What is the diagnosis and treatment for a patient with intermittent bilateral leg pain and mottling that improves with walking, suggestive of intermittent claudication and possible peripheral artery disease?

Diagnosis: Atypical Presentation Requiring Careful Differentiation

This presentation is highly atypical for peripheral artery disease (PAD) and warrants immediate consideration of alternative diagnoses, as true intermittent claudication worsens with walking and improves with rest—not the reverse. 1

Critical Diagnostic Distinction

The described symptom pattern—bilateral leg pain and mottling that improves with walking—is fundamentally inconsistent with classic intermittent claudication from PAD, which is characterized by:

• Pain that increases with walking/exercise 1
• Pain that resolves quickly at rest (typically within minutes) 1
• Reproducible symptoms with consistent walking distances 1, 2

Alternative Diagnoses to Consider

Venous disease is the most likely diagnosis given this presentation, as venous claudication characteristically:

• Presents with pain at rest 1
• Increases in the evening 1
• Often improves with muscle activity/walking 1
• May present with skin mottling or discoloration 1

Lumbar spinal stenosis ("neurogenic claudication") should also be strongly considered:

• Causes leg pain with walking 1
• However, typically worsens with standing/extension and improves with sitting/flexion 1
• Does not improve simply by walking 1

Other differential diagnoses include:

• Hip or knee arthritis (pain persists at rest, not relieved by stopping walking) 1
• Peripheral neuropathy (instability while walking, pain not relieved by rest) 1
• Chronic compartment syndrome 1

Diagnostic Workup

Ankle-brachial index (ABI) measurement is the essential first step to definitively rule out PAD:

• ABI ≤0.90 confirms PAD diagnosis 1
• Normal post-exercise ABI effectively excludes PAD as the cause 1
• ABI is highly specific (>95%) for diagnosing PAD 1

If ABI is normal, arterial imaging is not indicated unless other atherosclerotic causes (e.g., isolated internal iliac artery disease, entrapment syndromes) are suspected 1.

Additional evaluation should include:

• Venous duplex ultrasound if venous disease suspected 1
• Lumbar spine imaging if neurogenic claudication suspected 1
• Assessment for inflammatory muscle diseases 1

Treatment Approach (If PAD Confirmed Despite Atypical Presentation)

First-Line Management

Supervised exercise therapy is the cornerstone of treatment (Class I, Level A recommendation):

• Recommended as initial therapy for all patients with intermittent claudication 1
• Improves maximal walking distance more than stenting at 6 months 1
• Should be implemented for 3 months before considering revascularization 1

Unsupervised exercise therapy is recommended when supervised programs are unavailable (Class I, Level C) 1.

Pharmacotherapy

Cilostazol 100 mg twice daily is first-line pharmacotherapy for lifestyle-limiting claudication:

• Improves maximal walking distance by 40-60% after 12-24 weeks 3, 4
• More effective than 50 mg twice daily dosing 3, 4
• Absolutely contraindicated in any degree of heart failure due to phosphodiesterase inhibitor mechanism 3, 4

Pentoxifylline 400 mg three times daily should only be considered as second-line therapy:

• Used when cilostazol is contraindicated or not tolerated 3, 5
• Has marginal and not well-established clinical effectiveness 3
• Not equivalent to cilostazol 3

Statin therapy is indicated to improve walking distance (Class I, Level A) 1.

Revascularization Considerations

Revascularization should be considered (Class IIa, Level C) when:

• Daily life activities are compromised despite exercise therapy 1
• Patient has significant disability affecting work or important activities 1
• Lesion anatomy suggests low risk and high probability of success 1

Revascularization should NOT be pursued until:

• Comprehensive risk factor modification and antiplatelet therapy initiated 1
• Patient has received information about supervised exercise and pharmacotherapy 1
• Adequate trial of conservative management (typically 3 months) 1

Critical Pitfalls to Avoid

Do not assume PAD based on symptoms alone when the presentation is atypical—always confirm with ABI measurement 1.

Do not prescribe cilostazol to patients with any history of heart failure, regardless of severity, as this represents an absolute contraindication 3, 4.

Do not proceed directly to revascularization without first implementing supervised exercise therapy and optimal medical management 1.

Do not overlook cardiovascular risk stratification, as PAD patients have 3.1 times greater all-cause mortality and 5.9 times greater cardiovascular mortality compared to patients without PAD 1.