A patient with no significant medical history, presenting with gradually increasing mild bilateral leg pain and fatigue after walking short distances over the past 3 months, has a normal physical examination, what is the likely diagnosis and recommended management for this patient?

Likely Diagnosis: Peripheral Artery Disease (PAD) with Atypical Symptoms

The most likely diagnosis is peripheral artery disease (PAD), and the patient requires ankle-brachial index (ABI) testing immediately to confirm the diagnosis, followed by comprehensive cardiovascular risk factor management regardless of symptom severity. 1

Clinical Reasoning

Why PAD is Most Likely

• Bilateral mild leg pain with gradual onset over 3 months and fatigue after walking short distances is consistent with PAD, even without classic intermittent claudication. 1 Only one-third of PAD patients present with typical claudication symptoms, while most have atypical exertional leg symptoms or are asymptomatic. 1

• Recent decrease in outdoor activities is a critical red flag. 1 Patients with PAD often become sedentary and self-limit walking due to discomfort, which may not be described as classic claudication pain. 1

• Normal physical examination does NOT exclude PAD. 1 The presence of all four pedal pulses (bilateral dorsalis pedis and posterior tibial) is associated with low likelihood of PAD, but pulse examination has limited sensitivity and specificity and must be supplemented by objective testing. 1

Alternative Diagnoses to Consider (But Less Likely)

While the differential includes several conditions, the clinical presentation makes PAD most probable:

• Lumbar spinal stenosis 1, 2: Would typically present with bilateral buttock and posterior leg pain that worsens with standing/spinal extension and improves with sitting or lumbar flexion. 2 The patient's symptoms lack this positional component and difficulty rising from sitting. 2

• Hip arthritis 1: Would cause lateral hip/thigh aching with variable exercise tolerance, not quickly relieved by rest, and improved when not bearing weight. 1 This doesn't match the bilateral leg pain pattern described. 1

• Venous claudication 1: Would present with tight, bursting pain in the entire leg (worse in calf), subsiding slowly with rest, and typically requires history of iliofemoral deep vein thrombosis with edema and venous stasis signs. 1

Diagnostic Algorithm

Step 1: Obtain Ankle-Brachial Index (ABI) Immediately

ABI is the mandatory first-line diagnostic test after clinical examination. 1, 3

• ABI ≤0.90 confirms PAD diagnosis (75% sensitivity, 86% specificity). 1, 3
• ABI 0.91-1.00 (borderline) requires further testing with post-exercise ABI and/or duplex ultrasound. 1
• ABI >1.40 indicates medial calcification (common in diabetes/chronic kidney disease) and requires alternative testing such as toe-brachial index or Doppler waveform analysis. 1

Step 2: If ABI is Normal but Clinical Suspicion Remains High

• Perform exercise ABI (treadmill test) using Strandness protocol (3 km/h, 10% slope). 1 A post-exercise ankle systolic blood pressure decrease >30 mmHg or post-exercise ABI decrease >20% confirms PAD. 1

Step 3: Additional Vascular Assessment

• Auscultate for femoral and abdominal bruits (femoral bruit has LR 4.80 for PAD diagnosis). 1, 4
• Examine for elevation pallor/dependent rubor, asymmetric hair growth, nail bed changes, or calf muscle atrophy. 1

Management Recommendations

Immediate Cardiovascular Risk Reduction (Regardless of Symptom Severity)

PAD is a marker of systemic atherosclerosis with dramatically increased cardiovascular mortality—patients have 3.1 times greater all-cause mortality and 5.9 times greater cardiovascular mortality compared to those without PAD. 1

1. Antiplatelet therapy: Clopidogrel is preferred over aspirin. 3

2. High-intensity statin therapy for lipid management. 3

3. Blood pressure control targeting appropriate goals. 3

4. Smoking cessation if applicable (critical intervention). 3

5. Diabetes management with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors when applicable. 3

Symptom Management

1. Structured exercise therapy is first-line treatment for claudication symptoms. 3 Patients should be encouraged to maintain physical activity rather than becoming sedentary. 1

2. Consider cilostazol 100 mg twice daily for symptomatic improvement. 5 Clinical trials demonstrate 28-100% improvement in maximal walking distance compared to placebo. 5 However, cilostazol is contraindicated in patients with heart failure. 5

3. Duplex ultrasound should be obtained to assess anatomic disease severity and guide further management. 1

When to Consider Revascularization

• Patients who do not improve with initial medical management should be evaluated for revascularization with imaging (CTA or MRA) to determine location and severity of arterial disease. 3

• Immediate vascular surgery referral is indicated if critical limb-threatening ischemia develops (rest pain, non-healing wounds, gangrene). 3

Critical Clinical Pitfalls to Avoid

1. Do not assume normal examination excludes PAD. 1 Up to 50% of PAD patients are asymptomatic, and 70% do not have classic claudication. 1, 6

2. Do not delay ABI testing based on "atypical" symptoms. 1 The broad spectrum of PAD presentations includes atypical exertional leg pain, leg pain at rest and with exertion, and even absence of exertional leg pain in inactive individuals. 6

3. Do not overlook the systemic cardiovascular risk. 1 Even asymptomatic PAD patients have similar cardiovascular event risk as those with claudication. 1 The 5-year cardiovascular morbidity is 13% versus 5% in reference populations. 1

4. Do not assume bilateral symptoms exclude PAD. 2, 7 While bilateral presentation may suggest neurogenic causes, PAD commonly presents bilaterally and requires objective testing to differentiate. 1

5. Do not initiate compression therapy without first obtaining ABI. 8 If ABI <0.6, compression therapy is contraindicated. 8