Does Imuran Lessen the Risk of CVST in Behçet's Disease?
Azathioprine (Imuran) does not directly prevent cerebral venous sinus thrombosis (CVST) in Behçet's disease, but it reduces the risk of venous thrombotic events including thrombophlebitis and may lower the risk of recurrent deep venous thrombosis when used as part of long-term immunosuppressive therapy. 1
Evidence for Azathioprine's Effect on Venous Thrombosis
The evidence supporting azathioprine's role in reducing thrombotic risk comes from randomized controlled trial data showing:
In the pivotal azathioprine trial, the number of patients who developed thrombophlebitis was significantly less in the azathioprine arm (NNT = 8), demonstrating a protective effect against peripheral venous thrombosis. 1
Retrospective data indicate that the risk for recurrent deep venous thrombosis and post-thrombotic syndrome was significantly lower in patients receiving immunosuppressives compared to those who were not. 1
The mechanism is through suppression of vessel wall inflammation, which is the primary pathology leading to venous thrombosis in Behçet's disease, rather than hypercoagulability. 1
Treatment Approach for CVST in Behçet's Disease
When CVST occurs in Behçet's disease, the treatment paradigm differs from prevention:
The first episode of cerebral venous thrombosis should be treated with high-dose glucocorticoids followed by tapering, with anticoagulants added only for a short duration. 1
High-dose intravenous methylprednisolone (1 g/day for 3-7 days) followed by oral prednisolone tapering is the primary acute treatment. 1, 2
For long-term management after CVST, azathioprine (2.5 mg/kg/day) is recommended as maintenance therapy to prevent recurrences, as CVST in Behçet's disease may recur without adequate immunosuppression. 3
Important Clinical Distinctions
The evidence reveals critical nuances about CVST in Behçet's disease:
CVST in Behçet's disease is considered an extension of vascular involvement rather than parenchymal neurological disease, requiring screening for vascular disease at extracranial sites. 1
The prognosis of CVST due to Behçet's disease is more favorable than CVST from other causes, with less tendency for venous infarcts and seizures. 3
Anticoagulation can be safely stopped during follow-up when patients are on optimal Behçet's disease treatment (corticosteroids with immunosuppressants like azathioprine), with only one relapse observed in six patients treated with steroids plus immunosuppressants in one series. 4
Critical Contraindications
Cyclosporine A should be avoided in patients with any central nervous system involvement, including CVST, due to significant neurotoxicity risk, despite its effectiveness for other Behçet's manifestations. 1, 2, 5
Long-term oral anticoagulation is unnecessary for CVST in Behçet's disease, unlike CVST from other etiologies. 3
Practical Algorithm for Prevention
For patients at high risk of vascular complications:
Young males with early disease onset should be considered for prophylactic azathioprine 2.5 mg/kg/day, as they carry higher risk for severe vascular disease including thrombotic events. 1, 6, 5
For patients with acute deep vein thrombosis, azathioprine 2.5 mg/kg/day is recommended as part of the immunosuppressive regimen. 1
More potent immunosuppression with cyclophosphamide may be preferred for thrombosis of superior vena cava or Budd-Chiari syndrome. 1
Strength of Evidence
The evidence base has important limitations:
There are no randomized controlled trials directly addressing CVST prevention or treatment in Behçet's disease; recommendations are based on Category III evidence (observational studies) with Strength of Recommendation C. 1
The azathioprine data showing reduced thrombophlebitis comes from a randomized trial for ocular disease, representing extrapolated evidence for vascular protection. 1
The incidence of CVST in Behçet's disease is 3 per 1,000 person-years overall, and 15.1 per 1,000 person-years among patients with neurologic involvement. 7