背景:IgG4相关疾病(IgG4-RD)是一种几乎可以影响任何器官的纤维炎症性疾病。IgG4相关的眼科疾病是涉及眼眶和眼附件的蛋白质病症。尽管已经报道了一些葡萄膜炎病例,IgG4相关眼内表现的确切模式尚不清楚.这里,我们报道了法国全国多中心的IgG4-RD合并葡萄膜炎患者队列,并进行了文献综述.
方法:患有葡萄膜炎并同时明确诊断为IgG4-RD的患者(修订的综合诊断标准,美国风湿病学会/欧洲抗风湿病联盟对IgG4-RD的分类标准,自身免疫性胰腺炎的国际共识诊断标准,或IgG4相关垂体炎的诊断标准),从我们的国家IgG4-RD和系统性纤维化数据库中筛选。同时,我们进行了PubMed文献综述,并选择了明确的IgG4-RD合并葡萄膜炎的病例.
结果:我们报告了16例患者(8例来自我们的数据库,8例来自文献)和总共30例葡萄膜炎发作。在IgG4-RD和系统性纤维化的国家数据库中,葡萄膜炎病例占IgG4-RD患者总数的3%。葡萄膜炎在IgG4-RD中有4/16例(25%)(出现在任何其他IgG4相关症状之前,中位数为9个月),9/16例(56%)与其他IgG4相关症状同时发生(在IgG4-RD诊断前的中位数为15个月),并在随访期间出现3/16患者(19%)(首次出现IgG4相关症状后的中位数为57个月).当在随访期间发生葡萄膜炎时,在6/9例(67%)患者中,它与其他器官的IgG4-RD表现相关.双侧葡萄膜炎8/16例(50%),肉芽肿5/10例(50%)。在8/13(62%)前,中间在3/13(23%),和全球性(全葡萄膜炎)患者4/13(31%)。诊断时血清IgG4中位数为3.2g/L。中位随访时间为6年,在此期间,8/16患者(50%)经历了至少一次葡萄膜炎复发。治疗数据可用于29/30葡萄膜炎耀斑。类固醇用于28/29例葡萄膜炎(97%),导致葡萄膜炎缓解16/28例(57%)。甲氨蝶呤和利妥昔单抗(与全身性类固醇联合使用)作为二线或三线治疗在6/29(21%)和5/29(17%)葡萄膜炎发作中,分别,并导致4/6例(67%)和4/5例(80%)葡萄膜炎缓解,分别。三分之一的uveitides需要至少两种不同的治疗方法来诱导缓解(主要是全身性类固醇和甲氨蝶呤或利妥昔单抗的组合)。
结论:葡萄膜炎可能是IgG4-RD的初始症状之一,在葡萄膜炎的诊断检查中应考虑IgG4-RD。其在IgG4-RD中的早期发作可能有助于疾病的早期诊断和治疗。类固醇单一疗法可能足以治疗IgG4相关的葡萄膜炎,然而复发频繁(50%),最终三分之一的患者需要至少两行治疗.因此,类固醇保护剂可以在疾病的早期阶段考虑,特别是对于复发或类固醇相关并发症风险高的患者。
BACKGROUND: IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder that can affect almost any organ. IgG4-related ophthalmic disease is a protean condition involving the orbit and ocular adnexa. Although a few cases of uveitis have been reported, the exact pattern of IgG4-related intraocular manifestations remains unclear. Here, we report on a nationwide French multicenter cohort of patients with IgG4-RD and uveitis and conducted a literature
review.
METHODS: Patients with uveitis and a concomitant definite diagnosis of IgG4-RD (Revised Comprehensive Diagnostic criteria, American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-RD, International Consensus Diagnostic Criteria for auto-immune pancreatitis, or diagnostic criteria for IgG4-related hypophysitis), were screened from our national IgG4-RD and systemic fibrosis database. Concomitantly, we conducted a PubMed literature
review and selected cases of definite IgG4-RD with uveitis.
RESULTS: We reported on 16 patients (8 from our database and 8 from the literature) and a total of 30 episodes of uveitis. Uveitis cases represented 3 % of total IgG4-RD patients in the national database on IgG4-RD and systemic fibrosis. Uveitis was inaugural in IgG4-RD in 4/16 cases (25 %) (appearing before any other IgG4-related symptom, at a median of 9 months), occurred concurrently to other IgG4-related symptoms in 9/16 cases (56 %) (at a median of 15 months before IgG4-RD diagnosis), and appeared during follow up in 3/16 patients (19 %) (at a median of 57 months after first IgG4-related symptoms). When uveitis occurred during follow up, it was associated with IgG4-RD manifestations in other organs in 6/9 patients (67 %). Uveitis was bilateral in 8/16 cases (50 %) and granulomatous in 5/10 cases (50 %). It was anterior in 8/13 (62 %), intermediate in 3/13 (23 %), and global (panuveitis) in 4/13 patients (31 %). Median serum IgG4 at diagnosis was 3.2 g/L. Median follow up time was of 6 years, during which 8/16 patients (50 %) experienced at least one relapse of uveitis. Treatment data was available for 29/30 uveitis flares. Steroids were used in 28/29 episodes of uveitis (97 %), leading to remission of uveitis in 16/28 cases (57 %). Methotrexate and rituximab (in combination with systemic steroids) were administered as second- or third-line therapy in 6/29 (21 %) and 5/29 (17 %) episodes of uveitis, respectively, and led to remission of uveitis in 4/6 cases (67 %) and 4/5 cases (80 %), respectively. One third of uveitides required at least two different lines of treatment for remission induction (mainly a combination of both systemic steroids and methotrexate or rituximab).
CONCLUSIONS: Uveitis may be one of the initial symptoms of IgG4-RD, and IgG4-RD should be considered in the diagnostic workup of uveitis. Its early onset in IgG4-RD may help with early diagnosis and treatment of the disease. Steroid monotherapy may be sufficient to treat IgG4-related uveitis, yet relapses were frequent (50 %) and ultimately a third of patients required at least two lines of treatment. Hence, steroid-sparing agents can be considered at early stages of the disease, particularly for patients with a high risk of relapse or steroid-related complications.