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Superior vena cava occlusion caused by Behçet disease
Superior vena cava occlusion caused by Behçet disease Miao Yu, MD,a Anbing Shi, MD,d Bi Jin, MD,a Xionggang Jiang, MD,b Huimin Liang, MD,c and Chenxi Ouyang, MD, PhD,a,d Wuhan, China; and Palo Alto, Calif This case report described a patient of Behçet disease (BD)-related vascular lesions that initially presented as occlusion of superior vena cava (SVC) without any evidence of thrombosis. The patient was treated first by percutaneous transluminal angioplasty and stent implantation, and he developed thrombosis in the stent and then received open bypass operation. Pathologic examination of the SVC specimen and the postoperative manifestations revealed that the underlying cause of his symptoms as BD. Afterward, methylprednisolone plus anticoagulant therapy was routinely given, which relieved the symptoms of the patient. ( J Vasc Surg 2012;55:1488-91.)
Behçet disease (BD) is a heterogeneous, multisystem inflammatory condition and is a vasculitis syndrome with a wide array of clinical manifestations.1 The classical triad of BD consists of recurrent oral and genital ulcerations as well as uveitis. Other systemic changes include skin lesions, arthritis, neurologic, pulmonary involvement, and musculoskeletal manifestations.2 Supra vena cava (SVC) thrombosis is a rare but easily identified manifestation of BD, whereas reports of complete occlusion of SVC without evidence of thrombosis, has been scanty in the literature.3 The open surgery or endovascular procedure for the treatment of BD-related SVC syndrome has been rarely reported, with postoperative course being eventful in most cases. In this case report, we described a case of BD-related SVC occlusion without evidence of thrombosis and without any manifestations typical of BD. CASE REPORT A 36-year-old Chinese male presented with progressive facial and cervical swelling for 3 months, together with varicose veins in the chest wall, and was admitted into our hospital in 2010. The patient reported no history of thrombosis or family history of similar conditions. On admission, the patient did not have persistent fever, and he failed to mention that he had had oral ulceration and lower extremity ulcers with skin pigmentation and itching over the past several years and intermittent lower limb pain in the knee From the Department of Vascular Surgery,a Department of Cardiovascular Surgery,b and Department of Radiology,c Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; and Department of Biology, Howard Hughes Medical Institute, Stanford University, Palo Alto.d MY and AS contributed equally to this work. Author conflict of interest: none. Reprint requests: Chenxi Ouyang, MD, PhD, Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong, University of Science and Technology, Wuhan 430022, China (e-mail: ouyangchx@ yahoo.com). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a competition of interest. 0741-5214/$36.00 Copyright © 2012 by the Society for Vascular Surgery. doi:10.1016/j.jvs.2011.10.035
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with an impaired vision for 1 year, which led to our failure to include BD as a possible diagnosis. Computed tomography angiography, magnetic resonance angiography, and digital subtraction angiography revealed an extensive filling defect with thickened wall of the SVC from the left innominate vein down to the right atrium, and profuse amount of vascular collateral circulation in the soft tissue within the left shoulder (Fig 1). The other routine clinical examinations, including erythrocyte sedimentation rate yielded normal results. We first performed the balloon angioplasty under DSA to enlarge SVC and to see if the obstruction was of functional or structural nature. During the DSA, the guidewire passed through the narrow part of SVC without encountering any resistance, and after the balloon enlargement, the facial swelling disappeared immediately. However, the aforementioned symptoms recurred 1 week later and the patient’s general condition deteriorated after treatment with anticoagulants and diuretics to alleviate the edema. Thereafter, we performed an endovascular stent implantation at the site of SVC, with warfarin prescribed, which alleviated his symptoms for a short period of time. Unfortunately, the patient developed cervical swelling of similar severity 2-1/2 months later, and was readmitted into our department. The second chest CTA scan exhibited a 6.5-cmlong stent of high density in the SVC and, within it, a lumen of 4.0 mm in diameter with no obvious filling of contrast agent, which was considered to be thrombosis. We prescribed anticoagulants to treat the thrombosis, which was ineffective. Therefore, a mediastinotomy with replacement of the involved SVC was performed in our cardiac surgery operating room. After the successful establishment of cardiopulmonary bypass, the vessel wall was cut open and the wall of the SVC vein was found to be thickened. The bare stent was filled with dark red thrombi (Fig 2). We excised part of the thickened vessel wall for biopsy, removed the stent, and then performed a bypass of the right jugular vein, innominate vein, and right atrium by using a Y-shaped Dacron graft (Datascope 20 ⫻ 10 ⫻ 10 cm). The patient’s swelling disappeared soon after the surgery. However, 4 days after the mediastinotomy, the patient developed a persistent fever of 38°C and a small amount of pleural effusion. Laboratory tests mostly yielded normal results except for the following findings: WBCs were 11.27 ⫻ 109/L, protein
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Fig 1. The angiographic images of superior vena cava (SVC) by computed tomography angiography (CTA), magnetic resonance imaging (MRA), and digital subtraction angiography (DSA). A, The obvious stenosis of SVC with thickened wall.
Fig 2. View of the stent and thrombi during the bypass operation. A, The implanted stent in superior vena cava (SVC). B, Thrombi formed inside SVC.
C was 55.3%, FVIII: C% was 153.9, and HLA-B51 test was positive. Histologic investigation showed irregular fibrous hyperplasia of the SVC vessel wall, and a large number of small inflammatory vessels scattering among the hyperplasic tissues (Fig 3). Especially, during the postoperative recovery period, the patient began to complain of blurred vision and severe knee pain. These manifestations, strongly indicative of BD, led us to consider BD to be the cause of his symptoms. Methylprednisolone and anticoagulants were administered, which successfully controlled the fever that had lasted 2 weeks. Complete clinical resolution was achieved 7 days after the treatment. The patient was discharged and was ordered to take prednisone (60 mg/d, with progressive dose reduction) and warfarin. A 1-year follow-up showed that the patient did not have any signs of recurrence of the cervical swelling, and ultrasound investigation showed no sign of thrombosis among the upper
limb veins. Moreover, his vision blurriness did not deteriorate and the arthralgia was relieved.
DISCUSSION BD syndrome was first described in 1937 by Hulusi Behçet, a Turkish dermatologist.4 Although vascular lesions are not included in the criteria for the diagnosis of BD, a significant proportion of the patients, ranging from 7% to 38%, develop complications in arterial and venous vessels, which tend to cause deaths.5 The most frequent vascular lesions are superficial thrombophlebitis and venous occlusion of the upper limbs, followed by occlusion of large vessels such as the superior and inferior vena cava, aneurysm, or arterial occlusion.5,6 In addition, in 2006, Tohmé et al reported 18 cases, among 140 BD patients, of vascular lesions at different parts of body. They concluded that venous thrombosis was more com-
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complicated interactions among T cells, neutrophils, and antigen-presenting cells (APC) are implicated in the immunity-related pathogenesis of BD.8 Genetic abnormalities are generally accepted risk factors for BD. In this case, the patient’s parents were later found to be cousins. A recent study also suggested that major histocompatibility complex class I chain-related gene A, located near B51, might be the genetic locus for the condition in the Japanese population.9 Second, we strongly suggest that separate diagnostic criteria be established for BD with vascular involvement. Currently, the main diagnostic criteria for BD are the International Study Group (ISG) criteria, which were formulated on the basis of the clinical features of the disease. In this case, oral ulceration was not conspicuous and genital ulceration was totally absent. In 2008, Vandergheynst also reported a patient presenting signs completely different from those included in ISG diagnostic criteria of BD.10 Since a significant proportion of the patients develop complications in arterial and venous vessels,5 vascular lesions should be included in the diagnostic criteria of BD. As an autoimmune disease, BD could involve virtually all systems in the body and are subject to relapse. In this case and with other patients reported in the literature, BD symptoms tend to worsen after invasive treatment for the vascular lesions. Open surgery is associated with higher rate of failure with the condition, resulting in graft occlusion, stenosis, and pseudoaneurysm.11 The vasculitis-related vascular change is principally ascribed to the high morbidity and disruption of suture lines at the early stage or pseudoaneurysm at late stage, especially when the surgery is performed during the acute phase of the disease with inflammation as indicated by high erythrocyte sedimentation rate and C-reactive protein level.1 Moreover, the stressful impact caused by open surgery also stimulates the immune and coagulation systems, which will accelerate the progression of BD. In this case, the persistent fever and vision blurriness took place immediately after open operation, and thrombotic complications developed after endovascular stenting, which was consistent with the findings of other studies.12 Therefore, a standard treatment for BD with vascular involvement should also be established. CONCLUSIONS Fig 3. The pathologic findings of the resected superior vena cava (SVC). A, Profuse amount of newly formed vessels. B, Irregularly distributed fibrinogen and fibroblasts.
mon in males, while arterial occlusion occurred more frequently in females. In addition, arterial occlusions were more commonly observed than aneurysms and pulmonary embolism.7 To date, the mechanism of vascular lesions remains unknown and there are no specific laboratory tests for the definite diagnosis of BD. It is commonly believed that
On the basis of this case and review of the literature, we conclude that any invasive treatment for BD-related vascular lesions should be avoided before the complete control of active inflammation. Nevertheless, in the treatment of BD with involvement of large vessels, administration of immunosuppressors in conjunction of anticoagulants could achieve satisfactory results in some cases.3,13 REFERENCES 1. Marzban M, Mandegar MH, Karimi A, Abbasi K, Movahedi N, Navabi MA, et al. Cardiac and great vessel involvement in “Behçet’s disease”. J Cardiovasc Surg 2008;23:765-8.
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2. Ko GY, Byun JY, Choi BG, Cho SH. The vascular manifestations of Behçet’s disease: angiographic and CT findings. Br J Radiol 2000;73: 1270-1274. 3. de Paiva TF, Ribeiro HB, Campanholo CB, Gonçalves CR, Terigoe DY, de Souza BD. Behçet’s disease associated with superior vena cava syndrome without thrombosis. Clin Rheumatol 2007;26:804-6. 4. Behçet H. Uber rezidivierende aphtose, durch ein Virus verursachte Geschwure am Mund, am Auge und an den Genitalien. Dermatol Wochenschr 1937;105:1152-7. 5. de Jesus H, Rosa M, Queiroz MV. Vascular involvement in Behçet’s disease. An analysis of twelve cases. Clin Rheumatol 1997;16:220-1. 6. Ehrlich GE. Vasculitis in Behçet’s disease. Int Rev Immunol 1997;14:81-8. 7. Tohmé A, Aoun N, El-Rassi B, Ghayad E. Vascular manifestations of Behçet’s disease. Joint Bone Spine 2003;70:384-9. 8. Pay S, Sims¸ek I, Erdem H, Dinç A. Immunopathogenesis of Behçet’s disease with special emphasize on the possible role of antigen presenting cells. Rheumatol Int 2007;27:417-24.
9. Kontogiannis V, Powell RJ. Behçet’s disease. Postgrad Med J 2000; 76:629-37. 10. Vandergheynst F, Francois O, Laureys M, Decaux G. Superior vena cava syndrome without thrombosis revealing Behçet’s disease: two cases. Joint Bone Spine 2008;75:359-61. 11. Gueler A, Caglar N, Erol C. Behçet’s disease. In: O’Duffy J, Kokmen E, editors. Basic and clinical aspects. Minnesota: Marcel Dekker; 1991. p. 187-90. 12. Ozatli D, Kav T, Haznedaroglu IC, Büyükas¸ik Y, Kos¸ar A, Ozcebe O, et al. Cardiac and great vessel thrombosis in Behçet’s disease. Intern Med 2001;40:68-72. 13. Terzioglu E, Kirmaz C, Uslu R, Sin A, Kokuludag A, Sagduyu A, et al. Superior vena cava syndrome together with multiple venous thrombosis in Behçet’s disease. Clin Rheumatol 1998;17:176-7.
Submitted Aug 8, 2011; accepted Oct 12, 2011.
CME Credit Now Available to JVS Readers Readers can now obtain CME credits by reading selected articles and correctly answering multiple choice questions on the Journal website (www.jvascsurg.org). Four articles are identified in the Table of Contents of each issue and 2 questions for each are posted on the website. After correctly answering the 8 questions, readers will be awarded 2 hours of Category I CME credit.
Behçet disease (BD) is a heterogeneous, multisystem inflammatory condition and is a vasculitis syndrome with a wide array of clinical manifestations.1 The classical triad of BD consists of recurrent oral and genital ulcerations as well as uveitis. Other systemic changes include skin lesions, arthritis, neurologic, pulmonary involvement, and musculoskeletal manifestations.2 Supra vena cava (SVC) thrombosis is a rare but easily identified manifestation of BD, whereas reports of complete occlusion of SVC without evidence of thrombosis, has been scanty in the literature.3 The open surgery or endovascular procedure for the treatment of BD-related SVC syndrome has been rarely reported, with postoperative course being eventful in most cases. In this case report, we described a case of BD-related SVC occlusion without evidence of thrombosis and without any manifestations typical of BD. CASE REPORT A 36-year-old Chinese male presented with progressive facial and cervical swelling for 3 months, together with varicose veins in the chest wall, and was admitted into our hospital in 2010. The patient reported no history of thrombosis or family history of similar conditions. On admission, the patient did not have persistent fever, and he failed to mention that he had had oral ulceration and lower extremity ulcers with skin pigmentation and itching over the past several years and intermittent lower limb pain in the knee From the Department of Vascular Surgery,a Department of Cardiovascular Surgery,b and Department of Radiology,c Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; and Department of Biology, Howard Hughes Medical Institute, Stanford University, Palo Alto.d MY and AS contributed equally to this work. Author conflict of interest: none. Reprint requests: Chenxi Ouyang, MD, PhD, Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong, University of Science and Technology, Wuhan 430022, China (e-mail: ouyangchx@ yahoo.com). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a competition of interest. 0741-5214/$36.00 Copyright © 2012 by the Society for Vascular Surgery. doi:10.1016/j.jvs.2011.10.035
1488
with an impaired vision for 1 year, which led to our failure to include BD as a possible diagnosis. Computed tomography angiography, magnetic resonance angiography, and digital subtraction angiography revealed an extensive filling defect with thickened wall of the SVC from the left innominate vein down to the right atrium, and profuse amount of vascular collateral circulation in the soft tissue within the left shoulder (Fig 1). The other routine clinical examinations, including erythrocyte sedimentation rate yielded normal results. We first performed the balloon angioplasty under DSA to enlarge SVC and to see if the obstruction was of functional or structural nature. During the DSA, the guidewire passed through the narrow part of SVC without encountering any resistance, and after the balloon enlargement, the facial swelling disappeared immediately. However, the aforementioned symptoms recurred 1 week later and the patient’s general condition deteriorated after treatment with anticoagulants and diuretics to alleviate the edema. Thereafter, we performed an endovascular stent implantation at the site of SVC, with warfarin prescribed, which alleviated his symptoms for a short period of time. Unfortunately, the patient developed cervical swelling of similar severity 2-1/2 months later, and was readmitted into our department. The second chest CTA scan exhibited a 6.5-cmlong stent of high density in the SVC and, within it, a lumen of 4.0 mm in diameter with no obvious filling of contrast agent, which was considered to be thrombosis. We prescribed anticoagulants to treat the thrombosis, which was ineffective. Therefore, a mediastinotomy with replacement of the involved SVC was performed in our cardiac surgery operating room. After the successful establishment of cardiopulmonary bypass, the vessel wall was cut open and the wall of the SVC vein was found to be thickened. The bare stent was filled with dark red thrombi (Fig 2). We excised part of the thickened vessel wall for biopsy, removed the stent, and then performed a bypass of the right jugular vein, innominate vein, and right atrium by using a Y-shaped Dacron graft (Datascope 20 ⫻ 10 ⫻ 10 cm). The patient’s swelling disappeared soon after the surgery. However, 4 days after the mediastinotomy, the patient developed a persistent fever of 38°C and a small amount of pleural effusion. Laboratory tests mostly yielded normal results except for the following findings: WBCs were 11.27 ⫻ 109/L, protein
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Fig 1. The angiographic images of superior vena cava (SVC) by computed tomography angiography (CTA), magnetic resonance imaging (MRA), and digital subtraction angiography (DSA). A, The obvious stenosis of SVC with thickened wall.
Fig 2. View of the stent and thrombi during the bypass operation. A, The implanted stent in superior vena cava (SVC). B, Thrombi formed inside SVC.
C was 55.3%, FVIII: C% was 153.9, and HLA-B51 test was positive. Histologic investigation showed irregular fibrous hyperplasia of the SVC vessel wall, and a large number of small inflammatory vessels scattering among the hyperplasic tissues (Fig 3). Especially, during the postoperative recovery period, the patient began to complain of blurred vision and severe knee pain. These manifestations, strongly indicative of BD, led us to consider BD to be the cause of his symptoms. Methylprednisolone and anticoagulants were administered, which successfully controlled the fever that had lasted 2 weeks. Complete clinical resolution was achieved 7 days after the treatment. The patient was discharged and was ordered to take prednisone (60 mg/d, with progressive dose reduction) and warfarin. A 1-year follow-up showed that the patient did not have any signs of recurrence of the cervical swelling, and ultrasound investigation showed no sign of thrombosis among the upper
limb veins. Moreover, his vision blurriness did not deteriorate and the arthralgia was relieved.
DISCUSSION BD syndrome was first described in 1937 by Hulusi Behçet, a Turkish dermatologist.4 Although vascular lesions are not included in the criteria for the diagnosis of BD, a significant proportion of the patients, ranging from 7% to 38%, develop complications in arterial and venous vessels, which tend to cause deaths.5 The most frequent vascular lesions are superficial thrombophlebitis and venous occlusion of the upper limbs, followed by occlusion of large vessels such as the superior and inferior vena cava, aneurysm, or arterial occlusion.5,6 In addition, in 2006, Tohmé et al reported 18 cases, among 140 BD patients, of vascular lesions at different parts of body. They concluded that venous thrombosis was more com-
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complicated interactions among T cells, neutrophils, and antigen-presenting cells (APC) are implicated in the immunity-related pathogenesis of BD.8 Genetic abnormalities are generally accepted risk factors for BD. In this case, the patient’s parents were later found to be cousins. A recent study also suggested that major histocompatibility complex class I chain-related gene A, located near B51, might be the genetic locus for the condition in the Japanese population.9 Second, we strongly suggest that separate diagnostic criteria be established for BD with vascular involvement. Currently, the main diagnostic criteria for BD are the International Study Group (ISG) criteria, which were formulated on the basis of the clinical features of the disease. In this case, oral ulceration was not conspicuous and genital ulceration was totally absent. In 2008, Vandergheynst also reported a patient presenting signs completely different from those included in ISG diagnostic criteria of BD.10 Since a significant proportion of the patients develop complications in arterial and venous vessels,5 vascular lesions should be included in the diagnostic criteria of BD. As an autoimmune disease, BD could involve virtually all systems in the body and are subject to relapse. In this case and with other patients reported in the literature, BD symptoms tend to worsen after invasive treatment for the vascular lesions. Open surgery is associated with higher rate of failure with the condition, resulting in graft occlusion, stenosis, and pseudoaneurysm.11 The vasculitis-related vascular change is principally ascribed to the high morbidity and disruption of suture lines at the early stage or pseudoaneurysm at late stage, especially when the surgery is performed during the acute phase of the disease with inflammation as indicated by high erythrocyte sedimentation rate and C-reactive protein level.1 Moreover, the stressful impact caused by open surgery also stimulates the immune and coagulation systems, which will accelerate the progression of BD. In this case, the persistent fever and vision blurriness took place immediately after open operation, and thrombotic complications developed after endovascular stenting, which was consistent with the findings of other studies.12 Therefore, a standard treatment for BD with vascular involvement should also be established. CONCLUSIONS Fig 3. The pathologic findings of the resected superior vena cava (SVC). A, Profuse amount of newly formed vessels. B, Irregularly distributed fibrinogen and fibroblasts.
mon in males, while arterial occlusion occurred more frequently in females. In addition, arterial occlusions were more commonly observed than aneurysms and pulmonary embolism.7 To date, the mechanism of vascular lesions remains unknown and there are no specific laboratory tests for the definite diagnosis of BD. It is commonly believed that
On the basis of this case and review of the literature, we conclude that any invasive treatment for BD-related vascular lesions should be avoided before the complete control of active inflammation. Nevertheless, in the treatment of BD with involvement of large vessels, administration of immunosuppressors in conjunction of anticoagulants could achieve satisfactory results in some cases.3,13 REFERENCES 1. Marzban M, Mandegar MH, Karimi A, Abbasi K, Movahedi N, Navabi MA, et al. Cardiac and great vessel involvement in “Behçet’s disease”. J Cardiovasc Surg 2008;23:765-8.
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2. Ko GY, Byun JY, Choi BG, Cho SH. The vascular manifestations of Behçet’s disease: angiographic and CT findings. Br J Radiol 2000;73: 1270-1274. 3. de Paiva TF, Ribeiro HB, Campanholo CB, Gonçalves CR, Terigoe DY, de Souza BD. Behçet’s disease associated with superior vena cava syndrome without thrombosis. Clin Rheumatol 2007;26:804-6. 4. Behçet H. Uber rezidivierende aphtose, durch ein Virus verursachte Geschwure am Mund, am Auge und an den Genitalien. Dermatol Wochenschr 1937;105:1152-7. 5. de Jesus H, Rosa M, Queiroz MV. Vascular involvement in Behçet’s disease. An analysis of twelve cases. Clin Rheumatol 1997;16:220-1. 6. Ehrlich GE. Vasculitis in Behçet’s disease. Int Rev Immunol 1997;14:81-8. 7. Tohmé A, Aoun N, El-Rassi B, Ghayad E. Vascular manifestations of Behçet’s disease. Joint Bone Spine 2003;70:384-9. 8. Pay S, Sims¸ek I, Erdem H, Dinç A. Immunopathogenesis of Behçet’s disease with special emphasize on the possible role of antigen presenting cells. Rheumatol Int 2007;27:417-24.
9. Kontogiannis V, Powell RJ. Behçet’s disease. Postgrad Med J 2000; 76:629-37. 10. Vandergheynst F, Francois O, Laureys M, Decaux G. Superior vena cava syndrome without thrombosis revealing Behçet’s disease: two cases. Joint Bone Spine 2008;75:359-61. 11. Gueler A, Caglar N, Erol C. Behçet’s disease. In: O’Duffy J, Kokmen E, editors. Basic and clinical aspects. Minnesota: Marcel Dekker; 1991. p. 187-90. 12. Ozatli D, Kav T, Haznedaroglu IC, Büyükas¸ik Y, Kos¸ar A, Ozcebe O, et al. Cardiac and great vessel thrombosis in Behçet’s disease. Intern Med 2001;40:68-72. 13. Terzioglu E, Kirmaz C, Uslu R, Sin A, Kokuludag A, Sagduyu A, et al. Superior vena cava syndrome together with multiple venous thrombosis in Behçet’s disease. Clin Rheumatol 1998;17:176-7.
Submitted Aug 8, 2011; accepted Oct 12, 2011.
CME Credit Now Available to JVS Readers Readers can now obtain CME credits by reading selected articles and correctly answering multiple choice questions on the Journal website (www.jvascsurg.org). Four articles are identified in the Table of Contents of each issue and 2 questions for each are posted on the website. After correctly answering the 8 questions, readers will be awarded 2 hours of Category I CME credit.