Diabetes-related foot disease

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

General practitioners and primary care nurses are generally on the front line of care for patients with diabetes. As such, they have a key role in preventing and identifying active diabetic foot problems. Diabetologists, specialist podiatrists, and other medical specialists may also be involved in the evaluation and management of these patients, particularly when people with diabetes are admitted for other acute medical conditions.

As well as multidisciplinary care, there are five key principles which form the mainstay of management of diabetic foot ulcers:[9][36]

Wound debridement
Wound dressing
Pressure offloading
Treatment of infection
Treatment of ischaemia and restoration of tissue perfusion

The majority of foot ulcers will heal provided treatment is based on these principles, according to the International Working Group on the Diabetic Foot (IWGDF).[36] They also emphasise the importance of holistic, person-centred care that goes beyond the feet, to include optimising glycaemic control and cardiovascular risk factors, treating oedema, malnutrition, and depression, and addressing other psycho-social difficulties.[36]

It is important to remember the need for proper management of the diabetes itself (e.g., regular check-ups, maintenance of target blood glucose levels, blood pressure, and lipid management) according to current guidelines. These goals do not change in the presence or absence of diabetes-related foot disease. There is some evidence that intensive glucose control is associated with a long-term reduction in risk of developing diabetic foot ulcers in patients with type 1 diabetes.[53]

Sodium-glucose cotransporter-2 (SGLT2) inhibitors should not be started in drug-naïve people with a diabetes-related foot ulcer or gangrene, and temporary discontinuation should be considered in people who develop a foot ulcer or gangrene while already using them, until the foot is healed, according to joint guidelines from the IWGDF, European Society for Vascular Surgery and Society for Vascular Surgery.[11] This is due to a rare but serious side effect of diabetic ketoacidosis (DKA) with SGLT2 inhibitors, which is made more likely during acute illness and peri-operative periods. As patients with peripheral arterial disease, foot ulcers or gangrene are vulnerable to infections and may need to undergo urgent surgery, it is therefore pragmatic to avoid these medications to reduce DKA risk. Moreover, canagliflozin was associated with an increased risk of amputation in one randomised controlled trial.[54] Although this finding has not been borne out by other studies, the guidelines note that people with foot ulcers were frequently excluded from clinical trials of SGLT2 inhibitors so their safety in these patients remains uncertain.[11]

For more information on the medical management of diabetes in general, see Type 2 diabetes in adults and Type 1 diabetes.

Referral for multidisciplinary care in hospital and community settings

Make an immediate referral to acute services for any patient who has a limb-threatening or life-threatening diabetic foot problem.[9]

In the UK, the National Institute for Health and Care Excellence (NICE) recommends informing the multidisciplinary foot care service so the patient can be assessed and an individualised treatment plan can be put in place.

If the patient is already in hospital when the foot complication is identified, ensure the multidisciplinary foot care team is alerted and involved in their care.[9]

Examples of limb-threatening and life-threatening diabetic foot problems include:

Ulceration with fever or any signs of sepsis
Ulceration with limb ischaemia
Clinical concern that there is a deep-seated soft-tissue or bone infection (with or without ulceration)
Gangrene (with or without ulceration)

For any other patient with an active diabetic foot problem, refer within 1 working day to the multidisciplinary foot care/foot protection service (according to local protocols).[9]

The foot care service should triage the patient within 1 further working day.

It is worth noting that because of the impaired immune response and abnormal arteriovenous shunting present in the neuropathic foot, clinical signs of infection in people with diabetes may be more subtle than in people who do not have diabetes.

Always consider the possibility of other diagnoses, with a particular emphasis on more serious conditions such as sepsis, necrotising fasciitis, limb ischaemia, or osteomyelitis.[9]

See Sepsis in adults, Sepsis in children, and Osteomyelitis.

The multidisciplinary foot care team should be led by a named healthcare professional, and consist of specialists with skills in podiatry, wound care nursing, diabetology, diabetes specialist nursing, vascular surgery, orthopaedic surgery, infectious disease, biomechanics and orthoses, interventional radiology, and casting, as well as other allied health professionals who work together to optimise patient care.[9]

The American Diabetes Association (ADA) also advocates an interprofessional approach for all patients with foot ulcers and high-risk feet, ideally facilitated by a podiatrist.[37]

Wound debridement

Debridement of slough, necrotic tissue, and surrounding callus of the ulcer is recommended, after taking account of relative contraindications such as pain or severe ischaemia.[55] The goal of debridement is to create a clean wound bed and promote wound healing.

Sharp debridement of ulcers using surgical instruments remains the standard of care, despite a lack of high-quality clinical trials to support its use. [ ]
Neuropathic ulcers can usually be debrided without the need for local anaesthesia.[36]
Numerous alternative debridement techniques exist, including using enzymes, larvae, hydrogels, lasers, and ultrasound; however, there is currently insufficient evidence to support the routine use of any of these over sharp debridement, according to the International Working Group on the Diabetic Foot (IWGDF).[55]
Debridement of diabetic foot ulcers in a hospital setting should only be done by members of the multidisciplinary foot care team, using the technique that best matches their specialist expertise and clinical experience, the site of the diabetic foot ulcer, and the patient’s preference.[9] Community-based debridement should only be done by healthcare professionals with the relevant skills and training.[9]
There is reasonable-quality evidence that negative pressure wound therapy after surgical debridement may decrease the time to healing and both NICE and the IWGDF recommend its use in this circumstance.[9][55]

See Emerging treatments for discussion of adjunctive therapies to promote wound healing in diabetic foot ulcers, including hyperbaric and topical oxygen therapy. Topical medications, vitamins, physical therapies, and gasses other than oxygen are not currently recommended for this purpose.[55]

Wound dressing

The choice of wound dressing when treating diabetic foot ulcers should depend on the clinical assessment of the wound.[9]

Evidence is sparse to inform decisions about the best choice of wound dressing for diabetic foot ulcers. Dressings that maintain a moist environment, including non-adherent dressings covered with a layer of gauze or other absorptive material, are commonly used.[56] [ ] [ ]

NICE and the IWGDF have concluded that evidence supports the use of a sucrose octasulfate-impregnated wound dressing on diabetic foot wounds after other modifiable factors such as infection have been treated.[55][57][58]

See Emerging treatments for discussion of leucocyte, fibrin and platelet patch, and placental-derived products. No other specific types of dressings, including those containing topical antimicrobials, antiseptics, honey, collagen, alginate, herbal remedies, cell therapies, or hyaluronic acid, are recommended based on current evidence.[55][56]

Split-thickness skin grafting may be considered an option for achieving wound healing in patients with a large epithelial defect that has a tissue bed with healthy granulation. The success rate for autologous skin grafting is high; however, its use over high-pressure areas (namely, the heel and the plantar forefoot overlying the metatarsal heads) may be limited. [ ]

There are also several skin substitutes (i.e., non-autologous xenogenic or allogenic tissues) that have been approved for use on diabetic foot wounds. In contrast to autologous skin grafts, several applications of the skin substitute are generally needed at 1- to 2-week intervals to achieve complete re-epithelialisation. There is currently little evidence to support the use of skin substitutes for diabetic foot wounds and they are not recommended by the IWGDF.[55]

NICE recommends that dermal or skin substitutes should only be considered when healing is not progressing and following advice from the multidisciplinary foot care service.[9]

Offloading footwear and devices

Repetitive trauma sustained during ambulation is the most common cause of foot ulcers in patients with diabetes. All patients with diabetes should be encouraged to routinely wear appropriate footwear, even if they do not have any signs of active foot ulceration. See Screening and Prevention sections for more information.

For those with active ulceration, offloading the foot is essential to minimise or avoid this repetitive trauma, in order to achieve ulcer healing.

Total contact casts and non-removable cast-walkers are the most effective options for offloading footwear, although removable cast-walkers and modified footwear can be considered if frequent access to the wound is required.[28] [ ] Non-removable devices are contraindicated when there is both mild infection and mild ischaemia, or moderate infection or ischaemia, or heavy exudate present.[28]

NICE recommends non-removable casting to offload plantar neuropathic, non-ischaemic, uninfected forefoot, and midfoot diabetic ulcers. Offer an alternative casting device until casting can be provided.[9]

The IWGDF recommends the following:[28]

In a person with diabetes and a neuropathic plantar forefoot or midfoot ulcer, a non-removable knee-high device should be used as the first choice of offloading treatment: either a total contact cast or non-removable knee-high walker depending on the resources available, technician skills, patient preferences, and the extent of any foot deformity present.
If non-removable knee-high device is not tolerated or is contraindicated, a removable knee-high or ankle-high device is recommended second-line, with the patient encouraged to wear the device during all weight-bearing activities.
For neuropathic plantar rearfoot ulcers, consider a non-removable knee-high offloading device over a removable device.
For non-plantar foot ulcers, use a removable offloading device, footwear modifications, toe spacers, orthoses, or digital flexor tenotomy, depending on the type and location of the foot ulcer.
In any patient using a knee-high or ankle-high offloading device, consider adding a shoe lift on the contralateral limb to improve comfort and balance.

Nutritional support

Malnutrition, including sarcopenia, is very common in patients with diabetes and may impair wound healing. There is a clear correlation with nutritional status and healing, and as such, a balanced diet with adequate fluids, calories, proteins, and nutrients is fundamental to the healing process.[52] Patients should be screened for risk of malnutrition, and if present, malnutrition should be addressed with dietary counselling and supplementation as needed. Discuss individual nutritional goals with patients who have, or are at risk of, malnutrition, ideally within the context of a multidisciplinary team, which may include professionals such as podiatrists, dietitians, surgeons, general practitioners, dermatologists, wound care specialists, etc.[52]

Caloric needs are high when a diabetic foot ulcer is present. Use indirect calorimetry as the gold standard for identifying energy needs. If indirect calorimetry is unavailable, there are other formulas available that can provide a starting point.[52] As a general guide, offer most people at risk of nutritional deficiencies a minimum of 25-30 calories per kg body weight per day, 1.25 to 1.50 g of protein per kg body weight per day, and 1 mL/kcal/day of fluid intake. For people with a high body mass index, lower calorie intake while still meeting protein goals may be appropriate.[52] Give priority to nutrient dense foods. Oral nutrition supplements (ONSs) can be taken between meals as needed to help provide additional protein and micronutrients. If a patient is unable to meet estimated nutrient, energy, protein, and hydration needs despite nutrition interventions, discuss with them the benefits and harms of enteral or parenteral feeding to provide additional or an alternative source of nutrition support.[52] Vitamins and minerals are essential to the health of the body and should be included in all nutritional assessments and supplementation programmes.[52]

Antibiotic therapy

Culturing a specimen from a diabetic foot infection allows selection of appropriate antibiotic therapy. For guidance on collecting samples for microbiological culture, see Investigations.

Do not start antibiotics if there are no active signs or symptoms of infection, for example with the goal of reducing the risk of future infection, or to promote healing.[9][40]

Prompt initiation of an empirical antibiotic regimen is recommended when there are signs of infection: the choice of antibiotic should be based on the severity of the infection and the likely aetiological agents, with guidance from local agencies if available.[9][40] When choosing an antibiotic for people with a suspected diabetic wound infection, take account of:[9]

The severity of the diabetic foot infection according to IWGDF/IDSA or NICE classification (mild, moderate, or severe; see Criteria for more details)[40]
The risk of developing complications
Previous microbiological results (including previous multiresistant organisms)
Previous antibiotic use
Patient preferences

Always take local antibiotic prescribing policies into account. If your patient with a suspected diabetic foot infection is under 18 years of age, seek specialist advice on the most appropriate antibiotic regimen.[9]

Mild infection in an adult

Treat with oral antibiotics; gram-positive cocci (staphylococci and streptococci) are the most common pathogens in acute infection and narrow-spectrum therapy is appropriate.[9][51]
NICE recommends flucloxacillin as the first-line option for mild infection; if the patient has a penicillin allergy or flucloxacillin is unsuitable, clarithromycin or doxycycline are alternative options.[9] Flucloxacillin may need to be used at a higher-than-standard dose because of poor bioavailability in people with diabetes who have impaired circulation.[9]
Options recommended by the International Working Group on the Diabetic Foot (IWGDF) include cloxacillin or cefalexin if there are no complicating features. Alternative options are recommended for patients with allergy/intolerance, in those who have had recent antibiotic exposure and if they are at risk of MRSA.[40]
Most patients with mild infection can be treated in the community.[40]

Moderate or severe infection in an adult

NICE and the IWGDF both group their treatment recommendations for moderate and severe infections together.[9][40] Local antibiotic policy should apply and the advice of a microbiologist should be sought on the most appropriate regimen according to microbiological results.

NICE recommends the following options: flucloxacillin with or without gentamicin and/or metronidazole; or amoxicillin/clavulanate with or without gentamicin; or ceftriaxone plus metronidazole. If the patient has a penicillin allergy, trimethoprim/sulfamethoxazole with or without gentamicin and/or metronidazole is recommended. Oral or intravenous antibiotics are recommended. Oral antibiotics are first-line if the person can take oral medicines, and the severity of their condition does not require intravenous antibiotics.[9]
The IWGDF recommends amoxicillin/clavulanate, ampicillin/sulbactam, cefuroxime, cefotaxime, or ceftriaxone if there are no complicating features. Alternative options are recommended for patients who have had recent antibiotics, for a macerated ulcer or warm climate, for ischaemic limb/necrosis/gas forming, and for patients with risk factors for extended-spectrum beta-lactamase drug resistance.[40]
Consider hospital admission if the patient has a moderate infection that is complex (e.g., wound penetrates to subcutaneous tissues, contains a foreign body, or has discoloration, necrosis, or gangrene), associated with severe foot ischaemia or metabolic or haemodynamic instability, or if outpatient management has failed or is inappropriate, for example requiring intravenous therapy or frequent dressing changes.[40]
Severe infections are usually treated as an inpatient with parenteral, broad-spectrum, empirical antibiotics.

IWGDF recommend that oral antibiotics should generally not be used for severe infections, except as follow-on (switch) after initial parenteral therapy.[40]

Ensure review of intravenous antibiotics by 48 hours after initiation and consider switching to an oral regimen if possible.[9]

Review microbiology results when available and adjust antibiotic treatment choice as necessary. Definitive therapy should be based on culture results and clinical response to the empirical regimen.

If Pseudomonas aeruginosa is suspected or confirmed, NICE recommends the following additional antibiotics as suitable options: piperacillin/tazobactam; clindamycin plus ciprofloxacin (consider safety issues - see below) and/or gentamicin.[9]

In temperate climates, do not empirically target antibiotic therapy against P aeruginosa. But do use empirical treatment of P aeruginosa if it has been isolated from cultures of the affected site within the previous few weeks, in a person with moderate or severe infection who resides in tropical/subtropical climates.[40]

If MRSA is suspected or confirmed:

NICE recommends adding one of vancomycin, teicoplanin, or linezolid (with specialist advice) to the standard antibiotic options.[9]
For mild infections, the IWGDF recommends linezolid, trimethoprim/sulfamethoxazole, clindamycin, levofloxacin, moxifloxacin, or doxycycline. For moderate or severe infections, consider adding or substituting with vancomycin, teicoplanin, linezolid, daptomycin, fusidic acid, trimethoprim/sulfamethoxazole, or doxycycline.

Systemic fluoroquinolone antibiotics, such as ciprofloxacin, levofloxacin, and moxifloxacin, may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to, tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[59]

Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability).
Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.

Course length of antibiotic therapy should be based on clinical assessment for a minimum of 7 days.[9] Consider extending to 3-4 weeks if the infection is improving but extensive and resolving slower than expected, or if the patient has severe peripheral artery disease.[40] Six weeks of treatment may be required for osteomyelitis.[9]

Further diagnostic tests or alternative treatments may need to be considered if the infection has not resolved after 4 weeks.[40]

Surgery

For pressure offloading in patients with active ulceration, where conservative measures have failed, the IWGDF advises surgery can be considered as follows (to be used in combination with an offloading device):[28]

Achilles tendon lengthening or metatarsal head resection for neuropathic plantar metatarsal head ulcers
Joint arthroplasty for neuropathic hallux ulcers
Metatarsal osteotomy for neuropathic plantar ulcers on metatarsal heads 2-5
Digital flexor tenotomy for neuropathic plantar or apex ulcers on digits 2-5, secondary to a flexible toe deformity
Digital flexor tenotomy for non-plantar foot ulcers (depending on its location)

A revascularisation procedure should be considered for anyone with peripheral artery disease, a foot ulcer, and clinical findings of ischaemia (absent pulses, monophasic, or absent pedal Doppler waveforms, ankle pressure <100 mmHg or toe pressure <60 mmHg), and for those with ulcers that do not improve within 4 weeks despite appropriate management.[11] Seek an urgent vascular opinion if there are signs of severe ischaemia: ankle-brachial pressure index <0.4, ankle pressure <50 mmHg, toe pressure <30 mmHg, or transcutaneous oxygen pressure <30mmHg.

Revascularisation should aim to restore adequate arterial blood flow to at least one of the foot arteries. The main options for this type of procedure are endovascular (usually balloon angioplasty with or without stent placement), open (surgical bypass or endarterectomy), or hybrid (a combination of both). The choice of procedure should be based on the patient’s individual risks and preferences, limb threat severity, anatomical distribution of peripheral artery disease, and the availability of an autogenous vein for bypass.[11] In patients with infrapopliteal disease undergoing endovascular intervention by percutaneous transluminal angioplasty, addition of a stent probably increases rates of technical success of the procedure compared to no stenting, although the impact on complications, longer-term success rates and mortality is uncertain. [ ]

Seek an urgent surgical opinion in cases of severe infection, or moderate infection with extensive gangrene, necrotising infection, suspected deep abscess, compartment syndrome, or severe lower limb ischaemia.[40] Prompt removal of infected and necrotic tissues (within 24-48 hours), including bone if there is osteomyelitis, in combination with antibiotics has been shown to improve wound healing rates and lower major amputation rates.[40]

Minor amputations (i.e., toe or partial foot resections) may be performed on areas with irreversible gangrene, osteomyelitis, or deep-tissue infection. Major amputation is determined on a patient-by-patient basis but is generally reserved for the following situations:

Infection or gangrene that is so extensive that reconstruction either is not possible or will not preserve meaningful function in the affected limb
Patients who have very little or no function in the limb (excluding previous history of stroke or paralysis)
Severe peripheral arterial disease which cannot be revascularised

Management of cardiovascular risk factors and considerations for associated comorbidities

In addition to optimising glycaemic control, management of other risk factors and associated conditions is important for course and outcomes.

Chronic kidney disease

Renal function should be considered when selecting antibiotic therapy. Check your local drug information source.
End-stage renal disease and renal replacement therapy in patients with diabetes-related foot disease is associated with high rates of amputation and mortality.[60][61][62]
In patients with diabetes receiving renal replacement therapy, feet should be protected during the haemodialysis session (e.g., offloading with protective boot).[39]

Cardiovascular disease and risk factors

Patients with diabetic foot ulcers are at increased risk of cardiovascular-related morbidity and mortality compared with patients with diabetes without foot ulcers.[63][64][65]
Control of blood pressure and lipid levels may reduce risk of vascular complications.[18] All patients should receive regular blood pressure and lipid monitoring along with lifestyle advice and optimal pharmacological management.
Aggressive cardiovascular risk management (blood pressure, lipids, glycaemic control) has been demonstrated to reduce mortality in patients with diabetic foot ulcers in one study.[66]
Note that overly aggressive antihypertensive treatment may result in reduced limb perfusion, increasing the risk of complications.[67]

Heart failure

Patients with diabetic foot ulcers have a higher prevalence of heart failure compared with patients with diabetes without foot ulcers, and the prevalence increases with increasing severity.[68]
Comorbid heart failure is associated with a worse prognosis, with lower healing rates, and increased risk of recurrence and amputations.[68]
Oedema (associated with heart failure) may affect tissue perfusion and wound healing and should be treated where present.[36]

Depression

Depression and other mental health issues such as anxiety are common comorbidities in those with diabetes-related foot disease.[69]
Depression has been associated with a higher risk of developing diabetic foot ulcers and also a higher risk of major lower-limb amputation and mortality.[70][71][72][73]
Screening for depression is recommended.[67]

Follow-up and referral

Non-healing foot ulcers and foot infections have the potential to progress suddenly, with few warning signs. Multidisciplinary or interdisciplinary care has repeatedly been demonstrated to significantly lower leg amputation rates.[74][75][76][77]

In the UK, NICE recommends that any patient with an active diabetic foot problem is referred to a multidisciplinary clinic within 1 working day.[9] In healthcare systems in some other countries, primary care physicians may provide basic clinical care at an initial visit for a new diabetic foot ulcer, but they should have a low threshold to refer to interdisciplinary foot clinics or inpatient units for more focused care.

Lack of recognition of ischaemia and infection are two major, but avoidable, pitfalls that lead to delayed referral.[78]

Reassess patients with a suspected diabetic foot infection if:[9]

Symptoms worsen rapidly, or significantly
Symptoms do not start to improve within 1-2 days
The patient becomes systemically unwell or has pain out of proportion to the infection

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