MICHAEL SCHÖMIG*,
EBERHARD RITZ*,
EBERHARD STANDL and
JENS ALLENBERG
*Department of Internal Medicine, Ruperto Carola University, Heidelberg,
Germany Department of Surgery, Ruperto Carola University, Heidelberg,
Germany Diabetes Research Institute, Munich, Germany
Correspondence to Dr. Eberhard Ritz, Department of Internal Medicine,
University of Heidelberg, Bergheimer Strasse 58, D-69115 Heidelberg, Germany.
Phone: +49 6221 91120; Fax: +49 6221 162476; E-mail:
prof.e.ritz{at}t-online.de
Foot lesions are the single most commonly mismanaged problemof patients
with diabetes mellitus and associated renal disease.They are often
incorrectly considered to be a minor clinicalproblem, yet not infrequently
they impact upon patient survival.
What Is the Epidemiology of Foot Lesions in Diabetes?
The cumulative lifetime frequency of amputations in type 1 andtype 2
diabetic patients overall is approximately 15% both inEurope and in the
United States
(1,2).
In Germany, two of threepatients undergoing amputation suffer from diabetes,
and thedirect annual cost from this procedure amounts to 3 billionDM
(approximately $1.5 billion U.S. dollars)
(3). Amputationis a
much-feared tragedy in the life of a diabetic patient,and the tragedy is
compounded by the fact that a great numberof amputations are either
unnecessary or unnecessarily aggressive.Above-ankle amputation carries a
perioperative mortality of20%, and more than one-third of the patients remain
unable tocare for themselves. The best evidence that appropriate management
preventsan excess of amputations comes from Sweden
(4) and the UnitedKingdom
(5), where so-called
"Foot Clinics" with appropriateinterdisciplinary care for
patients with diabetic foot lesionsreduced amputations, particularly
above-ankle amputations, by50 to 80%.
What Is the Epidemiology of Foot Lesions in Diabetic Patients with
Renal Disease?
In the United States, the rate of lower limb amputation in patientswhose
renal failure was attributed to diabetic nephropathy hasrecently risen to 14%
(2). The risk is excessive in
the diabeticpatient with uremia: the rate is 10 times higher than in the
diabeticpopulation at large. When diabetic patients enter renal replacement
programs,approximately 10% already have a history of above- or below-ankle
amputation(6), and the
proportion of patients requiring amputation ondialysis is approximately 4%
per year. In an ongoing Germanstudy in patients with type 2 diabetes on
dialysis (4D study),16% of incident patients have a history of amputation for
gangreneand 44% have a diagnosis of peripheral arterial disease
(7).
What Causes the Diabetic Foot Lesion?
Diabetic foot lesions occur either as a consequence of ischemiafrom
macroangiopathy (ischemic foot) or as a result of one aspectof
microangiopathy, i.e., neuropathy with loss of sensory, autonomous,
andmotor innervation (neuropathic foot). The distinction betweenthese two
varieties is important, because the interventionalstrategies are completely
different. In practice, however, thetwo causes often coexist
(8,9,10).
In the study of Reike (12),
34%of diabetic foot lesions were due to neuropathic, 21% to ischemic,and 40%
to combined neuropathic plus ischemic lesions. The mechanismsthrough which
macroangiopathy and neuropathy predispose to footlesions and the exogenous
factors that trigger the lesions areschematically summarized in
Figure 1. The major clinical
featuresthat allow one to distinguish the neuropathic and the ischemic
lesionsare listed in Table 1.
We also refer to some recent reviews
(8,9,10,11,13).
In patients with advanced diabetic nephropathy, diabetic footlesions are
particularly frequent and, conversely, diabeticnephropathy is found in no
less than 50% and overt coronaryheart disease in 49% of the patients with
diabetic foot lesions.The association of diabetic foot lesions with advanced
diabeticnephropathy may be explained by: (1) the long duration of
diabetes,which predisposes to both nephropathy and foot lesions; (2)
theparticularly high risk of nephropathic patients to develop
macroangiopathicor neuropathic complications; or (3) a combination
of both.Whatever the explanation, diabetic foot lesions are particularly
frequentin patients seen by the nephrologist. The high comorbidity in
patientswith diabetic foot lesions also explains the considerably worse
prognosisin amputated compared with nonamputated patients on dialysisor
after renal transplantation. The potential for full rehabilitationafter
amputation is poor in diabetic patients compared withnondiabetic amputees,
and patients may lose self-managementto a degree that necessitates
institutional care (2).
Diabetic peripheral neuropathy in patients with renal failureis aggravated
by superimposed uremic peripheral neuropathy,thus explaining the particularly
frequent and severe lesionsin the uremic diabetic patient. Perception of pain
is impaired("the neuropathic foot is silent and the patient is
silent").Loss of protective sensation predisposes to episodes of
cumulativeunnoticed trauma. Patients may also wear damaging footwear because
painfrom injury is not perceived. Additional mechanisms are operativein the
damage to the neuropathic foot. In particular, the equilibriumof muscular
forces is disrupted by the atrophy of the anteriormuscles of the lower leg
and atrophy of the lumbrical and interosseousmuscles, thus destabilizing the
metatarsophalangeal joint
(14).The forefoot is further
exposed to unphysiologically high pressuresbecause of the adductor varus
position of the toes. All of thisleads to foot deformity. Mechanical trauma
is further aggravatedby factors that reduce the viscoelasticity of the foot,
e.g.,stiffening of connective tissue and diminished joint mobility
(asa result of nonenzymatic glycation), loss of fat tissue, andedema
formation. Neuropathic lesions are also associated withimpaired energy
metabolism, fatty infiltration, and increasedintracellular pH of plantar
muscles (15).
As a result, excessive shear forces and pressure are generatedwhen the
deformed foot of a patient with loss of sensation andwith lower limb muscle
dysfunction resulting from disturbedinnervation hits the ground in an
uncoordinated manner (16).The
importance of an additional factor, i.e., faulty loadingcaused by
reduced joint mobility and foot deformity, is illustratedby the observation
of Fernando et al.
(17) that metatarsal ulcers
werefound in 60% of diabetic patients who had neuropathy plus footdeformity,
but in only 5% of patients who had neuropathy alone.
Neuropathy further causes abnormalities of the skin and subcutaneous
tissue,which predispose to bacterial invasion and necrosis with ulcer
formation.Autonomic neuropathy gives rise to vasodilation and anhidrosis,
causingdry skin with cracks and fissure formation, as well as capillary
hypertensionwith edema formation. It is an error to ascribe all leg edemaof
a diabetic patient to renal failure. Hyperkeratosis and ulcersoccur at sites
exposed to maximal pressure loads, i.e., themetatarsal head
(Figure 2), the tips of the
toes, or the lateralaspect of the foot, if the latter is exposed to pressure
fromtightly fitting shoes. The hypoxic tissue with reduced vitality
underneatha hyperkeratotic callus easily develops necrosis, ultimately
resultingin ulcer formation (Mal perforant).
Figure 2. Neuropathic ulcer. (A) Deep callous ulcer of the lateral plantar forefoot
resulting from faulty loading and massive increase of plantar pressure. (B)
Same ulcer 3 d later after surgical removal of callous wall and relief of
pressure by bed rest. (C) Complete healing 2 wk later.
In advanced cases, major destruction of the foot skeleton architectureis
triggered by trivial trauma. Acro-osteolysis, aseptic bonenecrosis, and
severe foot deformity may develop (Charcot's foot).This lesion in diabetic
patients is similar to that seen incases of syringomyelia, leprosy, and
polyneuropathy.
Peripheral arterial disease is observed more frequently in diabetic
comparedwith matched nondiabetic patients
(18,19).
When ultrasound Dopplerassessment of pulses is used, peripheral artery
disease is foundin 30% of all diabetic patients
(18), the prevalence being 15
to20% in those 70 yr of age and increasing to more than 50% atage 80 and
above. Lower limb atherosclerosis in the diabeticpatient is characterized by
preferential involvement of thelower leg, e.g., in 70% of diabetic
patients compared with only20% of nondiabetic patients who suffer from
peripheral arterialdisease. Involvement of the deep femoral artery is also
typicalof diabetes. Often, multiple arterial segments are stenosed.The
majority of patients do not complain of claudication
(Table 2).The risk factors
predisposing to macroangiopathy and ischemicfoot lesions are the same as the
risk factors in nondiabeticpatients, particularly smoking, but the diabetic
patient hasan excess risk for any given constellation of risk factors.
Peripheralarterial disease is 2.5 to 6 times more frequent than in
nondiabeticpatients and occurs 10 yr earlier. An important role of
uncontrolledhyperglycemia is suggested by several epidemiologic studies,and
this may explain in part the higher risk in the diabeticpatient.
Table 2. Characteristics of peripheral arterial disease of the lower extremity
in diabetes mellitus
Calcification of the media of arteries is common in the diabeticpatient
and can be recognized by linear calcification on ultrasonography.Such
calcification of the media is a risk predictor for severeatherosclerotic
lesions of the intima. Media calcification makesmeasurements of arterial
blood pressure unreliable and causesspuriously elevated values because of the
reduced compressibilityof the arteries.
The trigger event leading to the clinically manifest diabeticfoot lesion
in patients at risk (20) is
very often trivial.Skin lesions resulting from high pressure are caused by
excessivelytight shoes, minor trauma, and/or inadequate foot care,
e.g.,removal of hyperkeratotic plaques with sharp instruments or
inadvertentcuts during nail trimming. Trauma is often incurred when walking
barefootand treading on sharp objects.
Neuropathic lesions usually start as hyperkeratotic plaqueswith necrosis
underneath, whereas ischemic lesions usually startas superficial ulcers or
blisters.
Infection is a major aggravating factor. Ports of entry areoften ingrowing
nails, paronychia, fissures, and interdigitalmycoses. One usually finds mixed
infections with an averageof five different microbes, usually staphylococci,
includingmethicillin-resistant staphylococci
(21), hemolytic or
nonhemolyticstreptococci, Gram-negative Escherichia coli, and
anaerobes
(9,22,23).
Themost feared complication is spread of infection to ligaments,tendons, and
bones. This may lead to septic thrombosis and secondarilyto gangrene even in
the absence of macroangiopathy
(20). Thediagnosis of
osteomyelitis by x-ray is difficult, particularlyits differentiation from
neuropathic changes, e.g., from Charcot'sfoot. Both complications
cause osteolysis, fragmentation ofbone, and osteoarticular destruction. Bone
scintigraphy maybe of some help to make the distinction.
Examination of the Patient with Diabetic Foot Lesions
Table 3 summarizes the
necessary points. A history of traumashould be sought. One should look for
tissue trauma from thepressure of tight-fitting shoes; shoes and socks should
be inspected;one should examine nails, inspect for interdigital mycosis,
hyperkeratoticplaques, minor lesions, and look for deformities of the foot,
particularlyloss of the pedal arch with flat-footedness associated with
downwardmovement of the metatarsal heads and hammer toe formation.
Table 3. Examination of the patient with diabetic foot lesions
To recognize tissue ischemia, it is useful to measure ankle,and, if
possible, toe perfusion pressure by Doppler measurements.Arterial media
calcifications and diminished arterial compressibilitymay give rise to
spuriously high arterial pressure values, butwhen pressures are lower by 10
mmHg or more compared with brachialpressure, one should suspect arterial
stenoses. Ankle pressurevalues <50 mmHg and toe pressure values <30
mmHg indicatecritical ischemia. This can be confirmed by transcutaneous
oxygenpartial pressure measurements, with values <10 mmHg indicating
criticalischemia.
In the management of the diabetic foot lesion, it is of crucialimportance
to establish whether the patient complains of pain.The absence of pain
indicates a neuropathic component but unfortunatelydoes not exclude the
concomitant presence of ischemia.
Neurologic examination comprises eliciting reflexes, testingfor thermal
sensation, perception of vibration (quantitativetuning fork), and perception
of touch and pain. Measurementof the dynamic distribution of foot pressure by
pedography (Figure 3)is
helpful to recognize faulty loading and to guide selectionof proper
footwear.
Figure 3. Pedographic pressure patterns (red = highest pressure). (Left) Normal
pattern. (Middle and Right) Two diabetic patients with increased pressure in
the forefoot area and reduced (middle) or deficient toe function (right)
Acute Management of the Patient with Diabetic Gangrene
Although there is little controlled information
(24), patientsshould be
hospitalized and managed according to recently standardizedguidelines
(25). The aims of management
are:
to control infection;
to assess the potential need for revascularization;
to assess the potential need for amputation; and
to providein the long-term adequate foot care and footwearto prevent
recurrence
(18,19,20).
Table 4 summarizes treatment
strategies in the patient withdiabetic gangrene. Local administration of
powders or ointmentsis contraindicated. Wound care should differ according to
thestage of evolution. If correctable ischemia is present, thisintervention
has priority. Otherwise, surgical debridement,removal of necrotic tissue, and
antiseptic measures are usuallyindicated. For neuropathic ulcers, an active
approach is frequentlynecessary. One has then to remove callus and luxuriant
growthand relieve pressure from massive tissue infiltration usingbroad
incisions. If tendons and bones are affected, minimalsurgery should be
considered, e.g., resection of metatarsalheads and toes
(26,27).
Excessively aggressive surgery shouldbe avoided. Generally for foot lesions
with severe infection,we prefer open wound care and try to avoid attempts at
amputation.If amputation is necessary, the defect should be covered withan
interpolated flap if possible.
Table 5. Prophylactic measures to prevent diabetic foot problems
To increase fibroblast proliferation, moist wound dressingsshould be
applied later. To promote epithelialization, tullegras wound contact
dressings should be used subsequently. Ischemicgangrenous toes must be kept
dry, and the surrounding skin mustbe cleaned. If at all possible, one should
wait for spontaneousdemarcation.
Bacterial inflammation of ulcers and fissures usually resultsfrom mixed
infections
(9,22,23,28)
including anaerobes. Bacterialcultures should be obtained because frequently
microbes requiringspecific antibiotics are found, e.g., pseudomonas
or methicillin-resistantStaphylococcus aureus.
The major antibiotics used currently for systemic treatmentinclude
quinolones, ß-lactam antibiotics with or withoutclavulanic acid,
cephalosporins, clindamycin, and metronidazole.The risk of failure is high in
patients with fever and gangrenewho often require amputation
(29).
In patients with below-ankle microamputation, follow-up careis necessary
to ensure that pressure loads are properly redistributedin order to prevent
reappearance of ulcers at new sites or inthe opposite foot.
If one considers revascularization, some basic rules shouldbe followed.
First, minimal surgery should be tried wheneverpossible, i.e., as
little reconstruction as possible, but asmuch as necessary. Second, if
revascularization is feasible,it should precede local surgery measures such
as fenestration,debridement, or microamputation, because wound healing is
delayedand infections tend to be more progressive in ischemic tissues.
Stenoses and occlusions can be treated either by the endovascularor open
surgical approach. If several stenoses in series arepresent, it may be
advisable to correct the most proximal stenosis(even if it is not critical)
by endovascular techniques in combinationwith distal bypass techniques.
Adequate imaging of vasculature before therapy is necessary,bearing in
mind the risk of acute renal failure after administrationof a radiocontrast
agent in diabetic nephropathy. In the future,carbon dioxide and nuclear
magnetic resonance angiography maybecome the procedure of choice
(30). The interventional
strategydepends on the level and extension of the arterial lesion.
Iliac Arteries
The best results are achieved in patients with short proximalocclusions
that are susceptible to percutaneous transluminalarterioplasty (PTA) with or
without stents (Figure 4).
Noveladvanced prosthesis, e.g., stent grafts under regional or local
anesthesia,may permit stenting even of more extended occlusions.
Figure 4. (A and B) Female diabetic patient, 48 year old, with occlusion of the left
common iliac artery before (A) and after (B) treatment with balloon
angioplasty.
If iliac artery stenoses or occlusions are associated with lesionsat the
inguinal level, or if the percutaneous endovascular approachhas been
unsuccessful, open surgery is required. In patientswith unilateral occlusion
of the iliac artery, we have successfullyused extra-anatomical femoral or
iliaco-femoral cross-over bypass.In patients with bilateral pelvic artery
occlusion, one canuse either bifurcation bypass or axillo-bifemoral graft
bypass.
Femoral Arteries
If the superficial femoral artery is occluded and the originof the deep
femoral artery is stenosed, perfusion may be sufficientlyimproved by
correcting the deep femoral artery alone. Unfortunately,in diabetic patients
one often finds, in addition, atheroscleroticlesions in the periphery of the
deep femoral artery, so thatcollateral formation to the popliteal artery may
not be sufficient.In this case, superficial femoral artery bypass to the
poplitealartery is recommended. For short stenoses or occlusions of the
superficialfemoral artery, PTA is the procedure of first choice. Currently,
thesuccess rate for stents at the level of the femoral artery is
unsatisfactory.Stents should not be used except to correct occluding
dissectioncomplicating PTA, but stent-reinforced vascular prostheses are
currentlyunder evaluation and may change the practice in the future.For
occlusions exceeding 10 to 15 cm in length, open bypasssurgery should be
performed. When the superficial femoral arteryis reconstructed and the distal
anastomosis is located abovethe knee, bypass prostheses should be used to
save veins forfuture reconstructions. If the anastomosis is located at or
belowthe level of the popliteal artery, an autologous venous bypassis the
preferred approach.
Popliteal Artery
Occlusions at the level of the popliteal artery and trifurcation,
i.e.,the point of origin of tibial and peroneal arteries, shouldbe
treated exclusively with autologous venous bypass. If thelong saphenous vein
is not suitable, the short saphenous veincan be used. Some surgeons use arm
veins, but this should bediscouraged in view of the potential future need for
hemodialysisaccess. Another possibility is the in situ venous bypass
technique,i.e., the use of the local veins, if the diameter of the
saphenousvein is <4 mm.
Peroneal and Tibial Arteries
If the pedal arteries are patent, correction by popliteopedalvenous or
even lower tibiopedal bypass is possible. Correctionwith PTA is an extremely
difficult issue because, although insertionof stents is technically feasible,
the reocclusion rate is extremelyhigh and it is therefore contraindicated.
Postoperatively, medicationwith platelet aggregation inhibitors (low dose
aspirin and/orclopidogrel) is mandatory in all patients with peripheral
reconstructions.In selected cases, warfarin therapy can be used
(31), but iflarge
fluctuations of international normalized ratio occur,e.g., because
of patient noncompliance, paradoxically even aprothrombotic tendency may be
created.
Prophylaxis of the diabetic foot syndrome cannot be achievedwithout
adequate education and motivation of the patient. Ithas been shown that
implementation of an adequate educationprogram can reduce by half the number
of leg amputations evenwithout revascularization procedures.
Table 5 summarizes prophylactic
measuresto prevent diabetic foot problems.
Proper fitting of footwear, i.e., shoes and in-soles, is a
cornerstoneof primary and secondary prevention. A step-care approach
accordingto the risk category should be followed. As long as there areno
deformities, properly fitted in-soles are sufficient forpressure relief.
Enough space especially in the forefoot ofthe shoes is mandatory. Patients
with deformities, severe neuropathy,peripheral vascular disease, or a history
of foot ulcer needspecially fitted shoes. Often a stiff sole and a forefoot
rollare necessary. For patients with acute forefoot ulcers, a therapeutic
halfshoe for total pressure relief is required.
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Top
Epidemiology
The Neuropathic Foot Lesion
