What's the differential diagnosis for sudden onset leg pain?

Differential Diagnosis for Sudden Onset Leg Pain

The differential diagnosis for sudden onset leg pain must immediately prioritize life- and limb-threatening vascular emergencies—specifically acute limb ischemia and deep vein thrombosis—before considering musculoskeletal or other causes. 1, 2

Life-Threatening Vascular Emergencies (Immediate Priority)

Acute Limb Ischemia (ALI)

• Classic presentation: sudden onset of the "6 Ps"—Pain, Pallor, Pulselessness, Poikilothermia (coldness), Paresthesias, and Paralysis 3, 4
• Pain is typically severe and the first prominent symptom, accompanied by a cold, pale extremity with diminished or absent pulses 2, 3
• Critical pitfall: Any delay beyond 4-6 hours dramatically increases risk of permanent tissue damage, limb loss, and mortality 2
• Most common etiologies are arterial embolism (often from atrial fibrillation) or acute thrombosis superimposed on chronic atherosclerotic disease 1
• Embolic occlusion presents more severely with sudden onset because there are no established collaterals, while thrombotic occlusion may have gradual onset with history of claudication 3

Deep Vein Thrombosis (DVT)

• Presents with deep tension, heaviness, swelling, and a "dead weight" feeling in the affected limb 5
• Pain typically affects the calf but may involve the sole, heel, thigh, groin, or pelvis 5
• Pain increases with standing and walking, with tenderness on palpation of venous tracts 5
• Critical distinction: DVT causes a warm, swollen leg versus the cold, pale leg of arterial ischemia 1, 5
• Can progress to phlegmasia cerulea dolens (blue leg) with severe, intolerable pain if untreated 5

Musculoskeletal Causes (After Excluding Vascular Emergency)

Muscle/Tendon Injuries

• Muscle contusions, strains (including "tennis leg"—gastrocnemius-soleus tear), or tendonitis present with localized pain related to specific movements 6, 7
• History of trauma or overuse is typically present 8, 7

Bone Stress Injuries

• Medial tibial stress syndrome and tibial stress fractures cause exertional pain that worsens with activity 8, 7
• Pain is typically gradual in onset rather than sudden, though acute fractures can occur 7

Ruptured Baker's Cyst (Pseudothrombophlebitis)

• Presents with acute calf pain and swelling that can closely mimic DVT 6, 9
• Often associated with knee pathology and may have palpable mass in popliteal fossa 9

Inflammatory/Infectious Causes

Cellulitis

• Presents with warmth, erythema, swelling, and pain in the affected area 6
• Systemic signs (fever, elevated white blood cell count) often present 6

Superficial Thrombophlebitis

• Moderate burning tension overlying thrombosed superficial vein, increased by palpation 5
• Visible or palpable cord along superficial venous system 6

Nerve Entrapment Syndromes

• Entrapment of common peroneal, superficial peroneal, or saphenous nerves causes pain with specific dermatomal distribution 7
• Typically associated with paresthesias and sensory changes rather than pure pain 7

Chronic Exertional Compartment Syndrome

• Pain occurs during exercise and resolves with rest, not typically "sudden onset" 8, 7
• Requires specific compartment pressure testing for diagnosis 7

Popliteal Artery Entrapment Syndrome

• Exertional leg pain in young athletes due to anatomic compression of popliteal artery 7
• Pain occurs with exercise, not at rest 7

Critical Clinical Algorithm

Step 1: Assess for vascular emergency immediately

• Check for the "6 Ps" of acute limb ischemia and measure ankle-brachial index if available 3, 4
• Assess for DVT signs: unilateral swelling, warmth, tenderness along venous tracts 1, 5

Step 2: If vascular emergency suspected

• For cold, pulseless leg: Start anticoagulation immediately and obtain CT angiography urgently (or proceed directly to catheter angiography if Rutherford Class IIb/III with motor weakness) 2, 4
• For warm, swollen leg: Obtain compression ultrasound for DVT evaluation 1

Step 3: If vascular emergency excluded

• Evaluate for musculoskeletal causes based on mechanism of injury, location of pain, and relationship to activity 6, 8
• Consider inflammatory/infectious causes if systemic signs present 6

Major pitfall: Clinical signs alone are unreliable—42% of patients would receive unnecessary anticoagulation if DVT were diagnosed on clinical grounds alone, yet missing these diagnoses has catastrophic consequences 6