Abstract
Behçet syndrome is a rare, chronic inflammatory disease of unknown aetiopathogenesis, most commonly presenting with mucocutaneous and ocular manifestations. Vascular involvement, most frequently superficial vein and deep vein thrombosis, can occur in up to 50% of patients with Behçet syndrome. Venous thrombosis at atypical sites (inferior and superior vena cava, suprahepatic veins with Budd–Chiari syndrome, portal vein, cerebral sinuses and right atrium and/or ventricle) and arterial involvement (mostly in situ thrombosis and aneurysms of the pulmonary arteries, as well as aneurysms of the abdominal aorta, and peripheral and visceral arteries) are also unique features of Behçet syndrome. Behçet syndrome is considered a natural model of inflammation-induced thrombosis in humans, with an impaired immune-inflammatory response rather than traditional cardiovascular risk factors contributing to thrombogenesis. Specifically, neutrophil hyperactivation and neutrophil-mediated mechanisms of damage directly promote endothelial dysfunction, platelet activation and thrombogenesis in Behçet syndrome. This unusual pathogenesis directly determines the treatment approach, which relies mostly on immunosuppressants rather than anticoagulants for treatment of thrombosis and for secondary prevention. This Review discusses the main histopathological, pathogenetic and clinical aspects of vascular Behçet syndrome, addressing their implications for therapeutic management. Future perspectives in terms of pathogenetic studies, disease monitoring and treatment strategies are also discussed.
Key points
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Vascular involvement occurs in up to 50% of patients with Behçet syndrome, mostly in the form of superficial and deep vein thrombosis.
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Behçet syndrome is considered a natural model of inflammation-induced thrombosis in humans, as thrombogenesis is mostly due to an impaired immune-inflammatory response rather than traditional cardiovascular risk factors.
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Neutrophil hyperactivation and neutrophil-mediated mechanisms of damage directly sustain endothelial dysfunction, platelet activation and thrombogenesis in Behçet syndrome.
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Venous thrombosis at atypical sites (such as Budd–Chiari syndrome, inferior and superior vena cava, and cerebral venous sinus thrombosis), and pulmonary and non-pulmonary artery involvement are also unique features of Behçet syndrome.
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Thrombosis treatment and secondary prevention in Behçet syndrome currently relies mostly on immunosuppressants rather than on anticoagulants.
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Research is needed to address the contribution of epigenetic modulators in Behçet syndrome thrombogenesis, to assess the diagnostic performance of vascular imaging to support Behçet syndrome diagnosis, and to identify new pharmacological and non-pharmacological therapeutic approaches.
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F.A.-O. has received honoraria, consulting or speaker fees from Pfizer, AbbVie and Amgen. H.D. has received honoraria, consulting and speaker fees from AbbVie, Pfizer, Roche, Novartis, UCB Pharma, Amgen and Celltrione. G.E. has received honoraria and speaker fees from Novartis, Roche, Sobi, AstraZeneca, Boehringer Ingelheim, Janssen, Sanofi and GSK. G.H. has received research grants, honoraria and speaker fees from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Celltrion, Janssen, Novartis, Pfizer, Silk Road Therapeutics and UCB Pharma. D.S. has received honoraria, consulting or speaker fees from Novartis, Amgen, Celltrion, Celgene, Roche Chugai, Viatris, Sanofi and AbbVie. E.S. has received honoraria, consulting or speaker fees from Novartis, Pfizer and AbbVie. A.B. and D.P. declare no competing interests.
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Bettiol, A., Alibaz-Oner, F., Direskeneli, H. et al. Vascular Behçet syndrome: from pathogenesis to treatment. Nat Rev Rheumatol 19, 111–126 (2023). https://doi.org/10.1038/s41584-022-00880-7
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DOI: https://doi.org/10.1038/s41584-022-00880-7
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