Novel NLRP3/cryopyrin mutations and pro-inflammatory cytokine profiles in Behçet's syndrome patients

The role of mutations in NLRP3 in inflammatory features of Behçet's syndrom

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

Treatment strategies for Behcet's disease

Background: Behcet's disease (BID) is a multisytemic vasculitis characterized by oral and genital ulceration, other skin lesions, uveitis and manifestations affecting the blood vessels, CNS and gastrointestinal system. It is rare in the Western world but is frequent in the Middle and Far East. Objective: The aim of this review is to discuss treatment strategies in BD. These might vary between simple reassurance and a combination of immunosuppressives. Methods: A systematic literature search was done using the Cochrane and Medline databases in June 2008. The EULAR recommendations for the management of BID were also taken into account. Conclusion: The last two decades have witnessed considerable improvement in eye disease and musculoskeletal involvement. However, the treatment of thrombophlebitis, CNS, and gastrointestinal manifestations remains problematic

Behcet's syndrome: disease manifestations, management, and advances in treatment

The acne lesions characteristic of Behcet's syndrome are not sterile and are commonly observed in combination with arthritis. The two main nodular skin lesions-superficial thrombophlebitis and erythema nodosum - are equally frequent, and rather difficult to distinguish. Superficial thrombophlebitis is usually observed in combination with thrombosis in large veins, and thrombosis of the large veins usually clusters with dural sinus thrombi, which make up approximately 20% of all central nervous system (CNS) lesions of Behcet's syndrome. The remaining CNS lesions are parenchymal, mainly located in the brainstem, and associated with a graver prognosis than dural sinus thrombi. The presence of clinical clusters indicates that there are at least two pathogenetic pathways in Behcet's syndrome: a reactive arthritis pathway and a thrombophilia pathway. Research into the pathogenesis of Behcet's syndrome has shown that the most consistent genetic marker of Behcet's syndrome is HLA-B51; however, the genetic association of this true-to-form 'complex' disorder with HLA-B51 is only 20%, and a whole-genome study showed associations with 16 different loci. The severity of Behcet's syndrome and the mortality associated with it tend to decrease with time, and there is no associated increase in incidence of atherosclerosis. Although treatment of skin-mucosa manifestations, eye disease and pulmonary artery aneurysms has improved significantly in the past decades, the treatment of CNS lesions and thrombophilia are still problematic

Increased enthesopathy among Behcet's syndrome patients with acne and arthritis

Objective. Behcet's syndrome is characterized by clusters of disease expression, one of which is the coexistence of acne and arthritis. The aim of this study was to test the hypothesis that enthesopathy is increased in this cluster, having features reminiscent of acne-associated arthritis