Outcomes of children with juvenile idiopathic arthritis-associated uveitis

描述（由申请人提供）：青少年特发性关节炎相关性葡萄膜炎（JIA- u）是一种炎症性眼病，影响20%的JIA患儿，可导致白内障、青光眼、视力丧失和失明。目前的筛查指南旨在确定JIA中存在眼病风险的儿童。然而，儿科风湿病学家和眼科医生提供全面筛查葡萄膜炎的能力有限，因为指南尚未更新以包括所有幼年关节炎亚型和JIA视力限制并发症的其他已知危险因素。JIA和其他相关儿童自身免疫性疾病的筛查至关重要，因为早期发现葡萄膜炎可以预防视觉并发症并影响治疗管理。同样，在需要的时候尽早进行积极的治疗可以避免严重的视觉并发症。为了改善JIA-U儿童的健康结果和生活质量，我们需要更好地了解葡萄膜炎的危险因素、长期视力结果以及视力和身体残疾对儿童生活的影响。通过识别葡萄膜炎易感性和严重程度的危险因素，标准化结局测量指标，阐明HLA危险等位基因的意义，早期准确地识别JIA-U，将有助于提高JIA-U影响的评价以及对疾病病因、发病机制和转归的认识。同样，改进的风险分层方案可以减少不必要的眼科就诊，并帮助我们识别严重眼病和并发症风险较大的儿童。本研究的目的是：1)确定欧洲和非洲裔JIA患儿JIA- u的临床特征和病程的差异，以确定葡萄膜炎的临床和遗传风险标志物；2)检查在一组诊断为早期JIA的儿童队列中进行的为期4年的前瞻性研究中发现的危险因素，以确定哪些因素与葡萄膜炎的最终发展相关，并提供其纵向分布的数据。3)使用主观和客观的测量方法确定同时患有关节炎和葡萄膜炎对身体和视力残疾、视力特异性生活质量和总体生活质量的影响。通过综合生物学、遗传学和社会心理方法，我们希望根据JIA亚型制定更广泛适用的风险分层方案，并确定新的风险因素，从而确定严重残疾和失明风险最高的儿童群体，从而制定干预措施，改善他们的总体结果。该候选人是一名儿科风湿病学家，也是埃默里大学（Emory University）儿科助理教授。她获得了临床研究理学硕士学位。她致力于自身免疫性眼病儿童的临床结果研究。她组建了一个优秀的指导团队，在儿科风湿病学、儿科眼科、儿科流行病学、结果研究和测量方面具有丰富的经验，这些都与她的目标相关。这个导师奖将帮助她成为一名成功的独立临床科学家。

DESCRIPTION (provided by applicant): Juvenile idiopathic arthritis-associated uveitis (JIA-U) is an inflammatory eye disease that affects 20% of children with JIA and can lead to cataracts, glaucoma, vision loss and blindness. Current screening guidelines are designed to identify children at risk for eye disease in JIA. However, pediatric rheumatologists' and ophthalmologists' ability to provide comprehensive screening for uveitis is limited because the guidelines have not been updated to include all juvenile arthritis subtypes and other known risk factors for vision-limiting complications of JIA. Screening in JIA and other related autoimmune diseases of childhood is crucial because early uveitis detection can prevent visual complications and influence therapeutic management. Likewise, institution of early aggressive therapy when needed may avert serious visual complications. To improve health outcomes and quality of life of children with JIA-U, we need a better understanding of risk factors for uveitis, long-term visual outcomes, and the effects of visual and physical disability on children's lives. Early and accurate identification of JIA-U through the identification of risk factors for susceptibility and severity of uveitis, standardization of outcome measures, and elucidation of the significance of HLA risk alleles would improve the evaluation of the impact of JIA-U and the understanding of disease etiology, pathogenesis and outcome. Likewise, an improved risk stratification scheme could reduce unnecessary ophthalmology visits and help us identify children at greater risk for severe eye disease and complications. The objectives of this study are to 1) Identify differences in the clinical characteristics and course of JIA-U in patients of European and African descent in children with JIA to identify clinical and genetic risk markers for uveitis, 2) Examine the risk factors identified over a 4-year prospective study of a cohort of children diagnosed with early JIA to determine which factors are associated with eventual development of uveitis, and provide data on their longitudinal profile, 3) Determine the impact of having both arthritis and uveitis on physical and visual disability, vision-specific QOL, and overall QOL using subjective and objective measures. Using a comprehensive biologic, genetic and psychosocial approach, we hope to develop more widely applicable risk stratification schemes based on JIA subtype, and to identify new risk factors that will identify the populations of children at greatest risk for severe disability and blindness so that interventions can be developed to improve their overall outcome. The candidate is a pediatric rheumatologist and an assistant professor of pediatrics at Emory University. She has obtained a Masters of Science in Clinical Investigation. She is devoted to a career in clinical outcomes research in children with autoimmune eye diseases. She has assembled an outstanding mentoring team with experience in pediatric rheumatology, pediatric ophthalmology, pediatric epidemiology, outcomes research and measurement, which are relevant to her objectives. This mentored award will help her become a successful independent clinician scientist. PUBLIC HEALTH RELEVANCE: Juvenile idiopathic arthritis-associated uveitis (JIA-U) is an inflammatory eye disease that affects 20% of children with JIA. This research will validate known risk factors and identify new risk markers of JIA-U, identifying populations of children at greatest risk for severe disability and blindness. It is anticipated that early detection of JIA-U, regular monitoring for eye disease and complications, and institution of appropriate therapy can significantly improve our children's quality of life and long-term outcomes.