What is the differential diagnosis for unilateral leg swelling?

Differential Diagnosis for Unilateral Leg Swelling

Deep vein thrombosis (DVT) is the most critical diagnosis to exclude first in any patient presenting with unilateral leg swelling, as it carries significant morbidity and mortality risk if untreated. 1

Primary Diagnostic Considerations

Deep Vein Thrombosis (Most Critical)

• Classic presentation includes unilateral extremity swelling, heaviness in the extremity distal to thrombosis, pain, and unexplained persistent calf cramping 1
• However, classic symptoms are not present in all cases—DVT may be asymptomatic or an incidental finding 1
• In the MASTER registry, the most common presenting symptoms were extremity edema (80%), pain (75%), and erythema (26%) 1
• Risk factors include indwelling venous devices (catheters, pacemakers), cancer, postoperative state, hypercoagulability, heart failure, advanced age, and trauma 1

Chronic Venous Insufficiency

• Results from venous hypertension and valve incompetence 2
• Typically presents with more gradual onset compared to acute DVT 2
• May have associated skin changes, varicosities, and history of previous DVT 2

Lymphedema

• Can be primary (congenital) or secondary (due to malignancy, surgery, radiation, or infection) 2, 3
• Lymphedema praecox presents in adolescence or early adulthood 3
• Distinguished by non-pitting edema in advanced stages and absence of venous Doppler abnormalities 2

Infectious/Inflammatory Causes

• Cellulitis presents with erythema, warmth, and tenderness 1, 3
• Must be differentiated from DVT, as both can present with unilateral red, warm, swollen leg 1
• Superficial thrombophlebitis causes local pain, induration, and palpable cord but rarely causes diffuse arm/leg swelling 1

Musculoskeletal/Traumatic Causes

• Trauma, ruptured Baker's cyst, compartment syndrome 2
• Charcot neuro-osteoarthropathy in diabetic patients with neuropathy presents with unilateral red, warm, swollen foot with intact skin 1
• Post-surgical complications including arteriovenous fistula formation 4

Extrinsic Compression

• Pelvic or abdominal masses compressing iliac or femoral veins 5
• Ganglion cysts causing venous compression (rare but recognized) 5
• Malignancy causing lymphatic or venous obstruction 1, 2

Systemic Causes (Usually Bilateral, But Can Present Unilaterally)

• Heart failure causing increased capillary hydrostatic pressure 1, 2
• Hypoproteinemia from liver or renal failure (decreased oncotic pressure) 1, 2
• Drug-induced edema (calcium channel blockers, NSAIDs, corticosteroids) 2

Other Considerations

• Lipedema (misnomer)—important differential, typically bilateral but asymmetric 2
• Idiopathic cyclic edema 2
• Reflex sympathetic dystrophy 1
• Allergic reactions causing increased capillary permeability 1

Critical Clinical Pitfall

In patients with diabetes and peripheral neuropathy presenting with unilateral red, warm, swollen foot with intact skin, always suspect active Charcot neuro-osteoarthropathy after excluding infection, gout, and DVT. 1 This condition, if left untreated, carries high risk of bone fractures, dislocations, deformity, ulceration, infection, and amputation. 1

Key Distinguishing Features

• Unilateral swelling indicates obstruction at the level of major veins (brachiocephalic, subclavian, axillary, iliac, or femoral) 1
• Bilateral edema should prompt investigation for systemic causes (cardiac, hepatic, renal, or drug-induced) before attributing to venous pathology 6
• Temperature asymmetry >2°C between limbs suggests active inflammatory process (DVT, infection, or Charcot arthropathy) 1
• Presence of indwelling catheters or recent surgery significantly increases DVT risk 1