What is the appropriate diagnostic and treatment approach for a patient with chronic swelling of one extremity?

Chronic Unilateral Left Extremity Swelling: Differential Diagnosis

The most critical first step is to rule out deep venous thrombosis (DVT) with duplex Doppler ultrasound, as this represents the most immediately life-threatening cause of unilateral limb swelling. 1

Immediate Priority: Exclude DVT

• Duplex Doppler ultrasound is the mandatory first diagnostic test for any patient presenting with unilateral extremity swelling to exclude acute or chronic DVT 1
• Even in chronic presentations, unrecognized DVT can lead to pulmonary embolism and post-thrombotic syndrome 2, 3
• If ultrasound is negative but clinical suspicion remains high, proceed to MR venography to evaluate for pelvic or proximal thigh venous thrombosis that may be missed on standard duplex imaging 3

Primary Differential Diagnoses for Chronic Unilateral Swelling

1. Chronic Venous Insufficiency (Most Common)

• Results from primary valvular incompetence or prior DVT causing valve destruction 1
• Clinical features to identify: dependent edema that worsens throughout the day, hemosiderin deposition (brownish skin discoloration), varicosities, skin induration, venous dermatitis, and potential ulceration 1, 3
• Duplex ultrasound with reflux assessment is diagnostic, showing retrograde venous flow >500 milliseconds 1
• Affects over 33 million Americans with significant morbidity 1

2. Lymphedema

• Distinguishing feature: brawny, non-pitting edema with thickened skin texture 3, 4
• Key history elements: prior pelvic surgery, inguinal lymphadenectomy, radiation therapy, trauma, or malignancy 3, 4
• Often a clinical diagnosis; lymphoscintigraphy can confirm if diagnosis is unclear 4
• Unlike venous edema, lymphedema typically does not improve significantly with overnight elevation 3

3. Post-Thrombotic Syndrome

• Develops in patients with prior DVT, even if previously treated 3
• Presents with chronic pain, swelling, skin changes, and potential ulceration 1
• Duplex ultrasound shows post-thrombotic changes including venous wall thickening and persistent obstruction 1

4. Venous Obstruction (Iliac or IVC)

• Critical to identify: May be caused by extrinsic compression from tumor, May-Thurner syndrome, or post-thrombotic scarring 1
• Standard duplex ultrasound may miss proximal obstruction 1
• If suspected based on clinical presentation or inadequate ultrasound visualization: proceed to CT venography or MR venography of abdomen/pelvis 1
• Intravascular ultrasound (IVUS) is the most sensitive modality for detecting iliac vein stenosis, identifying significant lesions missed in 26.3% of cases by venography alone 1

5. Soft Tissue Infection/Cellulitis with Underlying Pathology

• Consider if there is erythema, warmth, skin lesions, or recent trauma 1
• May coexist with venous insufficiency or lymphedema 1
• Plain radiographs should be obtained first to exclude foreign body or osteomyelitis if there is history of puncture wound or ulceration 1

6. Inflammatory Arthropathy (Less Likely for Isolated Limb Swelling)

• Rheumatoid arthritis, seronegative spondyloarthropathy, or crystalline arthropathy can cause limb swelling if multiple joints are involved 1
• Initial imaging: Plain radiographs of affected joints 1
• Typically presents with joint pain and stiffness rather than isolated limb edema 1

Diagnostic Algorithm

Step 1: Obtain duplex Doppler ultrasound of entire affected extremity to assess for DVT and venous insufficiency with reflux measurements 1

Step 2: If ultrasound shows venous insufficiency, this is your diagnosis; proceed to compression therapy 1

Step 3: If ultrasound is negative or shows proximal obstruction, obtain CT venography or MR venography of pelvis and affected extremity to evaluate for iliac vein or IVC pathology 1

Step 4: If imaging shows significant iliac stenosis (>50% area reduction), consider IVUS for definitive assessment and potential intervention planning 1

Step 5: If all venous imaging is negative and clinical features suggest lymphedema (non-pitting, brawny edema), diagnose clinically or confirm with lymphoscintigraphy 4

Common Pitfalls to Avoid

• Do not assume chronic presentation excludes DVT—chronic DVT and post-thrombotic syndrome are common causes of unilateral swelling 2, 3
• Do not rely solely on standard duplex ultrasound if obesity limits visualization or if proximal obstruction is suspected; proceed to cross-sectional imaging 1
• Do not overlook medication causes—calcium channel blockers, NSAIDs, and hormonal therapies commonly cause edema, though typically bilateral 4
• Do not miss May-Thurner syndrome in young women with left leg swelling—this anatomic variant causes left iliac vein compression and requires cross-sectional imaging for diagnosis 1