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S. Tesfaye and T. Didangelos
patch, similar in magnitude to other treatments with known
efcacy but without systemic side effects or sensory deterioration [114, 115]. Recently, both the Food and Drug
Administration (FDA) and European Medicines Agency
(EMA) have granted approval for a label extension for
QUTENZA (capsaicin 8% patch) to include the treatment of
adult diabetic patients with peripheral neuropathic pain,
either alone or in combination with other medicinal products
for pain [112]. Although there were initially safety concerns
as capsaicin causes small bre degeneration, the treatment
appears to be safe as the small bres do regenerate and has
been likened to the “pruning of roses” that may explain the
mechanism of action [116].
Intravenous Lignocaine
Intravenous lignocaine at a dose of 5mg per kg body weight
with another 30min with a cardiac monitor in situ has also
been found to be effective in relieving neuropathic pain for
up to 2weeks [117]. This form of treatment is useful in subjects who are having severe pain that is not responding to the
above agents, although it does necessitate bringing the
patient to a hospital for a few hours.
Recent Guidelines forPharmacological
Treatment
The European Federation of Neurological Society (EFNS)
[118]) and the UK National Institute for Health and Clinical
Excellence (NICE) [119] proposed that rst-line treatments
might comprise TCAs, SNRIs, gabapentins or pregabalins.
The American Academy of Neurology (AAN) recommended
that pregabalin is “established as effective and should be
offered for relief of painful-DPN (Level A evidence)” [120],
whereas venlafaxine, duloxetine, amitriptyline, gabapentin,
valproate, opioid, and capsaicin were considered to be “probably effective and should be considered for treatment of
painful-DPN (Level B evidence).” However, this recommendation has now been changed in the updated 2022 guideline
[121]. The guideline recommends, in patients with painful
DPN, that clinicians offer TCAs, SNRIs, gabapentinoids
and/or sodium channel blockers to reduce pain (Level B) and
consider factors other than efcacy (Level B). Further, it recommends that clinicians offer patients a trial of medication
from a different effective class when they do not achieve
meaningful improvement or experience signicant adverse
effects with the initial therapeutic class (Level B) and not use
opioids for the treatment of PAINFUL DPN (Level B).
Finally, a more recent International Consensus Panel on
Diabetic Neuropathy recommended TCAs, duloxetine, pregabalin and gabapentin as rst-line agents having carefully
Table 3.8 Pharmacological treatment of painful DPN
• Tricyclic antidepressants (TCAs)
Amitriptyline 25–150mg/day
Imipramine 25–150mg/day
• Serotonin noradrenaline reuptake inhibitors (SNRIs)
Duloxetine 60–120mg/day
• Anticonvulsants
Gabapentin 300–3600mg/day
Pregabalin 900–600mg/day
• Opiates (given by a specialist for short-term use only)
Tramadol 200–400mg/day
Oxycodone 20–80mg/day
Morphine sulphate SR 20–80mg/day
• Capsaicin
Cream (0.075%) applied sparingly three to four times per day
Patch (8%)—Treatment must be performed only by a healthcare
provider
• IV lignocaine
5mg/kg given IV over 1hour with ECG monitoring
reviewed all the available literature regarding the pharmacological treatment of painful DPN [13], the nal drug choice
tailored to the particular patient based on demographic prole and co-morbidities (Table3.8). Table3.8 shows the doses
of commonly prescribed neuropathic pain drugs for painful
DPN.There is a reluctance to prescribe opiates because of
addiction potential, particularly in the United States. Opiates
should only be initiated as third-line drugs by an experienced
pain specialist, endocrinologist or neurologist and only for
short-term use in patients with less addiction potential.
Comparator andCombination Trials
A major deciency in the treatment of neuropathic pain in
diabetes is the relative lack of comparative or combination
studies. Virtually, all previous trials have been of active
agents against placebo, whereas there is a need for more
studies that compare a given drug with an active comparator
and indeed lower-dose combination treatments [104]. These
issues have been highlighted by recent consensus guidelines
from international institutions that have emphasised the need
for large comparative and combination treatment trials in
painful DPN as a matter of priority [104].
Comparator Trials
Bansal etal. compared amitriptyline with pregabalin in painful DPN in a small, randomised, double-blind, crossover trial
[122]. This study conrmed that whereas there was little difference in efcacy, pregabalin was the preferred drug because
of a superior adverse event prole. However, a major drawback of this study was its small size involving 51 patients
only with many patients failing to complete the study [122].
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Another recent small, crossover study from the same
group as the above study has compared duloxetine with amitriptyline [123]. The study found that both drugs were
equally efcacious, although of the reported adverse events,
dry mouth was more common with amitriptyline than duloxetine (55 vs. 24%; P<0.01). Numerically more patients preferred duloxetine, although this was not statistically
signicant (48 vs. 36%; P=0.18).
The lack of direct comparator studies led to an indirect
comparison of the efcacy and tolerability of duloxetine
with that of pregabalin and gabapentin in participants with
painful DPN using a placebo as a common comparator [124].
Efcacy criteria were reduction in 24h pain severity for all
three treatments and treatment response rate (≥50% pain
reduction) and overall health improvement (as measured on
the Patient Global Impression of Improvement/Change questionnaire) for duloxetine and pregabalin only. An indirect
comparison between duloxetine and gabapentin found no
statistically signicant differences. Comparing duloxetine
with pregabalin, the authors found signicant differences in
overall health improvement, favouring pregabalin, and in
dizziness, favouring duloxetine. There was no signicant difference in 24h pain severity between duloxetine and pregabalin [124].
Combination Trials
Gilron et al. studied nortriptyline and gabapentin either in
combination or alone in a randomised trial and conrmed
that when given together, they were more efcacious than
either drug given alone [125]. In another crossover study by
the same group, low-dose combination therapy with gabapentin and morphine was signicantly more effective than
higher doses of either [126].
The COMBO-DN study [127] is the largest combination
trial in painful DPN, and it assessed whether combining
standard doses of duloxetine and pregabalin is superior to
increasing each drug to its maximum recommended dose in
patients with incomplete pain relief. Patients with painful
DPN with a daily pain score of at least 4 (scale 0–10) were
randomly assigned in a 1:1:1:1 ratio to one of four groups.
For the 8-week Initial Treatment period, patients in groups 1
and 2 were treated with 60-mg duloxetine/day; patients in
groups 3 and 4 received 300-mg pregabalin/day. Thereafter,
only non-responders (<30% improvement in pain relief)
received double-blind treatment for a further 8weeks of the
Combination vs. high-dose Monotherapy Treatment period
with duloxetine 120mg/day for group 1, duloxetine 60mg/
day+pregabalin 300mg/day for groups 2 and 3 and pregabalin 600 mg/day for group 4. The primary outcome was
change in the Brief Pain Inventory 24h average pain during
Combination vs. high-dose Monotherapy Treatment period
between (groups 1 and 4 pooled- i.e., high dose monotherapy) with combination therapy (groups 2 and 3 pooled).
Eight hundred four patients were evaluated in the Initial
and 339 in the Combination vs. high-dose Monotherapy
Treatment period, respectively. The difference between
Combination and Monotherapy in the mean change of BPIMSF average pain during the Combination vs. high-dose
Monotherapy Treatment period was not statistically signicant (Combination: −2.35; Monotherapy: −2.16; p=0.37).
Proportions of patients with treatment-emergent adverse
events were, however, similar: 36.7% (Combination) and
33.5% (Monotherapy). As a secondary end point, the
COMBO-DN study also compared the efcacy of standard
doses of duloxetine and pregabalin as initial treatment for
painful DPN, and duloxetine was found to have superior efcacy compared to pregabalin, without any safety ndings of
concern. At the end of the Combination vs. high-dose
Monotherapy Treatment period, although the groups are no
longer randomised, 50% pain relief was found in 46.9% of
subjects on 600-mg/day pregabalin compared to 28.4% on
120-mg/day of duloxetine.
Taken together, even though the primary end point was
not met, the COMBO-DN study demonstrated that at standard doses, duloxetine has better efcacy than pregabalin as
an initial treatment for painful DPN, without any safety ndings of concern. However, pregabalin catches up with duloxetine in terms of efcacy as the doses are increased to the
maximum.
The OPTION-DM Trial
The recent AAN guideline [121] identied gaps in the current knowledge regarding painful-DPN management, including the following: a few studies alone have investigated the
effect of interventions on the quality of life, patient functioning, mood or sleep; there are a few comparator studies of
rst-line drugs and their combinations; and scarce data are
available on which patients respond to a specic intervention. OPTION-DM, a multi-centre, randomised, doubleblind, crossover trial in patients with painful DPN [128],
tried to address all these limitations [121]. This longest-ever
crossover neuropathic pain trial compared amitriptyline supplemented with pregabalin, pregabalin supplemented with
amitriptyline and duloxetine supplemented with pregabalin,
each pathway lasting for 16weeks [128]. Monotherapy was
given for 6weeks and was supplemented with the combination medication if there was suboptimal pain relief (NRS>3),
reecting current clinical practice. Both treatments were
titrated towards the maximum tolerated dose (75mg per day
for amitriptyline, 120mg per day for duloxetine and 600mg
per day for pregabalin). The primary outcome was the difference in 7-day average daily pain during the nal week of
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S. Tesfaye and T. Didangelos
each pathway. Secondary outcomes included the quality of
life, mood, and sleep [128]. The study showed that all three
treatment pathways and monotherapies had similar analgesic
efcacy. The mean maximum tolerated doses per day and the
number (percentage) of participants on the maximum dose at
week 6 was 56mg (53 [51%] participants) for amitriptyline,
76mg (46 [46%]) for duloxetine and 397mg (59 [55%]) for
pregabalin. Moreover, combination treatment was well tolerated and led to 37% improved pain relief in patients with
suboptimal pain control with monotherapy.
Adverse events were predictable for the monotherapies.
The pregabalin supplemented by the amitriptyline pathway had the fewest discontinuations due to treatmentemergent adverse events compared with the other pathways
(p=0·031) [128].
Management ofDisabling Painful Neuropathy
Not Responding toPharmacological Treatment
Neuropathic pain can sometimes be extremely severe, interfering signicantly with patients’ sleep and daily activities.
Unfortunately, some patients are not helped by conventional
pharmacological treatment. Such patients may respond to
electrical spinal cord stimulation, which relieves both background and peak neuropathic pain [129]. The modalities of
treatment include conventional waveform, burst and highfrequency stimulation. The treatment requires an operation
under local anaesthesia. Signicant pain relief is found in
around 60% of patients; however, this treatment should only
be performed in specialist centres with appropriate expertise.
In a longitudinal follow-up from a multi-centre randomised
controlled trial (RCT) of epidural spinal cord stimulation
(ESCS), about one-third of recipients reported at least a 50%
reduction in pain at 5years [130]. The most robust evidence
for spinal cord stimulation comes from a recent high frequency (10-kHz) ESCS multi-centre randomised controlled
trial of 216 patients with PDN who had not experienced
improvement with at least one gabapentinoid and had a
visual analogue scale score> 50 mm, to medical management alone or 10-kHz ESCS [131, 132]. Substantial pain
relief and improved health-related quality of life sustained
over 6months demonstrate that 10-kHz ESCS can safely and
effectively treat patients with refractory painful DPN [132].
Five experienced implantation-related adverse events, with
two requiring explants [131]. Control participants were
allowed to cross over to 10-kHz ESCS after 6months of
follow-up and showed similar signicant improvement in
pain measures as participants randomised to ESCS at baseline [132]. Quality-of-life measures improved signicantly
after 10-kHz ESCS.However, this study was not sham controlled. ESCS is particularly advantageous as the patient may
not require as many pain-relieving medications with all their
side effects. This treatment is now available in specialist centres in most developed countries.
Tailoring Treatment toIndividual
Requirements
Neuropathic pain in people with diabetes affects daily life, is
devastating and remains under-diagnosed and under-treated
in clinical practice [133]. Moreover, patients have low expectations of treatment despite the availability of therapeutic
options that could relieve their pain. So the initial selection
of a particular rst-line treatment should be inuenced by the
assessment of contraindications, the evaluation of comorbidities (including sleep disturbance, mood disorders
and other chronic medical/diabetic complications) and cost.
For example, in diabetic patients with a history of heart disease, elderly patients on other concomitant medications such
as diuretics and anti-hypertensives and patients with comorbid orthostatic hypotension TCAs have relative contraindications. In patients with liver disease, duloxetine should
not be prescribed, and in those with peripheral oedema, pregabalin or gabapentin should be avoided. Moreover, although
pharmaceutical companies may recommend a particular
starting dose for their drugs based on their clinical trials, one
has to appreciate that the clinical practice scenario is different from the clinical trial scenario as many elderly patients
with multiple co-morbidities would have been excluded
from trials. Therefore, treatment must be individualised to
take patient co-morbidities, including occupation, renal
impairment etc., into account and caution advised to start at
lower than recommended doses and titrating gradually.
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Clinical Features andDiagnosis
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ofPeripheral Arterial Disease
NicholasJ.Swerdlow andAllenD.Hamdan
4
Abstract
Diabetes mellitus is a well-established risk factor for the
development of peripheral arterial disease (PAD). The
spectrum of disease in PAD ranges from asymptomatic to
rest pain and tissue loss. Patients with diabetes frequently
are asymptomatic until they develop a foot wound and
subsequently experience poor wound healing due to the
lack of perfusion. PAD is broadly dened as an anklebrachial index (ABI) of less than 0.9. The evaluation of
PAD in patients with diabetes begins with a good physical
exam, including an inspection of the feet and a thorough
pulse exam. The American Diabetes Association recommends that all patients with diabetes undergo screening
ABI every 5years. If the ABI is decreased or there is a
concern for ischemia upon examination, further noninvasive arterial testing should be performed. Duplex ultrasound and computed tomography (CT) angiography are
important adjuncts to this workup, providing information
on the anatomy of atherosclerotic disease. The gold standard in the evaluation of lower extremity PAD remains to
be digital subtraction angiography, which allows for a
detailed assessment of the arterial anatomy, especially of
the smaller tibial and pedal arteries, and allows for endovascular revascularization if warranted or if planning for
open revascularization.
N. J. Swerdlow
Division of Vascular and Endovascular Surgery, Brigham and
Women’s Hospital, Harvard Medical School,
Boston, MA, USA
A. D. Hamdan (*)
Division of Vascular and Endovascular Surgery, Beth Israel
Deaconess Medical Center, Harvard Medical School,
Boston, MA, USA
e-mail: ahamdan@bidmc.harvard.edu
Pathogenesis
Peripheral arterial disease (PAD) is characterized by progressive blockage or complete obstruction of the arteries
supplying the lower extremities, broadly dened as an anklebrachial index of less than 0.9. Its clinical presentation
ranges from asymptomatic to severe ischemia leading to tissue loss, infection, and ultimately amputation if not treated.
PAD has a signicant global burden of disease. While hard to
quantify precisely, as of 2015, it was estimated that over
235million adults globally were living with PAD, with those
numbers continuing to rise [1–3]. Diabetes mellitus is a wellestablished risk factor for PAD—patients diagnosed with
diabetes have an estimated two to four times increased risk
of developing PAD [2, 4]. Furthermore, diabetes is an independent risk factor for amputation in patients with PAD [4].
The pathogenesis of PAD in patients with diabetes is
complex and multifactorial, with multiple synergistic mechanisms that together lead to the development of lower
extremity ischemia. In general, alteration in the lower
extremity and pedal blood ow of diabetic patients occurs
both at the macrovascular level, with the disease most frequently occurring at the level of the tibial and pedal vessels,
and at the microvascular level, which makes the diabetic foot
particularly susceptible to even mild levels of ischemia [5–
7]. Endothelial dysfunction plays an important role in the
development of PAD in diabetic patients. Hyperglycemia
and insulin resistance inhibit nitric oxide production through
multiple pathways, which makes the endothelium of multiple vascular beds prone to atherosclerosis. Advanced glycation end products, produced at higher levels in patients with
diabetes, also play an important role in the endothelial dysfunction seen in these patients [5, 7].
Systemic inammation is also thought to play an important role in the pathogenesis of PAD in patients with diabetes. Elevated C-reactive protein, seen in diabetes, inhibits
endothelial nitric oxide production, promotes the production
of tissue factor and leukocyte adhesion molecules, and
impairs brinolysis. Additionally, pro-inammatory cyto-
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
A. Veves et al. (eds.), The Diabetic Foot, Contemporary Diabetes, https://doi.org/10.1007/978-3-031-55715-6_4
47
48
https://t.me/med1917
N. J. Swerdlow and A. D. Hamdan
kines promote the transcription of endothelial cell adhesion
molecules, leading to increased binding of leukocytes and
platelets and, ultimately, increased plaque inammation and
instability [5, 6]. Finally, diabetes leads to microvasculature
dysfunction through multiple mechanisms, which plays an
important role in pedal ischemia seen in patients with diabetes [7, 8]. Details of the pathophysiology of vascular disease
in patients with diabetes is discussed in detail in Chap. 10.
Clinical Features
Patients with diabetes may present with atherosclerosis in
any peripheral artery. However, the characteristic lesions of
these patients are most commonly found in the infrageniculate vasculature, specically the tibial vessels of the calf and
the pedal vessels of the foot. Therefore, there is a wide
spectrum of presentations of PAD in this patient population.
For example, patients with a concomitant smoking history
may present with buttock or thigh claudication related to aortoiliac occlusive disease. Patients may also present initially
with calf claudication from supercial femoral artery occlusion. However, isolated tibial disease in diabetic patients frequently remains asymptomatic until an inciting factor for
tissue loss or infection occurs, such as foot trauma.
Additionally, diabetic neuropathy may make patients with
diabetes less likely to report claudication or rest pain due to
blunted sensation [9].
The vast majority of amputations of inpatients with diabetes are preceded by a foot ulcer. Therefore, in 1999, Reiber
et al. identied the most common pathways leading to an
incident foot ulcer and ultimately amputation [10]. The three
most important factors in this pathway were peripheral neuropathy, foot deformity, and minor trauma. PAD and the
resulting tissue ischemia led to poor wound healing and the
progression of ulceration and infection, and thus PAD is a
strong independent risk factor for amputation in patients
with diabetes. However, PAD alone was rarely the inciting
factor for ulcer formation in this population [4, 10].
While frequently asymptomatic, the presence of PAD can
frequently be identied by careful physical examination in
patients with diabetes. Peripheral pulse examination may
demonstrate absent dorsalis pedis (DP) and posterior tibial
(PT) pulses. Additional physical examination ndings consistent with decreased perfusion include the absence of hair
growth, cool and ssured skin, elevation pallor, and dependent rubor [9, 11]. Therefore, a careful vascular history and
physical examination should be routinely performed in the
initial assessment of patients with diabetes. History should
attempt to elucidate evidence of symptomatic PAD, including claudication and rest pain. It should also include a
detailed of history of prior foot wounds/infections, minor or
major amputations, and vascular surgery procedures.
Physical examination should include a detailed description of the foot, together with a detailed description of any
ulcers, along with appearance and location as well as signs
of decreased perfusion, as discussed above. A formal pulse
examination should also be documented in all patients.
This begins with the femoral pulse, identied approximately two nger-breaths lateral to the pubic tubercle
below the inguinal ligament. Next, the popliteal pulse is
palpated with the patient supine and the knee slightly
exed. The clinician places their thumb on the tibial tuberosity and wraps the second and third ngers of each hand
around the knee, palpating the pulse posteriorly between
the medial and lateral tendons. Finally, the DP and PT
pulses are palpated. The DP pulse is found between the rst
and second metatarsals, just lateral to the extensor halluces
longus tendon. The PT pulse is found behind the medial
malleolus, typically approximately halfway between the
malleolus and the Achilles tendon. No additional testing is
required in patients with palpable pulses, no additional evidence of ischemia, and no ulcers or infection.
Diagnostic Criteria
Ankle-Brachial Index
The American Diabetes Association consensus panel on
PAD recommends the baseline assessment of ankle-brachial
index (ABI) as part of the baseline assessment of patients
with diabetes over 50years old or in younger patients with
additional risk factors for PAD. These studies should be
repeated every 5 years if normal, while abnormal results
should prompt a further investigation [12]. The ABI is the
ratio of pressures in the ankle in relation to the branchial
artery. It is low cost and can be performed with just a blood
pressure cuff and handheld Doppler. First, the brachial artery
pressure is determined by applying a blood pressure cuff to
the upper arm and the Doppler probe over the brachial artery
at the antecubital fossa. The cuff is inated until the arterial
Doppler signal can no longer be heard and then deated until
the signal returns, at which point the pressure is recorded.
This is performed in both arms, and the higher of the two
brachial pressures is used in the calculation. This process is
then repeated for each leg with the cuff placed over the lower
leg. Assessment is made of both the DP and PT signals. The
ratios for both the DP artery and PT artery in relation to the
brachial artery pressure are calculated for each leg, with the
higher of the two ratios used for diagnosis.
Broadly, an ABI between 0.9 and 1.3 is considered normal, and PAD is dened as and ABI as less than 0.9. More
specically, and ABI between 0.4 and 0.9 indicates moderate
ischemia, while an ABI of less than 0.4 indicates severe ischemia [13]. The ABI is an excellent tool to rule out PAD in
4 Clinical Features andDiagnosis ofPeripheral Arterial Disease
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49
patients without active ulceration. However, it is noteworthy
that there are important limitations to the ABI. Medial calcinosis of the tibial vessels, frequently observed in patients
with diabetes-associated PAD, leads to noncompressible
vessels and an elevated ABI of greater than 1.3. Patients with
less severe calcication may still have falsely elevated ABIs
that fall within the normal range [11]. Therefore, further testing is required to establish or rule out a diagnosis of PAD in
a patient with an active diabetic foot ulcer or other evidence
of impaired tissue perfusion in the foot.
WIfI Classication
Beyond a simple binary diagnosis of PAD, there are numerous PAD classication schemes to categorize the severity of
PAD, most notably the Rutherford and Fontaine classications. However, these classications look at gangrene or
tissue loss as a broad category and therefore fail to account
for the broad range of wounds that can be present in patients
with diabetes. They therefore tend to perform poorly in this
population. In 2014, Mills etal. published the new Society
for Vascular Surgery (SVS) CLTI classication system, the
wound, ischemia, and foot infection (WIfI) score (Table4.1)
[14]. This classication system, designed to be analogous to
the tumor/node/metastasis (TNM) staging system used in
cancer, utilizes a detailed assessment of foot ulcers/gangrene, degree of ischemia, and the severity of infection to
classify the patient’s risk of major amputation and the potential benet for revascularization. Subsequent studies have
demonstrated that the WIfI score is a good predictor of
wound healing and revascularization benets in patients with
diabetic foot ulcers [15, 16]. The 2019 global vascular guidelines on the management of chronic limb-threatening ischemia endorse the WIfI score as the primary classication
system that should be used for the evaluation and management of CLTI [17].
Noninvasive Diagnostic Testing
Segmental Doppler Pressures withABIs
Segmental pressures are obtained by placing cuffs at the
level of the thigh, calf, and ankles. A Doppler probe is placed
distal to each cuff. The cuffs are sequentially inated, yielding pressure at each level. The pressures at the ankle are used
with the higher of the two brachial pressures to calculate the
ABI (Fig.4.1). A drop in pressure of greater than 20mmHg
between levels indicates arterial disease in the intervening
segment. Furthermore, an ABI of less than 0.6 or an absolute
ankle pressure of less than 70mmHg suggests likely poor
wound healing in the foot. However, as mentioned above,
segmental pressures, particularly in the tibial vessels at the
level of the ankle, are frequently unreliable in patients with
diabetes due to arterial calcication [11, 18].
Toe Pressures
The medial calcication in the tibial vessels frequently seen
in patients with diabetes and resulting in unreliable ABIs is
typically absent from the vessels of the toes. Therefore,
absolute toe pressures or toe brachial index (TBI) are used to
assess the adequacy of tissue perfusion in the diabetic foot.
To obtain toe pressure, a photoplethysmography (PPG)
probe detects changes in skin capillary blood ow while
used in conjunction with a toe cuff to occlude ow in the toe
vessels. The hallux is most frequently used, but other toes
can be used as well if the hallux has been amputated or has a
wound. To perform the test, a baseline PPG tracing is
obtained. The toe cuff is then inated until the waveform is
lost and then deated until the baseline tracing returns, at
which point the absolute pressure is recorded. The TBI is
then calculated in relation to the higher brachial pressure,
analogous to the ABI (Fig.4.1). A toe pressure of less than
Table 4.1 Wound, infection, and foot ischemia (WIfI) score criteria
Component Score Description
W (Wound) 0 No ulcer (ischemic rest pain)
I (Ischemia) ABI Ankle pressure (mm Hg) Toe pressure or TcPO
fI (foot Infection) 0 No symptoms/signs of infection
a
Adapted from Mills etal. (2014) [14]
a
1 Small, shallow ulcer on distal leg or foot without gangrene
2 Deeper ulcer with exposed bone, joint or tendon±gangrenous changes limited to toes
3 Extensive deep ulcer, full-thickness heel ulcer±calcaneal involvement±extensive gangrene
0
1 0.60–079 70–100 40–59
2 0.40–0.59 50–70 30–39
3 <0.40 <50 <30
1 Local infection involving only skin and subcutaneous tissue
2 Local infection involving deeper than skin/subcutaneous tissue
3 Systemic inammatory response syndrome
≥0.80
>100
≥60
2
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