What could be causing joint pain and numbness in the hands and feet that improves throughout the day in a 54-year-old female with a history of deep vein thrombosis (DVT) and superficial vein thrombosis, long-standing back pain, and well-controlled hypertension on Amlodipine (calcium channel blocker) 10mg daily?

Differential Diagnosis: Behçet's Syndrome

This patient's constellation of joint pain, numbness in hands and feet that improves throughout the day, recurrent thromboses (both deep and superficial), and long-standing back pain is highly suggestive of Behçet's syndrome, a systemic vasculitis that causes venous thrombosis through inflammatory vessel wall damage rather than hypercoagulability. 1

Key Clinical Features Supporting Behçet's Syndrome

Thrombotic Pattern

• Behçet's syndrome characteristically causes both deep vein thrombosis and superficial vein thrombosis through inflammatory vessel wall damage, not hypercoagulability 1
• The sequential occurrence of DVT followed by superficial vein thrombosis is a classic pattern in Behçet's syndrome, where venous involvement is more common than arterial 1
• Post-thrombotic syndrome is frequent in Behçet's patients, especially with recurrent episodes, and may result in leg symptoms that are difficult to treat 1

Joint and Neurological Symptoms

• Joint pain is a common manifestation of Behçet's syndrome, typically presenting as symmetric polyarthritis 1
• Morning stiffness that improves as the day progresses (lasting 1 hour or longer) is characteristic of inflammatory arthritis, which occurs in Behçet's syndrome 1
• Numbness in hands and feet that improves throughout the day may represent paresthesias from peripheral neuropathy or vascular involvement affecting nerve perfusion 1

Back Pain Considerations

• Long-standing back pain in the context of inflammatory arthritis may represent sacroiliitis or spondyloarthropathy, which can occur in Behçet's syndrome 1
• Alternatively, lumbar spinal stenosis could cause pseudoclaudication with leg numbness, though this typically worsens (not improves) with activity 1

Critical Diagnostic Workup Required

Immediate Vascular Assessment

• Obtain compression ultrasound of bilateral lower extremities to assess for active DVT, extent of superficial vein thrombosis, and post-thrombotic changes 1, 2, 3
• Document specific vein measurements, reflux duration, and presence of venous obstruction 1
• Screen for pulmonary embolism if any respiratory symptoms present, as 8% of patients with superficial vein thrombosis develop thromboembolic complications within 3 months 2, 4

Behçet's Syndrome Evaluation

• Assess for oral and genital ulcers (may be historical), uveitis, skin lesions (erythema nodosum, papulopustular lesions), and pathergy test 1
• Obtain inflammatory markers (ESR, CRP) to assess disease activity 1
• Consider HLA-B51 testing, though not diagnostic, as it is associated with more severe disease 1
• Rule out other causes of recurrent thrombosis: antiphospholipid antibodies, factor V Leiden, prothrombin gene mutation, protein C/S deficiency 3

Rheumatologic Assessment

• Rheumatoid factor and anti-CCP antibodies to evaluate for rheumatoid arthritis 1
• ANA, anti-dsDNA for systemic lupus erythematosus 1
• Imaging of sacroiliac joints if inflammatory back pain suspected 1

Treatment Algorithm Based on Diagnosis

If Behçet's Syndrome with Acute DVT

For acute deep vein thrombosis in Behçet's syndrome, glucocorticoids and immunosuppressives such as azathioprine, cyclophosphamide, or cyclosporine-A are recommended 1

• High-dose glucocorticoids (typically three successive intravenous methylprednisolone pulses followed by oral prednisolone 1 mg/kg/day) 1
• Add azathioprine as first-line immunosuppressive for long-term management 1
• Anticoagulants may be added, but the primary treatment is immunosuppression, as thrombosis results from vessel wall inflammation rather than hypercoagulability 1

If Refractory Venous Thrombosis

• Monoclonal anti-TNF antibodies (infliximab, adalimumab) should be considered in refractory patients 1
• Anticoagulants may be added provided bleeding risk is low and pulmonary artery aneurysms are ruled out 1

If Superficial Vein Thrombosis

For superficial vein thrombosis ≥5 cm in length, fondaparinux 2.5 mg subcutaneously daily for 45 days reduces symptomatic thromboembolic complications by 85% 5, 2, 4

• Alternative: rivaroxaban 10 mg orally daily for 45 days 5
• If SVT is within 3 cm of saphenofemoral junction, treat as DVT-equivalent with therapeutic anticoagulation for at least 3 months 5
• In Behçet's syndrome specifically, immunosuppression should be added to anticoagulation 1

Adjunctive Management

• Compression stockings (20-30 mmHg) for post-thrombotic syndrome symptoms 1, 6
• NSAIDs for pain control (if no contraindications) 6, 4
• Early ambulation rather than bed rest to reduce DVT risk 5, 6

Critical Pitfalls to Avoid

Do Not Treat as Simple Thrombophilia

• Failing to recognize Behçet's syndrome leads to inadequate treatment with anticoagulation alone, resulting in recurrent thromboses and post-thrombotic syndrome 1
• Standard anticoagulation without immunosuppression does not address the underlying inflammatory vessel wall pathology 1

Do Not Attribute All Symptoms to Amlodipine

• While amlodipine can cause peripheral edema (10.8% at 10 mg dose), it does not cause recurrent thromboses or inflammatory joint pain 7
• Numbness and paresthesias are not typical amlodipine side effects (hypoesthesia and paresthesia occur in <1% of patients) 7

Do Not Delay Rheumatology Referral

• Behçet's syndrome requires prompt immunosuppressive therapy to prevent serious complications including blindness from uveitis, neurological involvement, and arterial aneurysms 1
• Mortality is high in untreated vascular Behçet's disease, particularly with pulmonary artery involvement 1

Alternative Diagnoses to Consider

If Behçet's Syndrome Ruled Out

• Antiphospholipid syndrome: recurrent thromboses with positive antiphospholipid antibodies, may cause joint pain and neurological symptoms 3
• Rheumatoid arthritis: symmetric polyarthritis with morning stiffness, but does not typically cause recurrent thromboses 1
• Peripheral arterial disease with venous insufficiency: claudication symptoms, but numbness typically worsens (not improves) with activity 1
• Post-thrombotic syndrome alone: explains leg symptoms after DVT, but does not explain joint pain or recurrent thromboses 1