Intermittent claudication

Intermittent claudication is reproducible muscle pain, cramping or fatigue in the calf, thigh or buttock that comes on with walking and eases within 10 minutes of rest, caused in most cases by atherosclerotic narrowing of the arteries to the leg. It is the commonest presentation of peripheral artery disease and a marker of widespread atherosclerosis.

Clinical relevance. Peripheral artery disease affects about 10% of adults over 55 and 20% over 70, though most are asymptomatic or have atypical symptoms. Only 1% to 2% of patients with claudication a year progress to critical limb ischaemia, but 5 year mortality is 15% to 30%, mainly from myocardial infarction and stroke. Therefore, treatment is chiefly cardiovascular risk reduction plus exercise, with revascularisation for lifestyle limiting symptoms.

Classification.

• By location of symptoms: buttock and thigh (aortoiliac disease, Leriche syndrome with erectile dysfunction), calf (femoropopliteal disease), foot (tibial disease).
• Fontaine stage: I asymptomatic; IIa mild claudication (walks over 200 metres); IIb moderate to severe (under 200 metres); III rest pain; IV tissue loss. Rutherford category 1 to 3 for claudication.
• Atherosclerotic versus non atherosclerotic: Buerger disease, popliteal entrapment, adventitial cystic disease, fibromuscular dysplasia, vasculitis, radiation arteritis, coarctation.
• Vascular versus non vascular claudication: neurogenic claudication (lumbar spinal stenosis), venous claudication, musculoskeletal pain.

Mechanism. A fixed stenosis limits increase in muscle blood flow during exercise; supply cannot meet demand, so anaerobic metabolites accumulate and cause pain, which resolves with rest.

History.

• Location, character (cramp, ache, tightness), onset after a consistent walking distance (claudication distance), uphill or fast walking worsens, relief within 1 to 10 minutes of standing still (no need to sit or bend forward), reproducibility.
• Atypical presentations: exertional leg fatigue, heaviness, pain in the foot, or no pain with reduced walking speed (common in diabetes and older adults).
• Progression, rest pain (burning in the forefoot at night, relieved by hanging the leg down), ulcers, tissue loss, hair loss.
• Risk factors: smoking (current and pack years), diabetes, hypertension, hyperlipidaemia, chronic kidney disease, family history, age over 50, obesity, inflammatory disease, HIV, Buerger risk (young male smoker).
• Coronary, cerebrovascular and renal artery disease; aneurysm (aortic, popliteal).
• Medication: antiplatelet, statin, antihypertensives, beta blockers (do not worsen claudication), ergots, cilostazol.
• Back pain, sciatica, bilateral leg weakness, relief by bending forward or sitting (neurogenic claudication); varicose veins, past thrombosis, bursting pain relieved by elevation (venous claudication); knee and hip arthritis.
• Erectile dysfunction, buttock pain (aortoiliac); sudden worsening (acute occlusion).

Examination.

• Pulse rhythm, blood pressure in both arms, body mass index, waist.
• Legs: skin colour, temperature, hair loss, shiny skin, thick nails, muscle wasting, ulcers, gangrene, capillary refill, dependent rubor, elevation pallor (Buerger angle).
• Pulses: femoral, popliteal, dorsalis pedis, posterior tibial; bruits over iliac, femoral and adductor canal; abdominal aortic aneurysm; popliteal aneurysm (pulsatile fullness); carotid bruits.
• Neurological: reflexes, sensation, straight leg raise, power after exercise.
• Joints: hip and knee examination.
• Foot inspection and sensation in diabetes.

Red flags.

• Rest pain, nocturnal foot pain, ulceration, gangrene or infection (chronic limb threatening ischaemia).
• Sudden worsening, cold pale limb or acute onset of symptoms (acute limb ischaemia).
• Pulsatile abdominal or popliteal mass.
• Short claudication distance (under 50 metres) with rapid progression.
• Young age (under 50) or a heavy smoker with distal disease (Buerger disease).
• Neurological deficit, bladder or bowel dysfunction (cauda equina).
• Unequal arm pressures, carotid bruits or angina (polyvascular disease).

Vascular. Atherosclerotic peripheral artery disease (aortoiliac, femoropopliteal, tibial), Leriche syndrome, thromboangiitis obliterans, popliteal artery entrapment syndrome, adventitial cystic disease, fibromuscular dysplasia, Takayasu arteritis, radiation arteritis, coarctation, chronic venous insufficiency and venous claudication (iliofemoral outflow obstruction), compartment syndrome (chronic exertional), sickle cell vaso-occlusion.

Neurological. Lumbar spinal stenosis (neurogenic claudication: relief by sitting or flexion, pain with standing), lumbar radiculopathy, peripheral neuropathy, cauda equina compression, diabetic neuropathy.

Musculoskeletal. Hip and knee osteoarthritis, Baker cyst, shin splints and stress fracture, muscle strain, plantar fasciitis, myopathy, statin related muscle pain, restless legs.

Other. Anaemia and heart failure with exercise limitation, chronic exertional compartment syndrome, deconditioning, fibromyalgia, cramps from electrolyte disturbance, hypothyroid myopathy.

1. Ankle brachial pressure index: lowest ankle systolic pressure divided by highest arm systolic pressure, measured at rest with a hand held Doppler. Normal 1.0 to 1.4; 0.91 to 0.99 borderline; 0.9 or under confirms peripheral artery disease (sensitivity about 90%, specificity about 95%); 0.41 to 0.9 mild to moderate; 0.4 or under severe; over 1.4 suggests calcified incompressible vessels (diabetes, kidney disease, older adults).
2. If resting index is normal but symptoms suggest claudication: exercise ankle brachial index (fall of 20% or more, or ankle pressure drop over 30 mmHg after treadmill exercise) or treadmill testing (constant 3.2 km/hour at 10% to 12% incline); toe brachial index (under 0.7 abnormal) and toe pressure in calcified vessels.
3. Duplex ultrasound for site and severity of stenosis; used to plan intervention.
4. CT angiography or MR angiography, only when revascularisation is considered (catheter angiography when intervention is to be done in the same sitting); avoid contrast loads in kidney disease (MR angiography without gadolinium, or duplex).
5. Blood tests: full blood count, urea, creatinine, eGFR, glucose and HbA1c, fasting lipids, liver function, thyroid stimulating hormone, C reactive protein, urinalysis and urine albumin to creatinine ratio.
6. Cardiovascular risk assessment: ECG, blood pressure, carotid duplex when bruit, echocardiography when indicated, screening for abdominal aortic aneurysm in men over 65 and in smokers.
7. For non vascular candidates: lumbar spine MRI (spinal stenosis), knee and hip imaging, nerve conduction studies.
8. Young patients: coagulation and vasculitis screens, tobacco and cannabis history, imaging for entrapment (provocative duplex or MR angiography), hypercoagulable and Buerger work up.
9. Walking test: record maximum and pain free walking distance as baseline.

Limits. Ankle brachial pressure index is falsely high in calcified arteries and may be normal at rest in mild disease. Many patients have atypical symptoms or none. Spinal stenosis and peripheral artery disease can coexist. Duplex accuracy depends on the operator.

Cardiovascular risk reduction (all patients).

• Stop smoking: counselling plus nicotine replacement (patch 21 mg daily for 6 weeks, 14 mg for 2 weeks, 7 mg for 2 weeks) or varenicline (0.5 mg daily for 3 days, 0.5 mg twice daily for 4 days, then 1 mg twice daily for 12 weeks) or bupropion 150 mg daily for 3 days then 150 mg twice daily; the single most effective intervention.
• Antiplatelet therapy: aspirin 75 mg daily or clopidogrel 75 mg daily (clopidogrel is slightly more effective and is preferred where available after symptomatic disease). For stable disease at low bleeding risk, rivaroxaban 2.5 mg twice daily plus aspirin 75 to 100 mg daily reduces cardiovascular events and limb events more than aspirin alone.
• Statin: atorvastatin 40 to 80 mg daily (or rosuvastatin 20 to 40 mg), aiming for LDL cholesterol under 1.8 mmol/L (under 1.4 mmol/L with very high risk, with ezetimibe 10 mg daily and further agents if needed).
• Blood pressure to under 130/80 mmHg: ACE inhibitor (ramipril 2.5 to 10 mg daily) or angiotensin receptor blocker, plus a calcium channel blocker or thiazide like diuretic; beta blockers are safe in mild to moderate disease.
• Diabetes control (HbA1c about 53 mmol/mol, 7%; sodium glucose co-transporter 2 inhibitors and glucagon like peptide 1 agonists for cardiovascular benefit) and foot care.
• Weight loss, Mediterranean diet, and influenza and pneumococcal vaccination.

Structured exercise therapy (first line for symptoms). Supervised walking programme at least 30 to 60 minutes, three times a week, for at least 12 weeks: walk to near maximal leg pain, rest until pain eases, repeat; improves walking distance by 50% to 200%. A home based programme with a pedometer or monitor and coaching can be used where supervised classes are not available.

Drugs for symptoms (add when exercise is insufficient).

• Cilostazol 100 mg twice daily (take 30 minutes before or 2 hours after food); contraindicated in heart failure of any grade, unstable angina, and use with strong CYP3A4 or CYP2C19 inhibitors (halve the dose); side effects headache, diarrhoea, palpitations.
• Naftidrofuryl oxalate 100 to 200 mg three times daily, reviewed at 3 to 6 months where available.
• Pentoxifylline 400 mg three times daily offers only modest benefit.
• Avoid vasodilators without proven benefit and avoid unneeded polypharmacy.

Revascularisation. Offered for lifestyle limiting claudication despite 3 months of exercise, risk factor control and drugs, when anatomy is suitable and the risk to benefit ratio is acceptable; aortoiliac disease responds best (angioplasty and stenting, or bypass); femoropopliteal disease (angioplasty, drug coated balloons and stents, atherectomy, bypass with vein); tibial disease rarely treated for claudication.

After intervention: antiplatelet therapy (aspirin 75 mg plus clopidogrel 75 mg for 1 to 3 months after stenting), then lifelong single antiplatelet or rivaroxaban 2.5 mg twice daily with aspirin, and surveillance duplex.

Non vascular claudication. Spinal stenosis: physiotherapy, analgesia, epidural steroid injection, decompression surgery; venous claudication: anticoagulation, compression, venous stenting; popliteal entrapment and compartment syndrome: surgical release; Buerger disease: stop all tobacco, iloprost and sympathectomy.

Foot care and education. Daily inspection, well fitting footwear, avoid injury and heating pads, early treatment of fungal infection, podiatry for diabetes or neuropathy.

Monitoring. Review every 3 to 6 months initially, then annually: walking distance, claudication symptoms, ankle brachial index, blood pressure, lipids, HbA1c, smoking status, creatinine, feet; duplex after intervention at 1, 6 and 12 months; cardiovascular screening.

Referral and escalation. Vascular surgery or interventional radiology for lifestyle limiting claudication, rapid progression, aneurysm and revascularisation planning; urgent assessment for rest pain, tissue loss or sudden worsening; cardiology for coronary symptoms; diabetes team and podiatry.

Admission. Acute limb ischaemia, rest pain with tissue loss or infection, critical limb threatening ischaemia, or severe comorbidity needing urgent intervention.

Safety netting. Return immediately for sudden cold, pale, painful or numb leg; rest pain at night; ulcers, black skin or infection; chest pain; neurological symptoms; or a rapidly shortening walking distance. Keep walking every day.

Special groups. Diabetes: symptoms may be masked by neuropathy; check feet; high rates of tibial disease.

Older adults: walking limited by cardiac, respiratory and joint disease; exercise remains beneficial. Women: atypical presentations, worse outcomes after revascularisation. Young patients: consider Buerger disease, entrapment, vasculitis, hypercoagulable states and cystic adventitial disease. Chronic kidney disease: calcified vessels give falsely high indices; use toe pressures. Endemic regions: Buerger disease with tobacco and cannabis use, HIV vasculopathy and late presentation with gangrene.