We recently granted $232,357 to childhood arthritis research. Grants are funded through theChildhood Arthritis and Rheumatology Research Alliance (CARRA). Small grants were given to pediatric rheumatologists and fellows; more awards were given to third-year fellowship students. The following projects have been funded from July 1, 2019, through June 30, 2020.
Children’s Hospital of Philadelphia
Project Title: “Biologic Discontinuation in Systemic JIA Predictors of Subsequent Disease Flare: A Cohort Study in the Childhood Arthritis and Rheumatology Research Alliance Registry”
Award Amount: $7,386
Lay Summary: Systemic juvenile idiopathic arthritis (JIA) is distinct from other types of JIA, characterized by daily fevers, rashes, joint swelling and risk of macrophage activation syndrome (MAS), a rare but life-threatening complication. Treatments that block IL-1 and IL-6 (termed “biologics”) have been shown to be very effective. Now that a higher proportion of systemic JIA patients are achieving disease control, important questions have emerged surrounding 1) the optimal duration of biologic therapy, 2) drivers of biologic discontinuation, and 3) predictors of disease flare after biologic withdrawal. This study will leverage data within the systemic JIA cohort of the CARRA registry to address these knowledge gaps. Results will help inform treatment decisions and have important implications for patients with systemic JIA, given the high cost of biologics, risk of medication-related adverse effects, burden of regular injections or infusions and potential for life-threatening disease flares.
Hospital for Special Surgery
Project Title: “Creation and Validation of a Modified Auto-inflammatory Disease Index (AIDAI) in Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) Syndrome”
Award Amount: $25,000
Lay Summary: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is the most common recurrent fever syndrome in children. Children with PFAPA have fevers that last three to five days and recur every three to six weeks, in the presence of the symptoms listed in the disease name. Although many different therapies are used to treat PFAPA, it is difficult to compare them because there are no reliable tests to measure disease activity. A disease activity index is a scoring system that accounts for different signs and symptoms of a disease to determine how severe it is. The goal of this study is to modify an already established Auto-Inflammatory Diseases Activity Index (AIDAI) and validate it to be used as an activity measure for PFAPA. This would be helpful to physicians because they would be able to treat children on a more individual level.
Montefiore Medical Center
Project Title: “Association Between UV Index and Disease Flare in Pediatric SLE Patients”
Award Amount: $12,053
Lay Summary: Systemic lupus erythematosus (SLE) is a chronic, multiorgan autoimmune disease that can occur during childhood. Rash is one of the most common signs of active disease in lupus and can range from mild to very severe and disfiguring. Although UV radiation is widely thought to be a trigger of an SLE flare, studies evaluating the relationship between sun exposure and disease activity are contradictory. This study proposes to evaluate the relationship between sun exposure (using UV index) and presence of both SLE-associated rash and overall disease activity. We will also examine the impact SLE rash has on patients’ overall quality of life. Increased understanding of the impact of this ubiquitous risk factor on pediatric SLE patients will enable us to better advise patients on protective practices and better control the disease.
Ann & Robert H. Lurie Children’s Hospital of Chicago
Project Title:“Mental Health Screening in Juvenile Myositis: Pilot and Feasibility Study”
Award Amount: $25,000
Lay Summary: Juvenile myositis (JM) causes severe weakness and disfiguring skin rashes. JM symptoms and side effects of treatment can worsen quality of life for youth with JM and their families. Despite the effects JM can have on quality of life, little is known about mental health in JM. Studies suggest that depression, anxiety and other mental health issues are common in children with chronic conditions. This study will first assess the feasibility of mental health screening in a JM Center of Excellence. The study will also evaluate the relationship of mental health with indicators of physical health in JM. In addition, the study will assess how mental health affects behaviors that are important for overall health maintenance, such as taking medications, staying physically active and protecting against sun exposure. Future studies will build on these findings with the goal of improving mental and physical health in youth with JM.
Duke University Medical Center
Project Title: “Hydroxychloroquine Dosing and Pharmacokinetics in Pediatric Lupus”
Award Amount: $25,000
Lay Summary: Active systemic lupus in children can result in long-term organ damage and disability. Hydroxychloroquine is a medication that improves disease activity in lupus and may help prevent long-term complications; however, the ideal dose of this medication in children is unknown. We propose to develop an optimal dosing strategy for hydroxychloroquine to improve the health of children who have systemic lupus.
Kristine Carandang, PhD, OTR/L
University of California, San Diego
Project Title: “Eliciting Perspectives of Adolescents and Young Adults With Pediatric Rheumatic Conditions Around the Implementation of Health Care Transition”
Award Amount: $25,000
Lay Summary:在青春期和成年早期，风湿病患者被要求在控制他们的疾病、健康和福祉和导航卫生保健系统方面变得独立。尽管卫生保健提供者认识到这是持续监测患者的关键时期，但在卫生保健如何赋予他们发展这些技能方面仍存在重大差距。本研究的目的是了解青少年和青壮年的经验，从儿科到成人风湿病设置，并获得他们的具体建议，如何改进这一过程。为此，我们将结合焦点小组的结果和一项全国性调查的结果，该调查询问参与者如何关联和解释医疗保健转型™的六个核心要素，这是一种改善当地医疗保健环境中的过渡护理的模型。我们的目标是利用这些结果，为这一高危人群提供更有针对性的、以患者为中心的护理。
Polly Ferguson, MD & Christian Hedrich, MD, PhD
University of Iowa & University of Liverpool
Project Title: “Patient Stratification Through Muscular Immune Phenotyping in Psoriasis and Psoriatic JIA”
Award Amount: $23,000
Lay Summary:银屑病是一种炎症性皮肤病，可与关节炎症(关节炎)有关。儿童牛皮癣往往比成人发病的疾病更严重。对成年人的研究表明，牛皮癣是由激活的免疫细胞造成的损害。然而，疾病机制、治疗反应和结果在很大程度上没有在儿童中研究。免疫细胞参与牛皮癣已被确定。确定免疫细胞的类型和数量可以早期诊断和预测关节炎的发展。在这项研究中确定的模式可能允许个性化的治疗方法。利用现代单细胞成像技术，该研究旨在研究对照组和患者的免疫细胞，以了解疾病机制，并提供个体结果的标志物，如关节炎的发展。了解银屑病免疫细胞的组成和特征将有助于预测疾病结局和新的个体化治疗。
Harvard Pilgrim Health Care
Project Title: “Serious Infectious Complications Associated With Rituximab Use in Children With Rheumatic Diseases”
Award Amount: $24,918
Lay Summary: Although rituximab is increasingly used off-label for the treatment of pediatric rheumatic diseases, there remains a paucity of published data evaluating the potential adverse effects of rituximab in children. Several case studies and retrospective case series reported an increased risk of serious infections following rituximab treatment in children, including cases of death from infections. However, questions remain as to whether infections in these children were caused by rituximab and not the underlying disease or concomitant treatments, and whether closer immunologic surveillance of children undergoing treatment may be warranted. Here, we seek to better understand the risk and predictors of serious infectious complications following rituximab treatment in pediatric rheumatic diseases. A further goal is to identify gaps in immunologic monitoring for children receiving rituximab for a rheumatic disease. Findings from our study will create an evidence base for developing standardized practice guidelines that would benefit the prescribing and patient communities.
University of Pittsburgh
Project Title: “Feasibility and Reliability of Handheld 3D Photogrammetry for Imaging Linear Scleroderma of the Head”
Award Amount: $25,000
Lay Summary:头部线状硬皮病是一种罕见的自身免疫性皮肤病，对儿童的医疗和美容有重要影响。监测疾病进展(定义为皮肤组织变薄)是困难的，因为准确的评估需要大量的临床经验和与患者接触的时间。虽然固定模型既麻烦又昂贵，但非侵入式3D相机可以提供更精细的皮肤变化评估。新型手持式3D摄像机可能提供跨多个临床站点和提供者的疾病状态的准确监测，而无需考虑专业知识。本初步研究将比较低成本、商用手持3D面部摄像头与已建立的基于临床的固定式3D摄像头系统的可行性和可靠性，以准确分析和表征儿童硬皮病病变。如果这项研究成功，手持3D摄像机将使患者更好地接触硬皮病专家，消除不必要的旅行，并提供皮肤变化的客观测量，以协助治疗决定和临床试验。
University of Alabama at Birmingham
Project Title: “Evaluating Care and Outcomes in Childhood-Onset Systemic Lupus Erythematosus”
Award Amount: $25,000
Lay Summary: Systemic lupus erythematosus, or lupus, is a chronic condition that can cause inflammation in multiple organ systems. When lupus is diagnosed before 18 years of age, there is more risk for long-term complications. Inflammation in the kidneys, called lupus nephritis, is one of the subtypes of lupus with the most risk for permanent damage. This project will study the short-term outcomes for people who are diagnosed with lupus nephritis in childhood. First, we will look at the data that has been collected from patients with lupus nephritis in the CARRA registry. Then, we will compare how the kidneys respond to different types of medicines. Finally, we will test if there are differences in outcomes based on demographics of the patients. This research will help pediatric rheumatologists better understand how to prevent long-term damage for children with lupus.
Cincinnati Children’s Hospital Medical Center
Project Title: “Comprehensive Assessment of Viral Exposures in JIA patients”
Award Amount: $25,000
Lay Summary: Arthritis in children most commonly begins before the age of 6, often seeming to appear out of the blue. Seasonal variation in onset and other clues have long suggested that the disease is triggered by viral infection, but there are so many different viruses that have been difficult to test. Here, we will employ a next-generation, DNA-sequencing-based method term, VirScan, to evaluate past exposure to over 200 viruses in almost 100 young children with new onset arthritis, from two sites within the CARRA network. We will compare this with a similar number of healthy children matched for age, gender and geographic location. We predict that we will find important differences in the types and number of viral infections these children have experienced, potentially pointing the way to new options for treatment, and even prevention, of juvenile idiopathic arthritis.