Behçet’s Syndrome and Thrombosis

Behçet syndrome (BS) is a multisystem vasculitis with unknown etiology and a unique geographic distribution. The disease course is characterized by exacerbations and remissions while abating as the years pass. The usual onset is in the third decade. Recurrent skin mucosa lesions and sight threatening panuveitis are the hallmark of the disease. Males are more severely affected than females. Vascular involvement can occur in up to 40% of cases. BS is unique among the vasculitides in that it may involve all sizes and types of vessels. It affects the veins more than the arteries. Lower extremity vein thrombosis is the most frequent manifestation of vascular involvement, followed by vena cava thrombosis, pulmonary artery aneurysms, Budd-Chiari syndrome, peripheral artery aneurysms, dural sinus thrombosis and abdominal aorta aneurysms. Vascular involvement is frequently associated with constitut onal symptoms and increased acute phase response and is the major cause of increased mortality. A predominantly neutrophilic vasculitis around the vaso vasorum is typical of BS. The thrombus is tightly adherent to the vessel wall which probably explains why thromboembolism is so rare despite the high frequency of venous disease. Thrombophilic factors do not seem to explain thrombotic tendency in BS. Immunosuppressive treatment is essential in suppression and preventing the attacks

Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

Behcet's disease: How to diagnose and treat vascular involvement

Behcet's disease is a multisystem disorder with unknown etiology and a unique geographic distribution. The disease is characterized by recurrent skin-mucosa lesions and sight-threatening panuveitis. Vascular involvement, which is more common and more severe among males, has also equally characteristic features such as affecting mostly veins, having a significant tendency for thrombosis, and running a relapsing course. Lower extremity vein thrombosis (LEVT) is the most frequent manifestation, followed by vena cava inferior thrombosis. Pulmonary artery involvement (PAI), the most common form of arterial involvement, manifests as aneurysms and "in situ" thrombosis. PAI and Budd Chiari syndrome are the leading causes of increased mortality. In vascular cluster, typically, several types of venous or arterial vascular involvement may accumulate in the same individual. LEVI or cerebral venous sinus thrombosis is often present in these subgroups as the first event. Immunosuppressive treatment is essential in preventing the attacks and increasing survival. (C) 2016 Elsevier Ltd. All rights reserved

Phenotypes in Behcet's syndrome

Behcet syndrome (BS) is a multi-systemic complex disorder with unknown etiology and a unique geographic distribution. It could not be possible to include it into specific classification schemes and it is certainly not a uniform disease. Several cluster and association studies revealed that it has been composed of multiple phenotypes ascribing the principal problem such as skin-mucosa, joint, eye, vascular, neurological and gastrointestinal involvement. Each phenotype has its own characteristic demographic and clinical features as such their management strategies and prognosis differ substantially. Actually, the concept of phenotyping has been well known for some time and is considered one of the basic elements of the still continuing debate whether to call this entity disease' or syndrome'. Further supporting evidence comes from the observation of the geographical differences of disease expression. In this setting, BS resembles rather a construction made of several dynamic and interactive LEGO pieces of different shapes and colors. These pieces presenting phenotypes with their own disease mechanism have presumably different genetic determinants. The analysis of phenotyping could help us to identify this disorder and hence could contribute to find better ways of treatment

Takayasu arteritis: an update

Purpose of reviewTakayasu arteritis has long been considered as an uncommon disease, rather specific to the Far-East; however recent surveys show that the disease can be seen in all ethnicities around the world with increasing prevalence rates. Nowadays, it would not be fair to consider Takayasu arteritis as a rare disease.Recent findingsAlthough involvement of the thoracic aorta and its branches was more common among females, males had a tendency toward limited involvement of the abdominal aorta and its branches. Pregnancy seems to cause serious risks for both maternal and fetal health. Takayasu arteritis frequently coexist with inflammatory bowel diseases and the two diseases may have common genetic background and molecular pathways. New imaging tools such as computerized tomography or magnetic resonance angiography, fludeoxyglucose positron emission tomography-computerized tomography and recently contrast-enhanced ultrasonography are frequently used in the diagnosis and to assess vascular inflammation. Accumulating evidence shows that biological agents such as anti-tumor necrosis factor agents, tocilizumab and rituximab could be used effectively in refractory cases. The restenosis or occlusion risks are still high with vascular interventions. The mortality seems to be decreasing in recent years.SummaryThe ethiopathogenesis of the disease should be clarified. Our feature goals should be to discriminate better active inflammation from quiescent disease enabling more effective treatment

Behcet's syndrome: pulmonary vascular disease

Purpose of reviewPulmonary artery involvement (PAI) due to Behcet's syndrome, although rare, has always been a focus of interest not only in endemic areas but also in many parts of the world. This interest is shared by many disciplines other than internal medicine, such as radiology, cardiothoracic surgery, cardiology and respiratory medicine. Most importantly, our understanding of PAI has significantly changed in recent years.Recent findingsRecent work found the following: pulmonary artery aneurysms are not the only form of PAI. Solo in-situ' pulmonary artery thrombosis (PAT) can be found in up to one-third of the patients at presentation. Both pulmonary artery aneurysms and PAT present with similar clinical symptoms, whereas abundant hemoptysis is less frequent in PAT. PAI is strongly associated with thrombosis in the lower-extremity deep veins and right side of the heart. Varying and multiple pulmonary parenchymal lesions such as nodules, consolidations and cavities are part of this involvement as well. While either aneurysms or thrombosis could disappear successfully with immunosuppressives in up to 70% of the patients, the condition can be fatal still in one-fourth. Large aneurysms and high pulmonary artery pressures are associated with a poor prognosis.SummaryAlthough we now know the condition and its associated complications better, we need to study how we can predict development of PAI, its pathogenesis and finally what can we do to improve the survival

Behcet syndrome: the vascular cluster

Although skin-mucosa lesions are common in almost all patients with Behcet syndrome (BS), clinical properties may differ from one patient to another. Within BS, there are subsets with different organ involvement and hence probably different pathological pathways. These subsets can be described as a) solo skin-mucosa disease with no major organ involvement, b) eye disease, c) seronegative spondyloarthropathy-like disease (arthritis, enthesopathy, and folliculitis), d) Crohn-like disease, and finally the topic of this chapter: e) vascular disease. In the vascular disease subset, not surprisingly, several types of vascular involvement may be observed in the same individual. These subsets may make up the total clinical picture all at the same time or step by step with each relapse. Significant correlations exist between cerebral vascular thrombosis and pulmonary artery involvement, intracardiac thrombi and pulmonary artery involvement, Budd-Chiari syndrome, and inferior vena cava syndrome. Lower extremity vein thrombosis is often present in these associations and even precedes them. The recognition of these clusters is not only important in diagnosis and management but also in basic science, including genetic studies