What is a good differential diagnosis for calf pain?

Differential Diagnosis for Calf Pain

The differential diagnosis for calf pain must prioritize life-threatening vascular causes first—specifically deep vein thrombosis and peripheral arterial disease—followed by musculoskeletal, neurologic, and inflammatory etiologies.

Life-Threatening Vascular Causes (Exclude First)

Deep Vein Thrombosis (DVT)

• Entire leg swelling with tight, bursting pain that worsens with activity and persists at rest is the classic presentation 1
• Calf DVT is one of the most frequent locations for DVT, both isolated and in combination with proximal disease 2
• Localized calf tenderness is more frequently associated with calf muscle venous thrombosis (CMVT), and untreated cases may propagate proximally leading to pulmonary embolism 2
• Compression ultrasound has 97.8% specificity for calf DVT and should be performed when clinical suspicion exists 1
• A single complete compression ultrasound carries only 0.57% risk of missed venous thromboembolic disease at 3 months 1

Peripheral Arterial Disease (PAD)

• Aching, burning, or cramping pain in the calf that occurs with walking and resolves within 10 minutes of rest defines claudication 1
• The anatomic site of stenosis correlates with symptoms: femoral-popliteal disease typically causes calf pain 1
• Distance-dependent symptoms that predictably resolve with rest distinguish PAD from other causes 1
• Risk factors include age ≥65 years, age 50-64 with diabetes/smoking/dyslipidemia/hypertension, or known atherosclerotic disease 1
• Physical examination should document femoral and popliteal pulses, vascular bruits, and signs of chronic ischemia 1
• Calf pain while walking in middle-aged individuals is an independent predictor of ischemic cerebrovascular disease (odds ratio 1.9), highlighting the systemic nature of vascular disease 3

Musculoskeletal Causes

Muscle and Tendon Injuries

• Muscle tears, tendon ruptures (particularly gastrocnemius and Achilles), and muscle strains are common musculoskeletal causes identified on ultrasound 4, 5
• Acute onset with specific trauma or eccentric loading suggests muscle or tendon injury 6
• Point tenderness localizes to the specific muscle belly or tendon insertion 6

Baker's Cyst (Popliteal Cyst)

• Baker's cyst rupture can mimic DVT with acute calf pain and swelling 4, 5
• Ultrasound confidently differentiates ruptured Baker's cyst from DVT 4
• History may reveal known knee pathology or osteoarthritis 5

Stress Fractures

• Progressively worsening pain following increased activity or change to harder walking surface suggests stress fracture 7
• Tibial and fibular stress fractures are among the most common overuse leg injuries 6
• Pain on compression of the affected bone is highly suspicious 7
• Symptoms often precede radiographic findings; technetium bone scanning or MRI required for early diagnosis 7

Chronic Exertional Compartment Syndrome

• Pain during exercise that resolves with rest, but requires longer rest periods than PAD (typically 15-30 minutes) 6
• Tightness and pressure sensation in specific muscle compartments 6
• Compartment pressure testing confirms diagnosis 6

Medial Tibial Stress Syndrome (Shin Splints)

• Pain along the posteromedial tibial border, typically in the distal two-thirds 6
• Associated with running or repetitive impact activities 6
• Tenderness spans several centimeters along the tibial border, unlike the focal tenderness of stress fracture 6

Inflammatory and Infectious Causes

Soft Tissue Infection

• Cellulitis presents with warmth, erythema, and systemic symptoms including fever 4, 5
• Ultrasound can identify abscess formation or necrotizing fasciitis 4
• Immediate subspecialist referral required for suspected infection 8

Inflammatory Conditions

• Bilateral calf symptoms raise concern for systemic inflammatory arthritides 8
• Inflammatory muscle diseases can cause diffuse calf pain 1
• Associated joint pain or known inflammatory conditions support this diagnosis 7

Neurologic Causes

Lumbar Radiculopathy

• Sharp lancinating pain radiating down the leg from the lumbar spine 1
• Induced by sitting, standing, or walking; often present at rest 1
• Improved by position change; history of back problems supports diagnosis 1
• Must screen lumbar spine as competing source before attributing pain solely to calf pathology 9

Peripheral Neuropathy

• Burning, tingling, or numbness suggests neurologic etiology 7, 8
• Consider diabetic neuropathy in appropriate patient populations 8
• Immediate subspecialist referral for neurologic symptoms including electromyography and nerve conduction studies 7

Rare but Critical Causes

Tumors

• Insidious onset, night pain, constitutional symptoms, and inability to bear weight suggest malignancy 9
• Both benign and malignant tumors are rare causes requiring appropriate referral 7

Vascular Compromise Beyond PAD

• Venous insufficiency can cause chronic calf discomfort 1
• Acute arterial occlusion presents with severe pain, pallor, pulselessness, and paresthesias 7

Diagnostic Algorithm

Initial Assessment

1. Rule out DVT first using compression ultrasound if swelling, tenderness, or risk factors present 1
2. Assess for PAD with pulse examination, ankle-brachial index if claudication symptoms present 1
3. Obtain plain radiographs to exclude fracture, tumor, or bone pathology 7

Advanced Imaging

• MRI without contrast or technetium bone scanning if radiographs negative but pain persists >1 week 7
• Ultrasound provides detailed anatomical information and can confidently diagnose musculoskeletal causes when DVT excluded 4, 5

Common Pitfalls

• Failing to exclude DVT before attributing symptoms to musculoskeletal causes—always maintain high index of suspicion given potentially fatal complications 1, 2
• Overlooking stress fractures—radiographs may initially be negative while symptoms are present 7
• Missing lumbar radiculopathy—always consider referred pain from spine 1, 9
• Underestimating significance of bilateral symptoms—should prompt evaluation for systemic inflammatory or metabolic causes 8
• Dismissing claudication in younger patients—PAD can occur in patients 50-64 with risk factors 1