Outcomes of children with juvenile idiopathic arthritis-associated uveitis

描述(申请人提供)：幼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儿童，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眼病的风险儿童。然而，儿科风湿科医生和眼科医生为葡萄膜炎提供全面筛查的能力是有限的，因为指南尚未更新，以包括所有幼年关节炎亚型和其他已知的JIA视力限制并发症的风险因素。在JIA和其他相关的儿童自身免疫性疾病中进行筛查是至关重要的，因为早期检测葡萄膜炎可以预防视觉并发症并影响治疗管理。同样，在需要时进行早期积极治疗可能会避免严重的视觉并发症。为了改善患有JIA-U的儿童的健康状况和生活质量，我们需要更好地了解葡萄膜炎的危险因素、长期的视觉结果以及视觉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，标准化预后指标，阐明人类白细胞抗原风险等位基因的意义，及早准确地识别JIA-U，将有助于评估JIA-U的影响，提高对疾病病因、发病机制和预后的了解。同样，改进的风险分层方案可以减少不必要的眼科就诊，并帮助我们识别出患严重眼病和并发症的风险更高的儿童。本研究的目的是1)确定JIA-U的临床特征和病程在欧洲和非洲裔儿童JIA-U中的差异，以确定葡萄膜炎的临床和遗传风险标志物；2)检查一项对一组早期JIA儿童进行的为期4年的前瞻性研究，以确定哪些因素与葡萄膜炎的最终发展有关，并提供其纵向分布的数据；3)使用主客观测量方法确定关节炎和葡萄膜炎对身体和视力残疾、特定视力的生活质量和总体生活质量的影响。我们希望采用综合的生物、遗传和心理社会方法，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，以确定严重残疾和失明风险最大的儿童群体，以便制定干预措施，改善他们的总体结局。这位候选人是一名儿科风湿学家，也是埃默里大学的儿科学助理教授。她获得了临床调查理学硕士学位。她致力于自身免疫性眼病儿童的临床结果研究。她组建了一支优秀的指导团队，拥有与她的目标相关的儿科风湿病、儿科眼科、儿科流行病学、结果研究和测量方面的经验。这个导师奖将帮助她成为一名成功的独立临床科学家。 公共卫生相关性：幼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儿童。这项研究将验证已知的风险因素，并确定新的JIA-U风险标记，确定严重残疾和失明风险最大的儿童群体。预计及早发现JIA-U，定期监测眼病和并发症，并制定适当的治疗方案，可以显著提高我们儿童的生活质量和长期结局。

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.