Diagnostic Approach to Unilateral Leg Swelling After Prolonged Walking

Immediate Diagnostic Approach

The American College of Chest Physicians guidelines emphasize that objective testing is essential even when clinical suspicion seems low, and recommend performing proximal compression ultrasound (CUS) or whole-leg ultrasound as the initial test, rather than relying on clinical assessment alone 1, 2
Clinical assessment alone is unreliable for detecting thrombosis, even in young, healthy individuals without traditional risk factors, and prolonged walking can trigger DVT 1, 2

If ultrasound is negative but clinical concern persists, obtain a highly sensitive D-dimer test, as recommended by the American College of Chest Physicians 1, 2
If D-dimer is positive with negative initial ultrasound, repeat proximal CUS in 1 week, to exclude deep vein thrombosis (DVT) 1, 2
In patients with extensive unexplained leg swelling and negative proximal/whole-leg US, image the iliac veins to exclude isolated iliac DVT, which can present with unilateral leg swelling and may be missed on standard lower extremity ultrasound 1, 2

Chronic venous insufficiency is a common cause of leg edema in adults, and prolonged walking can exacerbate underlying venous insufficiency, causing acute-on-chronic swelling, with symptoms worsening with prolonged standing or walking and improving with rest or elevation 3, 4, 5
Patients with chronic venous insufficiency may present with heaviness, aching, or fatigue in the affected limb 3, 4, 5

Do not rely on the absence of traditional risk factors to exclude DVT, as young, otherwise healthy individuals can develop DVT, particularly with provocation such as prolonged immobility during extended walking or travel 6
Do not dismiss the possibility of occult DVT based on negative clinical signs alone, as most DVTs originate in the calf and may not produce obvious clinical findings initially, and approximately 70% of patients with proven PE have proximal thrombus, often clinically undetectable 1, 2, 6