Neuropathic Foot Ulcer

Ulcer of the foot (usually plantar) in a patient with loss of protective sensation, most often from diabetic peripheral neuropathy, and less often from alcohol, leprosy, hereditary neuropathy, spinal cord disease, vitamin B12 deficiency, chemotherapy or other neuropathies.

• Lifetime risk of foot ulcer in a person with diabetes is about 19 to 34%. About 50% of ulcers become infected, and about 20% of moderate to severe infections lead to a lower extremity amputation. Diabetic foot disease precedes about 85% of diabetes related amputations, and 5-year mortality after a foot ulcer is about 40 to 50%.
• Mechanism: sensory loss removes the pain warning, motor neuropathy causes foot deformity (claw toes, prominent metatarsal heads) and altered pressure, and autonomic neuropathy causes dry, fissured skin and reduced sweating. Repetitive pressure or minor trauma then causes callus, subcallus haemorrhage and ulceration. Ischaemia, infection and oedema delay healing.
• Risk factors: previous ulcer or amputation (the strongest), loss of protective sensation, deformity, callus, peripheral arterial disease, poor glycaemic control, kidney disease, visual impairment, poor foot care, barefoot walking and ill fitting shoes.
• Ulcers are classified by depth and the presence of infection and ischaemia (grade 0 intact high risk foot, 1 superficial ulcer, 2 deep ulcer to tendon or capsule, 3 deep ulcer with abscess or osteomyelitis, 4 forefoot gangrene, 5 whole foot gangrene).

• Painless, round or oval ulcer with a punched out appearance and a rim of thick callus, on weight bearing sites: plantar metatarsal heads (the commonest), the great toe, heel, and tips or dorsum of deformed toes. The base is pink and granulating or covered by slough. The foot is usually warm with bounding pulses and distended veins, unless peripheral arterial disease coexists.
• Features of neuropathy: loss of sensation to 10 g monofilament and vibration, absent ankle reflexes, dry skin with fissures, claw toes, prominent metatarsal heads, and pes cavus.
• Infection: erythema around the ulcer of more than 0.5 cm, warmth, swelling, purulent discharge, foul odour, lymphangitis, and in severe cases fever, rigors and systemic illness. Systemic signs may be absent despite deep infection in diabetes. Probing to bone, exposed bone, or a sausage like swollen toe suggests osteomyelitis.
• Acute Charcot neuroarthropathy: a warm, red, swollen foot (temperature difference more than 2 C compared with the opposite foot) with little pain, which can progress to midfoot collapse and rocker bottom deformity.
• Differential diagnosis: arterial (ischaemic) ulcer, venous ulcer, pressure ulcer, traumatic ulcer, pyoderma gangrenosum, vasculitic ulcer, infectious ulcer (tuberculosis, leprosy, fungal), malignancy (squamous cell carcinoma, melanoma), and gout.
• Complications: infection, abscess, necrotising fasciitis, osteomyelitis, gangrene, sepsis, Charcot foot, amputation, and death.

• Examine both feet in full, with shoes and socks removed, every visit. Record ulcer site, size, depth, base, edge, exudate, odour, and surrounding skin. Perform a probe-to-bone test with a sterile blunt probe: a positive test has a high predictive value for osteomyelitis in a patient with a high pre-test probability.
• Neuropathy: 10 g monofilament at 3 to 4 sites per foot, 128 Hz tuning fork vibration, pinprick, and ankle reflexes.
• Perfusion: palpate pulses, measure ankle brachial index (falsely high with calcification), toe pressure and toe brachial index, transcutaneous oxygen pressure and arterial duplex. Toe pressure below 30 mmHg or transcutaneous oxygen below 25 to 30 mmHg predicts poor healing and an urgent need for vascular review.
• Infection: clinical signs. Tissue culture (deep tissue or bone, obtained after debridement) is preferred over surface swabs. Blood tests: full blood count, CRP (above 100 mg/L suggests deep infection), ESR (above 70 mm/hour suggests osteomyelitis), creatinine, glucose, HbA1c and blood cultures if septic.
• Imaging: plain foot X-ray (gas, foreign body, bone destruction, Charcot changes), and MRI for suspected osteomyelitis, abscess or Charcot foot, since X-ray changes lag 2 to 4 weeks. Bone biopsy, with culture and histology, is the most accurate test for osteomyelitis, and guides antibiotic choice.
• Look for foot deformity, footwear fit, callus, and screen for retinopathy and nephropathy.

• Multidisciplinary foot care (diabetes physician, podiatrist, vascular, orthopaedic and plastic surgeon, orthotist, infection specialist, and wound nurse) is key to limb salvage.
• Offloading, the most important intervention for plantar neuropathic ulcers:
  • Total contact cast (applied and changed weekly), or an irremovable knee high walker (a removable walker made non-removable with a cast wrap), which heals about 80 to 90% of uncomplicated forefoot and midfoot ulcers in 6 to 8 weeks.
  • Removable knee high walker, half shoe, post-operative shoe or custom footwear is used when casting is contraindicated (active infection, moderate to severe ischaemia, heavy exudate), with strict advice to wear it at all times when standing or walking.
  • Crutches, wheelchair or bed rest as needed, with heel offloading for heel ulcers.
  • Avoid barefoot walking, even at home.
• Debridement: sharp surgical debridement of callus, slough and necrosis to healthy bleeding tissue, at each visit (weekly or more often), by a trained clinician. Do not debride dry ischaemic necrosis until perfusion is restored. Remove the callus to reduce pressure by about 30%.
• Wound dressings: maintain a moist, balanced wound. Use foam, alginate, hydrofibre, hydrogel or hydrocolloid dressings according to exudate. No dressing is proven superior. Avoid wet-to-dry gauze and prolonged soaking of feet. Use negative pressure wound therapy for post-surgical or deep wounds. Becaplermin 0.01% gel, cellular or tissue based products, platelet rich plasma and hyperbaric oxygen have limited evidence for slow healing ulcers after the basics are optimised.
• Infection (use clinical signs, not culture of surface swabs, to decide to treat):
  • Mild (superficial, erythema 0.5 to 2 cm): oral amoxicillin clavulanate 875/125 mg 12 hourly (or 500/125 mg 8 hourly), or cefalexin 500 mg 6 hourly, for 1 to 2 weeks (up to 4 weeks if slow response). In penicillin allergy: clindamycin 300 to 450 mg 8 hourly. If MRSA risk: add or choose co-trimoxazole 160/800 mg, 1 to 2 tablets 12 hourly, or doxycycline 100 mg 12 hourly.
  • Moderate (erythema more than 2 cm, or deeper tissue involvement) or severe (systemic signs): admit and start IV therapy: piperacillin tazobactam 4.5 g 6 to 8 hourly, or ceftriaxone 2 g daily plus metronidazole 500 mg 8 hourly, plus vancomycin 15 to 20 mg/kg 8 to 12 hourly (adjusted to levels) or linezolid 600 mg 12 hourly for MRSA. Add ciprofloxacin or another Gram negative active agent for ischaemic limbs or previous Pseudomonas. Meropenem 1 g 8 hourly in extensive or resistant disease, with doses adjusted to renal function.
  • Narrow cover once culture results are known. Convert to oral therapy when clinically improving. Duration is 1 to 2 weeks for soft tissue infection (up to 3 to 4 weeks if slowly resolving or if there is severe ischaemia).
  • Urgent surgical drainage and debridement for abscess, necrotising infection, gas in tissues, compartment syndrome and wet gangrene, within hours.
  • Osteomyelitis: bone resection with 2 to 5 days of antibiotics if the margin is clean (or 3 weeks if residual infected bone), or about 6 weeks of antibiotics without surgery (oral options with good bone penetration: rifampicin 300 to 450 mg 12 hourly with a second agent, fluoroquinolones, co-trimoxazole, linezolid, clindamycin or amoxicillin clavulanate, guided by culture).
• Vascular: refer urgently for revascularisation when toe pressure is below 30 mmHg, ulcers fail to improve in 4 weeks despite optimal care, or there is rest pain or gangrene.
• Metabolic and systemic:
  • Optimise glucose: insulin is preferred in acute infection (basal bolus insulin to reach glucose 6 to 10 mmol/L), with a long term HbA1c about 53 to 64 mmol/mol (7 to 8%).
  • Treat oedema, heart failure, anaemia and malnutrition (protein 1.25 to 1.5 g/kg per day, correct vitamin D, zinc and iron deficiency only if low).
  • Blood pressure, lipid control (atorvastatin 40 to 80 mg daily), smoking cessation, and renal care.
  • Neuropathic pain: duloxetine 30 mg increasing to 60 mg daily, pregabalin 75 mg 12 hourly increasing to 150 to 300 mg 12 hourly, gabapentin 300 mg at night titrated to 1800 to 3600 mg daily, or amitriptyline 10 to 25 mg at night, with dose adjustment in renal impairment.
• Charcot neuroarthropathy: immobilise in a total contact cast or non-weight-bearing device until temperature difference falls to less than 2 C and imaging stabilises (usually 3 to 6 months or more), followed by custom footwear. Surgery (exostectomy, arthrodesis, reconstruction) for unstable or ulcerated deformity.
• Surgery for recurrent ulcers from deformity: tendon lengthening (Achilles tenotomy or gastrocnemius recession), toe flexor tenotomy, metatarsal head resection, exostectomy, or osteotomy once the ulcer has healed or when infection is controlled. Amputation (toe, ray, transmetatarsal, below knee) when salvage is not possible.
• Prevention of recurrence (about 40% in 1 year, 60% in 3 years):
  • Daily foot inspection (mirror or help from a carer), washing and drying carefully between the toes, emollient for dry skin (urea 10% cream), and avoiding self-cutting of callus or use of chemical corn removers.
  • Protective footwear (extra depth shoes, custom insoles and rocker soles) with 2 pairs in rotation, and never walking barefoot, with socks that are seamless.
  • Podiatry every 1 to 3 months (frequency by risk), treating callus and nails.
  • Skin temperature monitoring of the foot at home (more than 2 C difference on two successive days warrants rest and review).
  • Structured education, and prompt review of any new blister, break in skin, or colour change.
• Special groups:
  • Chronic kidney disease and dialysis: higher amputation risk, adjust antibiotic and gabapentinoid doses, and review for calcific arterial disease.
  • Leprosy: multidrug therapy, nerve protection, and footwear, with the same offloading principles.
  • Elderly and visually impaired: carer assisted foot checks, and podiatry at home where possible.
  • Pregnancy: offloading, wound care, cefalexin or amoxicillin clavulanate for infection, and avoid fluoroquinolones, doxycycline and metronidazole high doses in the first trimester.
• Follow up: weekly review until the ulcer is healed (a wound area reduction of at least 50% in 4 weeks predicts healing at 12 weeks), then monthly for 3 months, and then according to risk category. If healing stalls, reassess perfusion, infection (including osteomyelitis), offloading adherence, glucose, nutrition, and consider biopsy. Refer early to a diabetic foot or limb salvage service.