Rheumatology Advance Access originally published online on May 3, 2007
Rheumatology 2007 46(7):1213-1214; doi:10.1093/rheumatology/kem103
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Infliximab in the treatment of hepatic vein thrombosis (Budd-Chiari syndrome) in three patients with Behçet's syndrome
Division of Rheumatology, Department of Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey
Correspondence to: Emire Seyahi, MD, Halaskargazi cad. No: 209-211, D: 2, Sisli/Istanbul, 34380, Istanbul, Turkey. E-mail: emire{at}superonline.com
SIR, Hepatic vein thrombosis leading to Budd–Chiari syndrome (BCS) constitutes approximately 2% of all vascular complications of Behçet's syndrome (BS) and has a poor prognosis [1]. In a retrospective study, 10 out of 14 BS patients with BCS had died within a mean of 10.4 months [2]. Immunosuppressives are empirically used for this complication but their effect on outcome is not known. Transjugular intrahepatic portosystemic shunting (TIPS) or hepatic transplantation can be considered as alternative life saving interventions [3]. However, there has been no experience in BS with these procedures and the heightened inflammatory response of BS to penetrating trauma (the pathergy reaction) may complicate invasive procedures [4, 5].
Anti-TNF agents, especially infliximab, have shown rapid and dramatic effect in the treatment of refractory ocular, mucocutaneous, joint, gastro-intestinal and CNS manifestations of BS in several case reports and case series [6]. However, no data exist about the effect of infliximab or other anti-TNF agents on venous involvement of BS.
We here present our experience with infliximab on three BS patients with severe BCS.
Case 1: a 12-yr-old male BS patient was hospitalized because of haemoptysis and abdominal swelling. He was diagnosed as having pulmonary arterial aneurysms and BCS. Treatment with prednisolone 1 g/kg/day and cyclophosphamide 1 g/month was started but 10 days later he had an emergency lobectomy following an abundant haemoptysis. Two months later while under treatment with cyclophosphamide and prednisolone, he developed signs of hepatic encephalopathy. A Doppler examination showed extension of thrombosis to all three hepatic veins. Infliximab 200 mg (5 mg/kg) was added to his treatment. However, his clinical status continued to deteriorate and he died 4 weeks later.
Case 2: a 28-yr-old male BS patient was diagnosed as having BCS when he presented with ascites and hepatosplenomegaly. All three hepatic veins and the suprahepatic segment of the inferior vena cava were thrombosed. Treatment was started with prednisolone 1 mg/kg/day and monthly boluses of 1 g cyclophosphamide but he developed signs of liver failure 6 months later. A CT scan showed the extension of the thrombus in the inferior vena cava and formation of new thrombus in the brachiocephalic vein. Infliximab 3 mg/kg was given along with 1 g methyl prednisolone. He developed hepatic encephalopathy the following day and died in hepatic coma 3 weeks later.
Case 3: a 15-yr-old male BS patient was diagnosed as having BCS when he developed abdominal swelling. Physical examination revealed pustules at the intravenous needle insertion sites (suggesting a positive pathergy test), bilateral papilloedema, ascites and hepatomegaly. A Doppler USG examination showed thrombosis in the right hepatic vein and in the inferior vena cava. No cranial sinus thrombosis was detected with MRI. He was prescribed infliximab 200 mg (5 mg/kg). On the fourth day of the first infliximab perfusion papilloedema had disappeared but Doppler USG findings remained unchanged. He was administered three pulses of 1 g methylprednisolone followed by prednisolone 1 mg/kg/day. Three weeks after the second infusion of infliximab he developed severe headache and diplopia. Further investigation revealed the presence of bilateral papilloedema and emergence of cranial sinus thrombosis. There was no change in the size of the thrombus in the right hepatic vein but the thrombus in the inferior vena cava had regressed. Infliximab treatment was stopped and monthly pulses of 1 g cyclophosphamide were started. Six months later he had no papilloedema and ascites had disappeared. Doppler USG showed regression of the thrombi in the hepatic vein and inferior vena cava.
A recent case report described the dramatic and long lasting effect of infliximab in a BS patient with pulmonary artery aneurysms and life-threatening haemoptysis [7]. Rapid resolution of the thrombi in the pulmonary arteries was seen within 2 weeks following the administration of infliximab. Our experience in three BS patients complicated with BCS was not as promising. On the other hand we cannot say for sure that infliximab was ineffective. The two patients who had died had almost end-stage liver failure when infliximab was given. In the third patient, although we have noted a regression in the size of the thrombus in the inferior vena cava, the rather simultaneous development of cranial sinus thrombosis prompted us to stop infliximab in the light of isolated reports of patients developing thrombophlebitis during treatment with infliximab. Some of these thromboses were seen in patients with sarcoidosis [8] or Crohn's disease [9], conditions that are known to have increased thrombotic tendency. In contrast, the development of cerebral vein thrombosis in a patient with ankylosing spondylitis [10] causes concern since thrombosis is not a known feature of this disease. On the other hand, until now we have used infliximab in 14 additional BS patients mostly with severe and resistant uveitis, and except in the case we report here we have not seen any other patient developing thrombosis. Further experience is needed to determine the efficacy and safety of infliximab in the treatment of venous thrombosis of BS.
The authors have declared no conflicts of interest.
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