Major Vessel Involvement in Behçet's Disease: An Update
Major Vessel Involvement in Behçet's Disease: An Update
Superficial venous thrombosis (SVT) should raise the suspicion for Behçet's disease in candidate patients, especially when it is migratory or recurrent. In an analysis of 2319 patients followed in a dermatology department in Istanbul, the presence of vascular lesions was 14.3% with superficial thrombophlebitis found to be the dominant lesion in 53%. Thrombosis of superficial veins may occur following venipuncture and has been reported at sites of heparin infusions. SVT should be considered as a risk factor for future vascular events and treated from this perspective. It is associated with deep venous thrombosis (DVT) and both conditions are associated with caval thrombosis as well as for arterial disease.
DVT occurs primarily in the lower extremities, but involvement is possible at any site and may be extensive without peripheral venous involvement. DVT of the legs make up 70% of all vascular manifestations and is the first vascular event in 78% of patients. Pulmonary artery involvement, in the low-pressure lung vessels that are much like veins, usually follows thrombosis elsewhere. Arterial disease is a later complication, found to occur after a median of 7 years.
Findings of chronic venous insufficiency in the lower extremities are common in Behçet's disease patients from areas of high prevalence (Fig. 2). Stasis ulceration should be differentiated from vasculitic lesions and pyoderma gangrenosum.
(Enlarge Image)
Figure 2.
Chronic venous insufficiency with ulceration in a Behçet patient
Behçet's disease is a common cause of vena cava syndromes in areas where the disease is prevalent. Thrombosis of the vena cava may begin in proximal large veins or in the cava itself. Radiological studies are necessary to appreciate contributing causes of thrombosis in atypical cases, including that due to mediastinal fibrosis or vasculitic thickening of the vessel wall without thrombosis. With adequate collateral vessels, patients may tolerate chronic caval occlusion for many years, but deaths have been reported as a result of extensive thrombosis, treatment, hemoptysis, or other vascular causes including, very rarely, pulmonary embolus.
Extension of inferior vena cava clot to the hepatic vein ostia may be the mechanism for Budd–Chiari syndrome in patients with Behçet's disease. In a recent retrospective survey from Turkey, 12 of 22 patients with Budd–Chiari syndrome had inferior vena cava thrombosis at initial presentation and 19 of them had vena caval disease in their disease course. Patients present with right upper quadrant pain, hepatosplenomegaly, and ascites. The prognosis of hepatic vein thrombosis is poor with a 1-year survival of about 50%. About 1/3 of these patients follow an acute course, often leading to death from hepatic failure within weeks. Spontaneous improvement occurs in some patients, but most remain at risk for slowly progressive liver failure, elevated portal pressure, and esophageal varices.
Behçet's disease patients may have portal vein thrombosis, resulting in cavernous transformation. Patients present with splenomegaly, but hepatomegaly and ascites are found in patients with coexisting Budd–Chiari syndrome and those with inferior vena cava involvement have lower extremity edema. An obstructive pattern of liver enzymes may result from the compression of the biliary tree by the enlarged collaterals in portal tract or as a result of co-existing hepatic vein thrombosis.
Right ventricular thrombi are found in patients with vasculo-Behçet, often associated with pulmonary aneurysms thus complicating anticoagulant treatment. Endomyocardial fibrosis has been reported rarely in Behçet's disease, but should be considered in patients with a cardiac mass.
Cerebral venous thrombosis (CVT) results in signs and symptoms of increased intracranial pressure. MRI and venous magnetic resonance angiography are the diagnostic imaging procedures of choice. Other vascular manifestations of Behçet's disease, particularly venous thromboses, are often present in Behçet's disease patients with CVT, suggesting common pathogenic mechanisms. Comparing 36 Behçet's disease patients with CVT with 32 patients with CVT of other causes, Behçet's disease patients were younger (median age of 26 years), more likely to be men and present with subacute or chronic symptoms. Venous infarcts were infrequent. CVT was recognized in 7.8% of a large cohort of Behçet's disease patients in France. Visual loss due to optic atrophy complicated the disorder in 15% of affected patients, associated with the presence of concurrent prothrombotic risk factors.
For the management of acute deep vein thrombosis in Behçet's disease, immunosuppressive agents such as corticosteroids and azathioprine are recommended. Monthly pulse cyclophosphamide should be considered for thrombosis of the superior vena cava or Budd–Chiari syndrome. These recommendations are based on the belief that the cause of clot is inflammation of the vascular wall. Support for the value of anticoagulants is lacking and progression or recurrence of venous thrombosis despite standard anticoagulation is frequently recognized. Anticoagulation is not recommended in the EULAR guidelines. The conspicuous rarity of pulmonary emboli in Behçet's disease with venous thrombosis has long been noted, attributed to adherent clot formation on the inflamed vessel wall. Ahn et al. from Korea reported the results of a retrospective study comparing the efficacy of immunosuppressive agents with and without anticoagulants in the treatment of venous thrombosis in Behçet's disease. There was no difference in the recurrence rate in these two groups. Three of four patients treated with anticoagulants alone experienced a recurrence. The use of anticoagulants for DVT (in addition to immunosuppression) differs in various centers. Anticoagulants were used in 90% of patients treated for thrombosis prior to the diagnosis of Behçet's disease, with a low risk of bleeding complications. In Behçet's disease cases with coexisting prothrombotic conditions, individualization of treatment may require anticoagulation.
Thrombus in the cardiac chambers has been treated successfully with corticosteroids and cyclophosphamide, often with anticoagulants.
Thrombolytic therapy has been used in large vessel thrombosis syndromes with mixed results but may be a better option if used early in acute cases. Infliximab has been used in the treatment of three patients with Budd–Chiari syndrome, two with advanced disease, without success. Portocaval shunting can be considered in Budd–Chiari syndrome if the inferior vena cava is patent.
There is no consensus regarding the treatment of CVT in Behçet's disease. Anticoagulants are used in some centers with a low risk of hemorrhagic complications. Most patients also received corticosteroids and immunosuppressives, but these agents did not improve the outcome or prevent thrombotic relapse. In other centers anticoagulants are not routinely used but immunosuppressive drugs are employed as in parenchymal CNS disease or other vascular complications. The EULAR recommendation for the treatment of dural sinus thrombosis is with brief courses of corticosteroids.
Venous Occlusions
Superficial venous thrombosis (SVT) should raise the suspicion for Behçet's disease in candidate patients, especially when it is migratory or recurrent. In an analysis of 2319 patients followed in a dermatology department in Istanbul, the presence of vascular lesions was 14.3% with superficial thrombophlebitis found to be the dominant lesion in 53%. Thrombosis of superficial veins may occur following venipuncture and has been reported at sites of heparin infusions. SVT should be considered as a risk factor for future vascular events and treated from this perspective. It is associated with deep venous thrombosis (DVT) and both conditions are associated with caval thrombosis as well as for arterial disease.
DVT occurs primarily in the lower extremities, but involvement is possible at any site and may be extensive without peripheral venous involvement. DVT of the legs make up 70% of all vascular manifestations and is the first vascular event in 78% of patients. Pulmonary artery involvement, in the low-pressure lung vessels that are much like veins, usually follows thrombosis elsewhere. Arterial disease is a later complication, found to occur after a median of 7 years.
Findings of chronic venous insufficiency in the lower extremities are common in Behçet's disease patients from areas of high prevalence (Fig. 2). Stasis ulceration should be differentiated from vasculitic lesions and pyoderma gangrenosum.
(Enlarge Image)
Figure 2.
Chronic venous insufficiency with ulceration in a Behçet patient
Behçet's disease is a common cause of vena cava syndromes in areas where the disease is prevalent. Thrombosis of the vena cava may begin in proximal large veins or in the cava itself. Radiological studies are necessary to appreciate contributing causes of thrombosis in atypical cases, including that due to mediastinal fibrosis or vasculitic thickening of the vessel wall without thrombosis. With adequate collateral vessels, patients may tolerate chronic caval occlusion for many years, but deaths have been reported as a result of extensive thrombosis, treatment, hemoptysis, or other vascular causes including, very rarely, pulmonary embolus.
Extension of inferior vena cava clot to the hepatic vein ostia may be the mechanism for Budd–Chiari syndrome in patients with Behçet's disease. In a recent retrospective survey from Turkey, 12 of 22 patients with Budd–Chiari syndrome had inferior vena cava thrombosis at initial presentation and 19 of them had vena caval disease in their disease course. Patients present with right upper quadrant pain, hepatosplenomegaly, and ascites. The prognosis of hepatic vein thrombosis is poor with a 1-year survival of about 50%. About 1/3 of these patients follow an acute course, often leading to death from hepatic failure within weeks. Spontaneous improvement occurs in some patients, but most remain at risk for slowly progressive liver failure, elevated portal pressure, and esophageal varices.
Behçet's disease patients may have portal vein thrombosis, resulting in cavernous transformation. Patients present with splenomegaly, but hepatomegaly and ascites are found in patients with coexisting Budd–Chiari syndrome and those with inferior vena cava involvement have lower extremity edema. An obstructive pattern of liver enzymes may result from the compression of the biliary tree by the enlarged collaterals in portal tract or as a result of co-existing hepatic vein thrombosis.
Right ventricular thrombi are found in patients with vasculo-Behçet, often associated with pulmonary aneurysms thus complicating anticoagulant treatment. Endomyocardial fibrosis has been reported rarely in Behçet's disease, but should be considered in patients with a cardiac mass.
Cerebral venous thrombosis (CVT) results in signs and symptoms of increased intracranial pressure. MRI and venous magnetic resonance angiography are the diagnostic imaging procedures of choice. Other vascular manifestations of Behçet's disease, particularly venous thromboses, are often present in Behçet's disease patients with CVT, suggesting common pathogenic mechanisms. Comparing 36 Behçet's disease patients with CVT with 32 patients with CVT of other causes, Behçet's disease patients were younger (median age of 26 years), more likely to be men and present with subacute or chronic symptoms. Venous infarcts were infrequent. CVT was recognized in 7.8% of a large cohort of Behçet's disease patients in France. Visual loss due to optic atrophy complicated the disorder in 15% of affected patients, associated with the presence of concurrent prothrombotic risk factors.
Therapeutic Considerations
For the management of acute deep vein thrombosis in Behçet's disease, immunosuppressive agents such as corticosteroids and azathioprine are recommended. Monthly pulse cyclophosphamide should be considered for thrombosis of the superior vena cava or Budd–Chiari syndrome. These recommendations are based on the belief that the cause of clot is inflammation of the vascular wall. Support for the value of anticoagulants is lacking and progression or recurrence of venous thrombosis despite standard anticoagulation is frequently recognized. Anticoagulation is not recommended in the EULAR guidelines. The conspicuous rarity of pulmonary emboli in Behçet's disease with venous thrombosis has long been noted, attributed to adherent clot formation on the inflamed vessel wall. Ahn et al. from Korea reported the results of a retrospective study comparing the efficacy of immunosuppressive agents with and without anticoagulants in the treatment of venous thrombosis in Behçet's disease. There was no difference in the recurrence rate in these two groups. Three of four patients treated with anticoagulants alone experienced a recurrence. The use of anticoagulants for DVT (in addition to immunosuppression) differs in various centers. Anticoagulants were used in 90% of patients treated for thrombosis prior to the diagnosis of Behçet's disease, with a low risk of bleeding complications. In Behçet's disease cases with coexisting prothrombotic conditions, individualization of treatment may require anticoagulation.
Thrombus in the cardiac chambers has been treated successfully with corticosteroids and cyclophosphamide, often with anticoagulants.
Thrombolytic therapy has been used in large vessel thrombosis syndromes with mixed results but may be a better option if used early in acute cases. Infliximab has been used in the treatment of three patients with Budd–Chiari syndrome, two with advanced disease, without success. Portocaval shunting can be considered in Budd–Chiari syndrome if the inferior vena cava is patent.
There is no consensus regarding the treatment of CVT in Behçet's disease. Anticoagulants are used in some centers with a low risk of hemorrhagic complications. Most patients also received corticosteroids and immunosuppressives, but these agents did not improve the outcome or prevent thrombotic relapse. In other centers anticoagulants are not routinely used but immunosuppressive drugs are employed as in parenchymal CNS disease or other vascular complications. The EULAR recommendation for the treatment of dural sinus thrombosis is with brief courses of corticosteroids.
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