Skin ulcer and nonhealing wound

An ulcer is loss of the epidermis and at least part of the dermis. A chronic wound is one that fails to progress through normal healing within 4 to 6 weeks.

Classification by cause

• Vascular: venous, arterial, mixed and lymphatic.
• Neuropathic: diabetes, leprosy, other neuropathies.
• Pressure related.
• Infective: bacterial, mycobacterial (Buruli ulcer, tuberculosis), fungal, treponemal (yaws, tertiary syphilis), protozoal (cutaneous leishmaniasis), tropical ulcer.
• Inflammatory and autoimmune: pyoderma gangrenosum, vasculitis, antiphospholipid syndrome.
• Haematological: sickle cell disease, thalassaemia, hereditary spherocytosis.
• Malignant: squamous cell carcinoma (including Marjolin ulcer), basal cell carcinoma, melanoma, lymphoma.
• Traumatic, factitious, drug related and metabolic (calciphylaxis).

Characteristic ulcers

• Venous: gaiter area, shallow, irregular, moist, with oedema, varicose veins, haemosiderin staining and lipodermatosclerosis. Venous disease is the commonest cause of leg ulceration.
• Arterial: punched out, pale or necrotic base, over toes, heels or malleoli, painful, with cold limb, absent pulses and hair loss.
• Neuropathic: plantar over pressure points, surrounded by callus, painless.
• Pyoderma gangrenosum: very painful, violaceous undermined edge, rapid enlargement, pathergy.
• Malignant: raised rolled or everted edge, friable base, bleeding.

Healing barriers. Infection, ischaemia, oedema, pressure, malnutrition, diabetes, corticosteroids, smoking, anaemia and malignancy.

History

• Duration, trigger, speed of enlargement, pain pattern (rest pain relieved by dependency suggests arterial disease; pain relieved by elevation suggests venous disease; very severe pain suggests pyoderma, vasculitis, calciphylaxis or infection).
• Claudication, previous deep vein thrombosis, varicose veins, leg surgery, diabetes, sickle cell disease, inflammatory bowel disease, rheumatoid arthritis, tuberculosis, leprosy, HIV, previous ulcers.
• Drugs (hydroxycarbamide, methotrexate, steroids, anticoagulants, beta blockers), smoking, alcohol, mobility, nutrition, topical products (contact sensitisation).
• Travel or residence in areas with Buruli ulcer, leishmaniasis, yaws or tropical ulcer.

Examination

• Measure and photograph size and depth. Record base (granulation, slough, necrosis, bone or tendon), edge, undermining, exudate and odour.
• Surrounding skin: erythema, eczema, induration, haemosiderin staining, atrophie blanche, callus, maceration.
• Signs of infection: increasing pain, spreading erythema, warmth, purulence, friable granulation, odour, delayed healing.
• Pulses (dorsalis pedis, posterior tibial), capillary refill, skin temperature, varicose veins, oedema, limb deformity, foot shape (Charcot).
• Sensation: 10 g monofilament and 128 Hz tuning fork.
• Probe to bone test: a positive result strongly suggests osteomyelitis in diabetic foot ulcers.
• Ankle brachial pressure index (ABPI) using Doppler: 0.9 to 1.3 is normal. 0.5 to 0.8 indicates moderate arterial disease. Under 0.5 is severe. Over 1.3 indicates incompressible calcified vessels (common in diabetes and chronic kidney disease), and toe pressures are then needed.
• Lymph nodes.

Red flags

• Rest pain, gangrene, ankle pressure under 50 mmHg or ABPI under 0.4 (critical limb ischaemia).
• Spreading infection, sepsis, crepitus or necrosis (necrotising infection).
• Exposed bone or positive probe to bone.
• Hot swollen foot in a patient with neuropathy (Charcot).
• Ulcer not healing after 3 months of appropriate care, or with raised rolled edge (malignancy).
• Painful purpuric, livedoid or necrotic lesions (vasculitis, calciphylaxis in dialysis patients).
• Undermined violaceous edge with rapid growth (pyoderma gangrenosum).
• Painless ulcer with undermined edges in Buruli ulcer endemic areas.

Special groups

• Diabetes: neuropathy plus ischaemia is the usual mechanism, and infection spreads rapidly.
• Sickle cell disease: malleolar ulcers that recur.
• Older adults: mixed arterial and venous disease is common, and reduced compression may be needed.
• Pregnancy and breastfeeding: avoid doxycycline, fluoroquinolones, metronidazole high doses, and miltefosine.

Vascular

• Venous leg ulcer.
• Arterial ischaemic ulcer.
• Mixed arteriovenous ulcer.
• Lymphoedema ulceration.
• Martorell hypertensive ischaemic ulcer.
• Thromboangiitis obliterans.
• Cholesterol embolism.

Neuropathic and pressure

• Diabetic foot ulcer.
• Leprosy plantar ulcer.
• Syringomyelia and spinal cord disease with trophic ulcers.
• Pressure ulcer.
• Charcot neuroarthropathy.

Infective

• Bacterial ulcer and ecthyma.
• Tropical phagedenic ulcer.
• Buruli ulcer.
• Cutaneous tuberculosis.
• Yaws.
• Tertiary syphilis (gumma).
• Cutaneous leishmaniasis.
• Deep fungal infection (sporotrichosis, chromoblastomycosis, mycetoma).
• Atypical mycobacterial infection.
• Anthrax eschar.
• Diphtheria skin ulcer.

Inflammatory and haematological

• Pyoderma gangrenosum.
• Leukocytoclastic and ANCA associated vasculitis.
• Rheumatoid vasculitis and lupus.
• Antiphospholipid syndrome.
• Cryoglobulinaemia.
• Sickle cell leg ulcer and other haemolytic anaemias.
• Necrobiosis lipoidica.

Neoplastic and other

• Squamous cell carcinoma and Marjolin ulcer.
• Basal cell carcinoma.
• Melanoma.
• Kaposi sarcoma.
• Cutaneous lymphoma.
• Calciphylaxis.
• Factitious ulcer.
• Drug induced ulcer (hydroxycarbamide, methotrexate).
• Contact dermatitis with secondary ulceration.
• Insect and spider bites with necrosis.

Step 1. Check for limb threat and sepsis. Measure vital signs, glucose, ABPI or toe pressures, and examine for necrosis, deep infection and bone exposure.

Step 2. Bedside tests. Capillary glucose, urinalysis, ABPI with Doppler (toe brachial index and toe pressure when ABPI is over 1.3; a toe pressure under 30 mmHg predicts poor healing).

Step 3. Blood tests

• Full blood count, ESR, CRP, HbA1c or glucose, urea, creatinine, eGFR, albumin, ferritin, lipids.
• Haemoglobin electrophoresis or sickling test in at risk patients.
• HIV and syphilis serology, hepatitis B and C serology.
• When vasculitis or autoimmune cause is suspected: ANA, ANCA, rheumatoid factor, complement, cryoglobulins, antiphospholipid antibodies and lupus anticoagulant, and serum protein electrophoresis.
• Thrombophilia screen only for recurrent venous disease in a young patient.

Step 4. Imaging

• Venous duplex ultrasound: reflux time over 0.5 seconds in superficial and over 1 second in deep veins is abnormal.
• Arterial duplex, CT angiography or MR angiography when ABPI is under 0.8, pulses are absent or revascularisation is considered.
• Plain radiograph of the foot for osteomyelitis, gas and Charcot changes. MRI is the most sensitive test for osteomyelitis. ESR over 70 mm/h supports osteomyelitis in diabetic foot ulcers.

Step 5. Microbiology. Culture only when there are clinical signs of infection, using deep tissue after debridement. Surface swabs often grow colonisers. Bone biopsy for culture when osteomyelitis needs organism directed therapy.

Step 6. Skin biopsy. Take a 4 mm punch biopsy from the ulcer edge including normal skin when the ulcer is atypical, has not healed after 3 months of appropriate care, or malignancy, vasculitis, pyoderma gangrenosum or infection are suspected. Send tissue for histology, culture (bacterial, fungal, mycobacterial) and direct immunofluorescence when inflammatory. Pyoderma gangrenosum is a clinical diagnosis and biopsy mainly excludes other causes.

Step 7. Region specific tests. Buruli ulcer: IS2404 PCR and Ziehl-Neelsen stain of swab or biopsy. Leishmaniasis: slit skin smear, culture and PCR. Yaws: dark ground microscopy or serology.

Healing prediction. A reduction in ulcer area of under 40% after 4 weeks of appropriate treatment predicts failure to heal by 12 weeks and prompts review of the diagnosis.

Limits. ABPI is unreliable in calcified vessels. Superficial swabs do not separate infection from colonisation. Biopsy of a clinically typical pyoderma gangrenosum can provoke worsening through pathergy.

General care

• Treat the underlying cause.
• Debride slough and devitalised tissue (sharp, autolytic or larval), except dry ischaemic necrosis before vascular review.
• Moist wound dressings: hydrocolloid or hydrogel for low exudate, foam or alginate for moderate to high exudate, cadexomer iodine or silver for short courses in critically colonised wounds.
• Pain: paracetamol 1 g orally every 6 hours (maximum 4 g daily; 3 g daily in hepatic impairment, chronic alcohol use or weight under 50 kg), lidocaine 4% topical before debridement. Avoid NSAIDs in kidney impairment and with anticoagulants.
• Nutrition: protein 1.25 to 1.5 g/kg daily, correct anaemia and deficiencies. Stop smoking.
• Check tetanus immunisation. For tetanus prone wounds in a person with incomplete immunisation, give a tetanus toxoid dose and tetanus immunoglobulin 250 IU intramuscularly (500 IU if more than 24 hours since injury or heavy contamination).

Venous ulcer. Multilayer high compression bandaging (35 to 40 mmHg at the ankle) when ABPI is 0.8 or more, changed weekly (twice weekly with heavy exudate). Use reduced compression under specialist advice for ABPI 0.5 to 0.8, and no compression when ABPI is under 0.5. Elevate the legs and encourage walking. After healing, wear graduated compression stockings (23 to 32 mmHg at the ankle) indefinitely.

Refer for assessment of endovenous ablation of superficial reflux, which reduces recurrence. Pentoxifylline 400 mg orally 3 times daily as an adjunct has modest evidence (monitor for gastrointestinal upset and bleeding; reduce in kidney impairment).

Arterial ulcer. Urgent vascular assessment. Aspirin 75 mg orally once daily or clopidogrel 75 mg once daily, atorvastatin 40 to 80 mg orally at night (maximum 80 mg; monitor liver tests and muscle symptoms), blood pressure and glucose control, smoking cessation. Revascularisation is the definitive treatment. No compression.

Diabetic foot ulcer. Off loading with a total contact cast or removable walker is the central treatment. Optimise glucose. Infection severity: mild (erythema 0.5 to 2 cm around the ulcer), moderate (over 2 cm or deeper structures), severe (systemic signs).

• Mild: flucloxacillin 500 mg to 1 g orally 4 times daily for 7 days (clarithromycin 500 mg twice daily or doxycycline 100 mg twice daily if penicillin allergic).
• Moderate: amoxicillin with clavulanic acid 625 mg orally 3 times daily for 7 to 14 days.
• Severe: piperacillin with tazobactam 4.5 g intravenously every 6 hours (3.375 g every 6 hours when creatinine clearance is 20 to 40 mL/min; 2.25 g every 6 hours when under 20 mL/min), adding vancomycin 15 to 20 mg/kg intravenously every 8 to 12 hours when MRSA is likely.
• Osteomyelitis without resection: usually 6 weeks of directed antibiotics. Surgical debridement for abscess, necrosis, gas or spreading infection.
• Review within 24 to 48 hours of the first assessment, by a specialist foot service.

Specific ulcers

• Pyoderma gangrenosum: avoid surgical debridement. Small lesions: clobetasol propionate 0.05% ointment once daily or tacrolimus 0.1% ointment twice daily. Extensive disease: prednisolone 0.5 to 1 mg/kg orally daily, ciclosporin 3 to 5 mg/kg daily in 2 doses, or infliximab 5 mg/kg intravenously. Treat any underlying inflammatory bowel disease or arthritis.
• Buruli ulcer: rifampicin 10 mg/kg (maximum 600 mg) orally once daily plus clarithromycin 7.5 mg/kg (maximum 500 mg) orally twice daily, or moxifloxacin 400 mg orally once daily, for 8 weeks, with wound care and surgery for large lesions. Monitor liver tests; rifampicin induces many drug interactions.
• Cutaneous leishmaniasis: species and region directed. Options are sodium stibogluconate 20 mg/kg intravenously or intramuscularly daily for 20 days (monitor ECG, liver, pancreas and kidney) or miltefosine 2.5 mg/kg orally daily (maximum 150 mg daily) for 28 days (contraindicated in pregnancy; reliable contraception for 5 months).
• Yaws: azithromycin 30 mg/kg orally as a single dose (maximum 2 g).
• Tropical ulcer: metronidazole 400 mg orally 3 times daily for 7 days with phenoxymethylpenicillin 500 mg orally 4 times daily for 7 days. Evidence is limited.
• Leprosy plantar ulcer: off loading, wound care, and leprosy multidrug treatment under a specialist programme.
• Sickle cell ulcer: compression, wound care, optimisation of sickle cell disease, and haematology review; review hydroxycarbamide as a possible contributor.
• Calciphylaxis: wound care, pain control, and sodium thiosulphate 25 g intravenously after dialysis 3 times weekly (evidence limited), with nephrology review.
• Vasculitis or autoimmune ulcers: prednisolone and immunosuppression directed by rheumatology.
• Malignant ulcer: excision and oncology care.

Monitoring. Measure area weekly. Check for infection, maceration, new pain and systemic signs. Reassess the diagnosis and perfusion if there is no healing after 4 to 6 weeks.

Referral and escalation. Vascular surgery for ABPI under 0.8, critical limb ischaemia, or planned venous ablation. Diabetic foot service within 24 to 48 hours for any active diabetic foot ulcer, and same day for severe infection, gangrene or limb threat. Dermatology for atypical ulcers, pyoderma gangrenosum and biopsy. Plastic surgery for grafts or flaps. Orthopaedics for osteomyelitis and Charcot foot. Tissue viability and podiatry.

Admission criteria. Sepsis, necrotising infection, critical limb ischaemia, deep infection, osteomyelitis needing intravenous treatment, severe pain, inability to care for the wound.

Discharge and follow up. Weekly dressing changes and review. Safety net advice: return for fever, spreading redness, offensive discharge, new black skin, severe pain, cold or blue toes, or increasing ulcer size.