Behçet's Syndrome as a Model of Thrombo-Inflammation: The Role of Neutrophils

Behçet's syndrome (BS) is a systemic vasculitis, clinically characterized by different organ involvement and often complicated by thrombosis which occurs in vessels of all sizes. Thrombosis is more frequent in male patients with active disease and represents an important cause of morbidity and mortality. Neutrophil involvement in BS has been repeatedly suggested in the last few years. Indeed, neutrophils have been shown to be hyperactivated in BS patients, probably with a HLAB51 related contribution, and represent the main cells infiltrating not only oral and genital ulcers or erythema nodosum, but also other sites. Besides being deputed to host defense against micro-organisms, neutrophils display fundamental roles both in inflammation and tissue damage becoming inappropriately activated by cytokines, chemokines and autoantibodies and subsequently producing large amounts of superoxide anion (O2.) via NADPH oxidase (NOX2). The strict relationship between inflammation and hemostasis has been already demonstrated. Indeed, inflammation and immune-mediated disorders increase the risk of thrombosis, but the pathways that link these processes have not been completely elucidated. In this regard, we recently demonstrated, in a large population of BS patients, a new neutrophil-dependent pathogenetic mechanism of thrombosis. In particular, it was shown that neutrophils, mainly through NADPH oxidase, produce excessive amounts of reactive oxygen species (ROS), which are able to markedly modify the secondary structure of fibrinogen and hence the overall architecture of the fibrin clot that becomes less susceptible to plasmin-induced lysis. These data point out that BS represents “per se” a model of inflammation-induced thrombosis and suggest that neutrophils specifically contribute to thrombo-inflammation in this rare disease. In particular, it is suggested that an alteration in fibrinogen structure and function are associated with enhanced ROS production via neutrophil NADPH oxidase. Altogether, these findings improve our understanding of the intricate pathogenetic mechanisms of thrombo-inflammation and may indicate potential new therapeutic targets

Systemic vasculitis and the gut

Purpose of reviewGastrointestinal system can be involved in primary and secondary vasculitides. The recent data regarding the pathophysiology, clinical findings, diagnosis, management, and outcome of gastrointestinal involvement in different types of vasculitis are reviewed.Recent findingsDiagnosis of gastrointestinal vasculitis may be difficult and relies mostly on imaging, because biopsy samples are hard to obtain and superficial mucosal biopsies have a low yield. There are conflicting reports on the association of antineutrophilic cytoplasmic antibodies (ANCA) type with the frequency of gastrointestinal involvement in ANCA-associated vasculitis. Pancreatitis is a rare but serious complication of ANCA-associated vasculitis. Terminal ileitis may be observed in immunoglobulin A vasculitis and can be hard to distinguish from Crohn's disease. High fecal calprotectin levels can indicate active gastrointestinal involvement in both immunoglobulin A vasculitis and Behcet's syndrome. Refractory gastrointestinal involvement in Behcet's syndrome can be treated with thalidomide and/or TNF- antagonists. The outcome of mesenteric vasculitis in systemic lupus erythematosus can be improved with high-dose glucocorticoids and cyclophosphamide or rituximab.SummaryGastrointestinal system can be commonly involved in immunoglobulin A vasculitis, ANCA-associated vasculitis, polyarteritis nodosa, and Behcet's syndrome and can be an important cause of morbidity and mortality. Treatment depends on the type of vasculitis and is usually with high-dose corticosteroids and immunosuppressives

Apremilast for the treatment of Behcet's syndrome

Introduction: Mucocutaneous lesions can be disabling in Behcet's syndrome patients who experience these lesions frequently and can be an important cause of impaired quality of life. Apremilast may be a safe and effective alternative for the treatment of oral and genital ulcers in Behcet's syndrome

An evaluation of apremilast for the treatment of adult patients with oral ulcers associated with Behcet's syndrome

Introduction Behcet's syndrome is a chronic, multi-system, variable vasculitis of unknown etiology that can result in significant morbidity and mortality. Mucocutaneous lesions such as oral ulcers and genital ulcers are common manifestations that can affect the quality of life of patients significantly. Treatment for mucocutaneous lesions in Behcet's syndrome continues to be critical, and an unmet need remains a significant issue. Areas covered This review evaluates the mechanism of action of apremilast, its effect on the number and pain of oral ulcers, other manifestations, such as genital ulcers, disease activity, quality of life and safety profile in Behcet's syndrome patients. Data from clinical trials as well as observational studies were included. Expert opinion Two randomized placebo-controlled trials and real-world observational data suggest that apremilast is an effective and well-tolerated treatment modality for oral and genital ulcers in Behcet's syndrome. Observational studies additionally showed beneficial results for skin lesions, arthritis, and intestinal involvement

Recent Insights into the Management of Behcet Syndrome

Behcet syndrome (BS) is a multisystem vasculitis with variable vessel involvement that shows significant heterogeneity among patients in terms of clinical manifestations and disease course. Treatment choice and response are both influenced by this heterogeneity. BS treatments' main goals are to quickly suppress inflammatory exacerbations and prevent relapses in order to protect organ functions and provide good quality of life. Besides the long-term experience with steroids and traditional immunosuppressives, biologic drugs, especially TNF inhibitors, have gained increasing importance in the treatment of BS over the years. In this review, we aimed to give an overview of the studies with conventional and biological drugs with proven efficacy in the treatment of BS, as well as promising drugs and current management strategies according to clinical phenotypes