Differential Diagnosis for Unilateral Leg Swelling and Pain

Single Most Likely Diagnosis

• Deep Vein Thrombosis (DVT): This is the most common cause of unilateral leg swelling and pain in adults, especially in those with risk factors such as recent surgery, immobilization, cancer, or genetic predispositions to clotting.

Other Likely Diagnoses

• Cellulitis: A bacterial infection of the skin and subcutaneous tissue, which can cause swelling, redness, warmth, and pain in one leg.
• Muscle Strain or Tear: Direct injury to the muscles of the leg can lead to swelling and pain, especially if the injury is significant.
• Lymphedema: Swelling caused by impaired lymph drainage, which can be primary (genetic) or secondary (due to surgery, infection, or other causes).
• Varicose Veins: While often asymptomatic, large varicose veins can cause leg swelling and pain, especially if there is associated venous insufficiency.

Do Not Miss Diagnoses

• Compartment Syndrome: A medical emergency where increased pressure within a muscle compartment leads to muscle and nerve damage. It presents with severe pain, swelling, and sometimes paresthesia.
• Arterial Occlusion: Sudden blockage of an artery supplying the leg can cause severe pain, swelling, pallor, pulselessness, poikilothermia, paresthesia, and paralysis. It is a medical emergency.
• Osteomyelitis: Bone infection, which can cause localized pain, swelling, and sometimes systemic symptoms like fever.
• Necrotizing Fasciitis: A severe infection of the fascia, which can rapidly progress and is life-threatening if not promptly treated.

Rare Diagnoses

• Lipedema: A chronic condition characterized by the abnormal growth of fat cells in the legs, leading to swelling and pain.
• Erythromelalgia: A disorder that causes burning pain, heat, and redness in the hands and feet, which can sometimes present unilaterally.
• Chronic Venous Insufficiency: While not rare, its presentation can sometimes be atypical, leading to a delay in diagnosis. It causes swelling, skin changes, and sometimes pain due to the veins' inability to send blood back to the heart properly.
• Pheochromocytoma-induced Hypertension: Though extremely rare, pheochromocytoma (a tumor of the adrenal gland) can cause episodic hypertension, which might lead to vascular complications including unilateral leg swelling and pain.