What is the best course of treatment for a 64-year-old female patient with persistent left leg pain and swelling following a cortisone injection, with normal lab results and a negative Deep Vein Thrombosis (DVT) ultrasound?

Management of Persistent Leg Pain and Swelling Following Cortisone Injection

This patient requires immediate repeat complete duplex ultrasound imaging of the entire leg from groin to ankle, with specific attention to the iliac veins, given the persistent symptoms two months post-injection despite negative initial DVT workup. 1, 2

Immediate Diagnostic Workup

Repeat Ultrasound is Mandatory

• Obtain a comprehensive duplex ultrasound (CDUS) now, scanning from the inguinal ligament to ankle, including posterior tibial and peroneal veins in the calf, with compression and Doppler evaluation. 2, 3
• The initial negative ultrasound does not exclude DVT when symptoms persist or worsen—this is the exact clinical scenario where repeat imaging is mandated by guidelines. 1, 2
• Persistent unexplained bilateral leg swelling (even with unilateral predominance) after negative initial ultrasound is a specific indication for repeat imaging within 5-7 days of clinical decision, though given the 2-month duration here, imaging should be immediate. 1, 2

Expand Imaging if Standard Ultrasound is Negative

• If the repeat complete duplex ultrasound is negative but symptoms persist, image the iliac and pelvic veins with CT or MR venography. 4
• Extensive unexplained leg swelling with normal compression ultrasound suggests iliocaval DVT that may not be adequately visualized on standard ultrasound. 4, 2
• The American College of Chest Physicians specifically recommends iliac vein imaging when there is extensive unexplained leg swelling despite negative proximal or whole-leg ultrasound. 4

Consider Alternative Diagnoses

Post-Injection Vascular Complications

• Arterial thrombosis following intra-articular corticosteroid injection is a documented but rare complication, with symptoms developing within 24 hours of injection in reported cases. 5
• While this patient's symptom onset timing (same evening as injection) is consistent with this complication, the 2-month persistence suggests a different or evolving process. 5
• If ultrasound shows no venous pathology, consider arterial duplex and CT angiography to evaluate for arterial complications or post-traumatic arteriovenous fistula, which can present with chronic leg swelling. 6, 5

Non-Vascular Causes

• Ultrasound can identify Baker's cyst, lymphedema, or other "cystic" lesions causing leg swelling that mimic DVT. 2
• Chronic venous insufficiency is the most common cause of unilateral leg swelling and should be assessed during the ultrasound examination. 7

If Repeat Imaging Confirms DVT

Proximal DVT Management

• Initiate anticoagulation immediately with low-molecular-weight heparin or direct oral anticoagulant if proximal DVT is confirmed. 2
• For provoked DVT (potentially related to the injection), 3 months of anticoagulation is typically sufficient. 2

Isolated Distal DVT Management

• Assess severity of symptoms and risk factors for extension: positive D-dimer, extensive thrombosis, no reversible provoking factor, active cancer, history of VTE, or inpatient status. 2
• For severe symptoms (which this patient has given 2-month persistence), initiate anticoagulation rather than surveillance. 2
• For low-risk isolated calf DVT, serial ultrasound at 1 and 2 weeks is an alternative, but this patient's symptom severity argues against surveillance alone. 2

Referral Considerations

When to Refer to Vascular Surgery

• Refer immediately if arterial thrombosis or arteriovenous fistula is identified, as these require surgical intervention. 6, 5
• Refer to vascular surgery if iliocaval DVT is confirmed and symptoms are severe or refractory to anticoagulation. 4

When to Refer to Hematology

• Refer for thrombophilia workup if unprovoked DVT is confirmed, particularly given the temporal relationship to a minor procedure. 2
• Consider hematology consultation if DVT is confirmed to guide duration of anticoagulation and assess for underlying hypercoagulable state. 2

Critical Pitfalls to Avoid

• Do not assume the initial negative ultrasound definitively excludes DVT—persistent symptoms mandate repeat imaging regardless of initial results. 1, 2
• Do not accept limited proximal-only ultrasound—ensure complete leg evaluation from groin to ankle given the symptom severity and duration. 2, 3
• Do not miss iliocaval DVT by failing to image above the inguinal ligament when standard leg ultrasound is negative but symptoms persist. 4
• Do not overlook superficial thrombophlebitis, which can present with pain and swelling and may require treatment. 2
• Do not delay imaging—2 months of persistent symptoms following a procedure is not normal and requires definitive diagnosis now. 1, 2