major role that minor trauma (repetitive stress, shoe pressure, etc.)plays in the causal pathway to ulceration (15).

The choice of off-loading modality should be determined by the patient’s physicalcharacteristics and ability to comply with the treatment, as well as the location andseverity of the ulcer. Various centers prefer specific initial modalities, but the clinicianfrequently must alternate treatments based upon clinical progress of the wound. It is notunusual to practice step-up therapy where increasingly effective modalities are usedwhen little improvement is noted with initial therapy. Some centers prefer to applytotal contact casts (TCC) initially and then step-down to less restrictive modalitieswhen lesions have healed or are nearly healed.


The following off-loading techniques have been found to be useful in the manage-ment of diabetic foot ulcers:

ž Total nonweightbearing: crutches, bed, wheel chairž Total contact casting (145–147)ž Foot casts or boots (148,149)ž Removable walking braces with rocker bottom soles (150)ž Total contact orthoses — custom walking braces (144)ž Patellar tendon-bearing braces (151)ž Half shoes or wedge shoes (152)ž Healing sandal — surgical shoe with molded plastizote insole (38,153)ž Accommodative dressings: felt, foam, felted-foam, etc, (38,154,155)ž Shoe cutouts (toe box, medial, lateral, or dorsal pressure points)ž Assistive devices: crutches, walker, cane, etc.

It is critically important to remove the patient from the shoes that caused theulcer. In fact, the consensus of opinion is such that no patient with an active footulcer should be placed back into an unmodified shoe until complete healing hasoccurred (22,37,50,128).

Wound Management

Generally, a moist wound environment bandaged to protect it from trauma and localcontamination has been shown to facilitate the healing process (141,156). The typeof dressing selected depends upon such factors as size, depth, location, and thewound surface. Normal sterile saline or fractionalized sterile saline (such as 0.5%normal) are frequently used and are often considered as a standard for wound care.However, there is a conspicuous lack of formal clinical trials to support this practice.Many wound care products are available as viable alternatives to saline-moistenedgauze dressings, although few of these agents have been subjected to comparativetrials (157). These various agents are grouped into different categories and each hasits own indications for usage. A brief listing of the dressings and topical agentsavailable are presented in Table 7.

The length of time a wound must exist until it is considered chronic is not welldefined in the literature. The Wound Healing Society defines a chronic wound as onewhich has failed to proceed through an orderly and timely repair process to produceanatomic and functional integrity (138). Skin ulcers, including diabetic foot ulcers,are included in the category of chronic wounds (22,141). Recent clinical trials forthe treatment of such wounds have used a period of at least 8 weeks during whichthere have not been signs of active healing or attaining closure (143). The primarygoal in treating the chronic ulcer is to convert it to an acute wound which will thenpossess the active matrix and cells needed for healing. Reassessment of the entiretreatment program is the first step in establishing a new directed approach. The basicprinciples of treatment discussed for the acute ulcer apply here.

Chronic ulcers have demonstrated benefit from autologous platelet releasates orgenetically engineered products, such as recombinant DNA platelet-derived growthfactor (becaplermin) (143,158,159). These agents have been shown to stimulatechemotaxis and mitogenesis of neutrophils, fibroblasts, and monocytes as wellas other components that form the cellular basis on which wound healing candevelop (157,160). In one pivotal randomized placebo-controlled blinded trial inpatients with full-thickness diabetic foot ulcers, recombinant human platelet-derivedgrowth factor (becaplermin) demonstrated a 43% increase in complete closure versusplacebo gel (50% vs. 35%) (159). In an economic analysis based upon a large clinicaltrial, 358 patients treated with becaplermin demonstrated a 5% reduction in episode


TABLE 7 Wound care products

Category Indications Contraindications

DressingsTransparent films — polyurethane film Dry to minimally draining Infection; significant drainage;

with adhesive layer; semipermeable over prominence or frictionHydrogels — gel, sheet, Dry to minimally draining Moderate or heavy drainage

gauze; 95% water or glycerinFoam — polyurethane foam; Moderate, large exudate Dry wounds

open cell, absorbent clean wound surfaceHydrocolloids — wafer with adhesion Low to moderate Heavy drainage; sinus tract

carboxymethylcellulose; pectin drainage or deep wound requiresgelatin; impermeable to oxygen debridement, packing

prior to hydrocolloidCalcium alginates — pad Heavy exudative Minimal drainage or dry wounds

made of fiber from seaweed woundsGauze pads — Sterile cotton Low to heavily Undefined

draining wounds,surgical wounds

Collagen dressings — composite Low to heavily Dry woundspads with collagen component draining wounds

Antimicrobial dressings — contain Infected or clean Allergies to componentssilver or iodine in various preparations wounds to prevent

infection

Topical therapies/agentsSaline — amorphous hydrogels; skin Clean or infected Undefined

cleansers woundsDetergents/antiseptics — povidone- Contaminated or Healthy, granulating wounds

iodine, etc. infected woundsTopical antibiotics — Silver Contaminated or Healthy, granulating wounds

sulfadiazine, Bacitracin, Mupiricin, etc. infected woundsEnzymes — collagenase, papain- Necrotic or Healthy or infected wounds

urea, etc. escharotic woundsGrowth factors — Becaplermin gel Neuropathic Infected wounds, necrotic

(Regranex); Autologous platelets diabetic foot ulcers woundsDermal/skin substitutes — Apligraf; Venous stasis ulcers; Infected wounds, necrotic

Dermagraft(not available in U.S.) diabetic Foot Ulcers wounds

costs when compared to good wound care alone. Savings were largely due to a21% lower incidence of hospitalizations. However, such improvements in outcomesare also dependent on the presence or restoration of adequate vascular supplyin conjunction with good wound care regimens and frequent debridement (161).Becaplermin gel (Regranex) has received an indication from the FDA for thetreatment of neuropathic diabetic foot ulcers.

Tissue-engineered human dermal replacement (Dermagraft) and human skinequivalent (Apligraf) containing the characteristics of dermis or both dermisand epidermis, respectively, have also shown promise in preliminary clinicaltrials (141,162–164). These bioengineered tissue therapy products do not requirethe donor site needed for conventional split or full-thickness skin grafts. Theyfunction not only as biological dressings, but also as delivery systems for growthfactors and extracellular matrix components through the activity of live human


TABLE 8 Alternative technologies for wound management

Modality References

Hyperbaric oxygen therapy (HBO) 165–168Vacuum assisted closure (VAC) 170Heat therapy 157Laser therapy 171Mechanical constant tension 172Larval/maggot therapy (Biodebridement) 173Electrical stimulation (ESTR) 174,175

fibroblasts contained in their dermal elements (141,157). Apligraf has recentlyreceived approval for use on diabetic foot ulcers in the United States.

Hyperbaric oxygen therapy (HBO), might be of benefit although this has notbeen proven conclusively in prospective clinical trials (22). Several reviews andretrospective studies on this modality purport efficacy in difficult wounds wherethere might be nonreconstructible occlusive vascular disease or limb-threateninginfection (165–168). Local, topically applied oxygen has not been proven effectivein clinical trails and cannot be advocated for use (169). HBO and other alternative orunproven technologies which are occasionally used in the management of diabeticfoot wounds are listed in Table 8 (157,165–168,170–175).

A variety of other modalities have also been advocated for the chronic wound,although most lack supportive clinical trials. Efficacy for many of these has notclearly been demonstrated and studies supporting their use in diabetic foot ulcersare still needed (176,177).

Management of Infection

Pedal ulcerations provide a portal for pathogen entry and therefore can often leadto the secondary development of infection (88). Rarely does infection directly causeulceration in the diabetic foot (15). However, when unaddressed this process canthreaten both limb and life. Its presence must be determined and identified as eitherlocal (soft tissue or osseous), ascending and/or systemic. Treatment requires earlyincision and drainage with broad-spectrum empirical antimicrobial therapy (22,50).Debridement of all necrotic tissue including bone and joint resection when thesestructures are involved must also be performed followed by culture-directed antibiotictherapy. In cases involving gangrene or extensive tissue loss, early amputation atthe appropriate level should be considered to remove the focus of infection and toattain viable tissue margins (50,85,87). The necessity for culturing and antimicrobialtreatment of clinically uninfected wounds is still under investigation (22). A thoroughdiscussion of the management of infected wounds is presented later in this document.

Vascular Insufficiency

Arterial perfusion is a vital component for healing and must be assessed in theulcerated patient. Vascular reconstructive surgery of the occluded limb improvesprognosis and may be required prior to debridement, foot-sparing surgery, and/orpartial amputation (50,178,179).

Management of Comorbidities

Diabetes is a multiorgan systemic disease, and comorbidities must be assessedand managed via a multidisciplinary team approach for optimal outcomes. Patient


TABLE 9 Ulcer Treatment Guidelines

ž Debridement of necrotic tissue: surgical, mechanical, autolytic, enzymaticž Pressure reduction: crutches, healing sandal, contact cast, walking brace,

foot cast, felt aperture padding, etc.ž Wound care: topical saline gauze dressings, antiseptics, special dressings,

growth factors (becaplermin), bioengineered tissues, HBO, etc.ž Infection: incision and drainage, empiric and culture directed antibiotics, soft

tissue/bone/joint resection, amputationsž Vascular: pedal or proximal bypass, endovascular proceduresž Medical management: hyperglycemia, hypertension, nutritional status, renal

statusž Reduce the risk of recurrence:

Regular podiatric care and evaluationPatient preventative educationProtective footwearPressure reductionSurgery to reduce bony prominence / chronic pressure points

compliance has been identified as a significant factor in the expected prognosis andthe prevalence of both ulceration and limb loss (74,75,136,180).

Surgical Management

Surgical intervention can generally be classified as curative, ablative, or elec-tive (181). Curative surgery, as the name implies, is performed to effect healingof a nonhealing ulcer or a chronically recurring one when off-loading and stan-dard wound care techniques are not effective (181). Multiple surgical procedures areaimed at removing areas of chronically increased peak pressure. Curative proceduresinclude those used to resect infected bone and/or joints as an alternative to partialfoot amputation (22). Operations frequently performed in this regard include exos-tectomy, digital arthroplasty, sesamoidectomy, single or multiple metatarsal headresections, joint resections, or partial calcanectomy (38,153,181–189).

Ablative surgery, often synonymous with amputation, is a common sequelato gangrene and ulcers associated with osteomyelitis. Ablative surgical interventionrequires removal of all infected and necrotic tissue to the level of viable soft tissueand bone. When possible, it is also performed in a manner to allow for the maximumfunction from the remaining portion of the limb (50).

(See Color Plate 4 on page 30.) Wounds may be closed primarily if the surgeonis confident no infection or ischemic tissue remains and enough soft tissue isavailable. Other wounds may be packed open initially, requiring well controlledand frequently assessed wound care with delayed primary closure or closure bysecondary intention. Mechanical assistance using a variety of skin stretching devicesare the surgeon’s option and may help to attain delayed primary closure for somewounds (172). Plastic surgical techniques utilizing split- and full-thickness skingrafts and a variety of flaps are other options that may be utilized (190,191). Allpatients must be assessed on an individual basis for the selection of the surgicalmanagement that best meets their needs. Secondary wound healing with or withoutadjunctive wound therapies may still be the best choice for some patients.

Elective surgery will be discussed in the following section. The basic guide-lines or tenets for the management of diabetic foot ulcers are summarized in Table 9.


Diabetic Foot Service

Hospital Referral Primary Care Physician

Consultants

Infectious DiseaseOrthopedistCardiologistNeurologistNephrologistTeaching Nurse

VascularSurgeon

DiabetologistInternist

PodiatristGatekeeper

Ancillary services

Radiology / Nuclear MedicineVascular laboratoryClinical laboratoryPhysical therapyPedorthist / Orthotist

FIGURE 2 The multidisciplinary diabetic foot team.

Preventing Ulcer Recurrence

Prevention is considered a key element in avoiding ulcer recidivism and diabeticlower extremity amputation (16,22,30,34,51,92). This is best accomplished with amultidisciplinary approach consisting of a team of dedicated professionals committedto this ideal (36,74,75,192–196). Typical team members might include the followingspecialists: podiatrist or podiatric surgeon, internist, endocrinologist, infectiousdisease physician, cardiologist, nephrologist, neurologist, vascular surgeon, ortho-pedic surgeon, teaching nurse, and pedorthist (Fig. 2). Patient education assumesa primary role in this scheme and encompasses instruction in foot hygiene, theneed for daily inspection, proper footwear, and the necessity for prompt treatmentof new lesions (16,74,197–200). Regular podiatric visits, including debridementof calluses and ingrown toenails, provide an opportunity to reinforce appropriateself-care behavior as well as allowing early detection of new or impending footproblems (201). Therapeutic shoes with pressure-relieving insoles and high toebox which protect the high-risk foot are an essential element of the preventionprogram and have been associated with significant reductions in ulcer devel-opment (36,202–204). Walking/athletic style footwear or commercially availableorthopedic shoes can be accommodated with various types of foot orthoses to effec-tively relieve high plantar pressures. Custom-molded shoes are sometimes neces-sary for severely deformed feet which cannot be adequately protected by standardfootwear.


Prophylactic or elective surgical correction of structural deformities thatcannot be accommodated by therapeutic footwear in the carefully selectedpatient, serve to reduce high-pressure areas and ultimately prevent ulcerrecurrence (38,50,181,183,188,189,205,206). Many of the procedures previouslymentioned in the discussion on curative surgery would also be indicated in theelective reconstruction of the nonulcerated foot. Common operations performedin this regard include the correction of hammertoes, bunions, and variousexostoses of the foot. Tendo-Achilles lengthening procedures are often performedas ancillary procedures to reduce forefoot pressures which contribute to recurrentulcerations (207). Since patients with healed ulcers are at high risk for futureulceration, these prevention efforts must be incorporated into a life-long surveillanceand treatment program (16,22,34,37,51,74,92).

A Practice Pathway (algorithm) which summarizes the important parametersfor both assessment and treatment of foot ulcers is illustrated in Figure 3.

Diabetic Foot Infections

Foot infections are major causes for hospitalization of patients with diabetesand are also important causal factors leading to lower limb amputation (88).There may be various different presentations of diabetic foot infections as wellas several ways to classify these entities (208). They may be described in termsof severity, extent of involvement, clinical appearance, location, and etiology. Anysuch system for categorizing these infections should also serve to facilitate theirmanagement and predict outcomes. Recent literature suggests that a well-acceptedmethod of classifying such entities is to simply categorize them into non-limb-threatening or limb-threatening infections (18,22,50,88,94). This scheme does indeedimply severity of infection and, accordingly, directs subsequent management whileportending a general prognosis for outcome.

Non-Limb-Threatening Infections

Clinically, non-limb-threatening infections are usually seen with an ulceration whichis typically superficial. Significant ischemia is not present, and the wound should notprobe to bone or joint. Ulceration, however, does not need to be present since non-limb-threatening infections can result from small puncture wounds, scratches, orsimple fissures. Cellulitis is 2 cm or less from the ulceration or portal of entry.These patients are medically stable and usually do not present with signs andsymptoms of systemic involvement. This relatively mild to moderate infectioncan usually be managed on an outpatient basis with close supervision from thepractitioner (18,22,50).

Limb-Threatening Infections

(See Color Plate 5 on page 30.) Diabetic foot infections in this category havecellulitis that extends greater than 2 cm (18). Additional clinical features may includefever, edema, lymphangitis, hyperglycemia, leukocytosis, and/or ischemia. If anulcer is present, it may probe to bone or joint, which is highly predictive ofosteomyelitis (133). Because the diabetic patient with a relatively severe infectionmay not necessarily present with these signs and symptoms, it is important toreview the entire clinical assessment to guide the practitioner to the proper courseof treatment (95). Gangrene, abscesses, osteomyelitis, and necrotizing fasciitis mayalso be present. Hospitalization is required in order to treat the infection as wellas the systemic sequelae. Patients with poor vascular status and ischemia have an


Diabetic Foot Disorders ULCER: A Clinical Practice Pathway

See Infection Pathway Noninfected

HISTORYDurationPrior Ulcer?Pain / SensationPrior TreatmentVascular History

GENERAL FOOT EXAM

VascularNeurologicStructural DeformityDermatologic

CLINICAL SENSORYEXAM

Semmes-WeinsteinFilamentVibratoryProprioceptionOther as Needed

Ulcer Examination

Ulcer Appearance -e.g., GranulationTissue, Necrotic,Fibrotic Tissue

Ulcer Periphery - e.g.,Undermining,

Hyperkeratosis,Erythema

Noninvasive ExamDoppler PVRSegmental, TcPO2

and Toe Pressures

Pulses (+)

Pulses (-) IntactNo Further

StudiesIndicated

ImpairedEMG, NCS,

OtherStudies

Indicated prn

Normal

Abnormal

VascularConsult

Ulcer Size/Depth(Measurement)

Probe To Bone

Gangrene Present Amputation Likely

See Infection Pathway

See Infection Pathway Consider X-Ray

TREATMENT ASAPPROPRIATE

WOUND CAREDebridement,

Drainage, +/- CulturesFrom Base of Ulcer,

Dressings, Topical Rx:e.g. Growth Factors

(Becaplermin)

OFF-LOADINGCasts, Braces, Surgical Shoes,

Wheelchair,Crutches, Etc.

Positive forOsteomyelitis

Healed

Healed

Follow-Up andFrequent Re-evaluationto Prevent Recurrence,

Patient Education

Not Healed

Repeat Evaluation andTreatment as

Necessary

Consider SurgicalCorrection of Deformity Not Healed

Negative forOsteomyelitis

Consider Further Imaging, Bone Scan, MRI, Leukocyte Scan

Location - e.g.,Non-weightbearing,

Weightbearing, BonyDeformity

FIGURE 3 Ulcer: A Clinical Practice Pathway.


Plate 1 Below-knee amputation resulting from afoot ulcer.

Plate 2 Classic diabetic ‘‘malperforans’’foot ulcer.

Plate 3 Ischemic gangrene of the forefoot.


Plate 4 Transmetatarsal amputation.

Plate 5 Limb-threatening infection with largemidfoot ulceration.


Plate 6 Osteoarthropathy of the ankle showing severe osteolysis and talonaviculardislocation.

Plate 7 Classic appearance of the diabetic Charcot foot.


Plate 8 Radiographic appearance of Charcotfoot shown in Plate 7.

Plate 9 Midfoot osteoarthropathy.


increased potential for limb amputation and require prompt consultation for potentialrevascularization (22,50).

Assessment of Diabetic Foot Infections

When evaluating the patient, a problem-directed history and physical examinationshould be obtained. A systematic approach to the complete assessment of thesepatients is required since there is evidence that they are often inadequately evaluatedeven when hospitalized (99). The past medical history should assess the neurologic,cardiovascular, renal, and dermatological status of the diabetic patient. Medicationsthat the patient is currently taking, as well as prior antibiotic use, may interferewith planned treatments or indicate that standard treatments are likely to be ineffec-tive. Pain should be considered an unreliable symptom in persons with peripheralneuropathy. The patient should be questioned regarding previous ulcerations, infec-tions, trauma, and surgeries at the present site or any other past location of infection.Constitutional symptoms such as nausea, malaise, fatigue, vomiting, fever, or chillsare important clinical clues when presented with an infected diabetic foot. Severeinfection or sepsis may be present and must be considered. In approximately 50%of diabetic patients presenting with significant infection, however, systemic signs(fever and leukocytosis) are absent (95). Frequently, the only indication of infectionis unexplained or recalcitrant hyperglycemia (18). Laboratory testing might includeCBC with or without differential, blood cultures, glycosylated hemoglobin, fastingblood sugar, sedimentation rate, and urinalysis. Other tests should be performed asindicated by the patient’s condition or comorbidities.

The history of the wound or infection should include the onset, duration, andappearance before infection of the area. Depth or size of the ulcer, amount of drainage,swelling, color, odor, and extent of infection should be evaluated. The infection orulcer should be probed to determine the presence of bone or joint involvement, sinustracts, or extension into tendon sheaths. The latter are common routes for the spreadof infection both distally and proximally. If bone is exposed it is assumed that thepatient has osteomyelitis until proven otherwise (86,133). Both anaerobic and aerobiccultures should initially be obtained, since antibiotic therapy will be required. Reliablecultures should be obtained from pus or curettage of the ulcer base, since studieshave shown good concordance with the true pathogen (208–210). For patients withclinically uninfected or noninflamed neuropathic ulcers, the role of antibiotic therapyis still in question (22). In these instances, therefore, wound culture is most likelyunnecessary (209). If osteomyelitis is suspected, bone cultures are necessary to makethe definitive diagnosis as well as to isolate the true pathogen (96). However, this mustbe balanced against the possibility of contaminating noninfected bone in the presenceof an active soft-tissue infection.

Imaging studies are helpful in the overall assessment of diabetic foot infections,notwithstanding their shortcomings. Plain-film x-rays may indicate the presence ofbony erosions and/or gas in the soft-tissues. It is important to note that the demon-stration of osteomyelitis by plain radiographs lags the onset of bone involvementby 10–14 days (96,100). Radionuclide bone scans such as Tc99 may demonstrateabnormal uptake of the radionuclide before changes are visible on radiographs (98).This finding may be less specific in patients with peripheral neuropathy or with anypre-existing osseous condition that causes increased bone turnover ( e.g., surgery,fracture, neuropathic arthropathy) (102). A combination of scans such as the Tc99mand an indium-labeled leukocyte scan, or the Tc99m-HMPAO-labeled leukocytescan may aid in differentiating between Charcot arthropathy and osteomyelitis withgreater accuracy (104–106). MRI has generally supplanted the CT scan in the earlydiagnosis of osteomyelitis due to its higher tissue contrast and ability to detect


both soft-tissue and marrow inflammation (96,107,211). MRI can also be used tofollow the resolution of infection or as an aid in surgical planning (109). None of theaforementioned imaging modalities are 100% sensitive and specific for diagnosing orruling out the presence of bone infection. Furthermore, these tests may not be readilyavailable and are quite expensive. Appropriate clinical assessment and diagnosticacumen should therefore remain the guiding principles to management.

Potential items for initial patient evaluation on hospital admission include thefollowing:

ž History and physicalž Radiographsž Vascular testingž Possible consultations — medicine/endocrine, infectious disease, vascular

surgery, orthopaedic surgery, nutritionž Cultures — reliable wound cultures, blood culturesž Labs — CBC with differential, sedimentation rate, glucose, others

Treatment of Diabetic Foot Infections

Diabetic foot infections should be managed with a multidisciplinary team approach(88,95,192,194). This should include obtaining the appropriate consultations aswell as admitting the patient to a hospital setting in emergent cases or when thepatient does not respond to a course of outpatient treatment. Hospitalization oflimb-threatening infections should be considered mandatory. Diabetic foot infec-tions, whether non-limb-threatening or limb-threatening, need to be monitored veryclosely (50). Equally important, especially in the outpatient management of footinfections, patient compliance and education must be addressed in order to providethe best possible outcome.

Non-Limb-Threatening Infections

Non-limb-threatening infections complicating foot ulcers may be initially treated inan outpatient setting (18,22,88,212). Many of these mild or moderate infections aremonomicrobial, with Staphylococcus aureus, Staphylococcus epidermidis, and strep-tococci being the most common infecting organisms (86,88,213). Cultures shouldbe taken from a curettage of the ulcer base to obtain a reliable specimen (208).Antibiotic therapy should be initiated as soon as possible with an agent providingadequate gram-positive coverage, recognizing that gram-negative organisms mightalso be involved (22,50,86,87) (Table 10). Antibiotic therapy should be adjustedaccording to culture results and the patient’s response to treatment. The woundshould be assessed and cleansed thoroughly, using proper debridement as indicated.Of the several topical agents that can be used on the infected wound, no one agentor topical antibiotic has been proven superior. The wound itself should be managedaccording to principles discussed under “Wound Management.” Most importantly,the patient should be reassessed within 48–72 hours (18,87). If no improvement isnoted, hospitalization with intravenous antibiotics should be considered. Manage-ment of this type of infection should also include close monitoring of the patient’shyperglycemia and general health status. Patient compliance as well as a reductionin the pressure of the infected limb must be considered early on in the treatment ofany diabetic foot infection (50).

Limb-Threatening Infections

Limb-threatening infections may have life-threatening complications, especiallywhen left untreated. Due to immunosuppression from diabetes, up to 50% of these


TABLE 10 Empirical antibiotic therapy: non-limb-threatening infection

Oral Agents Parenteral Agents

Amoxicillin/ Clavulanate CefazolinCephalexin CefotaximeDicloxacillin Oxacillin or NafcillinClindamycin Ampicillin/ SulbactamLevofloxacin Clindamycin

patients may present with no systemic symptoms or leukocytosis (95,97,214). Otherpatients, however, do present with evidence of systemic toxicity including fever,chills, loss of appetite, and malaise. Such findings in diabetic patients shouldalert the clinician to the potential severity of infection (209). Often present is anuncontrollable hyperglycemia, despite routine therapy and a loss of appetite (85,215).

Limb-threatening infections have one or more of the following findings: greaterthan 2 cm of cellulitis, lymphangiitis, soft-tissue necrosis, fluctuance, odor, gangrene,and/ or osteomyelitis. When such an infection is recognized, the patient requiresemergent hospital admission for appropriate intervention (22). Upon admission, thepatient requires a complete history and physical examination. The patient’s cardio-vascular, renal, and neurologic risks should be evaluated to assess for secondarycomplications of diabetes and associated comorbidities. The foot requires a thor-ough evaluation to assess clinical extent of the infectious process. Vascular statusmust be assessed to ensure adequate arterial inflow is present. Ulceration, if present,must be probed for bone or joint involvement and subcutaneous sinus tracts,while also measuring for size and depth (50,133). Radiographs should be takenand evaluated for evidence of osteomyelitis or soft-tissue gas. If gas is identi-fied in the ankle or hindfoot, radiographs of the lower leg should be obtainedto assess the extent of the gas formation. Deep, reliable aerobic and anaerobiccultures should be obtained from the wound (87,210). Blood cultures should beobtained in the presence of high fever since such clinical findings are often indica-tive of septicemia (22). Other appropriate laboratory studies, including CBC withdifferential and sedimentation rate, should be obtained as appropriate. Glucosemanagement must be initiated to optimize metabolic perturbations and to improveleukocyte function (87). The patient’s nutritional and metabolic status must beassessed and properly maintained since such relatively common impairments inthese patients can have adverse effects on wound healing and resolution of infec-tion (216,217).

Consultations are typically required in the management of these complexpatients, and are indicated for risk assessment and medical management. Medical,endocrinology, cardiology, nephrology, and diabetic teaching nurse consultationsare often routinely necessary to optimize patient care and for full assessment ofsurgical risks (88). Infectious disease and vascular surgery consultations are obtainedwhen complex infections or significant ischemia are identified. A multidisciplinaryapproach to managing these patients has been shown to significantly improveoutcomes (36,74,192–195).

Early surgical treatment of the affected site is typically necessary as an integralpart of infection management (22,50,95,218). This may include simple debridementof the soft tissues, wide incision and drainage of the pedal compartments, oropen amputation to eliminate extensive areas of infection (95,219,220). Aerobic andanaerobic tissue cultures should be obtained at the time of debridement, and should


be obtained from the depth of the wound to provide reliability (210). Although manyinitial drainage procedures can be done at the bedside for neuropathic patients,most will require thorough debridement in the operating room (22). Anesthesiamay include local, regional, or general anesthetics. Spinal blocks are typicallyavoided in patients who may be septic. Even the sickest of patients should beconsidered for emergent incision, drainage, and debridement procedures since theirillness is directly attributable to the severity of their infection. Life-threateninginfections necessitate immediate surgical attention and such procedures should notbe delayed while waiting for radiologic or medical workup of other comorbidconditions (22,50,85,218).

Polymicrobial infection should be anticipated, with a variety of gram-positivecocci, gram-negative rods, and anaerobic organisms predominating. (Table 11).Empirical antibiotic therapy typically includes broad-spectrum coverage for morecommon isolates from each of these three categories (Table 12). Fully compre-hensive empiric coverage is usually unnecessary unless the infection is life threat-ening (86,214). Hospital therapies are usually initiated with intravenous medications,although most fluoroquinolones can be administered orally in conjunction withother parenteral therapy (86,209). Once wound culture results have been obtained,the initial antimicrobial therapy may require adjustment to provide more specificcoverage or to provide therapy against resistant organisms that are causing persistinginfection. Recent evidence also supports the efficacy of initial parenteral therapyfollowed by the appropriate oral agent (221). If the patient develops evidence ofrecurrent infection while under antibiotic therapy, repeat cultures should be obtainedto assess for superinfection. Methicillin-resistant staphylococci have been emergingas important pathogens in chronically treated diabetic foot ulcer patients (222). Theseorganisms must be detected early and treated appropriately to avoid further tissueloss or extension of infection.

The surgical wound may require repeated surgical debridements to completelyeradicate infection and soft-tissue necrosis. Wound care is initiated on the first or2nd postoperative day and may initially involve saline gauze dressing changes. Otherdressings may be utilized to aid with healing and are listed elsewhere. If the woundfails to progress, the patient’s vascularity, nutrition, infection control, and woundoff-loading must be re-evaluated.

Once soft-tissue infection is under control and management of any osseousinfection has been initiated, consideration may be given to wound closure ordefinitive amputation. Restoration and maintenance of function and independenceis the ultimate goal for the patient (50). The residual extremity requires closefollow-up, regular diabetic foot exams, periodic foot care, and appropriate footweartherapy (22,203,204).

Osteomyelitis and joint infection, when identified by clinical assessment orimaging studies, will require excision of bone for microbiological and histopatho-logical evaluation (96). If the patient’s soft-tissue infection is controlled, consid-eration may be given to stopping antibiotic therapy 24–48 hours preoperativelyto improve culture accuracy. Both studies should have positive findings includingnecrosis, chronic inflammatory infiltrates, and positive isolation of bacteria todiagnose osteomyelitis (96,223). Resection of infected bone with or without localamputation and concurrent antimicrobial therapy is the optimal management forosteomyelitis (220,224). If the affected bone has been completely resected or ampu-tated, the infection may be treated as a soft-tissue infection. However, if residual boneis present in the wound, the patient will likely require 4–8 weeks of antibiotic therapybased on the culture results (86,88,96). Intravenous or oral agents may be useddepending on the microbial isolates and the infection severity (209,221). Antibiotic-impregnated bone cement has been advocated for treatment of osteomyelitis but


TABLE 11 Common pathogens in diabetic foot infections

AerobesGram C

Staphylococcus aureus (methicillin-sensitive and resistant)Staphylococcus epidermidis (coagulase negative staphylococci)Streptococcus speciesEnterococcus (Strep. faecalis, Group D Streptococcus)Corynebacterium species (Diptheroids)

Gram �Proteus mirablisProteus vulgarisEscherichia coliKlebsiella speciesSerratia speciesEnterobacter cloacaePseudomonas aeruginosaAcinetobacter species

AnaerobesPeptococcus magnusPeptostreptococcus speciesBacteroides fragilisBacteroides speciesClostridium perfringensClostridium species

OtherCandida albicansCandida species

TABLE 12 Empirical antibiotic therapy: limb- or life-threatening infection

Limb-Threatening Life-Threatening

Ampicillin/Sulbactam Ampicillin/Sulbactam C AztreonamTicarcillin/Clavulanate Piperacillin/Tazobactam C

VancomycinPiperacillin / Tazobactam Vancomycin C Metronidazole C

CeftazidimeCeftazidime C Clindamycin Imipenem/CilistatinCefotaxime š Clindamycin Fluoroquinolone C Vancomycin C

MetronidazoleFluoroquinolone C ClindamycinVancomycin C Levofloxacin C Metronidazole

should only be utilized if the bone has been thoroughly debrided and the soft-tissueenvelope is adequate for wound closure after antibiotic-impregnated bead place-ment (95,225). Typically, gentamycin, tobramycin, or vancomycin are the agentsused in the beads. It is generally recommended that the antibiotic beads be removed2 weeks or so after placement.

Figure 4, A Practice Pathway (algorithm) presents a comprehensive overviewto the diagnosis and management of diabetic foot infections.


HistoryTrauma, Puncture Wound, Foreign BodyFever, Chills, Nausea, MalaiseUlcer? If so, DurationDrainage, Swelling, ErythemaPain / SensationDiabetes Duration / Control

NON-LIMB-THREATENING INFECTION

≤ 2 cm Cellulitis

Superficial Ulcer

Does Not Probe to Bone

No Bone, Joint Involvement

Mild Infection

No Systemic Toxicity

No Significant Ischemia

LIMB-THREATENING INFECTION

>2 cm Cellulitis

Lymphangitis

Edema

Fever +/-

Odor from Wound

Deep Ulcer

Purulent Drainage

Hypotension, Cardiac Arrhythmia (Systemic Toxicity)

Ischemic Changes

DIAGNOSTIC PROCEDURES

Deep Cultures from Base of Ulcer / Wound (Tissue Specimenif Possible)

Diagnostic Imaging - X-Ray, MRI, Nuclear / Bone / LeukocyteScans, Arteriography

Serologic Testing

CBC with Differential

Blood Cultures

ESR

Blood Glucose

Renal and Hepatic Profile as Appropriate

Oral Temperature

TREATMENT

Hospital Admission

Surgical Debridement by Podiatric Surgeon, with Resection of all Necrotic Soft Tissue and Bone

Exploration and Drainage of Deep Abscess

Wound Packing and Wound Care as Appropriate

Empiric Antibiotic Coverage, Modified as per ClinicalResponse and/or Culture Findings

Long-Term Antibiotics as Necessary, Pending Degree of Resolution After Debridement/Resection

Surgical Resection of Osteomyelitis

Continued Wound Care, Debridement as Needed

If Infection Improves but Ulcer Remains - See Ulcer Pathway

Refer to Podiatrist for Follow-Up Care, Patient Education,Special Shoes and Prostheses as Needed

Foot-Sparing Reconstructive Procedures

DIAGNOSTIC PROCEDURES

Cultures from Base of Ulcer / Wound (Tissue Specimen if Possible)

Diagnostic Imaging; X-Ray, MRI, Nuclear Scans asIndicated

Serologic Testing

CBC with Differential

ESR

Blood Glucose

Renal Profile

TREATMENT

Debridement of All Necrotic Tissue and Callus

Appropriate Off-Loading

Wound Care / Dressing

Empiric Antibiotic Coverage, Modified by Culture Findings

Outpatient Management, with Follow-Up in 24-72 Hours

Wound Care Continued - e.g., Pack, Dressings,Debridement as Needed

Hospital Admission if Infection Progresses or SystemicSigns / Symptoms Develop

If Infection Improves but Ulcer remains - See UlcerPathway

Refer to Podiatrist for Follow-Up Care, Patient Education,Special Shoes and Prostheses As Needed

Examination

Diabetic Foot Disorders INFECTION: A Clinical Practice Pathway

FIGURE 4 Infection: A Clinical Practice Pathway.


Long-standingDiabetes

NeuropathicDisease

InjurySprain or Fracture Infection

PainlessAmbulation

ContinuedWeightbearing

Neuropathy

AcuteCharcot Foot

Ligamentous LaxityJoint Instability

Joint Degenerationand Subluxation

Ulcer,Infection

FIGURE 5 Charcot pathogenesis.

Charcot Foot (Neuropathic Osteoarthropathy)

(See Color Plates 6–9 on pages 31–32.) Charcot foot (neuropathic osteoarthropathy)is a progressive condition characterized by joint dislocation, pathologic fractures,and severe destruction of the pedal architecture. Osteoarthropathy may thereforeresult in debilitating deformity or even amputation (79,80,226–228). The conditionis associated with severe peripheral neuropathy and the most common etiology todayis diabetes mellitus. The prevalence of this condition is variable, ranging from 0.15%of all diabetic patients to as high as 29% in a population of only neuropathic diabeticsubjects (80). The frequency of diagnosis of the diabetic Charcot foot appears to beincreasing as a result of increased awareness of its signs and symptoms (79,81,229).

Etiology of Neuropathic Osteoarthropathy

The etiology of Charcot neuropathic osteoarthropathy most likely is a combinedeffect of both the neurovascular and neurotraumatic theories (80,226–231). It isgenerally accepted that trauma superimposed on a severely neuropathic extremitycan precipitate the development of an acute Charcot foot. With the developmentof autonomic neuropathy, there is an increased blood flow to the foot, resulting inosteopenia and a relative weakness of the bone (232). The presence of sensoryneuropathy renders the patient unaware of the precipitating trauma and oftenprofound osseous destruction taking place during ambulation. A vicious cycle ensueswhereby the patient continues to walk on the injured foot, thereby allowing furtherdamage to occur (80–82,229) (Figure 5).

Clinical Diagnosis of Acute Charcot Neuropathic Osteoarthropathy

The initial diagnosis of acute Charcot arthropathy is often clinical, based on profoundunilateral swelling, increased skin temperature, erythema, joint effusion, and boneresorption in an insensate foot (79,80,228,233). These characteristics, in the presenceof intact skin, are often pathognomonic of acute Charcot arthropathy. In more than


75% of cases, the patient will present with some degree of pain in an otherwiseinsensate extremity (83,227). The diagnosis is complicated by the fact that in somecases, patients first present with a concomitant ulceration which raises questions ofpotential contiguous osteomyelitis (233).

When faced with a warm, edematous, erythematous, insensate foot, plainradiographs are invaluable in ascertaining the presence of osteoarthropathy (234). Inmost cases, no further imaging studies will be required to make the correct diagnosis.With a concomitant wound, it may initially be difficult to differentiate between acuteCharcot arthropathy and osteomyelitis solely based on plain radiographs (79,228).Additional laboratory studies may prove useful in arriving at a correct diagnosis.The white blood cell count (WBC) with a left shift will often be elevated inacute osteomyelitis, although this can be blunted in persons with diabetes (97).While the erythrocyte sedimentation rate may also be elevated in the case ofacute infection, it often responds similarly to any inflammatory process and istherefore nonspecific. As in the case with any ulcer, it should be probed to ascertainpenetration to bone. A bone biopsy, when indicated, should be considered as themost specific method of distinguishing between osteomyelitis and osteoarthropathyin these circumstances. A biopsy consisting of multiple shards of bone and softtissue embedded in the deep layers of synovium is pathognomonic for neuropathicosteoarthropathy (235).

Technetium bone scans are relatively expensive and generally nonspecific inassisting in the differentiation between osteomyelitis and acute Charcot arthro-pathy (98). Indium scanning, while still expensive, has been shown to be morespecific (103). Additional studies utilized in differentiating Charcot arthropathy fromosteomyelitis include bone scans utilizing white blood cells labeled with Tc-HMPAOand magnetic resonance imaging (106,211).

The Classification of Charcot Arthropathy

The most common classification system of Charcot arthropathy is based on radio-graphic appearance as well as physiologic stages of the process. The Eichenholtzclassification divides osteoarthropathy into developmental, coalescent, and recon-structive stages (235). The developmental stage is characterized by significantsoft-tissue swelling, osteochondral fragmentation, or joint dislocation of varyingdegrees. The coalescent stage is marked by a reduction in soft-tissue swelling,bone callus proliferation, and consolidation of fractures. Finally, the reconstruc-tive stage is denoted by bony ankylosis and hypertrophic proliferation. While thesystem radiologically is very descriptive and useful, its practical clinical applica-bility is less so. In clinical practice, the initial stage is considered active, while thecoalescent and reconstructive stages are considered to be the quiescent or repar-ative stages. A more recent classification system has been described based uponanatomic sites of involvement but does not describe the activity of the disease (80)(Fig. 6).

Management of Acute Charcot Neuropathic Osteoarthropathy

Immobilization and reduction of stress are the mainstays of treatment for acuteCharcot arthropathy (79–81,226–229). Many investigators advocate completenonweightbearing through the use of crutches or other assistive modalities during theinitial acute period. While this is an accepted form of treatment, three-point gait may,in fact, increase pressure to the contralateral limb, thereby predisposing it to repetitivestress and ulceration or neuropathic fracture (236). Following a period of off-loading,


FIGURE 6 Sanders/Frykberg Classification of Diabetic Neuropathic Osteoarthro-pathy. (Reprinted, with permission, from Sanders L.J., Frykberg, R.G. Diabeticneuropathic osteoarthropathy: the Charcot foot. In: The High Risk Foot in DiabetesMellitus, p. 297, (edited by R.G. Frykberg, Churchill Livingstone, New York, 1991)).

a reduction in skin temperature and edema indicates the stage of quiescence at whichpoint the patient progresses into the post-acute phase of treatment. Progression toprotected weightbearing is permitted, usually with the aid of some type of assistivedevice. Through the use of appropriately applied total contact casts or other off-loading modalities (e.g., fixed ankle walker, bivalved casts, total contact prostheticwalkers, patellar tendon-bearing braces, etc.), most patients may safely ambulatewhile bony consolidation of fractures progresses (80,227,230) (Table 13). The meantime of rest and immobilization (casting followed by removable cast walker) priorto return to permanent footwear is approximately 4–6 months (80,83,226–228,234).There is recent interest in the adjunctive use of bisphosphonate therapy in acuteCharcot arthropathy to help expedite the conversion of the acute process to thequiescent, reparative stage (229,237). Similarly, there is interest in managing acutecases with ancillary bone growth stimulation to promote rapid consolidation of frac-tures (238). Although promising in theory, neither of these adjunctive treatments todate have been conclusively proven effective through large prospective, randomizedclinical trials.


TABLE 13 Off-loading modalities

ž Wheelchairž Crutchesž Walkerž Total contact castž Bi-valved castž Prefabricated walking bracež Unna boot with walking bracež Total contact custom walking bracež Patellar tendon-bearing bracež Posterior splintž Surgical shoe with insert

Reconstructive surgery may be considered if a deformity or instability existsthat cannot effectively be controlled or accommodated by prescription footwear orbracing (229,230,233239–243). If the arthropathy is identified in its early stagesand nonweightbearing is instituted, surgery is usually unnecessary. The consensusof opinion is such that surgery in the acute stage is generally not advisable dueto the extreme hyperemia, osteopenia, and edema present (226–230,239,242,243).Surgical intervention during the acute phase, however, may be considered in thepresence of acute subluxation without osteochondral fragmentation (236). One recentreport, however, indicates successful arthrodesis rates with preserved foot functionin patients with acute arthropathy of the midfoot (244). Notwithstanding, this smallretrospective study needs confirmation through larger trials prior to adopting thisapproach in the routine management of the acute Charcot foot.

As few as 4% to as many as 51% of patients presenting to tertiary centersare reported to undergo surgical procedures for Charcot deformities (242,243). Suchcenters, however, are often receiving chronic patients from multiple referral sourceswith various degrees of deformity present. Their rate of operation on these patientsdoes not reflect the true incidence or need for such treatment in the community. Largepopulation-based studies are needed to assess the need for surgical intervention aswell as to contrast the efficacy of various conservative therapies (229,234).

The goal of any surgery undertaken on the Charcot foot is to create a stable,plantigrade foot that may be appropriately accommodated (226–230,244). Surgeryis generally undertaken only after radiographic, dermal thermometric and clin-ical signs of quiescence. Most operations on persons with Charcot feet consist ofexostectomies for prominent plantar (“rocker-bottom”) deformities causing ulcera-tion when the remainder of the foot is stable (226,227,239,245). However, morecomplex arthrodesis procedures are being utilized with increasing frequency andsuccess rates (230,233,236,239–243,244,246). These include isolated or multiplemidfoot fusions, triple arthrodeses, tibio-calcaneal, and ankle fusions. Followingsurgery, patients are immobilized until skin temperatures and postoperative edemanormalize. As with those treated nonsurgically, following prolonged cast immo-bilization patients progress to a removable cast walker followed by permanentprescription footwear (227). Mean times from operation to the wearing of thera-peutic shoes have been reported in the range of 27 weeks (7 months) (83,244).Careful patient selection and management is the rule with these complex diabeticpatients since amputation can be an unwanted complication of failed surgical proce-dures (239,240,242,243).

Figure 7 illustrates a suggested Practice Pathway (algorithm) for the assessmentand management of diabetic neuropathic osteoarthropathy.


HISTORY

Onset of Changes

Progressive / Static

Erythema

Swelling

Trauma - Type, When, Repetitive?

Pain / Sensation

Previous Ulcer and/or Charcot Arthropathy

Diabetes Duration / Control

Plain X-Ray

Site(s) Involved

Osteolysis, Fractures, Dislocation

Soft-Tissue Edema

Medial Arterial Calcification

ADDITIONAL DIAGNOSTIC PROCEDURES AS INDICATED

Imaging Studies

CT Scan

MRI

Bone Scan - e.g., Leukocyte Scan

Serologic Tests

CBC with Differentials

ESR

Blood Glucose

Hemoglobin A1c

Bone Biopsy and Culture

Foot Stable

Refer to Podiatrist for SupportiveMeasures, Patient Education, TimelyRe-Evaluations to Prevent Recurrence

If Ulcer Occurs See Ulcer Pathway and orRefer for Podiatric Surgery Consult

Foot Unstable

Refer to Podiatrist for Orthopedic orMolded Foot Wear, Bracing, Insoles

Foot Unstable, NotResponsive to Special FootWear or Prostheses Refer

for Podiatric SurgeryConsult

Foot Stable

Absolute Restriction on Weightbearing

Crutches

Wheelchair

Immobilization of Foot

Splint, Cast, Removable Cast Until Hyperemia Resolved

Continue Immobilization 4-6 monthsuntil Quiescence (Chronic)

Once Quiescent Treat as Chronic

TreatmentAcute Chronic

See Ulcer PathwaySee Infection Pathway EXAMINATION

Dermatologic - Erythema, Warmth, Cellulitis / Ulcer

Musculoskeletal - Swelling, Deformation, “Rockerbottom”

Neurologic - Degree of Neuropathy Assessed by Semmes-Weinstein Fiber, Vibratory, Proprioception

Vascular - Pulses, Swelling

Diabetic Foot Disorders CHARCOT FOOT: A Clinical Practice Pathway

FIGURE 7 Charcot Foot: A Clinical Practice Pathway.


SURGICAL PROTOCOLS

Site of Surgery

Surgical treatment of the complications of the diabetic foot may be performed ina variety of settings including the hospital, either as an inpatient or outpatient, anambulatory surgical center or office based surgical facility. In today’s environment ofmanaged care and Medicare requirements for hospital admission, often a combinationof settings for the surgical treatment of the diabetic with ulcerations, infections andablative or reconstructive surgery is the rule. The hospital is a good central corethat allows the group of physicians and support personnel to interact and coordinatecare in an efficient manner, whether care is provided as an in-patient, out-patient orthrough home health services.

Generally hospitalization is indicated, but not necessarily limited to thefollowing:

ž Coexisting medical conditions that generally require the more intensivemanagement afforded by inpatient care, for example, diabetic control, cardio-vascular disease, and peripheral vascular disease.

ž The initial workup and management of a limb threatening diabetic footinfection.

ž Necessity for parenteral medications when administration at home, outpatientor an extended care facility is inappropriate or impractical.

ž High risk of perioperative complications.

Preoperative Laboratory Testing

Preoperative laboratory requirements for surgery in a diabetic patient are generallymore extensive than those considered for surgery in healthy patients. For example,glucose control, renal function assessment, cardiovascular status and peripheralvascular analysis are among the most common medical concerns which impact thecare rendered.

Anesthesia

In most cases, monitored anesthesia care is desirable due to the patient’s medicalcondition, even in cases where the patient may be insensate. General, regional orlocal field blocks are all appropriate in the surgical management of diabetic footdisorders. Local anesthesia usually is avoided with ascending infections, for examplewith an initial incision and drainage of a foot infection, but may be appropriate forlater debridement or definitive reconstruction.

Prophylactic Antibiotics

Prophylactic antibiotics may be indicated in patients with diabetes undergoingelective surgery due to their immunocompromised status. As with non-diabeticpatients, the chief concern is for staphylococci and streptococci infection. Therefore,standard prophylactic regimens should be utilized with appropriate recognition ofthe patient’s renal status.


Hemostasis

Hemostasis in diabetic patients undergoing surgery usually is in the form of judicioususe of electrocautery. Generally, there is an attempt to avoid ligatures in infectionsand avoidance of tourniquets in patients with significant ischemia or after undergoingdistal revascularization procedures. Tourniquets, however, may be used in wellperfused neuropathic limbs. Often, with wounds that are left open in cases of initialmanagement of infections, various packing materials or wound dressings may beused to control blood loss.

PREVENTION

Prevention is considered a pivotal element in avoiding ulceration and subsequentmajor amputation in the diabetic patient (16,22,30,34,37,74,92). This is best accom-plished with a multidisciplinary approach consisting of a team of specialists andpersonnel providing a coordinated process of care. Team members typically include:podiatrist, podiatric surgeon internist, endocrinologist, infectious disease specialist,cardiologist, nephrologist, vascular surgeon, orthopedic surgeon, nurse educator,visiting home nurse, and pedorthist. Patient and family education assumes a primaryrole and encompasses instruction in glucose assessment and insulin administration,diet, daily foot inspection and care, proper footwear, and the necessity for prompttreatment of new lesions. Regularly scheduled podiatric visits, including debride-ment of calluses and toenails, provide an opportunity for frequent foot examinationand patient education (74,201). Such visits can provide early warning of impendingproblems and subsequent modification of activity and care (22). Risk stratificationbased on the presence of predisposing causal risk factors, including prior history ofulceration, will also act as a guide to the necessary frequency of foot care visits (37).Identification of the high risk patient and tailoring a total foot care preventionprogram according to the level of risk assigned is considered effective in reducingthe incidence of ulceration and lower extremity amputation (37,74,195,199–201).

Therapeutic shoes with pressure relieving insoles and a high toe box whichprotects the high risk foot are essential to reduce ulceration and ultimately theincidence of amputation (16,202–204). For severe foot deformities which cannotbe accommodated by standard therapeutic footwear, custom molded shoes shouldbe fabricated according to these same guidelines. Prophylactic correction of struc-tural deformities that cannot be accommodated by therapeutic foot wear shouldbe considered, but patients must be carefully selected. Elective surgery should beundertaken under optimal metabolic conditions and with the full understandingof rationale, goals, and attendant risks (181,189,206,247). Diabetes is a life-longproblem and the incidence of diabetic foot complications increases with age andduration of the disease. Patients, particularly those at risk due to prior infection,ulceration, or amputation must be educated that a program of lifelong surveillancemust be incorporated to prevent repeated episodes of these complications. Providerand physician education is equally important in this regard since not all healthcare providers are cognizant of important signs and risk factors for pedal compli-cations (74,248). Furthermore, provider education is effective in reinforcing properdiabetes management and foot care practices with consequent reductions in ulcer-ation and adverse lower extremity outcomes (89,199). Table 14 lists the importantattributes of a diabetic foot prevention program undertaken within the framework ofthe multidisciplinary team.


TABLE 14 Diabetic foot prevention program

1. Podiatric CareRegular visits, examinations, and footcareRisk assessmentEarly detection and aggressive treatment of new lesions

2. Protective ShoesAdequate room to protect from injury; well cushioned

walking sneakers, extra depth, custom-molded shoesspecial modifications as necessary

3. Pressure ReductionCushioned insoles, custom orthoses, padded hosiery,

pressure measurements — computerized or Harris mat4. Prophylactic Surgery

Correct structural deformities — hammertoes, bunions, CharcotPrevent recurrent ulcers over deformitiesIntervene at opportune time

5. Preventive EducationPatient education — need for daily inspection and

necessity for early interventionPhysician education — significance of foot lesions,

importance of regular foot examination, andcurrent concepts of diabetic foot management

CONCLUSION

Ulceration, infection, gangrene and lower extremity amputation are complicationsoften encountered in patients with diabetes mellitus. These often result in extensivemorbidity, repeated hospitalizations and mortality to the patient. They take atremendous toll on the physical, mental and financial well-being of the patient aswell as potentially removing the patient from a country’s work force and financialdrain on our health care system.

All diabetic foot complications cannot be prevented but it is indeed possible todramatically reduce their incidence through appropriate management and preventionprograms. The multidisciplinary team approach to diabetic foot disorders has beendemonstrated as the optimal method to achieve favorable rates of limb salvage in thehigh risk diabetic patient. Foot care programs emphasizing preventive managementcan reduce the incidence of foot ulceration through modification of self care practices,appropriate evaluation of risk factors, and the formulation of treatment protocolsaimed at early intervention, limb preservation, and the prevention of new lesions.The podiatric surgeon should play an integral role in this scheme, providing ongoingsurveillance, education, and management of new or impending lesions. The goal of a40–50% reduction in diabetic limb amputations is certainly attainable if we embracethese principles and incorporate them into daily patient care.

ACKNOWLEDGMENTS

The authors are indebted to Ms. Susan Couture of the ACFAS staff for herunfailing coordination and assistance in the completion of this project. We are alsograteful to the American College of Foot and Ankle Surgeons (ACFAS) and theAmerican College of Foot and Ankle Orthopedics and Medicine (ACFAOM) for


the development and support of this effort. We further acknowledge the generouseducational grant provided by Ortho-McNeil Pharmaceuticals in support of thisactivity. In addition, we recognize the input we received from the Pedorthic FootwearAssociation (PFA). Finally, we are each indebted to the thousands of patients withdiabetes from whom we learned through both success and failure, the true magnitudeof diabetic foot disease. It is to these patients and the millions of persons withdiabetes mellitus worldwide that we dedicate this work.


APPENDIX 1: Adapted from NIDDK Diabetic Foot Screening Form


REFERENCES

1. American Diabetes Association. Diabetes Facts and Figures. American Diabetes Asso-ciation, Alexandria, VA, 2000.

2. Harris, M.I., Flegal, K.M., Cowie, C.C., Eberhardt, M.S., Goldstein, D.E., Little, R.R.,Wiedmeyer, H.-M., Byrd-Holt, D.D. Prevalence of diabetes, impaired fasting glucose,and impaired glucose tolerance in U.S. adults. Diabetes Care 21:518–524, 1998.

3. Centers for Disease Control. Diabetes. a serious health problem. At-A-Glance 2000.Centers for Disease Control and Prevention, Atlanta, GA, 2000.

4. U.S. Department of Health and Human Services. Diabetes Surveillance, 1997. Centersfor Disease Control and Prevention, Atlanta, GA, 1997.

5. American Diabetes Association. Report of the Expert Committee on the diagnosis andclassification of diabetes mellitus. Diabetes Care 23(Suppl. 1):S4–S19, 2000.

6. Harris, M.I. Diabetes in America: epidemiology and scope of the problem. DiabetesCare 21(Suppl. 3):C11–C14, 1998.

7. American Diabetes Association. Diabetes 1996 Vital Statistics. American DiabetesAssociation, Alexandria, VA, 1996.

8. Palumbo, P.J., Melton, L.J. Peripheral vascular disease and diabetes. In: Diabetes inAmerica. Data Compiled 1984 (NIH publ. no. 85–1468), p. 1. U.S. Government PrintingOffice, Washington, DC, 1985.

9. Reiber, G.E., Boyko, E.J., Smith, D.G. Lower extremity foot ulcers and amputationsin diabetes. In: Diabetes in America, 2nd ed. (NIH publ. no. 95–1468), edited byM.I. Harris, C. Cowie, and M.P. Stern, U.S. Government Printing Office, Washington,DC, 1995.

10. Frykberg, R.G., Habershaw, G.M., Chrzan, J.S. Epidemiology of the diabetic foot:ulcerations and amputations. In: Contemporary Endocrinology: Clinical Managementof Diabetic Neuropathy, p. 273, edited by A Veves, Humana Press, Totowa, NJ, 1998.

11. Moss, S.E., Klein, R., Klein, B. The prevalence and incidence of lower extremityamputation in a dibetic population. Arch. Intern. Med. 152:610–616, 1992.

12. Ramsey, S.D., Newton, K., Blough, D., McCulloch, D.K., Sandhu, N., Reiber, G.E.,Wagner, E.H. Incidence, outcomes, and cost of foot ulcers in patients with diabetes.Diabetes Care 22:382–387, 1999.

13. Abbott, C.A., Vileikyte, L., Williamson, S., Carrington, A.L., Boulton, A.J.M. Multi-center study of the incidence and predictive risk factors for diabetic neuropathic footulceration. Diabetes Care 21:1071–1075, 1998.

14. Walters, D.P.,Gatling, W., Mullee, M.A., Hill, R.D. The distribution and severity ofdiabetic foot disease: a community study with comparison to a non-diabetic group.Diabetic Med. 9:354–358, 1992.

15. Reiber, G.E., Vileikyte, L., Boyko, E.J., Del Aguila, M., Smith, D.G., Lavery, L.A.,Boulton, A.J.M. Causal pathways for incident lower-extremity ulcers in patients withdiabetes from two settings. Diabetes Care 22:157–162, 1999.

16. Frykberg, R.G. Diabetic foot ulcers: current concepts. J. Foot Ankle Surg. 37:440–446,1998.

17. Frykberg, R.G., Lavery, L., Pham, H., Harvey, C., Harkless, L.,Veves, A. Role of neuro-pathy and high foot pressures in diabetic foot ulceration. Diabetes Care 21:1714–1719,1998.

18. Gibbons, G.W., Eliopoulos, G.M. Infection of the diabetic foot. In: Management ofDiabetic Foot Problems, p. 121, edited by G.P. Kozak, D.R. Campbell, R.G. Frykberg,and G.M. Habershaw, WB Saunders, Philadelphia, 1995.

19. Levin, M.E. Foot lesions in patients with diabetes mellitus. Endocrin. Metab. Clin. NorthAm. 25:447–462, 1996.

20. Pecoraro, R.E., Reiber, G., Burgess, E.M. Pathways to diabetic limb amputation: basisfor prevention. Diabetes Care 13:513, 1990.

21. Larsson, J., Agardh, C.-D., Apelqvist, J., Stenstrom, A. Long term prognosis afterhealed amputation in patients with diabetes. Clin. Orthop. 350:149–158, 1998.

22. American Diabetes Association. Consensus development conference on diabetic footwound care. Diabetes Care 22:1354–1360, 1999.


23. Frykberg, R.G. Epidemiology of the diabetic foot: ulcerations and amputations. Adv.Wound Care 12:139–141, 1999.

24. Lavery, L.A., Ashry, H.R., van Houtum, W., Pugh, J.A., Harkless, L.B., Basu, S. Vari-ation in the incidence and proportion of diabetes-related amputations in minorities.Diabetes Care 19:48–52, 1996.

25. Resnick, H.E., Valsania, P., Phillips, C.L. Diabetes mellitus and nontraumatic lowerextremity amputation in Black and White Americans. Arch. Intern. Med. 159:2470–2475,1999.

26. American Diabetes Association. Economic consequences of diabetes mellitus in the U.S.in 1997. Diabetes Care 21:296–309, 1998.

27. Holzer, S.E.S., Camerota, A., Martens, L., Cuerdon, T., Crystal-Peters, J., Zagari, M.Costs and duration of care for lower extremity ulcers in patients with diabetes. Clin.Therap. 20:169–181, 1998.

28. Amato, D., Persson, U., Lantin, M., Basso, K., Martens, L. The cost of illness in patientswith diabetic foot ulcers [Abstract]. 59th Annual Meeting of the American DiabetesAssociation, San Diego, CA, June 1999.

29. Shaw, J.E., Boulton, A.J.M. The pathogenesis of diabetic foot problems. an overview.Diabetes 46 (suppl.):S58–S61, 1997.

30. Boulton, A.J., Meneses, P., Ennis, W.J. Diabetic foot ulcers. a framework for preventionand care. Wound Rep. Reg. 7:7–17, 1999.

31. Boyko, E.J., Ahroni, J.H., Stensel, V., Forsberg, R.C., Davignon, D.R., Smith, D.G. Aprospective study of risk factors for diabetic foot ulcer: The Seattle Diabetic Foot Study.Diabetes Care 22:1036–1042, 1999.

32. Young, M.J., Breddy, J.L., Veves, A., Boulton, A.J.M. The prediction of diabetic neuro-pathic foot ulceration using vibration perception thresholds: a prospective study. DiabetesCare 17:557–560, 1994.

33. McNeely, M.J., Boyko, E., Ahroni, J.H. The independent contributions of diabeticneuropathy and vasculopathy in foot ulceration: How great are the risks? Diabetes Care18:216–219, 1995.

34. Mayfield, J.A., Reiber, G.E., Sanders, L.J., Janisse, D., Pogach, L.M. Preventive footcare in people with diabetes: technical review. Diabetes Care 21:2161–2177, 1998.

35. Lavery, L.A., Armstrong, D.G., Vela, S., Quebedeux, T.L., Fleischli, J.G. Practicalcriteria for screening patients at high risk for diabetic foot ulceration. Arch. Intern.Med. 158:157–162, 1998.

36. Edmonds, M.E., Blundell, M.P., Morris, M.E., et al. Improved survival of the diabeticfoot. the role of a specialised foot clinic. Q. J. Med. 232:763, 1986.

37. International Working Group on the Diabetic Foot. International Consensus on theDiabetic Foot, Amsterdam, The Netherlands, 1999.

38. Frykberg, R.G. Diabetic foot ulcerations. In: The High Risk Foot in Diabetes Mellitus,p. 151, edited by R.G. Frykberg, Churchill Livingstone, New York, 1991.

39. Flynn, M.D., Tooke, J.E. Aetiology of diabetic foot ulceration: a role for the microcir-culation? Diabetic Med. 8:320–329, 1992.

40. Parkhouse, N., Le Quesne, P.M. Impaired neurogenic vascular response in patients withdiabetes and neuropathic foot lesions. N. Engl. J. Med. 318:1306, 1988.

41. Boulton, A.J.M. The pathogenesis of diabetic foot problems: an overview. Diabetic Med.13:S12–S16, 1996.

42. Schoenhaus, H.D., Wernick, E., Cohen, R. Biomechanics of the diabetic foot. In: TheHigh Risk Foot in Diabetes Mellitus, p. 125, eidted by R.G. Frykberg, Churchill Living-stone, New York, 1991.

43. Frykberg, R.G. Biomechanical considerations of the diabetic foot. Lower Extremity2:207–214, 1995.

44. Veves, A., Murray, H., Young, M.J., et al. The risk of foot ulceration in diabetic patientswith high foot pressure: a prospective study. Diabetologia 35:660, 1992.

45. Brand, P.W. Repetitive stress in the development of diabetic foot ulcers. In: The DiabeticFoot, 4th ed., pp. 83–90, edited by M.E. Levin, and J.K. Davidson, Mosby, St Louis,MO, 1988.


46. Murray, H.J., Young, M.J., Hollis, S., Boulton, A.J.M. The association between callusformation, high pressures and neuropathy in diabetic foot ulceration. Diabetic Med.13:979–982, 1996.

47. Young, M.J., Cavanagh, P.R., Thomas, G., Johnson, M.M., Murray, H., Boulton, A.J.M.The effect of callus removal on dynamic plantar foot pressures in diabetic patients.Diabetes Med. Suppl. 9:55–57, 1992.

48. Apelqvist, J., Larsson, J., Agardh, C.D. The influence of external precipitating factorsand peripheral neuropathy on the development and outcome of diabetic foot ulcers. J.Diab. Compl. 4:21, 1990.

49. Pecoraro, R.E., Ahroni, J., Boyko, E.J. Stensel, V.L. Chronology and determinants oftissue repair in diabetic lower-extremity ulcers. Diabetes 40:1305–1313, 1991.

50. Caputo, G.M., Cavanagh, P.R., Ulbrecht, J.S., Gibbons, G.W., Karchmer, A.W. Assess-ment and management of foot disease in patients with diabetes. N. Engl. J. Med.331:854–860, 1994.

51. Levin, M.E. Preventing amputation in the patient with diabetes. Diabetes Care 10:1383–1394, 1995.

52. Mills, J.L., Beckett, W.C., Taylor, S.M. The diabetic foot: consequences of delayedtreatment and referral. South Med. J. 84:970, 1991.

53. Boulton, A.J.M. The pathway to ulceration. In: The Foot in Diabetes, 3rd ed., pp. 19–31,edited by A.J.M. Boulton, H. Connor, and P.R. Cavanagh, John Wiley & Sons, Chich-ester, UK, 2000.

54. Fernando, D.J.S, Masson, E.A., Veves, A., Boulton, A.J.M. Relationship of limited jointmobility to abnormal foot pressures and diabetic foot ulceration. Diabetes Care 14:8,1991.

55. Mueller, M.J., Diamond, J., Delitto, A., Sinacore, D.R. Insensitivity, limited joint mobi-lity, and plantar ulcers in patients with diabetes mellitus. Phys. Ther. 69:453, 1989.

56. Delbridge, L., Perry, P., Marr, S., Arnold, N., Yue, D.K., Turtle, J.R., Reeve, T.S.Limited joint mobility in the diabetic foot: relationship to neuropathic ulceration.Diabetic Med. 5:333–337, 1988.

57. Ahroni, J.H., Boyko, E.J., Forsberg, R.C. Clinical correlates of plantar pressure amongdiabetic veterans. Diabetes Care 22:965–972, 1999.

58. Habershaw, G., Chrzan, J.S. Biomechanical considerations of the diabetic foot. In:Management of Diabetic Foot Problems, 2nd ed., p. 53–65, edited by G.P. Kozak,D.R. Campbell, R.G. Frykberg, and G.M. Habershaw, WB Saunders, Philadelphia, 1995.

59. Adler, A.I., Boyko, E.J., Ahroni, J., Smith, D.G. Lower-extremity amputation in diabe-tes: the independent effects of peripheral vascular disease, sensory neuropathy, and footulcers. Diabetes Care 22:1029–1035, 1999.

60. Moss, S., Klein, R., Klein, B. The 14-year incidence of lower extremity amputationsin a diabetic population: The Wisconsin Epidemiologic Study of Diabetic Retinopathy.Diabetes Care 22:951–959, 1999.

61. Humphrey, L.L., Palumbo, P.J., Butters, M.A., Hallet, J.W., Chu, C., O’Fallon, W.M.,Ballard, D.J. The contribution of non-insulin dependent diabetes to lower extremityamputation in the community. Arch. Intern. Med. 154:885–892, 1994.

62. Pirart, J. Diabetes mellitus and its degenerative complications: a prospective study of4,400 patients observed between 1947 and 1973. Diabetes Care 1:168, 1978.

63. Melton, L.J., Macken, K.M., Palumbo, P.J., Elveback, L.R. Incidence and prevalenceof clinical peripheral vascular disease in a population-based cohort of diabetic patients.Diabetes Care 3:48–654, 1980.

64. The Diabetes Control and Complications Trial Research Group. The effect of inten-sive treatment of diabetes on the development of long-term complications in insulin-dependent diabetes mellitus. N. Engl. J. Med. 329:977–986, 1993.

65. U.K. Prospective Diabetes Study Group. Intensive blood-glucose control with sulfony-lureas or insulin compared with conventional treatment and risk of complications inpatients with type 2 diabetes (UKPDS 33). Lancet 352:837–853, 1998.

66. American Diabetes Association. Implications of the Diabetes Control and ComplicationsTrial. Diabetes Care 23(Suppl. 1):S24–S26, 2000.

67. American Diabetes Association. Implications of the United Kingdom ProspectiveDiabetes Study. Diabetes Care 23(Suppl. 1):S27–S31, 2000.


68. Selby, J.V., Zhang, D. Risk factors for lower extremity amputation in persons withdiabetes. Diabetes Care 18:509–516, 1995.

69. Reiber, G.E., Pecoraro, R.E., Koepsell, T.D. Risk factors for amputation in patients withdiabetes mellitus: a case-control study. Ann. Intern. Med. 117:97–105, 1992.

70. Nelson, R.G., Gohdes, D.M., Everhart, J.E., Hartner, J.A., Zwemer, F.L., Pettit, D.J.,Knowler, W.C. Lower extremity amputations in NIDDM: 12-yr follow-up study in PimaIndians. Diabetes Care 11:8–16, 1988.

71. Lee, J.S., Lu, M., Lee, V.S., Russel, D., Bahr, C., Lee, E.T. Lower-extremity amputa-tion. Incidence, risk factors, and mortality in the Oklahoma Indian Diabetes Study.Diabetes 42:876–882, 1993.

72. Lehto, S., Ronnemaa, T., Pyorala, K., Laakso, M. Risk factors predicting lower extre-mity amputations in patients with NIDDM. Diabetes Care 19:607–612, 1996.

73. Humphrey, A., Dowse, G., Thoma, K., Zimmet, P. Diabetes and nontraumatic lowerextremity amputations. Incidence, risk factors, and prevention- a 12 year follow-upstudy in Nauru. Diabetes Care 19:710–714, 1996.

74. Frykberg, R.G. Team approach toward lower extremity amputation prevention indiabetes. J. Am. Podiatr. Med. Assoc. 87:305–312, 1997.

75. Larsson, J., Apelqvist, J., Agardh, C.-D., Stenstrom, A. Decreasing incidence of majoramputation in diabetic patients: a consequence of a multidisciplinary foot care teamapproach? Diabetic Med. 12:770–776, 1995.

76. Apelquist, J., Larsson, J., Agardh, C.-D. Long term prognosis for patients with footulcers. J. Intern. Med. 233:485–491, 1993.

77. Ebskov, L.B. Diabetic amputation and long-term survival. Int. J. Rehab. Res. 2:403–408,1998.

78. Sinha, S., Munichoodappa, C., Kozak, G.P. Neuro-arthropathy (Charcot joints) in diabe-tes mellitus: clinical study of 101 cases. Medicine (Baltimore) 52:191, 1972.

79. Sanders, L.J., Frykberg, R.G. Charcot foot. In: The Diabetic Foot, 5th ed., p. 149, editedby M.E. Levin, L.W. O’Neal, and J.H. Bowker, Mosby Yearbook, St. Louis, 1993.

80. Sanders, L.J., Frykberg, R.G. Diabetic neuropathic osteoarthropathy. The Charcot foot.In: The High Risk Foot in Diabetes Mellitus, p. 297, edited by R.G. Frykberg, ChurchillLivingstone, New York, 1991.

81. Frykberg, R.G., Kozak, G.P. The diabetic Charcot foot. In: Management of Diabetic FootProblems, 2nd ed., p. 88–97, edited by G.P. Kozak, D.R. Campbell, R.G. Frykberg, andG.M. Habershaw, WB Saunders, Philadelphia, 1995.

82. Frykberg, R.G., Kozak, G.P. Neuropathic arthropathy in the diabetic foot. Am. Fam.Phys. 17:105, 1978.

83. Armstrong, D.G., Todd, W.F., Lavery, L.A., Harkless, L.B., Bushman, T.R. The naturalhistory of acute Charcot’s arthropathy in a diabetic foot specialty clinic. Diabetic Med.14:357–363, 1997.

84. Frykberg, R.G. Osteoarthropathy. Clin. Podiatr. Med. Surg. 4:351, 1987.85. Gibbons, G.W., Eliopoulos, G.M. Infection of the diabetic foot. In: Management of

Diabetic Foot Problems, p. 121, edited by G.P. Kozak, D.R. Campbell, R.G. Frykberg,and G.M. Habershaw, WB Saunders, Philadelphia, 1995.

86. Grayson, M.L. Diabetic foot infections. antimicrobial therapy. Infect. Dis. Clin. NorthAm. 9:143–161, 1995.

87. Lipsky, B.A., Pecoraro, R.E., Wheat, L.J. The diabetic foot: soft tissue and bone infec-tion. Infect. Dis. Clin. North Am. 4:409–432, 1990.

88. Frykberg, R.G., Veves, A. Diabetic foot infections. Diabetes/Metab. Rev. 12:255–270,1996.

89. American Diabetes Association. Preventive foot care in people with diabetes (PositionStatement). Diabetes Care 23(Suppl. 1):S55–S56, 2000.

90. Rith-Najarian, S., Stolusky, T., Gohdes, D. Identifying diabetic patients at high risk forlower extremity amputation in a primary health care setting. a prospective evaluation ofsimple screening criteria. Diabetes Care 15:1386–1389, 1992.

91. Armstrong, D.G., Lavery, L.A., Harkless, L.B. Treatment-based classification system forassessment and care of diabetic feet. J. Am. Podiatr. Med. Assoc. 86:311–316, 1996.

92. Armstrong, D.G., Lavery, L.A. Diabetic foot ulcers. prevention, diagnosis and classifi-cation. Am. Fam. Phys. 57:1325–1332, 1998.


93. Armstrong, D.G., Perales, T.A., Murff, R.T., Edelson, G.W., Welchon, J.G. Value ofwhite blood cell count with differential in the acute diabetic foot infection. J. Am.Podiatr. Med. Assoc. 86:224–227, 1996.

94. Caballero, E., Frykberg, R.G. Diabetic foot infections. J. Foot. Ankle Surg. 37:248–255,1998.

95. Eneroth, M., Apelqvist, J., Stenstrom, A. Clinical characteristics and outcome in 223diabetic patients with deep foot infections. Foot Ankle Int 18:716–722, 1997.

96. Lipsky, B.A. Osteomyelitis of the foot in diabetic patients. Clin. Infect. Dis. 25:1318–1326, 1997.

97. Armstrong, D.G., Lavery, L.A., Sariaya, M., Ashry, H. Leukocytosis is a poor indicatorof acute osteomyelitis of the foot in diabetes mellitus. J. Foot Ankle Surg. 35:280–283,1996.

98. Keenan, A.M., Tindel, N.L., Alavi, A. Diagnosis of pedal osteomyelitis in diabeticpatients using current scintigraphic techniques. Arch. Intern. Med. 149:2262–2266,1989.

99. Edelson, G.W., Armstrong, D.G., Lavery, L.A., Caicco, G. The acutely infected diabeticfoot is not adequately evaluated in an inpatient setting. Arch. Intern. Med. 156:2373–2378, 1996.

100. Longmaid, H.E., Kruskal, J.B. Imaging infections in diabetic patients. Infect. Dis. Clin.North Am. 9:163–182, 1995.

101. Zlatkin, M.B., Pathria, M., Sartoris, D.J., Resnick, D. The diabetic foot. Radiol. Clin.North Am. 25:1095, 1987.

102. Watkins, P.J., Edmonds, M.E. Sympathetic nerve failure in diabetes. Diabetologia 25:73,1983.

103. Schauwecker, D.S., Park, H.M., Burt, R.W., Mock, B.H., Wellman, H.N. Combinedbone scintigraphy and Indium-111 leukocyte scans in neuropathic foot disease. J. Nucl.Med. 29:1651–1655, 1988.

104. Johnson, J.E., Kennedy, E.J., Shereff, M.J., Patel, N.C., Collier, B.D. Prospective studyof bone, Indium-111-labeled white blood cell, and Gallium-67 scanning for the evalua-tion of osteomyelitis in the diabetic foot. Foot Ankle Int. 17:10–16, 1996.

105. Maurer, A.H., Millmond, S.H., Knight, L.C., Mesgarzadeh, M., Siegel, J.A., Shuman,C.R., Adler, L.P., Greene, G.S., Malmud, L.S. Infection in diabetic osteoarthropathy:use of Indium-labeled leukocytes for diagnosis. Radiology 161:221, 1986; J. Nucl. Med.29:1651, 1988.

106. Blume, P.A., Dey, H.M., Daley, L.J., Arrighi, J.A., Soufer, R., Gorecki, G.A. Diagnosisof pedal osteomyelitis with Tc-99m, HMPAO labeled leukocytes. J. Foot Ankle Surg.36:120–126, 1997.

107. Yuh, W.T.,Corson, J.D., Baraniewski, H.M., et al. Osteomyelitis of the foot in diabeticpatients: evaluation with plain film, 99mTc-MDP bone scintigraphy, and MR imaging.Am. J Roentgen 152:795, 1989.

108. Zeiger, L.S., Fox, I.M. Use of indium 111-labeled white blood cells in the diagnosis ofdiabetic foot infections. J. Foot Surg. 29:46, 1990.

109. Durham, J.R., Lukens, M.L., Campanini, D.S., Wright, J.G., Smead, W.L. Impact ofmagnetic resonance imaging on the management of diabetic foot infections. Am. J.Surg. 162:150–154, 1991.

110. Akbari, C.M., LoGerfo, F.W. The impact of micro- and macrovascular disease ondiabetic neuropathy and foot problems. In: Clinical Management of Diabetic Neuropathy,pp. 319–331, edited by A. Veves, Humana Press, Totowa, NJ, 1998.

111. Pomposelli, F.B. Noninvasive evaluation of the peripheral arterial system in the diabeticlower extremity. In: Management of Diabetic Foot Problems, 2nd ed., pp. 138–148,edited by G.P. Kozak, D.R. Campbell, R.G. Frykberg, and G.M. Habershaw, WB Saun-ders, Philadelphia, 1995.

112. Young, M.J., Adams, J.E., Anderson, G.F., Boulton, A.J.M, Cavanagh, P.R. Medialarterial calcification in the feet of diabetic patients and matched non-diabetic controlsubjects. Diabetologia 36:615–621, 1993.

113. Chantelau, E., Lee, K.M., Jungblut, R. Association of below-knee atherosclerosis tomedial arterial calcification in diabetes mellitus. Diabetes Res. Clin. Pract. 29:169–172,1995.


114. Stevens, M.J., Goss, D.E., Foster, A.V.M, Pitei, D., Edmonds, M.E., Watkins, P.J. Ab-normal digital pressure measurements in diabetic neuropathic foot ulceration. DiabeticMed. 10:909–915, 1993.

115. Apelqvist, J., Castenfors, J., Larsson, J.,Stenstom, A., Agardh, C.-D. Prognostic value ofsystolic ankle and toe blood pressure levels in outcome of diabetic foot ulcers. DiabetesCare 12:373–78, 1989.

116. Bone, G.E., Pomajzl, M.J. Toe blood pressure by photoplethysmography. an index ofhealing in forefoot amputation. Surgery 89:569, 1981.

117. Kalani, M., Brismar, K., Fagrell, B., Ostergren, J., Jorneskog, G. Transcutaneous oxy-gen tension and toe blood pressure as predictors for outcme of diabetic foot ulcers.Diabetes Care 22:147–151, 1999.

118. Karanfilian, R.G., Lynch, T.G., Zirul, V.T., Padberg, F.T., Jamil, Z., Hobson, R.W. Thevalue of laser Doppler velocimetry and transcutaneous oxygen tension determinationin predicting healing of ischemic forefoot ulcerations and amputations in diabetic andnondiabetic patients. J. Vasc. Surg. 4:511–516, 1986.

119. Matsen, F.A., Wyss, C.R., Robertson, C.L., Oberg, P.A., Holloway, G.A. The relation-ship of transcutaneous, P.O.2 and laser Doppler measurements in a human model oflocal arterial insufficiency. Surg. Gynecol. Obstet. 159:418–422, 1984.

120. Adera, H.M., James, K., Castronuovo, J.J., Byrne, M., Deshmukh, R., Lohr, J. Predic-tion of amputation wound healing with skin perfusion pressure. J. Vasc. Surg.21:823–829, 1995.

121. Castronuovo, J.J., Adera, H.M., Smiell, J.M., Price, R.M. Skin perfusion pressure mea-surement is valuable in the diagnosis of critical limb ischemia. J. Vasc. Surg.26:629–637, 1997.

122. Stokes, K.R., Pomposelli, F.B., Longmaid, H.E. Arteriography. In: Management of Dia-betic Foot Problems, 2nd ed., pp. 149–157, edited by G.P. Kozak, D.R. Campbell,R.G. Frykberg, and G.M. Habershaw, WB Saunders, Philadelphia, 1995.

123. Faglia, E., Favales, F., Quarantiello, A., Calia, P., Clelia, P., Brambilla, G., Rampoldi, A.,Morabito, A. Angiographic evaluationof peripheral arterial occlusive disease and its roleas a prognostic determinant for major amputation in diabetic subjects with foot ulcers.Diabetes Care 21:625–630, 1998.

124. Mercer, K.G., Berridge, D.C. Peripheral vascular disease and vascular reconstruction.In: The Foot in Diabetes, 3rd ed., pp. 215–234, edited by A.J.M. Boulton, H. Connor,P.R. Cavanagh, John Wiley & Sons, Chichester, UK, 2000.

125. Armstrong, D.G., Lavery, L.A., Vela, S.A., Quebedeux, T.L., Fleischli, J.G. Choosinga practical screening instrument to identify patients at risk for diabetic foot ulceration.Arch. Intern. Med. 158:289–292, 1998.

126. Kumar, S., Fernando, D.J.S, Veves, A., Knowles, E.A., Young, M.J., Boulton, A.J.M.Semmes-Weinstein monofilaments. a simple, effective and inexpensive screening devicefor identifying diabetic patients at risk of foot ulceration. Diabetes Res. Clin. Pract.13:63–68, 1991.

127. Pham, H., Armstrong, D.G., Harvey, C., Harkless, L.B., Giurini, J.M., Veves, A. Screen-ing techniques to identify people at high risk for diabetic foot ulceration. Diabetes Care23:606–611, 2000.

128. Cavanagh, P.R., Ulbrecht, J.S., Caputo, G.M. What the practising physician shouldknow about diabetic foot biomechanics. In: The Foot in Diabetes, 3rd ed., pp. 33–59,edited by A.J.M. Boulton, H. Connor, P.R. Cavanagh, John Wiley & Sons, Chichester,UK, 2000.

129. Donaghue, V.M., Veves, A. Foot pressure measurement. Orthop. Phys. Ther. Clin. NorthAm. 6:1–16, 1997.

130. Duckworth, T., Boulton, A.J.M, Betts, R.P., et al. Plantar pressure measurements andthe prevention of ulceration in the diabetic foot. J. Bone Joint Surg. 67-B:79, 1985.

131. Boulton, A.J.M, Betts, R.P., Franks, C.I., et al. The natural history of foot pressureabnormalities in neuropathic diabetic subjects. Diabetes Res. 5:73, 1987.

132. Harris, R.I., Beath, T. Army Foot Survey — An Investigation of Foot Ailments inCanadian Soldiers (NRC No. 1574), Ottawa, National Research Council of Canada,1947.


133. Grayson, M.L., Gibbons, G.W., Balogh, K., Levin, E., Karchmer, A.W. Probing to bonein infected pedal ulcers: a clinical sign of underlying osteomyelitis in diabetic patients.JAMA 273:721–723, 1995.

134. Young, M.J. Classification of ulcers and its relevance to management. In: The Foot inDiabetes, 3rd ed., pp. 61–72, edited by A.J.M. Boulton, H. Connor, P.R. Cavanagh,John Wiley & Sons, Chichester, UK, 2000.

135. Lavery, L.A., Armstrong, D.G., Harkless, L.B. Classification of diabetic foot wounds.J. Foot Ankle Surg. 35:528–531, 1996.

136. Armstrong, D.G., Lavery, L.A., Harkless, L.B. Validation of a diabetic wound classifi-cation system; the contribution of depth, infection, and ischemia to risk of amputation.Diabetes Care 21:855–859, 1998.

137. Wagner, W.F. The dysvascular foot: a system for diagnosis and treatment. Foot Ankle2:62–122, 1981.

138. Lazarus, G.S., Cooper, D.M., Knighton, D.R., Margolis, D.J., Pecoraro, R.E., Rodehea-ver, G., Robson, M.C. Definitions and guidelines for assessment of wounds and evalu-ation of healing. Arch. Dermatol. 130:489–493, 1994.

139. Levin, M. Diabetic foot wounds. pathogenesis and management. Adv. Wound. Care10:24–30, 1997.

140. Steed, D.L., Donohoe, D., Webster, M.W., Lindsley, L., Diabetic Ulcer Study Group.Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. J.Am. Coll. Surg. 183:61–64, 1996.

141. Eaglestein, W., Falanga, V. Chronic wounds. Surg. Clin. North Am. 77:689–700, 1997.142. Scott, R.G., Loehne, H.B. 5 questions and answers about pulsed lavage. Adv. Skin

Wound Care 13:133–134, 2000.143. Steed, D.L., Diabetic Ulcer Study Group. Clinical evaluation of recombinant human

platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. J.Vasc. Surg. 21:71–81, 1995.

144. Catanzariti, A.R., Haverstock, B.D., Grossman, J.P., Mendocino, R.W. Off-loading tech-niques in the treatment of diabetic plantar neuropathic foot ulceration. Adv. Wound Care12:452–45, 1999.

145. Mueller, M.J., Diamond, J.E., Sinacore, D.R., Delito, A., Blair, V.P., Drury, D.A., Rose,S.J. Total contact casting in treatment of diabetic plantar ulcers; controlled clinical trial.Diabetes Care 12:384–388, 1989.

146. Laing, P. Diabetic foot ulcers. Am. J. Surg. 167(Suppl. 1A):31S–36S, 1994.147. Laing, P.W., Cogley, D.I., Klenerman, L. Neuropathic foot ulceration treated by total

contact casts. J. Bone Joint Surg. 74-B:133, 1992.148. Burden, A.C., Jones, G.R., Jones, R., Blandford, R.L. Use of the Scotchcast boot in

treating diabetic foot ulcers. Br. Med. J. 286:1555, 1983.149. Hissink, R.J., Manning, H.A., van Baal, J.G. The MABAL shoe, an alternative method

in contact casting for the treatment of neuropathic diabetic foot ulcers. Foot Ankle Int.21:320–323, 2000.

150. Lavery, L.A., Vela, S.A., Lavery, D.C., Quebedeaux, T.L. Reducing dynamic foot pres-sures in high-risk diabetic subjects with foot ulcerations. Diabetes Care 19:818–821,1996.

151. Saltzman, C.L., Johnson, K.A., Goldsteion, R.H., Donnelly, R.E. The patellar tendon-bearing brace as treatment for neurotrophic arthropathy: a dynamic force monitoringstudy. Foot Ankle 13:14–21, 1992.

152. Chantelau, E., Breuer, U., Leisch, A.C., Tanudjaja, T., Reuter, M. Outpatient treatmentof unilateral diabetic foot ulcers with ‘Half Shoes’. Diabetic Med. 10:267–270, 1993.

153. Frykberg, R.G. Podiatric problems in diabetes. In: Management of Diabetic Foot Prob-lems, 2nd ed., p. 66–87, edited by G.P. Kozak, D.R. Campbell, R.G. Frykberg, andG.M. Habershaw, WB Saunders, Philadelphia, 1995.

154. Ritz, G., Kushner, D., Friedman, S. A successful technique for the treatment of diabeticneurotrophic ulcers. J. Am. Podiatr. Med. Assoc. 82:479–481, 1992.

155. Guzman, B., Fisher, G., Palladino, S.J., Stavosky, J.W. Pressure-removing strategies inneuropathic ulcer therapy. Clin. Podiatr. Med. Surg. 11:339–353, 1994.

156. Canter, K.G. Conservative management of wounds. Clin. Podiatr. Med. Surg. 8:787,1991.


157. Hogge, J., Krasner, D., Nguyen, H., Harkless, L.B., Armstrong, D.G. The potentialbenefits of advanced therapeutic modalities in the treatment of diabetic foot wounds.J. Am. Podiatr. Med. Assoc. 90:57–65, 2000.

158. Knighton, D.R., Ciresi, K., Fiegel, V.D., et al. Stimulation of repair in chronic, nonheal-ing, cutaneous ulcers using platelet-derived wound healing formula. Surg. Gynecol.Obstet. 170:56–60, 1990.

159. WiemanTJ, Smiell, J.M., Su Yachin. Efficacy and safety of a topical gel formulationof recombinant human platelet-derived growth factor–BB (Becaplermin) in patientswith chronic neuropathic diabetic ulcers. a phase, I.I.I randomized placebo-controlleddouble-blind study. Diabetes Care 21:822–827, 1998.

160. Bennett, N., Schultz, G.S. Growth factors and wound healing: Part II. Role in normaland chronic wound healing. Am. J. Surg. 166:74–81, 1993.

161. Lewin Group. An estimate of medical cost savings from treatment of diabetic foot ulcerswith a topical growth factor and good wound care in the Medicare population. Posterpresentation. American Diabetes Association Annual Meeting, San Diego, CA, 1999.

162. Gentzkow, G.D., Iwasaki, S.D., Hershon, K.S., Mengel, M., Prendergast, J.J., Ricotta, J.J.,Steed, D.P., Lipkin, S.L. Use of Dermagraft, a cultured human dermis, to treat diabeticfoot ulcers. Diabetes Care 19:350–354, 1996.

163. Naughton, G., Mansbridge, J., Gentzkow, G. A metabolically active human dermalreplacement for the treatment of diabetic foot ulcers. Artificial Organs 21:1203–1210,1997.

164. Eaglestein, W.H., Falanga, V. Tissue engineering and the development of Apligraf, ahuman skin equivalent. Adv. Wound Care 11(Suppl. 1):1–8, 1998.

165. Faglia, E., Favales, F., Aldeghi, A., Calia, P., Quarantiello, A., Oriani, G., Michael, M.,Campagnoli, P., Morabito, A. Adjunctive systemic hyperbaric oxygen therapy in treat-ment of severe prevalently ischemic diabetic foot ulcer: a randomized study. DiabetesCare 19:1338–1343, 1996.

166. Baroni, G., Porro, T., Faglia, E., Pizzi, G., Mastropasqua, A., Oriani, G., Pedesini, G.,Favales, F. Hyperbaric oxygen in diabetic gangrene therapy. Diabetes Care 10:81–86,1987.

167. Brakora, M.J., Sheffield, P.J. Hyperbaric oxygen therapy for diabetic wounds. Clin.Podiatr. Med. Surg. 12:105–117, 1995.

168. Tibbles, P.M., Edelsberg, J.S. Hyperbaric-oxygen therapy. N. Engl. J. Med. 334:1642–1648, 1996.

169. Leslie, C.A., Sapico, F.L., Ginunas, V.J., Adkins, R.H. Randomized controlled trialof topical hyperbaric oxygen for treatment of diabetic foot ulcers. Diabetes Care11:111–115, 1988.

170. Argenta, L., Morykwas, M.J. Vacuum-assisted closure. a new treatment method forwound control and treatment. clinical experience. Ann. Plast. Surg. 38:563–576, 1997.

171. Schindl, A., Schindl, M., Pernerstorfer-Schon, H., Kerschan, K., Knobler, R., Schindl,L. Diabetic neuropathic foot ulcer: successful treatment by low-intensity laser therapy.Dermatology 198:314–316, 1999.

172. Ger, R., Evans, J.T. A clinical trial of wound closure by constant tension approximation.Am. J. Surg. 171:331–334, 1996.

173. Stoddard, S.R., Sherman, R.M., Mason, M.E., Pelsang, D.J. Maggot debridement therapy.an alternative treatment for nonhealing ulcers. J. Am. Podiatr. Med. Assoc. 85:218–221,1995.

174. Baker, L.L., Chambers, R., DeMuth, S.K., Villar, F. Effects of electrical stimulation onwound healing in patients with diabetic ulcers. Diabetes Care 20:405–412, 1997.

175. Fleischli, J.G., Laughlin, T.J. Electrical stimulation in wound healing. J. Foot AnkleSurg. 36:457–461, 1997.

176. Sussman, K.E., Reiber, G., Albert, S.F. The diabetic foot problem — a failed system ofhealth care? Diabetes Res. Clin. Pract. 17:1, 1992.

177. Mason, J., O’Keefe, C., Hutchinson, A., McIntosh, A., Young, R., Booth, A. A system-atic review of foot ulcer in patients with type 2 diabetes mellitus. II: Treatment. DiabeticMed. 16:889–909, 1999.

178. Gibbons, G.W., Marcaccio, E.J., Burgess, A.M., Pomposelli, F.B., Freeman, D.V., Camp-bell, D.R., Miller, A., LoGerfo, F.W. Improved quality of diabetic foot care, 1984 vs 1990.


reduced length of stay and costs, insufficient reimbursement. Arch. Surg. 128:576–581,1993.

179. Pomposelli, F.B., Marcaccio, E.J., Gibbons, G.W., Campbell, D.R., Freeman, D.V.,Burgess, A.M., Miller, A., LoGerfo, F.W. Dorsalis pedis arterial bypass. durable limbsalvage for foot ischemia in patients with diabetes mellitus. J. Vasc. Surg. 21:375–84,1995.

180. Apelqvist, J., Larsson, J., Agardh, C.-D. Medical risk factors in diabetic patients withfoot ulcers and severe peripheral vascular disease and their influence on outcome. J.Diab. Comp. 6:167–174, 1992.

181. Frykberg, R.G., Giurini, J., Habershaw, G.M., Rosenblum, B.I., Chrzan, J.S. Prophy-lactic surgery in the diabetic foot. In: Medical and Surgical Management of the DiabeticFoot, pp. 399–439, edited by S.J. Kominsky, Mosby Yearbook, St. Louis, 1994.

182. Smith, D.G., Stuck, R.M., Ketner, L., Sage, R.M., Pinzur, M.S. Partial calcanectoy forthe treatment of large ulcerations of the heel and calcaneal osteomyelitis. J. Bone. JointSurg. 74-A:571–576, 1992.

183. Giurini, J.M., Chrzan, J.S., Gibbons, G.W., Habershaw, G.M. Sesamoidectomy for thetreatment of chronic neuropathic ulcerations. J. Am. Podiatr. Med. Assoc. 81:167–173,1991.

184. Giurini, J.M., Habershaw, G.H., Chrzan, J.S. Panmetatarsal head resection in chronicneuropathic ulceration. J. Foot Surg 26:249, 1987.

185. Rosenblum, B.I., Giurini, J.M., Chrzan, J.S., Habershaw, G.M. Preventing loss of thegreat toe with the hallux interphalangeal joint arthroplasty. J. Foot Ankle Surg.33:557–560, 1994.

186. Rosenblum, B.I., Pomposelli, F.B., Giurini, J.M., Gibbons, G.W., Freeman, D.V.,Chrzan, J.S., Campbell, D.R., Habershaw, G.M., LoGerfo, F.W. Maximizing foot sal-vage by a combined approach to foot ischemia and neuropathic ulceration in patientswith diabetes. Diabetes Care 17:983–987, 1994.

187. Fleischli, J.E., Anderson, R.B., Davis, W.H. Dorsiflexion metatarsal osteotomy for treat-ment of recalcitrant diabetic neuropathic ulcers. Foot Ankle Int. 20:80–85, 1999.

188. Giacalone, V.F., Krych, S.M., Harkless, L.B. The University of Texas Health ScienceCenter at San Antonio. Experience with foot surgery in diabetics. J. Foot Ankle Surg.33:590–597, 1994.

189. Catanzariti, A.R., Blitch, E.L., Karlock, L.G. Elective foot and ankle surgery in thediabetic patient. J. Foot Ankle Surg. 34:23–41, 1995.

190. Colen, L.B., Miller, L. Plastic surgical approaches to the diabetic foot. In: The High RiskFoot in Diabetes Mellitus, p. 403, edited by R.G. Frykberg, Churchill Livingstone, NewYork, 1991.

191. Attinger, C.E. Use of soft tissue techniques for the salvage of the diabetic foot.In: Medical and Surgical Management of the Diabetic Foot, pp. 323–366, edited byS.J. Kominsky, Mosby Yearbook, St. Louis, 1994.

192. Holstein, P.E., Sorensen, S. Limb salvage experience in a multidisciplinary diaetic footunit. Diabetes Care. 22(Suppl. 2):B97–B103, 1999.

193. Dargis, V., Pantelejeva, O., Jonushaite, A., Vileikyte, L., Boulton, A.J.M. Benefits of amultidisciplinary approach in the management of recurrent diabetic foot ulceration inLithuania. Diabetes Care 22:1428–1431, 1999.

194. Van Gils, C.C., Wheeler, L.A., Mellstrom, M., Brinton, E.A., Mason, S., Wheeler, C.G.Amputation prevention by vascular surgery and podiatry collaboration in high-riskdiabetic and nondiabetic patients: the Operation Desert Foot experience. Diabetes Care22:678–683, 1999.

195. Armstrong, D.G., Harkless, L.B. Outcomes of preventative care in a diabetic footspecialty clinic. J. Foot Ankle Surg. 37:460–466, 1998.

196. Thomson, F.J., Veves, A., Ashe, H., Knowles, E.A., Gem, J., Walker, M.G., Hirst, P.,Boulton, A.J.M. A team approach to diabetic foot care- the Manchester experience.Foot 2:75–82, 1991.

197. Malone, J.M., Snyder, M., Anderson, G., Bernhard, V.M., Holloway, G.A., Bunt, T.J.Prevention of amputation by diabetic education. Am. J. Surg. 158:520–23, 1989.


198. Ronnemaa, T., Hamalainen, H., Toikka, T., Liukkonen, I. Evaluation of the impact ofpodiatrist care in the primary prevention of foot problems in diabetic subjects. DiabetesCare 20:1833–1837, 1997.

199. Litzelman, D.K., Slemenda, C.W., Langefeld, C.D., Hays, L.M., Welch, M.A., Bild,D.E., Ford, E.S., Vinicor, F. Reduction of lower extremity clinical abnormalities inpatients with non-insulin dependent diabetes mellitus. A randomized, controlled trial.Ann. Intern. Med. 119:36–41, 1993.

200. Spraul, M. Education- can it prevent diabetic foot ulcers and amputations? In: The Footin Diabetes, 3rd ed., pp. 111–120, edited by A.J.M. Boulton, H. Connor, P.R. Cavanagh,John Wiley & Sons, Chichester, UK, 2000.

201. Frykberg, R.G. Podiatrist’s role in the care and treatment of the diabetic foot. In:Diabetes 1994, pp. 734–743, edited by S. Baba and T. Kaneko Elsevier Science, B.V.,Amsterdam, 1995.

202. Uccioli, L., Faglia, E., Monticone, G., Favales, F., Durola, L., Aldeghi, A., Quarantiello,Q., Calia, P., Mezinger, G. Manufactured shoes in the prevention of diabetic foot ulcers.Diabetes Care 18:1376–1378, 1995.

203. Lavery, L.A., Vela, S.A., Fleischli, J.G., Armstrong, D.G., Lavery, D.C. Reducing plan-tar pressure in the neuropathic foot. a comparison of footwear. Diabetes Care20:1706–1710, 1997.

204. Mueller, M.J. Therapeutic footwear helps protect the diabetic foot. J. Am. Podiatr. Med.Assoc. 87:360–364, 1997.

205. Armstrong, D.G., Lavery, L.A., Stern, S., Harkless, L.B. Is prophylactic diabetic footsurgery dangerous? J. Foot Ankle Surg. 35:585–589, 1996.

206. Niklas, B.J. Prophylactic surgery in the diabetic foot. In: The High Risk Foot in DiabetesMellitus, edited by R.G. Frykberg, Churchill Livingstone, New York, 1991.

207. Armstrong, D.G., Stacpoole-Shea, S., Nguyen, H., Harkless, L.B. Lengthening of theAchilles tendon in diabetic patients who are at high risk for ulceration of the foot. J.Bone Joint Surg. 81-A:535–538, 1999.

208. Sapico, F.L., Bessman, A.N. Diabetic foot infections. In: High Risk Foot in DiabetesMellitus, edited by R.G. Frykberg, Churchill Livingstone, New York, 1991.

209. Caputo, G.M. The rational use of antimicrobial agents in diabetic foot infection. In:The Foot in Diabetes, 3rd ed., pp. 143–151, edited by A.J.M. Boulton, H. Connor,P.R. Cavanagh, John Wiley & Sons, Chichester, UK, 2000.

210. Wheat, L.J., Allen, S.D., Henry, M., Kernek, C.B., Siders, J.E., Kuebler, T., Fineberg,N., Norton, J. Diabetic foot infections. bacteriologic analysis. Arch. Intern. Med.146:1935, 1986.

211. Croll, S.D., Nicholas, G.G., Osborne, M.A., Wasser, T.E., Jones, S. Role of magneticresonance imaging in the diagnosis of osteomyelitis in diabetic foot infection. J. VascSurg. 24:266–270, 1996.

212. Lipsky, B.A., Pecoraro, R.E., Larson, S.A., Hanley, M.E., Ahroni, J.H. Outpatient man-agement of uncomplicated lower-extremity infections in diabetic patients. Arch. Intern.Med. 150:790–797, 1990.

213. LeFrock, J.L., Joseph, W.S. Bone and soft tissue infections of the lower extremity indiabetics. Clin. Podiatr. Med. Surg. 12:87–103, 1995.

214. Grayson, M.L., Gibbons, G.W., Habershaw, G.M., Freeman, D.V., Pomposelli, F.B.,Rosenblum, B.I., Levin, E., Karchmer, A.W. Use of ampicillin/sulbactam versusimepenem/cilistatin in the treatment of limb-threatening foot infections in diabeticpatients. Clin. Infect. Dis. 18:683–693, 1994.

215. Leibovici, L., Yehezkelli, Y., et al. Influence of diabetes mellitus and glycemic controlon the characteristics and outcomes of common infections. Diabetic Med. 13(5):457–63,1996.

216. Dickhaut, S.C., DeLee, J.C., Page, C.P. Nutritional status: importance in predictingwound healing after an amputation. J. Bone Joint Surg. 66-A:71–75, 1984.

217. Leichter, S.B., Allweiss, P., Harley, J.,Clay, J., Kuperstein-Chase, J., Sweeney, G.J.,Kolkin, J. Clinical characteristics of diabetic patients with serious pedal infections.Metabolism 37:22, 1988.


218. Tan, J.S., Friedman, N.M., Hazelton-Miller, C., Flanagan, J.P., File, T.P. Can aggressivetreatment of diabetic foot infections reduce the need for above-ankle amputation? Clin.Infect. Dis. 23:286–291, 1996.

219. Scher, K.S., Steele, F.J. The septic foot in patients with diabetes. Surgery 104:661–666,1988.

220. Calhoun, J.H., Cantrell, J., Cobos, J., Lacy, J., Valdez, R.R., Hokanson, J., Mader, J.T.Treatment of diabetic foot infections. Wagner classification, therapy, and outcome. FootAnkle 9:101–106, 1988.

221. Lipsky, B.A., Baker, P.D., Landon, G.C., Fernau, R. Antibiotic therapy for diabetic footinfections: comparison of two parenteral-to-oral regimens. Clin. Infect Dis. 24:643–648,1997.

222. Tentolouris, N., Jude, E.B., SmirnofI, Knowles, E.A., Boulton, A.J.M. Methicillin-resis-tant Staphylococcus aureus. an increasing problem in a diabetic foot clinic. Diabetic Med.16:767–771, 1999.

223. Lew, D.P., Waldvogel, F.A. Osteomyelitis. N. Engl. J. Med. 336:999–1007, 1997.224. Ha Van, G., Siney, H., Danan, J.-P., Sachon, C., Grimaldi, A. Treatment of osteomyelitis

in the diabetic foot: contribution of conservative surgery. Diabetes Care 19:1257–1260,1996.

225. Roeder, B., Van Gils, C.C., Maling, S. Antibiotic beads in the treatment of diabetic pedalosteomyelitis. J. Foot Ankle Surg. 39:124–130, 2000.

226. Frykberg, R.G., Kozak, G.P. The diabetic Charcot foot. In: Management of Diabetic FootProblems, p. 103, edited by G.P. Kozak, C.S. Hoar, J. Rowbotham, et al., WB Saunders,Philadelphia, 1984.

227. Armstrong, D.G., Todd, W.F., Lavery, L.A., Harkless, L.B., Bushman, T.R. The naturalhistory of acute Charcot’s arthropathy in a diabetic foot specialty clinic. J. Am. Podiatr.Med. Assoc. 87:272–278, 1997.

228. Banks, A.S. A clinical guide to the Charcot foot. In: Medical and Surgical Managementof the Diabetic Foot, pp. 115–143, edited by S.J. Kominsky, Mosby Yearbook, St. Louis,1994.

229. Frykberg, R.G. Charcot foot. an update on pathogenesis and management. In: TheFoot in Diabetes, 3rd ed., pp. 235–260, edited by A.J.M. Boulton, H. Connor andP.R. Cavanagh, John Wiley & Sons, Chichester, UK, 2000.

230. Johnson, J.T.H. Neuropathic fractures and joint injuries: pathogenesis and rationale ofprevention and treatment. J. Bone Joint Surg. 49-A:1, 1967.

231. Brower, A.C., Allman, R.M. Pathogenesis of the neurotrophic joint. neurotraumatic vs.neurovascular. Radiology 139:349, 1981.

232. Young, M.J., Marshall, A., Adams, J.E., Selby, P.L., Boulton, A.J.M. Osteopenia, neuro-logical dysfunction, and the development of Charcot neuroarthropathy. Diabetes Care18:34–38, 1995.

233. Banks, A.S., McGlamry, E.D. Charcot foot. J. Am. Podiatr. Med. Assoc. 79:213–217,1989.

234. Caputo, G.M., Ulbrecht, J., Cavanagh, P.R., Juliano, P. The Charcot foot in diabetes:six key points. Am. Fam. Phys. 57:2705–2710, 1998.

235. Eichenholtz, S.N. Charcot Joints, Charles C Thomas, Springfield, IL, 1966.236. Lesko, P., Maurer, R.C. Talonavicular dislocations and midfoot arthropathy in neuro-

pathic diabetic feet: natural course and principles of treatment. Clin. Orthop. 240:226,1989.

237. Selby, P.L., Young, M.J., Boulton, A.J.M. Bisphosphonates. a new treatment for diabeticCharcot neuroarthropathy? Diabetic Med. 11:28–31, 1994.

238. Hanft, J.R., Goggin, J.P., Landsman, A., Surprenant, M. The role of combined magneticfield bone growth stimulation as an adjunct in the treatment of neuroarthropathy/Charcotjoint. an expanded pilot study. J. Foot Ankle Surg. 37:510–515, 1998.

239. Pinzur, M.S., Sage, R., Stuck, R., Kaminsky, S., Zmuda, A. A treatment algorithm forneuropathic (Charcot) midfoot deformity. Foot Ankle 14:189–197, 1993.

240. Myerson, M.S., HendersonMR, Saxby, T., Short, K.W. Management of midfoot diabeticneuroarthropathy. Foot Ankle Int. 15:233–241, 1994.

241. Sella, E.J., Barrette, C. Staging of Charcot neuroarthropathy along the medial columnof the foot in the diabetic patient. J. Foot Ankle Surg. 38:34–40, 1999.


242. Fabrin, J., Larsen, K., Holstein, P.E. Long-term follow-up in diabetic Charcot feet withspontaneous onset. Diabetes Care 23:796–800, 2000.

243. Pinzur, M.S. Benchmark analysis of diabetic patients with neuropathic (Charcot) footdeformity. Foot Ankle Int. 20:564–567, 1999.

244. Simon, S.R., Tejwani, S.G., Wilson, D.L., Santner, T.J., Denniston, N.L. Arthrodesis asan early alternative to nonoperative management of Charcot arthropathy of the diabeticfoot. J. Bone Joint Surg. 82-A:939–950, 2000.

245. Rosenblum, B.I., Giuini, J.M., Miller, L.B., Chrzan, J.S., Habershaw, G.M. Neuropathiculcerations plantar to the lateral column in patients with Charcot foot deformity: a flexibleapproach to limb salvage. J. Foot Ankle Surg. 36:360–363, 1997.

246. Schon, L.C., Marks, R.M. The management of neuroarthropathic fracture-dislocationsin the diabetic patient. Orthop. Clin. North Am. 26:375–392, 1995.

247. Laing, P. Prophylactic orthopaedic surgeryis there a role? In: The Foot in Diabetes, 3rded., pp. 261–277, edited by A.J.M. Boulton, H. Connor, P.R. Cavanagh, John Wiley &Sons, Chichester, UK, 2000.

248. Del Aguila, M.A., Reiber, G.E., Koepsell, T.D. How does provider and patient aware-ness of high-risk status for lower-extremity amputation influence foot-care practice?Diabetes Care 17:1050–1054, 1994.


diabetic foot disorders - pdfs.semanticscholar.org · work in progress and will require future...

Documents