Mesquida Marina, Molins Blanca, Llorenç Victor, Hernández María Victoria, Espinosa Gerard, Dick Andrew D, Adán Alfredo
Ophthalmology Department, Hospital Clinic of Barcelona, University of Barcelona, Sabino de Arana, 1, 08028, Barcelona, Spain,
Int Ophthalmol. 2014 Apr;34(2):365-81. doi: 10.1007/s10792-013-9788-5. Epub 2013 Jun 1.
Behçet's disease (BD) is a multisystem inflammatory disorder of uncertain origin, although it remains defined within the spectrum of systemic immune-mediated vasculitic disorders and also represents a spectrum of putative autoimmune disease. Major symptoms include oral aphthous ulcers, genital ulcerations, skin lesions, and ocular lesions. Despite afflicting many systems, ocular complications of BD are some of the more devastating for the patient and their quality of life. Eye involvement, which affects 60-80 % of BD patients, is characterized in its more severe form by posterior or panuveitis including occlusive retinal vasculitis. While pathogenesis of BD remains complex, association with Class I MHC (HLA-B*51) predisposing to inflammation with engagement of the innate-immune system (neutrophils, NK cells), and perpetuated by the adaptive T cell responses against infectious- and/or auto-antigens. Despite the choice of conventional immunosuppressive therapies available, only recently with the advent of biologic therapy has visual prognosis and outcomes been substantially and favorably altered. For example, both interferon-α (IFN-α) and tumour necrosis factor (TNF)-α antagonists deliver promising results and for the first time improve prognosis. With IFN-α therapy, durable remissions of uveitis can be achieved and lead to drug-free remission. Similarly, anti-TNF therapy with infliximab is reported to be rapidly effective in inducing and maintaining remission. Most recently, rising evidence reports on the use of adalimumab, etanercept, and golimumab, while use of anti-interleukin (IL)-1 agents (anakinra, canakinumab, gevokizumab), IL-6 blockers (tocilizumab), and rituximab (depleting anti-CD20 antibody) is also increasing. The aim of this review is to provide evidence for the role of conventional therapies combined with evidence for advantages and disadvantages of biologic therapies in the treatment of ocular BD. Although randomized controlled trials remain sparse, evidence remains strong and enticing that biologic agents are invaluable for the treatment of sight-threatening Behçet's uveitis and makes it an exciting time for Behçet's specialists worldwide.
白塞病（BD）是一种病因不明的多系统炎症性疾病，尽管它仍被定义为系统性免疫介导的血管炎疾病谱中的一种疾病，并且也代表了一系列假定的自身免疫性疾病。主要症状包括口腔溃疡、生殖器溃疡、皮肤病变和眼部病变。尽管BD会累及多个系统，但眼部并发症对患者及其生活质量的影响更为严重。眼部受累在60%-80%的BD患者中出现，其更严重的形式表现为后部或全葡萄膜炎，包括闭塞性视网膜血管炎。虽然BD的发病机制仍然复杂，但与I类主要组织相容性复合体（HLA-B*51）相关，该复合体通过先天免疫系统（中性粒细胞、自然杀伤细胞）的参与引发炎症，并由针对感染性和/或自身抗原的适应性T细胞反应持续存在。尽管有多种传统免疫抑制疗法可供选择，但直到最近生物疗法出现，视觉预后和结果才得到实质性的改善。例如，干扰素-α（IFN-α）和肿瘤坏死因子（TNF）-α拮抗剂都取得了有前景的结果，首次改善了预后。使用IFN-α疗法可以实现葡萄膜炎的持久缓解，并导致无药缓解。同样，据报道，英夫利昔单抗的抗TNF疗法在诱导和维持缓解方面迅速有效。最近，越来越多的证据报道了阿达木单抗、依那西普和戈利木单抗的使用，同时抗白细胞介素（IL）-1药物（阿那白滞素、卡那单抗、 gevokizumab）、IL-6阻滞剂（托珠单抗）和利妥昔单抗（抗CD20消耗性抗体）的使用也在增加。本综述的目的是提供传统疗法作用的证据，并结合生物疗法在治疗眼部BD中的优缺点的证据。尽管随机对照试验仍然很少，但有强有力且诱人的证据表明生物制剂对于治疗威胁视力的白塞氏葡萄膜炎非常重要，这对于全球的白塞病专家来说是一个令人兴奋的时期。
