What is the appropriate diagnosis and management for a patient presenting with unilateral leg swelling and redness?

Unilateral Leg Swelling with Redness: Diagnosis and Management

Immediate Action Required

Exclude deep vein thrombosis (DVT) first—this is the most critical diagnosis because untreated DVT carries 25-30% mortality risk from pulmonary embolism. 1, 2

Step 1: Assess Pretest Probability and Proceed to Imaging

• Calculate Wells score or similar clinical prediction rule based on risk factors: recent immobility, surgery, cancer, prior DVT, pregnancy, oral contraceptive use, or indwelling venous devices 2, 3
• For moderate-to-high pretest probability: proceed directly to proximal compression ultrasound (CUS) or whole-leg ultrasound WITHOUT D-dimer testing 2, 3
• If ultrasound is positive, initiate anticoagulation immediately without confirmatory venography 1, 2
• If proximal CUS is negative but suspicion remains high, repeat CUS in 1 week or perform whole-leg ultrasound 2

Critical Pitfall: Never delay anticoagulation in moderate-to-high probability DVT patients while awaiting imaging—this increases risk of pulmonary embolism and mortality 2

Step 2: Exclude Infection as Second Priority

After DVT is ruled out, assess for cellulitis or soft tissue infection:

• Infection requires at least two of the following: local swelling/induration, erythema, local tenderness/pain, local warmth, or purulent discharge 1, 2
• Important caveat: Fever, elevated white blood cell count, or elevated C-reactive protein may be absent in up to half of patients with significant infections 1
• Initiate systemic antibiotics promptly if infection is confirmed 2
• Consider ultrasound to identify abscess formation requiring drainage 2

Step 3: Obtain Plain Radiographs in All Cases

• Three-view radiographs (AP, oblique, lateral) of the affected leg to evaluate for fractures, dislocations, bone destruction, or foreign bodies 1

Special Consideration: Diabetic Patients with Neuropathy

In diabetic patients with neuropathy presenting with unilateral red, warm, swollen foot with intact skin, always suspect active Charcot neuro-osteoarthropathy (CNO) after excluding infection, gout, and DVT. 4, 1, 2

Diagnostic Approach for Suspected CNO:

• Use infrared thermometry to measure skin temperature difference between both feet 4
• Temperature difference ≥2°C between affected and unaffected foot strongly suggests active CNO 4, 2
• The site of maximum skin temperature difference correlates with radiographic imaging at diagnosis in 92% of cases 4
• Initiate knee-high immobilization/offloading immediately while awaiting diagnostic confirmation—delayed treatment leads to catastrophic consequences including fractures, deformity, ulceration, and amputation 4, 2
• Plain radiographs may be normal in early stages; MRI is preferred advanced imaging showing bone marrow edema 2

Critical Pitfall: Never assume absence of pain rules out serious pathology in diabetic patients with neuropathy—pain may be minimal or absent due to sensory neuropathy 1

Additional Differential Diagnoses to Consider

Chronic Venous Insufficiency:

• Differentiated from arterial disease by presence of distal pulses 2
• Assess for venous reflux and deep venous system using duplex ultrasound 3
• Compression therapy with minimum pressure of 20-30 mm Hg is recommended 3

Less Common Causes:

• Ruptured Baker's cyst: Can mimic DVT with acute calf pain and swelling; ultrasound readily identifies this diagnosis 2
• Lymphedema: Usually bilateral, but unilateral presentation can occur secondary to radiation, surgery, tumor compression, or early filariasis 5, 6
• Lipedema: Characterized by subcutaneous adipose tissue deposition, diagnosed in approximately one-fifth of cases in specialized clinics 7

Systemic Causes:

• Heart failure causing increased capillary hydrostatic pressure 3
• Hypoproteinemia from liver or renal failure causing decreased oncotic pressure 3, 8

Key Distinguishing Features

• Unilateral swelling indicates obstruction at the level of major veins 3
• Temperature asymmetry >2°C between limbs suggests active inflammatory process (DVT, infection, or Charcot arthropathy) 4, 3
• DVT presents with warm, swollen leg versus acute limb ischemia with cold, pale leg 2

When to Refer Urgently

• Suspected DVT with positive ultrasound: immediate anticoagulation and possible hospital admission if hemodynamically unstable 1
• Suspected active Charcot neuro-osteoarthropathy: immediate subspecialist referral 1