What is the appropriate diagnostic and management approach for a patient with 2 weeks of bilateral leg pain that worsens with activity?

Bilateral Leg Pain with Activity: Diagnostic Workup

Begin with ankle-brachial index (ABI) testing to objectively exclude peripheral artery disease (PAD), as this is the most critical diagnosis to rule out given the significant mortality risk (25-35% one-year mortality with critical limb-threatening ischemia). 1, 2

Initial Clinical Assessment

Key History Elements to Obtain

• Pain characteristics: Determine if pain is fatigue, discomfort, cramping that consistently resolves within 10 minutes of rest (classic claudication) versus atypical exertional symptoms 1
• Bilateral involvement: While PAD typically affects specific arterial distributions, bilateral symptoms warrant comprehensive vascular assessment 1, 3
• Timing pattern: Note if symptoms worsen in evening/night and improve with movement (suggests restless legs syndrome) versus worsening with activity only (suggests vascular or musculoskeletal) 1
• Positional factors: Pain improved by sitting/forward flexion suggests spinal stenosis; pain worse with leg elevation suggests vascular insufficiency 1

Critical Physical Examination Findings

• Bilateral lower extremity pulse palpation (femoral, popliteal, dorsalis pedis, posterior tibial): Presence of all four pedal pulses bilaterally makes PAD unlikely 1, 4
• Vascular examination: Check for bruits, elevation pallor/dependent rubor, capillary refill time, venous filling time 1, 2
• Neurological examination: Assess for sensory deficits, diminished reflexes, or radiculopathy to identify nerve root compression 1, 2

Diagnostic Testing Algorithm

First-Line Test: Ankle-Brachial Index

Obtain resting ABI with or without segmental pressures in all patients with bilateral leg pain worsening with activity 1, 4

ABI interpretation:

• ≤0.90: PAD confirmed 1, 3
• 0.91-0.99: Borderline, consider exercise ABI 3
• 1.00-1.40: Normal, pursue alternative diagnoses 3
• >1.40: Noncompressible arteries (often diabetes), obtain toe-brachial index 3

If Normal Resting ABI but Symptoms Persist

Perform exercise treadmill ABI testing to unmask exercise-induced arterial insufficiency 1, 3

Additional Testing Based on ABI Results

• If PAD confirmed: Consider duplex ultrasound, CT angiography, or MR angiography for anatomic detail if revascularization planning needed 4
• If ABI normal: Obtain plain radiographs or MRI to evaluate for arthritis, fracture, bone lesions, or soft tissue/nerve pathology 4

Differential Diagnosis Framework

Vascular Causes (Rule Out First)

Peripheral artery disease (claudication):

• Fatigue, discomfort, cramping consistently induced by exercise and consistently relieved by rest within 10 minutes 1
• Bilateral involvement possible with aortoiliac disease 1
• Risk factors: Age >65 years, age 50-64 with diabetes/smoking, or known atherosclerotic disease elsewhere 1

Neurogenic Causes

Lumbar spinal stenosis (neurogenic claudication):

• Pain worsens with standing/walking, improves with sitting or forward flexion 1, 3
• Often bilateral buttocks and posterior leg involvement 1
• Relief may take longer than vascular claudication 1

Nerve root compression:

• Sharp lancinating pain radiating down leg 1
• Induced by sitting, standing, or walking (variable pattern) 1
• History of back problems; worse with sitting; relief when supine or standing 1

Movement Disorder

Restless legs syndrome:

• Check serum ferritin: Values <50 ng/mL consistent with RLS and indicate need for iron supplementation 1, 2
• Must meet all five essential criteria: (1) urge to move legs with uncomfortable sensations, (2) symptoms begin/worsen during rest, (3) partially/totally relieved by movement, (4) worse in evening/night, (5) not solely accounted for by another condition 1, 2
• Critical pitfall: 16% of subjects without RLS will be misclassified if you only ask about symptoms without confirming all criteria 2

Musculoskeletal Causes

Hip or ankle arthritis:

• Aching discomfort after variable degree of exercise 1
• Not quickly relieved by rest 1
• Improved when not bearing weight 1

Chronic compartment syndrome:

• Tight, bursting pain in calf muscles after strenuous exercise 1
• Subsides very slowly 1
• Typically in heavy-muscled athletes 1

Venous Causes

Venous claudication:

• Entire leg involvement, worse in calf with tight, bursting pain 1
• Subsides slowly after walking 1
• Relief speeded by leg elevation 1
• History of iliofemoral deep vein thrombosis, edema, signs of venous stasis 1

Management Based on Findings

If PAD Confirmed (ABI ≤0.90)

Initiate comprehensive PAD management:

• Aggressive cardiovascular risk factor modification 3
• Antiplatelet therapy 3
• Structured/supervised exercise program as first-line therapy 3
• Statin therapy to improve walking distance 3
• Consider pharmacotherapy for symptom relief 3
• Revascularization only if daily activities severely compromised despite conservative therapy 3

If PAD Excluded (Normal Post-Exercise ABI)

Pursue alternative diagnoses systematically:

• Consider MRI lumbar spine if neurogenic claudication suspected 3
• Refer to appropriate specialist based on findings (orthopedics, neurology, rheumatology) 3

Critical Pitfalls to Avoid

• Do not assume all exertional leg pain is claudication: Only one-third of PAD patients present with typical claudication 1, 4
• Do not skip ABI testing in at-risk patients: PAD carries significant mortality risk and requires aggressive risk factor modification even if asymptomatic 2
• Do not skip bilateral pulse examination: Presence of all four pedal pulses bilaterally redirects workup away from PAD 4
• Do not diagnose RLS without confirming all five essential criteria: Misdiagnosis rate is high without systematic assessment 2