Section 1

Glenda, a 62-year-old woman with type 2 diabetes for 5 years, reports an uncomfortable tingling sensation in both of her feet that is most troublesome at night-time. She also mentions the feeling of walking on pebbles.

Current medication consists of metformin 1 g twice daily, amlodipine 5 mg once daily and atorvastatin 20 mg once daily. Glenda has background retinopathy. Recently, her HbA_1c was 61 mmol/mol and BP 142/77 mmHg.

How would you interpret Glenda’s symptoms?

Section 2

This sounds very much like diabetic peripheral neuropathic pain (DPNP). Neuropathic pain is characteristically described as feeling like pins and needles, electric shocks or a burning, shooting or stabbing sensation. There may additionally be hyperalgesia (an exaggerated reaction to a painful stimulus) and allodynia, where a normally non-painful stimulus, such as light touch, induces pain. In contrast to a possible differential diagnosis of ischaemic leg pain, neuropathic symptoms tend to be relieved by exercise. It is important to note that neuropathic pain can arise without loss of sensation on examination.

DPNP can seriously affect quality of life. Night pain and disturbed sleep are common, and depression can follow. Whilst DPNP is typically chronic, an acutely painful (treatment-induced) neuropathy can arise following a sudden and dramatic improvement in glycaemic control, although this will usually resolve over a matter of months.

You proceed to examine Glenda’s feet. What would you look and test for?

Section 3

Examine the feet in well-lit conditions, looking for deformity, areas of callus build-up over pressure points, blisters and frank ulceration. Assess temperature of the feet with the back of the hand, and palpate for posterior tibial and dorsalis pedis pulses.

10-g monofilament testing is recommended by NICE as a means of assessing foot sensation.¹ It is easy to perform, reliable and cheap. It is probably sufficient to test the plantar aspect of first, third and fifth toe tips bilaterally, avoiding any callus or scarred areas, with one negative response being enough to indicate sensory loss. The monofilament should be applied gently at 90 degrees to the skin surface, with just enough pressure to buckle. The individual should be asked to close their eyes and say “yes” whenever they feel the monofilament. Negative responses should be rechecked.²

An even simpler test of peripheral sensation is the Ipswich Touch Test in which the toes are lightly touched (peripherally on plantar aspect, as above) by the examiner’s finger, with the individual’s eyes closed.³ Touch testing of foot sensitivity can be performed by a family member at home, which is very pertinent given the rise in virtual consultations (driven by the COVID pandemic). A very useful video demonstrating how to carry out such an examination can be found on the Diabetes UK website.⁴

A 128 Hz tuning fork may be used to test vibration sensation on the tip of the individual’s big toes.²

Are there any other causes of peripheral neuropathy you might wish to rule out?

Section 4

Diabetes is the most common cause of peripheral neuropathy in the UK. Leaving aside specific medical conditions, vitamin B12 or folate deficiency, chronic kidney disease, abnormal liver function and hypothyroidism can potentially cause a peripheral neuropathy. It is also worth checking for excessive alcohol consumption.

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Glenda has recently had normal results from renal, liver and thyroid function tests. She consumes only small quantities of alcohol. A full blood count together with vitamin B12 and folate levels are requested, and come back within normal range. Bear in mind the possibilities of lower-back pathology, spinal nerve entrapment and peripheral nerve compression that could generate neuropathic symptoms.

Glenda is keen to try medication to ease her symptoms. What would you choose to treat her DPNP?

Section 5

NICE recommends offering a choice of amitriptyline, duloxetine, gabapentin or pregabalin as initial therapy, switching to another agent if one proves ineffective or is poorly tolerated.⁵ All of these classes of medication appear to possess similar efficacy. Further benefits include improved mood, sleep and quality of life.⁶

In general, start at a low dose and uptitrate gradually, monitoring for efficacy and side-effects, and allowing 6–8 weeks before deciding on the usefulness of the drug, including at least 2 weeks at maximum tolerated dose. If the medication is deemed ineffective, withdrawal should be gradual. Combination therapy may be tried, and evidence indicates that greater reductions in pain scores are achieved than with monotherapy.⁶ Some more detail is shown below.⁷ For those wishing to avoid oral agents, capsaicin cream is an option for localised neuropathic pain.⁵

Section 6

Sam is a 56-year-old male electrician who has had type 2 diabetes for over 10 years. He is known to have diabetic retinopathy, nephropathy and peripheral neuropathy. He has just noticed an area under his left foot that has been weeping (but is not painful), and attends his GP surgery for advice.

Examination reveals an area of callus build-up and frank ulceration under the first metatarsal head of the left foot. There is a small amount of bleeding from the ulcer, but no pus discharge and no indication of associated cellulitis. The foot does not appear obviously deformed and feels warm with good pulses. 10-g monofilament testing confirms a dense peripheral neuropathy.

What is your assessment of Sam’s problem?

Section 7

Sam has a neuropathic foot ulcer. The loss of protective peripheral sensation has allowed callus build up on a pressure point to proceed unnoticed, with subsequent tissue necrosis and ulceration.

Peripheral neuropathy is a major aetiological factor predisposing the individual with diabetes to foot ulceration (the other being peripheral arterial disease [PAD]).⁸ The key risk factors for developing peripheral sensory neuropathy (and other microvascular complications) are duration of diabetes, hypertension and hyperglycaemia.

A very helpful article on foot care and preventing foot ulceration is available from Diabetes & Primary Care.⁹ The ACT NOW tool has been devised as a practical means of identifying the warning signs that might lead to an amputation and trigger the need for urgent referral.¹⁰

What are your concerns?

Section 8

The worry is that the ulcer becomes infected, and this may progress to osteomyelitis (bone infection) and sepsis that require amputation.

Foot ulceration is the most common complication of diabetes leading to hospital admission in the UK, accounting for around half of all foot amputations. There is a strong association between foot ulceration and mortality, with a 10% risk of death within one year of developing a foot ulcer. Following a major amputation, only around 50% will be alive after 2 years.²

Apart from the personal suffering, foot ulcers in individuals with diabetes and their complications are estimated to cost the NHS approximately £1bn per year – 0.8% of the total NHS budget.¹¹

So how would you respond to Sam’s new foot ulcer?

Section 9

Sam’s ulcer is cleaned and dressed, and he is referred urgently to the hospital multidisciplinary foot care service.

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In line with NICE recommendations, you should refer Sam’s new foot ulcer to the hospital-based multidisciplinary foot care service as a matter of urgency, ideally to be seen within 24 hours.¹ There is evidence that rapid access to such teams can substantially reduce the risk of amputations.¹² This team should have access to specialists in diabetes, podiatry, diabetes specialist nursing, vascular surgery, microbiology, orthopaedic surgery, orthotics, interventional radiology, casting and wound care.¹

Foot ulcers are treated with debridement and dressing by podiatrists. Offloading devices, such as casts, are used to remove pressure from plantar neuropathic ulcers.

If Sam’s ulcer had signs of infection, would your response differ?

Section 10

The infected foot ulcer represents a limb-threatening situation. In addition to urgent referral, it is appropriate to take a swab and commence antibiotics whilst awaiting multidisciplinary foot care service assessment. If erythema, swelling or pus discharge are seen, then oral antibiotics that cover Staphylococcus aureus (such as flucloxacillin or, in cases of penicillin allergy, doxycycline or macrolide antibiotic) can be initiated. Metronidazole may be added to cover anaerobic infection. Check local microbiology recommendations for antibiotic regimens. With serious infection (as indicated by fever or signs of sepsis, or a rapidly progressing cellulitis or a suspicion of osteomyelitis), admit to hospital directly.¹

Intravenous antibiotics may be required to deal with severe infection. In cases of osteomyelitis, a prolonged course of antibiotics will be necessary, according to local protocols.

Wound samples (swabs, tissue samples and bone fragments) can provide useful information on specific bacterial infection and help guide antibiotic treatment. Osteomyelitis may be identified from X-rays and, if necessary, from an MRI scan.

Section 11

Proma is a 57-year-old woman of Asian ethnic origin who has had type 2 diabetes for 11 years. She presents with an ulcer on the lateral border of her right foot, which she first noticed around a week ago. She has background diabetic retinopathy. Two years ago, she suffered a myocardial infarction (MI).

Examination reveals a small ulcer over the lateral border of the 5^th metatarsal of her right foot. There is no surrounding cellulitis or discharge. The right posterior tibial pulse appears absent and the dorsalis pedis pulse is weak (left foot pulses are easily palpable). The foot is cool, with a dusky tinge to the toes, and toenails appear dystrophic. Peripheral sensation appears intact following an Ipswich touch test. There are signs of excessive wear and friction on the inside of the lateral aspect of Proma’s right shoe at the site where this would contact her ulcer.

What is the likely underlying cause of Proma’s foot ulcer?

Section 12

The location of the foot ulcer and the foot examination findings (poor foot pulses, intact sensation) suggest that this is an ischaemic foot ulcer. This conclusion is supported by the history of MI that implies atherosclerotic vascular disease (as would the presence of angina or a previous TIA/ischaemic stroke). Proma has footwear that appears too tight, and friction against the skin has led to ulceration.

Foot ulcers can be neuropathic or ischaemic in origin, though there may, of course, be dual pathology, with up to 20% of foot ulcers being appropriately described as neuroischaemic in origin.⁸

What other features of the history might strengthen the view that Proma’s ulcer arises from vascular insufficiency?

Section 13

Proma’s previous MI signals atherosclerotic disease. A history of intermittent claudication would indicate PAD. The presence of cardiovascular risk factors, including smoking, hypertension and hyperlipidaemia, should be sought.

Proma admits to pain in her right thigh and calf when walking up slopes, which is relieved by rest and is consistent with intermittent claudication.

How might vascular insufficiency of Proma’s right foot be quantified?

Section 14
Quantitative assessment of foot pulses can be ascertained by Doppler (ultrasound) assessment.¹³ An ankle–brachial blood pressure index (ABPI) <0.9 (the ratio of systolic BP in the foot compared to the arm) is consistent with PAD, with a reading as low as 0.5 representing severe ischaemia. A false negative result may arise from calcified leg arteries (commonly found in type 2 diabetes) that are more difficult to compress, resulting in an unrepresentatively high ABPI.
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Proma is referred urgently to the hospital multidisciplinary foot care service and, from there, is reviewed by the vascular surgeons.

What can primary care do to prevent diabetic foot problems?

Section 15

To reduce the risk of diabetic foot problems, optimisation of glycaemic control, management of hypertension and hyperlipidaemia (preferably with statins), and smoking cessation are all important. Antiplatelet therapy (e.g. clopidogrel or aspirin) is appropriate in the case of PAD.

Foot-care education is essential and should be reinforced at follow-up appointments. Advise individuals to regularly check their feet (or have someone else to do this, if necessary), and what signs indicate danger and the need to seek help. Washing feet daily and use of emollients should be encouraged.

Emphasise the importance of attendance for annual foot screening or, indeed, more regular podiatry appointments for the higher-risk foot.

Section 16: Referring appropriately

NICE advises the following risk-stratification scheme for diabetic foot problems.¹

• Low risk – no factors present, except callus alone
• Moderate risk – one of deformity; neuropathy; non-critical limb ischaemia
• High risk – one of previous ulceration; previous amputation; neuropathy and non-critical limb ischaemia together; neuropathy in combination with callus and/or deformity; non-critical limb ischaemia in combination with callus and/or deformity
• Active foot problems – one of ulceration; spreading infection; critical limb ischaemia; gangrene; Charcot arthropathy

People judged to be at moderate to high risk of developing a diabetic foot ulcer (whether at screening or not) should be referred to the foot protection service (community podiatry team) for assessment and education. Frequency of surveillance will depend on degree of risk and individual circumstances.

NICE recommends referring any new foot ulcer to the hospital-based foot care service as a matter of urgency, ideally to be seen within 24 hours. A further indication for immediate referral is where there is clinical suspicion of Charcot foot (see below).

Mild foot infections (without ulceration) can be managed initially in primary care with oral antibiotics that cover Staphylococcus aureus (such as flucloxacillin or, in cases of penicillin allergy, doxycycline or macrolide antibiotic). Metronidazole may be added to cover anaerobic infection. Refer to local guidelines, as necessary. A failure to respond within a few days should prompt urgent referral to the foot care service or hospital admission, as intravenous antibiotics may be necessary. Fungal skin infections should be treated in primary care with antifungal creams, as ulceration and secondary bacterial infection may follow.²

More serious infection (including all new ulceration) should be urgently referred; it is appropriate to take a swab and commence antibiotics whilst awaiting foot care service assessment. In severe infection (as indicated by fever or signs of sepsis, or a rapidly progressing cellulitis or a suspicion of osteomyelitis), admit to hospital directly.¹

In the case of acute critical limb ischaemia (severe obstruction of the arterial supply to a limb resulting in ischaemic pain at rest, non-healing ulceration or gangrene), admission under the vascular surgeons is required; an urgent outpatient appointment with the vascular surgeons would be appropriate for chronic critical limb ischaemia.

How would you recognise a Charcot foot?

Section 17

A Charcot foot classically has a “rocker bottom deformity” (a convex plantar surface) and is warm (typically at a higher temperature than the partner foot), erythematous and swollen (so, in these latter respects, it can be difficult to distinguish from infection).

The Charcot foot arises from repeated trauma in the foot affected by a dense peripheral neuropathy. Bone remodelling (osteolysis) and ligament laxity allow subluxation and dislocation of ankle and foot joints, leaving an anatomically compromised foot at very high risk of ulceration and infection.¹⁴