What are the possible causes of pain from the knee to the ankle that worsens when lying down, without any history of injury?

Causes of Pain from Knee to Ankle Worse When Laying Down (No Injury)

Most Likely Diagnosis: Peripheral Arterial Disease (PAD)

Pain from knee to ankle that worsens when lying down without injury history is most consistent with peripheral arterial disease, particularly when it represents rest pain—a hallmark of critical limb ischemia. 1

Understanding the Mechanism

• Rest pain occurs when lying down because gravity no longer assists blood flow to the lower leg, and the reduced perfusion pressure cannot meet even minimal metabolic demands of the tissues 1
• Occlusive disease in the femoral and popliteal arteries typically produces calf pain, while tibial artery disease may cause calf pain or foot pain and numbness 1
• Critical limb ischemia is defined as limb pain that occurs at rest, representing advanced PAD 1

Key Clinical Features to Assess

History Elements

• Assess for atherosclerotic risk factors: smoking, diabetes, hypertension, hyperlipidemia, and family history of atherosclerotic disease 1
• Pain characteristics: Does the patient get relief by dangling the leg over the side of the bed or standing up? This suggests arterial insufficiency 1
• Claudication symptoms: Does walking cause pain that resolves with rest? This indicates earlier-stage PAD 1

Physical Examination Findings

• Check for diminished or absent pulses in the femoral, popliteal, posterior tibial, and dorsalis pedis arteries 1
• Listen for femoral bruits, which indicate turbulence from focal stenoses and suggest systemic atherosclerosis 1
• Examine for skin changes: pallor, coolness, hair loss, or ulcerations that suggest chronic ischemia 1

Alternative Diagnoses to Consider

Venous Obstruction

• Severe venous obstructive disease can cause leg pain that worsens with dependency, though this typically improves (not worsens) with leg elevation 1

Chronic Compartment Syndrome

• This causes exertional leg pain but typically improves with rest and lying down, making it less likely in this scenario 1

Lumbar Spinal Stenosis (Neurogenic Claudication)

• Pain typically improves with sitting or leaning forward (flexion-based relief) and worsens with standing or walking 1
• Unlike vascular claudication, neurogenic pain may not have a consistent distance threshold and can persist after stopping activity 1
• This is less likely if pain specifically worsens when lying flat 1

Inflammatory Muscle Disease

• Consider if there are bilateral symptoms, pain in other joints, or known inflammatory conditions 2
• This would not typically worsen specifically when lying down 2

Diagnostic Approach

Initial Assessment

• Measure ankle-brachial index (ABI): An ABI <0.4 in a non-diabetic individual suggests critical limb ischemia and high risk for amputation 1
• Obtain plain radiographs of the affected area to exclude fracture, tumor, or other bony pathology 1

If Initial Workup is Negative

• Consider MRI without contrast if symptoms persist and radiographs are normal, to evaluate for osteonecrosis, stress fractures, or soft tissue pathology 1
• Vascular studies including arterial duplex ultrasound or CT/MR angiography if PAD is suspected clinically 1

Critical Red Flags Requiring Urgent Evaluation

• Patients with diabetes and lower extremity PAD who develop acute limb symptoms represent vascular emergencies and should be assessed immediately by a vascular specialist 1
• Skin breakdown, ulcerations, or signs of infection in the setting of PAD require prompt initiation of systemic antibiotics and vascular surgery consultation 1
• Rest pain with ABI <0.4 indicates critical limb ischemia requiring expedited vascular evaluation to prevent amputation 1

Common Pitfalls to Avoid

• Do not dismiss nocturnal leg pain as "growing pains" or benign muscle cramps without assessing vascular status, especially in patients with atherosclerotic risk factors 1
• Avoid attributing all leg pain to musculoskeletal causes when there is no history of injury—always consider vascular and neurologic etiologies 1, 2
• Do not overlook bilateral disease: PAD can be bilateral even when symptoms are predominantly unilateral 1

Management Algorithm

If PAD is Confirmed

• Immediate vascular surgery referral for patients with critical limb ischemia (rest pain, ABI <0.4) 1
• Risk factor modification: smoking cessation, diabetes control, lipid management, blood pressure control 1
• Antiplatelet therapy and statin therapy as appropriate for atherosclerotic disease 1

If Vascular Workup is Normal

• Reassess for neurogenic causes: Consider MRI of lumbar spine if spinal stenosis is suspected 1
• Evaluate for chronic exertional compartment syndrome if symptoms are activity-related, though this typically improves with rest 3
• Consider referral to neurology if burning or tingling suggests peripheral neuropathy 2